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  • CLASSES

    Aminoglycoside Antibiotics
    Respiratory Aminoglycoside Antibiotics

    BOXED WARNING

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Closely monitor patients receiving systemic aminoglycosides, such as amikacin, for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. In patients with preexisting renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring amikacin serum concentrations during use of conventional dose regimens, avoid peak concentrations above 35 mcg/mL and trough concentrations above 10 mcg/mL.[29874] However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted.[34173] [34175] [34186] [34172] Closely monitor renal function. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in amikacin removal in the event of overdose or toxic reactions, especially if renal function is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.[29874]

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Closely monitor patients receiving systemic aminoglycosides, such as amikacin, for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with preexisting renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring amikacin serum concentrations during use of conventional dose regimens, avoid peak concentrations above 35 mcg/mL and trough concentrations above 10 mcg/mL.[29874] However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted.[34173] [34175] [34186] [34172] Closely monitor eighth cranial nerve function. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Do not administer aminoglycosides concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended.[29874] [42984]

    Botulism, electrolyte imbalance, myasthenia gravis, neuromuscular blockade, neuromuscular disease, parkinsonism, respiratory depression, respiratory insufficiency

    Systemic aminoglycosides, such as amikacin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled after local irrigation and after topical application during surgical procedures. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). Corrective therapy is required for any electrolyte imbalance, which may aggravate risk for neuromuscular/neurological symptoms. During or after aminoglycoside therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia. In infants, tetany and muscle weakness have been described. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.

    Acute bronchospasm, asthma, chronic obstructive pulmonary disease (COPD), pulmonary disease

    Amikacin liposome inhalation suspension has been associated with an increased risk of respiratory adverse reactions, including exacerbation of underlying pulmonary disease with some cases requiring hospitalization. Consider pretreatment with a short-acting selective beta-2 agonist for patients with known hyperreactive airway disease, chronic obstructive pulmonary disease (COPD), asthma, or acute bronchospasm. Manage patients who develop a respiratory adverse reaction during amikacin liposome inhalation treatment as medically appropriate; discontinue amikacin liposome inhalation therapy if hypersensitivity pneumonitis develops.[63608]

    DEA CLASS

    Rx

    DESCRIPTION

    Inhalation and parenteral aminoglycoside antibiotic
    Used for a variety of gram-negative bacterial infections and Mycobacterium avium complex (MAC) lung disease
    Major toxicities include nephrotoxicity, ototoxicity, neurotoxicity; careful patient monitoring recommended

    COMMON BRAND NAMES

    Amikin, ARIKAYCE

    HOW SUPPLIED

    Amikacin/Amikacin Sulfate/Amikin Intramuscular Inj Sol: 1mL, 250mg
    Amikacin/Amikacin Sulfate/Amikin Intravenous Inj Sol: 1mL, 250mg
    ARIKAYCE Respiratory (Inhalation) Susp: 8.4mL, 590mg

    DOSAGE & INDICATIONS

    For the treatment of Mycobacterium avium complex infection (MAC).
    Inhalation dosage (Arikayce)
    Adