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    Oxazolidinone Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic oxazolidinone antibiotic
    Indicated for treatment of bacterial pneumonia, skin and skin structure infections, and for vancomycin-resistant enterococcal (VRE) infections, including infections due to susceptible organisms which are complicated by bacteremia
    Inhibits MAO and may cause drug interactions with adrenergic and serotonergic drugs

    COMMON BRAND NAMES

    Zyvox

    HOW SUPPLIED

    Linezolid/Zyvox Intravenous Inj Sol: 1mL, 2mg
    Linezolid/Zyvox Oral Pwd F/Recon: 5mL, 100mg
    Linezolid/Zyvox Oral Tab: 600mg

    DOSAGE & INDICATIONS

    For the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia, and nosocomial pneumonia.
    For the treatment of nosocomial pneumonia.
    Oral dosage
    Adults

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] [61215] Guidelines recommend empiric linezolid use in patients with risk factors for MRSA. Oral therapy is not addressed in guidelines, but de-escalation in general is recommended.[61215]

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for at least 7 days.[28599] [46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days.[28599] [46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response.[28599] [46693]

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] [61215] Guidelines recommend empiric linezolid use in patients with risk factors for MRSA.[61215]

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for at least 7 days.[28599] [46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days.[28599] [46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response.[28599] [46693]

    For the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia.
    Oral dosage
    Adults

    600 mg PO every 12 hours for at least 7 days as part of combination therapy for hospitalized patients with prior respiratory isolation of MRSA or risk factors for MRSA and recent hospitalization with parenteral antibiotic use.[28599] [34362] [46693] [64669]

    Adolescents

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693] In HIV-infected patients, linezolid is recommended as part of combination therapy for patients with risk factors for MRSA.[34362]

    Children 12 years

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for at least 7 days as part of combination therapy for hospitalized patients with prior respiratory isolation of MRSA or risk factors for MRSA and recent hospitalization with parenteral antibiotic use.[28599] [34362] [46693] [64669]

    Adolescents

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693] In HIV-infected patients, linezolid is recommended as part of combination therapy for patients with risk factors for MRSA.[34362]

    Children 12 years

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    For the treatment of skin and skin structure infections, including cellulitis and diabetic foot ulcer, due to susceptible organisms.
    For complicated skin and skin structure infections including diabetic foot infections (e.g., diabetic foot ulcer) without concomitant bone involvement and infections caused by Staphylococcus aureus (MSSA or MRSA), S. pyogenes, or S. agalactiae.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 10 to 14 days. NOTE: Linezolid has not been studied for decubital ulcers. The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 7 to 14 days as an option for MRSA-associated infections.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 10 to 14 days. NOTE: Linezolid has not been studied for decubital ulcers. The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 7 to 14 days as an option for MRSA-associated infections.

    Infants and Children 1 to 11 years

    10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 10 to 14 days in length. The Infectious Diseases Society of America (IDSA) recommends linezolid for 7 to 14 days as an option for MRSA-associated infections.

    Oral dosage
    Adults

    600 mg PO every 12 hours for 10 to 14 days. NOTE: Linezolid has not been studied for decubital ulcers. The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 7 to 14 days as an option for MRSA-associated infections.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 10 to 14 days. NOTE: Linezolid has not been studied for decubital ulcers. The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 7 to 14 days as an option for MRSA-associated infections.

    Infants and Children 1 to 11 years

    10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 7 to 14 days as an option for MRSA-associated infections.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 10 to 14 days in length. The Infectious Diseases Society of America (IDSA) recommends linezolid for 7 to 14 days as an option for MRSA-associated infections.

    For uncomplicated skin and skin structure infections due to Staphylococcus aureus (MSSA, MRSA†) or S. pyogenes.
    Oral dosage
    Adults

    400 mg PO every 12 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Children 5 to 11 years

    10 mg/kg/dose PO every 12 hours (Max: 600 mg/dose) for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Infants and Children 1 to 4 years

    10 mg/kg/dose PO every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 10 to 14 days. The Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. Total course of therapy should be 10 to 14 days in length. The Infectious Diseases Society of America (IDSA) recommends linezolid for 5 to 10 days as an option for MRSA-associated purulent or non-purulent cellulitis.

    For the treatment of pulmonary extensively drug-resistant tuberculosis infection (XDR-TB) or treatment-intolerant or nonresponsive multidrug-resistant tuberculosis infection (MDR-TB) as part of a combination regimen with bedaquiline and pretomanid.
    NOTE: Safety and effectiveness have not been established for use in combination with drugs other than bedaquiline and pretomanid.[64561]
    NOTE: This combination regimen is not indicated for the treatment of drug-sensitive tuberculosis, latent Mycobacterium tuberculosis infection, extra-pulmonary Mycobacterium tuberculosis infection, or MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy.[64561]
    Oral dosage
    Adults

    1,200 mg PO once daily for 26 weeks. May extend dosing of the combination regimen beyond 26 weeks if needed. If pretomanid or bedaquiline is discontinued, discontinue the entire combination regimen. If linezolid is permanently discontinued during the initial 4 consecutive weeks of treatment, discontinue the entire combination regimen. If linezolid is discontinued after the initial 4 weeks of consecutive treatment, continue pretomanid and bedaquiline therapy.[64561]

    For the treatment of sepsis† or bacteremia due to vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA)†.
    For the treatment of infections due to vancomycin-resistant enterococci (VRE) (i.e., E. faecium; E. faecalis), including those infections with concurrent bacteremia or sepsis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 14 to 28 days. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 14 to 28 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 14 to 28 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for 14 to 28 days.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for 14 to 28 days.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.

    Oral dosage
    Adults

    600 mg PO every 12 hours for 14 to 28 days. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 14 to 28 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 14 to 28 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 14 to 28 days.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 14 to 28 days.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.

    For the treatment of persistent Staphylococcus aureus (MRSA) bacteremia† with vancomycin failure and sepsis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours with high dose daptomycin for at least 2 weeks for persistent bacteremia. If reduced susceptibility to vancomycin and daptomycin are present, linezolid 600 mg IV every 12 hours may be administered as a single agent or in combination with other antibiotics. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Oral dosage
    Adults

    600 mg PO every 12 hours with high dose daptomycin for at least 2 weeks for persistent bacteremia. If reduced susceptibility to vancomycin and daptomycin are present, linezolid 600 mg PO every 12 hours may be administered as a single agent or in combination with other antibiotics. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    For the treatment of neonatal methicillin-resistant Staphylococcus aureus (MRSA) sepsis†.
    Intravenous dosage
    Neonates 34 weeks gestation and older

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose IV every 8 hours. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose IV every 8 hours. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    Oral dosage
    Neonates 34 weeks gestation and older

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose PO every 8 hours. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    Premature Neonates less than 34 weeks gestation and older than 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose PO every 8 hours. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited. The dosage used for other indications is 10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length. Linezolid is not recommended for the empiric treatment of central nervous system infections in pediatric patients.

    For the treatment of MRSA-associated bone and joint infections†, including osteomyelitis† and septic/infectious arthritis†, or an orthopedic device-related infection†.
    For the treatment of osteomyelitis†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours. Rifampin 600 mg PO daily or 300 to 450 mg PO twice daily may be added; however, in patients with concurrent bacteremia, rifampin should be added after the clearance of the bacteremia. A minimum duration of 8 weeks is recommended; an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus either sulfamethoxazole/trimethoprim, doxycycline, minocycline, clindamycin, or a fluoroquinolone may be necessary.

    Children and Adolescents 12 to 17 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 4 to 6 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 4 to 6 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 4 to 6 weeks.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours. Rifampin 600 mg PO daily or 300 to 450 mg PO twice daily may be added; however, in patients with concurrent bacteremia, rifampin should be added after the clearance of the bacteremia. A minimum duration of 8 weeks is recommended; an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus either sulfamethoxazole/trimethoprim, doxycycline, minocycline, clindamycin, or a fluoroquinolone may be necessary.

    Children and Adolescents 12 to 17 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 4 to 6 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 4 to 6 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 4 to 6 weeks.

    For the treatment of septic arthritis†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 3 to 4 weeks.

    Children and Adolescents 12 to 17 years

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 3 to 4 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 3 to 4 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 3 to 4 weeks.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 3 to 4 weeks.

    Children and Adolescents 12 to 17 years

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 3 to 4 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 3 to 4 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 3 to 4 weeks.

    For the treatment of prosthetic joint infections†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours for 2 weeks in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus a fluoroquinolone, sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin) should start after the completion of IV therapy and continue for 3 months for hip infections or for 6 months for knee infections.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours for 2 weeks in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus a fluoroquinolone, sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin) should continue for 3 months for hip infections or for 6 months for knee infections.

    For the treatment of spinal implant infections†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy (sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin +/- rifampin, or a fluoroquinolone plus rifampin) should follow parenteral therapy; however, the optimal duration of parenteral and/or oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy (sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin +/- rifampin, or a fluoroquinolone plus rifampin) should follow; however, the optimal duration of oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    For the treatment of central nervous system infections†, including meningitis†, ventriculitis†, brain abscess†, subdural empyema†, spinal epidural abscess†, and septic thrombosis of the cavernous or dural venous sinus†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours as an alternative to vancomycin is recommended by the Infectious Diseases Society of America (IDSA). The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Children and Adolescents 12 to 17 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg IV every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants and Children 1 to 11 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Oral dosage
    Adults

    600 mg PO every 12 hours as an alternative to vancomycin is recommended by the Infectious Diseases Society of America (IDSA). The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Children and Adolescents 12 to 17 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg PO every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants and Children 1 to 11 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    For the treatment of febrile neutropenia†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours has been studied. Guidelines suggest linezolid as an option in patients with MRSA or VRE. In a double-blind, randomized controlled trial, IV linezolid was equivalent to vancomyin in patients with suspected or confirmed gram-positive infection.

    Oral dosage
    Adults

    600 mg PO every 12 hours. Guidelines suggest linezolid as an option in patients with MRSA or VRE. In a double-blind, randomized controlled trial, IV linezolid was equivalent to vancomyin in patients with suspected or confirmed gram-positive infection.

    For the treatment of infective endocarditis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours for more than 6 weeks for endocarditis caused by Enterococcus sp. resistant to penicillin, aminoglycosides, and vancomycin.

    Children and Adolescents 12 to 17 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg IV every 12 hours.

    Infants and Children 1 to 11 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose).

    Neonates

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours.

    Oral dosage
    Adults

    600 mg PO every 12 hours for more than 6 weeks for endocarditis caused by Enterococcus sp. resistant to penicillin, aminoglycosides, and vancomycin.

    Children and Adolescents 12 to 17 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg PO every 12 hours.

    Infants and Children 1 to 11 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose).

    Neonates

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours.

    For the treatment of systemic anthrax† infection.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is a preferred therapy in systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Children and Adolescents 12 to 17 years

    15 mg/kg/dose IV every 12 hours (Max: 600 mg/dose) in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam/glycopeptide (i.e., meropenem, imipenem; cilastatin, vancomycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Infants and Children 1 to 11 years

    10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam/glycopeptide (i.e., meropenem, imipenem; cilastatin, vancomycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Neonates 35 weeks gestation and older

    10 mg/kg/dose IV every 8 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Premature Neonates 32 to 34 weeks gestation and older than 7 days

    10 mg/kg/dose IV every 8 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Premature Neonates 32 to 34 weeks gestation and 0 to 7 days of age

    10 mg/kg/dose IV every 12 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Oral dosage
    Children and Adolescents 12 to 17 years

    15 mg/kg/dose PO every 12 hours (Max: 600 mg/dose). Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Infants and Children 1 to 11 years

    10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose). Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Neonates 35 weeks gestation and older

    10 mg/kg/dose PO every 8 hours. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Premature Neonates 32 to 34 weeks gestation and older than 7 days

    10 mg/kg/dose PO every 8 hours. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Premature Neonates 32 to 34 weeks gestation and 0 to 7 days of age

    10 mg/kg/dose PO every 12 hours in combination with a fluoroquinolone. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1,200 mg/day PO or IV.

    Geriatric

    1,200 mg/day PO or IV.

    Adolescents

    1,200 mg/day PO or IV.

    Children

    12 years: 1,200 mg/day PO or IV.
    1 to 11 years: 10 mg/kg/dose PO or IV every 8 hours (Max: 600 mg/dose).

    Infants

    10 mg/kg/dose PO or IV every 8 hours.

    Neonates

    10 mg/kg/dose PO or IV every 8 hours.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is recommended in mild to moderate hepatic insufficiency (Child-Pugh class A or B). Linezolid has not been studied in severe hepatic dysfunction, but dosage adjustments are probably not needed. Linezolid and its inactive metabolites are not metabolized via the liver.

    Renal Impairment

    Similar plasma concentrations are achieved regardless of the degree of renal impairment, no dosage adjustment is needed (manufacturer's recommendations). Follow normal dosage.
     
    Intermittent hemodialysis
    Linezolid and its metabolites are removed by hemodialysis. Roughly 30% of a linezolid dose is eliminated in a 3-hour hemodialysis session. Timing of dosage should allow for administration of a normally scheduled dose after a hemodialysis session (manufacturer's recommendation). For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.
     
    Peritoneal dialysis
    No dosage adjustment is necessary in adults and pediatric patients receiving the adult dosage. For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.
     
    Continuous hemodialysis (CAVH, CVVH)
    Linezolid is significantly removed by CVVHD. The standard dose of at least 600 mg PO/IV twice daily is predicted to cover approximately 93% of organisms with an MIC up to 2 mg/L; higher doses may be required for organisms with an MIC up to 4 mg/L.

    ADMINISTRATION

    Oral Administration

    Administer without regard to food.[28599]
     
    When used for pulmonary extensively drug-resistant tuberculosis infection (XDR-TB) or treatment-intolerant or nonresponsive multidrug-resistant tuberculosis infection (MDR-TB) as part of a combination regimen with bedaquiline and pretomanid:
    Administer by directly observed therapy (DOT).
    Emphasize the need for compliance with the full course of therapy to patients.
    If the combination regimen is interrupted by a healthcare provider for safety reasons, missed doses can be made up at the end of treatment; do not make up doses of linezolid alone missed due to linezolid adverse reactions.
    If pretomanid or bedaquiline is discontinued, discontinue the entire combination regimen. If linezolid is permanently discontinued during the initial 4 consecutive weeks of treatment, discontinue the entire combination regimen. If linezolid is discontinued after the initial 4 weeks of consecutive treatment, continue pretomanid and bedaquiline therapy.[64561]

    Oral Liquid Formulations

    Before using, gently mix the constituted suspension well by turning the bottle gently upside down 3 or 5 times; do not shake the bottle before administration.
    Administer using a calibrated measuring device.[28599]
     
    Reconstitution of the oral suspension
    Review the manufacturer's reconstitution instructions for the particular product and package size; the amount of water to be used for reconstitution may vary between manufacturers.
    Prior to reconstitution, tap the bottle several times to loosen the powder.
    Add approximately half of the total amount of water needed and shake well. Add the remaining water and shake well.
    Storage: The prepared oral suspension may be kept at controlled room temperature, protected from light, for 21 days without significant loss of potency. Discard any unused suspension after 21 days.[28599]

    Injectable Administration

    Visually inspect parenteral products for leaks, particulate matter and discoloration prior to administration whenever solution and container permit. A yellow color may intensify over time but does not affect the potency of linezolid.

    Intravenous Administration

    Linezolid IV infusion is available in a concentration of 2 mg/mL as a pre-mixed sterile IV infusion in ready-to-use plastic infusion bags; no further dilution is required.
     
    Intermittent IV infusion
    Do not use the infusion bag in series connections. Do not introduce additives into the linezolid infusion solution.
    Linezolid is physically and chemically incompatible with several drugs during simultaneous Y-site administration. If the same intravenous line is used for the sequential infusion of several medications, the line should be flushed before and after the linezolid infusion.
    Compatible intravenous solutions for line flushing include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer's Injection.
    Keep the linezolid dose in the overwrap protected from light until ready to use.
    Infuse the ordered linezolid dosage IV over 30 to 120 minutes.

    STORAGE

    Zyvox:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Phenylketonuria

    Linezolid is contraindicated for use in patients known to be hypersensitive to the drug or any of the components of the formulations. Linezolid oral suspension should be used with caution in those patients with phenylketonuria because the linezolid oral suspension is formulated with aspartame, which supplies roughly 20 mg of phenylalanine per each 5 ml of suspension. Other linezolid products do not contain phenylalanine.

    Bone marrow suppression

    Myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment concentrations. Monitor complete blood counts weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than 2 weeks, those with pre-existing bone marrow suppression, those receiving concomitant drugs that produce bone marrow suppression, or those with chronic infection who have received previous or concomitant antibiotic therapy. Consider discontinuing linezolid in patients who develop or have worsening myelosuppression.[28599] In patients receiving linezolid as part of a combination regimen for tuberculosis, monitor complete blood counts at a minimum at baseline, at 2 weeks, and then monthly. Consider decreasing or interrupting linezolid dosing in patients who develop or have worsening myelosuppression during tuberculosis therapy.[64561]

    Hypertension, hyperthyroidism, pheochromocytoma, thyrotoxicosis

    Unless patients are monitored for potential increases in blood pressure, linezolid should not be administered to patients with uncontrolled hypertension, untreated hyperthyroidism/thyrotoxicosis, carcinoid syndrome, or pheochromocytoma. Additionally, patients receiving directly and indirectly acting sympathomimetic agents, vasopressive agents, and dopaminergic agents should be monitored closely for blood pressure changes while on concomitant linezolid. Blood pressure should be routinely measured in a patient receiving linezolid, particularly if they have pre-existing hypertension or cardiovascular disease.

    Alcoholism, MAOI therapy, spinal anesthesia, surgery

    Linezolid is a non-selective inhibitor of monoamine oxidase (MAO). Hypertensive crisis is the most serious side effect of MAO-inhibiting medications. The potential MAO-inhibiting activity of linezolid should be considered in a patient scheduled for surgery or who will receive spinal anesthesia. Linezolid-induced MAO inhibition will reduce the metabolism of pressor amines, which may increase blood pressure in these individuals. Blood pressure should be routinely measured in a patient receiving linezolid, particularly if they have pre-existing hypertension or cardiovascular disease. Linezolid should not be used concurrently or within 14 days of MAOI therapy. Certain non-MAOI medications interact with MAO inhibitors and should be used cautiously during linezolid therapy. Alcohol, excessive caffeine, or certain foods or beverages known to interact with MAO inhibitors should be avoided. Use linezolid with caution in patients with active alcoholism because of the reduced ability to follow necessary dietary restriction of alcoholic beverages.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Optic neuritis

    Optic neuritis, sometimes progressing to visual loss, has been reported in patients treated with linezolid, primarily those treated for longer than 28 days. In patients where optic neuropathy has progressed to visual loss, the duration of treatment was for extended periods beyond the recommended duration. Monitor visual function in all patients taking linezolid for extended periods (3 months or more), in all patients reporting new visual symptoms regardless of length of linezolid therapy, and in all patients receiving linezolid as part of combination therapy for tuberculosis. If patients experience symptoms of visual impairment, regardless of length of therapy, prompt ophthalmic evaluation is recommended. If optic neuropathy occurs, weigh continued use of linezolid against the potential risks; interrupt linezolid dosing for tuberculosis. Neuropathy associated with linezolid is generally reversible or improved with appropriate monitoring and linezolid dosing interruption, reduction, or discontinuation.[28599] [64561]

    Children, infants, neonates, premature neonates

    The safety and effectiveness of linezolid in the treatment of children, infants, and adolescents from birth through 17 years is supported by evidence from adult clinical trials, pharmacokinetic data in pediatric patients, and a comparator-controlled study. However, in pharmacokinetic data from children with ventriculoperitoneal shunts, cerebrospinal fluid (CSF) linezolid concentrations were variable and therapeutic concentrations were not consistently achieved or maintained; the manufacturer recommends to not use linezolid as empiric therapy in the treatment of CNS infections (e.g., shunt infections, meningitis) in pediatrics. In addition, linezolid has been studied in premature neonates (gestational age < 34 weeks); however, due to lower systemic clearance values, a reduction in the initial dosage is indicated in preterm neonates < 7 days of life (see Dosage).

    Pregnancy

    Linezolid is classified in FDA pregnancy risk category C. Linezolid was not teratogenic in rats at exposure levels 4-fold higher than the expected human exposure level based on AUC. However, embryo and fetal toxicities (non-teratogenic), such as increased rates of postimplantation embryo death, reduced fetal weight, reduced ossification, and increased pup mortality were seen. Because there are no well controlled studies in pregnant women and animal studies are not always predictive of human response, linezolid should only be used in pregnancy if the potential benefit justifies the potential fetal risk.

    Infertility

    In male rats, linezolid contributed to infertility, possibly via epithelial cell hypertrophy in the epididymis which affected proper maturation of sperm. In male dogs, decreased sperm motility was noted. No fertility changes occurred in female animals. Histologic pathological changes were not noted; decreased fertility was reversible on drug discontinuation. No human studies of the effects of linezolid on male fertility have been conducted.

    Breast-feeding

    Use linezolid with caution in breast-feeding females. Linezolid and its metabolites are excreted into the breast milk in rats at concentrations similar to maternal rat plasma. It is likely that linezolid is excreted in human milk. After a single dose of 600 mg of oral linezolid in a lactating woman, milk samples were taken at 10 time points over the next 24 hours. The peak concentration was 12.36 mg/L occurring 2 hours after the dose. Milk concentrations fell with a half-life of 6.47 hours and were detectable up to 24 hours after the dose. The AUC was 100.79 mcg x hour/mL. Based on a peak breast milk concentration of 12.36 mg/L and a daily intake of 150 mL/kg/day of breast milk, the maximum dose that an infant would receive via milk would be less than 2 mg/kg/day. In addition to antimicrobial effects, linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO), but no data are available on the risks of MAO inhibition to the breast-feeding infant. Vancomycin, daptomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. Site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed be fore choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Daptomycin has a high molecular weight; therefore, excretion into breast milk may be limited. In 1 patient with daptomycin breast milk concentration measured on day 27 of therapy (dose of 6.7 mg/kg IV), a peak concentration of 44.7 mcg/L was obtained 8 hours after the dose with an estimated milk:plasma ratio of 0.0012. Alternative antimicrobials that previous American Academy of Pediatrics recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.

    Seizure disorder, seizures

    Linezolid should be used with caution in patients with a history of a seizure disorder. Seizures have been reported with linezolid and in some of the cases, patients had a history of seizures or risk factors for seizures.

    Radiographic contrast administration

    Linezolid is relatively contraindicated when metrizamide or iohexol are used during radiographic contrast administration. Use of these contrast agents in patients receiving MAOIs can increase the risk of seizures by lowering the seizure threshold. Non-selective MAO inhibitors should usually be discontinued at least 48 hours before myelography; the drugs should not be resumed until 24 hours after the procedure.

    Diabetes mellitus, hypoglycemia

    Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving insulin or oral hypoglycemic therapy. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, a decrease in the dose of insulin or hypoglycemic agent may be necessary. Discontinuation of these agents or linezolid may be required in some patients. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or hypoglycemic agents.

    Geriatric

    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    pancytopenia / Delayed / Incidence not known
    sideroblastic anemia / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    lactic acidosis / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    thrombocytopenia / Delayed / 0-12.9
    anemia / Delayed / 0-5.6
    eosinophilia / Delayed / 0.4-1.9
    candidiasis / Delayed / 0-1.8
    elevated hepatic enzymes / Delayed / 0.4-1.6
    hypoglycemia / Early / 0-1.0
    hypertension / Early / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    bullous rash / Early / Incidence not known

    Mild

    diarrhea / Early / 8.0-11.0
    vomiting / Early / 2.0-9.4
    headache / Early / 0.9-8.8
    nausea / Early / 1.9-6.6
    dizziness / Early / 1.8-2.6
    abdominal pain / Early / 0.5-2.4
    rash / Early / 1.0-2.0
    dysgeusia / Early / 1.0-1.8
    pruritus / Rapid / 0.8-1.4
    tongue discoloration / Delayed / 0.3-1.3
    vertigo / Early / 0-1.2
    tooth discoloration / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Butalbital; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Dihydrocodeine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    Acetaminophen; Dextromethorphan: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Linezolid may enhance the hypertensive effect of isometheptene. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as isometheptene.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Oxycodone: (Major) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as linezolid. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Acetaminophen; Pentazocine: (Moderate) Patients receiving concurrent pentazocine and agents with monoamine oxidase inhibitor (MAOI) activity, such as linezolid may be at increased risk for developing serotonin syndrome. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including pentazocine. If concurrent use is clinically indicated, the patient needs to be carefully observed for any signs or symptoms of serotonin excess such as restlessness, myoclonus, confusion, hyperreflexia, diaphoresis, shivering, tachycardia, and tremor.
    Acetaminophen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Tramadol: (Severe) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Acetohexamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Aclidinium; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Acrivastine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Albiglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Albuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Albuterol; Ipratropium: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Alfentanil: (Major) In theory, the use of alfentanil in a patient taking linezolid may increase the risk of serotonergic symptoms. Linezolid has MAOI activity; the manufacturer of alfentanil does not recommend its use within 14 days of an MAO Inhibitor. Alfentanil belongs to the same group of opiate agonists, phenylpiperidines, as meperidine, a known serotonin reuptake inhibitor. Caution is advised until more data are available.
    Alogliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Alogliptin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Alogliptin; Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Amitriptyline: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Amitriptyline; Chlordiazepoxide: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Amoxapine: (Moderate) Amoxapine should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
    Amphetamines: (Severe) Amphetamines should not be administered during or within 14 days after the use of linezolid. Linezolid possesses MAO-inhibiting activity and can prolong and intensify the cardiac stimulation and vasopressor effects of the amphetamines, potentially resulting in hypertensive crisis. Linezolid also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. If serotonin syndrome occurs, discontinue serotonergic drugs and institute appropriate medical management.
    Arformoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Armodafinil: (Moderate) Use caution during coadministration of armodafinil with MAO inhibitors. Armodafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs), including drugs with MAO inhibiting activity (e.g., linezolid). Other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with MAO inhibitor activity.
    Articaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Carisoprodol; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    Aspirin, ASA; Oxycodone: (Major) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as linezolid. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Atenolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Atenolol; Chlorthalidone: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Atomoxetine: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa. Atomoxetine, a selective norepinephrine reuptake inhibitor, is contraindicated with the use of any MAOI due to the potential for serious reactions. Clinically, the potential for interaction between linezolid and atomoxetine has not been studied.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Atropine; Difenoxin: (Moderate) Linezolid may enhance the hypertensive effect of diphenoxylate. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate with MAOIs may, in theory, precipitate hypertensive crisis.
    Atropine; Diphenoxylate: (Moderate) Linezolid may enhance the hypertensive effect of diphenoxylate. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate with MAOIs may, in theory, precipitate hypertensive crisis.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids. (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Bendroflumethiazide; Nadolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Benzhydrocodone; Acetaminophen: (Major) The use of benzhydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of benzhydrocodone with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as benzhydrocodone.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Beta-adrenergic blockers: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Beta-agonists: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Betaxolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Bisoprolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Brimonidine: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Brinzolamide: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers. (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Bromocriptine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Brompheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Budesonide; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Buprenorphine: (Major) Concurrent use of opioids with other drugs that modulate serotonergic function, such as linezolid, has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
    Buprenorphine; Naloxone: (Major) Concurrent use of opioids with other drugs that modulate serotonergic function, such as linezolid, has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
    Bupropion: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid.
    Bupropion; Naltrexone: (Severe) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid.
    Buspirone: (Moderate) Linezolid should generally not be administered to patients taking serotonergic agents, such as buspirone, due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of buspirone; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Several cases of elevated blood pressure have been reported in patients in whom buspirone was added to a non-selective traditional MAO-inhibitor regimen.
    Cabergoline: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
    Caffeine; Ergotamine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Canagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Carbamazepine: (Major) Carbamazepine is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if carbamazepine could cause decreases in linezolid exposure if coadministered. Additionally, linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor; therefore, linezolid has the potential for interaction with carbamazepine. Carbamazepine, a dibenazepine-related drug, should not be coadministered with MAO inhibitors. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering carbamazepine.
    Carbetapentane; Chlorpheniramine: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pyrilamine: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbidopa; Levodopa: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Carbidopa; Levodopa; Entacapone: (Major) Avoid the concomitant use of entacapone or tolcapone in combination with a non-selective monoamine oxidase inhibitor such as linezolid. Monoamine oxidase and catechol-O-methyltransferase are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the co-administration of entacapone or tolcapone with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions. (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carbinoxamine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Carbinoxamine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carteolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Carvedilol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Cetirizine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    Chlorpheniramine; Dextromethorphan: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpropamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Citalopram: (Severe) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with linezolid, citalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with citalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Clomipramine: (Severe) According to the manufacturer of clomipramine, treatment initiation with clomipramine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than clomipramine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving clomipramine and requiring urgent treatment with linezolid, clomipramine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Clomipramine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with clomipramine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Cocaine: (Major) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of an indirect-acting sympathomimetic, like cocaine, to patients receiving a MAOI may invoke a hypertensive reaction. In general, traditional MAO inhibitors should be discontinued for 10 days prior to elective surgery with general anesthetics or spinal anesthesia if possible.
    Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    Codeine; Guaifenesin: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    Codeine; Phenylephrine; Promethazine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Codeine; Promethazine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine.
    COMT inhibitors: (Major) Avoid the concomitant use of entacapone or tolcapone in combination with a non-selective monoamine oxidase inhibitor such as linezolid. Monoamine oxidase and catechol-O-methyltransferase are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the co-administration of entacapone or tolcapone with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Cyclobenzaprine: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving cyclobenzaprine concomitantly.
    Dapagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Dapagliflozin; Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Desipramine: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Desloratadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Desvenlafaxine: (Severe) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving desvenlafaxine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, desvenlafaxine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with desvenlafaxine may be resumed 24 hours after the last dose of linezolid.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dexmethylphenidate: (Major) Psychostimulants, such as dexmethylphenidate, exhibit sympathomimetic actions and should be avoided with other drugs, such as linezolid, that enhance the pressor response of sympathomimetic agents. A clinically significant rise in systolic blood pressure is possible. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, a non-selective monoamine oxidase inhibitor (MAOI), and medications that enhance central serotonergic activity. Monoamine oxidase (MAO) is the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
    Dextromethorphan: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Dextromethorphan; Guaifenesin: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dextromethorphan; Promethazine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Dextromethorphan; Quinidine: (Major) Dextromethorphan should be used cautiously in patients receiving linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Dextromethorphan can block neuronal uptake of serotonin; excessive concentrations of serotonin in the CNS may result if dextromethorphan is combined with some non-selective MAO inhibitors. The potential for drug interaction was studied in healthy volunteers who were administered dextromethorphan (i.e., two 20 mg doses administered 4 hours apart) with or without linezolid. A 'serotonin syndrome' was not noted. However, this study involved limited co-exposure of the drugs in patients who were not acutely ill. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including dextromethorphan.
    Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Diethylpropion: (Major) Linezolid can prolong and intensify the cardiac stimulation and vasopressor effects of diethylpropion. Diethylpropion should not be administered during, or within 14 days following the use of MAOIs, or drugs with MAO-inhibiting activity.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dihydroergotamine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Diphenhydramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Dobutamine: (Major) Linezolid may enhance the hypertensive effect of dobutamine. Initial doses of dobutamine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as dobutamine.
    Dolasetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Dopamine: (Major) Linezolid may enhance the hypertensive effect of dopamine. Initial doses of dopamine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as dopamine.
    Dorzolamide; Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Doxepin: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than a TCA (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with doxepin or other TCAs can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Droxidopa: (Major) Avoid concurrent use of droxidopa and linezolid, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
    Dulaglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Duloxetine: (Severe) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as duloxetine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving duloxetine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, duloxetine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with duloxetine may be resumed 24 hours after the last dose of linezolid.
    Empagliflozin; Linagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Empagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Entacapone: (Major) Avoid the concomitant use of entacapone or tolcapone in combination with a non-selective monoamine oxidase inhibitor such as linezolid. Monoamine oxidase and catechol-O-methyltransferase are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the co-administration of entacapone or tolcapone with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Ephedrine: (Moderate) Linezolid may enhance the hypertensive effect of ephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as ephedrine.
    Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Ergoloid Mesylates: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergonovine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergot alkaloids: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergotamine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ertugliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Ertugliflozin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Escitalopram: (Severe) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with linezolid, escitalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with escitalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Esmolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethanol: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Some ethanol-based products also contain tyramine including some beers; wines; sherry; hard liquor; or liqueurs and should be avoided.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Desogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Etonogestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Exenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Fentanyl: (Major) The use of fentanyl is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of fentanyl with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as fentanyl.
    Fexofenadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Fluoxetine: (Severe) According to the manufacturer of fluoxetine, treatment initiation with fluoxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluoxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluoxetine and requiring urgent treatment with linezolid, fluoxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluoxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluoxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Fluoxetine; Olanzapine: (Severe) According to the manufacturer of fluoxetine, treatment initiation with fluoxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluoxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluoxetine and requiring urgent treatment with linezolid, fluoxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluoxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluoxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Fluticasone; Salmeterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluvoxamine: (Severe) According to the manufacturer of fluvoxamine, treatment initiation with fluvoxamine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluvoxamine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluvoxamine and requiring urgent treatment with linezolid, fluvoxamine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluvoxamine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluvoxamine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Food: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Foods containing tyramine should be avoided.
    Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Formoterol; Mometasone: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fosphenytoin: (Minor) Coadministration of linezolid and fosphenytoin, which is metabolized by the CYP2C9 isoenzyme, does not substantially alter the pharmacokinetics of phenytoin. No change in the fosphenytoin dosage regimen is necessary. Also, phenytoin is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if fosphenytoin could cause decreases in linezolid exposure if coadministered.
    Ginseng, Panax ginseng: (Major) There have been two reports in the literature describing a possible, but not definitive, interaction between ginseng, panax ginseng and phenelzine; it is not clear if other MAOIs or drugs that possess MAOI-like activity, such as linezolid, would interact, but caution is warranted. In one case, headache and tremulousness were reported in a 64-year old when ginseng was added to phenelzine. A second patient suffered from irritability, headache, and vague visual hallucinations during combined use of ginseng and phenelzine. Some of these effects have been reported with the use of phenelzine alone.
    Glimepiride: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glimepiride; Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glimepiride; Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glipizide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glipizide; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glyburide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glyburide; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glycopyrrolate; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Green Tea: (Moderate) Green tea use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Green tea catechins inhibit Catechol-O-methyltransferase (COMT) in animals. Monoamine oxidase (MAO) and COMT are the two major enzymes involved in the metabolism of catecholamines. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). In addition, some green tea products contain caffeine; caffeine interacts with MAOIs. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Guaifenesin; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Guanabenz: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Guanabenz withdrawal can result in an increase in serum catecholamine levels. Thus, drugs that alter the metabolism or uptake of catecholamines, such as monoamine oxidase inhibitors (MAOIs), should be used cautiously in patients who are undergoing guanabenz withdrawal.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Severe) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Hydrocodone; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Hydrocodone; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Hydromorphone: (Moderate) In theory, the use of hydromorphone in a patient taking linezolid may increase the risk of serotonergic symptoms. Linezolid has MAOI activity. Concomitant use of hydromorphone with monoamine oxidase inhibitors (MAOIs) can potentiate the effects of hydromorphone and may lead to additive CNS or respiratory depression. If concurrent use of hydromorphone and a MAOI is required, carefully monitor the patient for hypotension, CNS depression, and respiratory depression. The dose of hydromorphone and/or the dose of the MAOI should be reduced. Concurrent usage of a MAOI and hydromorphone extended-release tablets is not recommended. Discontinue use of a MAOI for at least 2 weeks before starting hydromorphone extended-release tablets.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibuprofen; Oxycodone: (Major) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as linezolid. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Ibuprofen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Imipramine: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Incretin Mimetics: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Indacaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Insulin Degludec; Liraglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Insulin Glargine; Lixisenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Insulins: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Iobenguane I 131: (Major) Discontinue linezolid for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart linezolid until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as linezolid, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Isoniazid, INH: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI. (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Isoniazid, INH; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI. (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Isoproterenol: (Major) Linezolid may enhance the hypertensive effect of isoproterenol. Initial doses of isoproterenol should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as isoproterenol.
    Kava Kava, Piper methysticum: (Major) The German Commission E and other groups warn that any substances that act on the CNS, including psychopharmacologic agents, may interact with the phytomedicinal kava kava, Piper methysticum. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action. Avoid use of psycho-active herbs with MAOIs or drugs that possess MAOI-like activity, such as linezolid, whenever possible.
    Labetalol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levalbuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Levobetaxolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Levobunolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Levodopa: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Levomilnacipran: (Severe) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as levomilnacipran is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving levomilnacipran may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, levomilnacipran should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with levomilnacipran may be resumed 24 hours after the last dose of linezolid.
    Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Linagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Linagliptin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Liraglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Lithium: (Major) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and linezolid. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Lixisenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Loratadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including linezolid, an antibiotic that is also a reversible, non-selective MAO inhibitor. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent clinical use of linezolid and medications that enhance central serotonergic activity.
    Maprotiline: (Moderate) Maprotiline should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
    Meglitinides: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Meperidine: (Severe) Meperidine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Severe reactions including coma, severe respiratory depression, cyanosis, and hypotension have occurred; some reactions have been fatal. The mechanism of these reactions is unclear; however, it may be related to a preexisting hyperphenylalaninemia. Concomitant use of meperidine with other serotonergic drugs such as MAOIs may result in serotonin syndrome with excitation; sweating; rigidity; hypertension; severe respiratory depression; coma; and circulatory collapse, possibly resulting in death. Intravenous hydrocortisone or prednisolone has been used to treat severe reactions, with the addition of intravenous chlorpromazine in cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of opiate antagonists in the treatment of these reactions is unknown.
    Meperidine; Promethazine: (Severe) Meperidine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Severe reactions including coma, severe respiratory depression, cyanosis, and hypotension have occurred; some reactions have been fatal. The mechanism of these reactions is unclear; however, it may be related to a preexisting hyperphenylalaninemia. Concomitant use of meperidine with other serotonergic drugs such as MAOIs may result in serotonin syndrome with excitation; sweating; rigidity; hypertension; severe respiratory depression; coma; and circulatory collapse, possibly resulting in death. Intravenous hydrocortisone or prednisolone has been used to treat severe reactions, with the addition of intravenous chlorpromazine in cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of opiate antagonists in the treatment of these reactions is unknown.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Metaproterenol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Repaglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Methadone: (Major) Use linezolid and methadone concurrently with caution and careful monitoring. The concomitant administration of methadone, a weak serotonin re-uptake inhibitor (SRI), and monoamine oxidase inhibitors (MAOIs), such as linezolid, may increase the risk of serious adverse events, such as serotonin syndrome. If concurrent use of methadone and a MAOI is required, a sensitivity test should be performed by administering repeated small incremental doses of methadone over several hours while carefully monitoring the patient's condition and vital signs. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methyldopa: (Severe) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Methylene Blue: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylergonovine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Methylphenidate: (Major) Psychostimulants, such as methylphenidate, exhibit sympathomimetic actions and should be avoided with other drugs, such as linezolid, that enhance the pressor response of sympathomimetic agents. A clinically significant rise in systolic blood pressure is possible. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, a non-selective monoamine oxidase inhibitor (MAOI), and medications that enhance central serotonergic activity. Monoamine oxidase (MAO) is the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
    Methysergide: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Metoclopramide: (Major) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs or drugs that possess MAOI-like activity, such as linezolid.
    Metoprolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Midodrine: (Major) Avoid the concomitant use of linezolid with midodrine. Linezolid may enhance the hypertensive effect of midodrine. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as midodrine.
    Milnacipran: (Severe) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as milnacipran is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving milnacipran may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, milnacipran should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with milnacipran may be resumed 24 hours after the last dose of linezolid.
    Mirtazapine: (Severe) Concurrent use of linezolid and mirtazapine is contraindicated due to an increased risk of serotonin syndrome. Mirtazapine is a serotonergic antidepressant and linezolid is a nonselective inhibitor of monoamine oxidase which increases central serotonin levels. If urgent psychiatric treatment is required, interventions other than mirtazapine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving mirtazapine and requiring urgent treatment with linezolid, mirtazapine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Mirtazapine may be resumed 24 hours after the last dose of linezolid.
    Modafinil: (Moderate) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of modafinil to patients receiving linezolid may invoke a hypertensive reaction. Such drugs should be avoided during and for up to 2 weeks following the discontinuation of linezolid.
    Morphine: (Severe) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine.
    Morphine; Naltrexone: (Severe) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine.
    Nadolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Naproxen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Nateglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Nebivolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Nebivolol; Valsartan: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Nefazodone: (Major) Linezolid should generally not be administered to patients taking serotonergic agents, such as nefazodone, due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of nefazodone; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Norepinephrine: (Major) Linezolid may enhance the hypertensive effect of norepinephrine. Initial doses of norepinephrine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as norepinephrine.
    Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Nortriptyline: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Olodaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Ondansetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering ondansetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue ondansetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Oxycodone: (Major) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as linezolid. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Paroxetine: (Severe) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with linezolid, paroxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with paroxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Penbutolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Pentazocine: (Moderate) Patients receiving concurrent pentazocine and agents with monoamine oxidase inhibitor (MAOI) activity, such as linezolid may be at increased risk for developing serotonin syndrome. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including pentazocine. If concurrent use is clinically indicated, the patient needs to be carefully observed for any signs or symptoms of serotonin excess such as restlessness, myoclonus, confusion, hyperreflexia, diaphoresis, shivering, tachycardia, and tremor.
    Pentazocine; Naloxone: (Moderate) Patients receiving concurrent pentazocine and agents with monoamine oxidase inhibitor (MAOI) activity, such as linezolid may be at increased risk for developing serotonin syndrome. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including pentazocine. If concurrent use is clinically indicated, the patient needs to be carefully observed for any signs or symptoms of serotonin excess such as restlessness, myoclonus, confusion, hyperreflexia, diaphoresis, shivering, tachycardia, and tremor.
    Pergolide: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Perphenazine; Amitriptyline: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Phendimetrazine: (Moderate) Linezolid may enhance the hypertensive effect of phendimetrazine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phendimetrazine.
    Phenobarbital: (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Phentermine: (Major) Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction. Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome.
    Phentermine; Topiramate: (Major) Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction. Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome.
    Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Phenylephrine; Promethazine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Phenytoin: (Minor) Coadministration of linezolid and phenytoin, which is metabolized by the CYP2C9 isoenzyme, does not substantially alter the pharmacokinetics of phenytoin. No changes in the phenytoin dosage regimen is necessary. Also, phenytoin is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenytoin could cause decreases in linezolid exposure if coadministered.
    Pindolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Pirbuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Pramlintide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Prilocaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Primidone: (Minor) Primidone is metabolized to phenobarbital, which is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if primidone could cause decreases in linezolid exposure if these drugs are coadministered.
    Procarbazine: (Severe) Concurrent use of linezolid with procarbazine or use of linezolid within 2 weeks of taking procarbazine is contraindicated due to the risk of severe hypertensive crisis. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Linezolid should not be used concurrently with other drugs that possess MAOI-like activity, such as procarbazine.
    Propranolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Protriptyline: (Severe) Concurrent use of drugs with MAO-inhibiting activity, such as linezolid, with tricyclic antidepressants (TCAs) can cause hyperpyrexia, hypertension, or seizures. The combination should be avoided whenever possible. In general, linezolid should generally not be administered to patients taking serotonergic agents due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of TCAs; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Racepinephrine: (Moderate) Linezolid may enhance the hypertensive effect of racepinephrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as racepinephrine.
    Rasagiline: (Severe) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Concurrent use of linezolid with medications that inhibit either monoamine oxidase A or B or use of linezolid within 2 weeks of taking monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of severe hypertensive crisis and possibly serotonin syndrome. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including agents like MAOIs, which can potentiate serotonin.
    Remifentanil: (Major) Remifentanil use is not recommended in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a nonselective MAOI. Concomitant use of remifentanil with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as remifentanil. If urgent use is necessary, use test doses of remifentanil with frequent titration of small doses and close monitoring. If serotonin syndrome is suspected, discontinue remifentanil and/or linezolid.
    Repaglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Reserpine: (Moderate) Concomitant use of linezolid and reserpine can cause hypertension and increased excitation. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Reserpine depletes intracellular catecholamines by initially causing their release from bound stores, so the acute administration of reserpine to patients currently taking an MAOI can lead to hypertensive crisis.
    Rifampin: (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Ritodrine: (Major) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of ritodrine to patients receiving linezolid may invoke a hypertensive reaction. Such drugs should be avoided during and for up to 2 weeks following the discontinuation of linezolid.
    Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Safinamide: (Severe) Concurrent use of linezolid with safinamide, a monoamine oxidase inhibitor type B, or use of linezolid within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including monoamine oxidase inhibitors (MAOIs), which can potentiate central serotonin levels.
    Salmeterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Semaglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Serotonin-Receptor Agonists: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO and should not be administered with serotonin-receptor agonists. The monoamine oxidase type A enzyme metabolizes serotonin. Non-selective MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. This interaction could lead to serotonin syndrome. The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors like linezolid or within 2 weeks of discontinuation of a MAO inhibitor.
    Sertraline: (Severe) According to the manufacturer of sertraline, treatment initiation with sertraline is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than sertraline (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving sertraline and requiring urgent treatment with linezolid, sertraline should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Sertraline may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with sertraline can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Sibutramine: (Major) Linezolid possesses weak non-selective MAO-inhibiting activity and concurrent use of any of these agents with sibutramine should be avoided if possible. The concomitant use of sibutramine with MAOIs is contraindicated. Sibutramine is a serotonin reuptake inhibitor. Since serotonin is deaminated by monoamine oxidase-A, concurrent administration of sibutramine with drugs that inhibit this enzyme such as MAOIs can lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. There should be at least a 2-week interval between discontinuation of MAOI therapy and initiation of sibutramine therapy. Similarly, there should be at least a 2-week interval after stopping sibutramine therapy and the start of MAOI therapy.
    Simvastatin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    St. John's Wort, Hypericum perforatum: (Severe) Linezolid should generally not be administered to patients taking serotonergic agents, such as St. John's wort, Hypericum perforatum, due to the potential for serious CNS reactions, such as serotonin syndrome. The FDA recommends that if linezolid must be administered to patients already taking serotonergic agents due to life-threatening conditions, the serotonergic agent should be discontinued immediately and the patient should be monitored for emergence of symptoms of CNS toxicity for two weeks, or until 24 hours after the last dose of linezolid, whichever comes first. For non-emergent situations, most serotonergic drugs should be stopped at least 2 weeks prior to instituting linezolid therapy. Treatment with serotonergic agents may resume 24 hours after the discontinuation of linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Sufentanil: (Major) In theory, the use of sufentanil in a patient taking linezolid may increase the risk of serotonergic symptoms. Linezolid has MAOI activity. Sufentanil belongs to the same group of opiate agonists, phenylpiperidines, as meperidine, a known serotonin reuptake inhibitor. Caution is advised until more data are available.
    Sulfonylureas: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tapentadol: (Severe) Tapentadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tapentadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tapentadol.
    Terbutaline: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Tetrahydrozoline: (Moderate) Linezolid may enhance the hypertensive effect of tetrahydrozoline. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as tetrahydrozoline.
    Thiazolidinediones: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Tiotropium; Olodaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Tolazamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tolbutamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tolcapone: (Major) Avoid the concomitant use of entacapone or tolcapone in combination with a non-selective monoamine oxidase inhibitor such as linezolid. Monoamine oxidase and catechol-O-methyltransferase are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the co-administration of entacapone or tolcapone with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity. Typically, at least 14-days should elapse between the discontinuation of the non-selective MAOI and the use of entacapone or tolcapone to avoid potential interactions.
    Tramadol: (Severe) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Trazodone: (Severe) Concurrent use of linezolid and trazodone is contraindicated due to an increased risk of serotonin syndrome. Trazodone is a serotonergic antidepressant and linezolid is a nonselective inhibitor of monoamine oxidase which increases central serotonin levels. If urgent psychiatric treatment is required, interventions other than trazodone (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving trazodone and requiring urgent treatment with linezolid, trazodone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Trazodone may be resumed 24 hours after the last dose of linezolid.
    Trimipramine: (Severe) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Umeclidinium; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Valerian, Valeriana officinalis: (Major) Any substances that act on the CNS may theoretically interact with valerian, Valeriana officinalis. The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes (valepotriates) have sedative activity. Patients taking MAOIs or drugs that possess MAOI-like activity, such as linezolid, should discuss the use of herbal supplements with their health care professional prior to consuming valerian; combinations should be approached with caution in the absence of clinical data.
    Venlafaxine: (Severe) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving venlafaxine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, venlafaxine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with venlafaxine may be resumed 24 hours after the last dose of linezolid.
    Vilazodone: (Severe) According to the manufacturer of vilazodone, treatment initiation with vilazodone is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than vilazodone (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving vilazodone and requiring urgent treatment with linezolid, vilazodone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Vilazodone may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with vilazodone can lead to serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Vortioxetine: (Severe) Treatment initiation with vortioxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than vortioxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving vortioxetine and requiring urgent treatment with linezolid, vortioxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 21 days or until 24 hours after the last dose of linezolid, whichever comes first. Vortioxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with vortioxetine can lead to serious reactions including serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Yohimbine: (Major) Avoid yohimbine during linezolid therapy and for 2 weeks after the discontinuation of linezolid. Linezolid is a reversible, non-selective monoamine oxidase inhibitor (MAOI). At high doses, yohimbine may nonselectively inhibit MAO and also, at normal doses, activates the sympathetic nervous system via selective central alpha 2-adrenoceptor antagonism. Some experts have cautioned against the combination of yohimbine with MAOIs and drugs with MAOI activity, since the activity of yohimbine might result in increased blood pressure or other serious side effects.

    PREGNANCY AND LACTATION

    Pregnancy

    Linezolid is classified in FDA pregnancy risk category C. Linezolid was not teratogenic in rats at exposure levels 4-fold higher than the expected human exposure level based on AUC. However, embryo and fetal toxicities (non-teratogenic), such as increased rates of postimplantation embryo death, reduced fetal weight, reduced ossification, and increased pup mortality were seen. Because there are no well controlled studies in pregnant women and animal studies are not always predictive of human response, linezolid should only be used in pregnancy if the potential benefit justifies the potential fetal risk.

    Use linezolid with caution in breast-feeding females. Linezolid and its metabolites are excreted into the breast milk in rats at concentrations similar to maternal rat plasma. It is likely that linezolid is excreted in human milk. After a single dose of 600 mg of oral linezolid in a lactating woman, milk samples were taken at 10 time points over the next 24 hours. The peak concentration was 12.36 mg/L occurring 2 hours after the dose. Milk concentrations fell with a half-life of 6.47 hours and were detectable up to 24 hours after the dose. The AUC was 100.79 mcg x hour/mL. Based on a peak breast milk concentration of 12.36 mg/L and a daily intake of 150 mL/kg/day of breast milk, the maximum dose that an infant would receive via milk would be less than 2 mg/kg/day. In addition to antimicrobial effects, linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO), but no data are available on the risks of MAO inhibition to the breast-feeding infant. Vancomycin, daptomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. Site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed be fore choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Daptomycin has a high molecular weight; therefore, excretion into breast milk may be limited. In 1 patient with daptomycin breast milk concentration measured on day 27 of therapy (dose of 6.7 mg/kg IV), a peak concentration of 44.7 mcg/L was obtained 8 hours after the dose with an estimated milk:plasma ratio of 0.0012. Alternative antimicrobials that previous American Academy of Pediatrics recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.

    MECHANISM OF ACTION

    Linezolid inhibits bacterial protein synthesis by interfering with translation. Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit; this action prevents the formation of a functional 70S initiation complex, an essential step in the bacterial translation process. Without proper protein production, susceptible bacteria cannot multiply. The action of linezolid is considered to be bacteriostatic against staphylococci and enterococci. Linezolid appears to be bacteriocidal against the majority of streptococcal strains tested.
     
    MAO inhibition:
    Linezolid is a reversible, non-selective inhibitor of monoamine oxidase (MAO). MAO is a complex enzyme system and is widely distributed throughout the body. Reduction of MAO activity results in an increased concentration of neurotransmitters, such as epinephrine, norepinephrine, and dopamine, at various storage sites in the central nervous system and sympathetic nervous system. MAO inhibition desensitizes alpha- and beta-adrenergic and serotonin receptors. The inhibition of MAO in the GI tract and liver can result in systemic absorption of large amounts of tyramine from the diet, which may cause hypertension.

    PHARMACOKINETICS

    Linezolid is administered orally or by intravenous infusion. The dosage of IV and tablet formulations are interchangeable, there is no need to make dose adjustments. Animal and human data indicate that linezolid distributes to well-perfused tissues, including concentration in saliva and sweat. In a study involving patients undergoing total hip replacement, a dose of 600 mg IV was shown to have significant penetration into bone, fat, muscle, and hematoma fluid when given preoperatively along with cefamandole, a conventional prophylactic antibiotic. Distribution into these tissues was rapid with concentrations exceeding the MIC for susceptible organisms (4 mg/L or less). Concentrations in bone, fat, and muscle were approximately 50%, 30%, and 90% of the corresponding serum concentration. Therapeutic concentrations were also maintained in hematoma fluid for more than 16 hours. Plasma protein binding is low (i.e., roughly 31%).
     
    Linezolid is metabolized via oxidation of the morpholine ring, which results in two inactive carboxylic acid metabolites: aminoethoxyacetic acid (metabolite A) and hydroxyethyl glycine (metabolite B). Metabolite A is presumed to be formed via an enzymatic pathway, while formation of metabolite B is mediated by a non-enzymatic chemical oxidation mechanism in vitro. In vitro studies have demonstrated that linezolid is minimally metabolized and the metabolism may be mediated by the CYP450 enzyme system; however, the metabolic pathway is not fully understood. In addition, linezolid does not inhibit or induce CYP450 isoenzymes. The half-life ranges from 4.26 to 5.4 hours. Non-renal clearance accounts for 65% of an administered dose. Roughly 30% of the dose appears unchanged in the urine, 40% as metabolite B, and 10% as metabolite A. The net renal clearance is low and is suggestive of net renal tubular reabsorption. Virtually no linezolid appears in the feces as unchanged drug, and the metabolites present in the feces only account for 9% of the total dose.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none
    Linezolid is not an inducer of the CYP450 enzyme system in animals, nor does it inhibit the activities of clinically active human CYP450 isoenzymes (i.e., 1A2, 2C9, 2C19, 2D6, 2E1, 3A4). In vitro studies have demonstrated that linezolid is minimally metabolized and the metabolism may be mediated by the human CYP450 enzyme system; however, the metabolic pathway is not fully understood. A study showed decreased linezolid Cmax and AUC when administered with a strong inducer of the CYP450 enzyme system. It is unknown if the CYP450 induction was the reason for this decrease, but caution may be warranted with strong inducers.

    Oral Route

    Oral bioavailability for linezolid is 100%. Food delays the rate but not the extent of oral absorption.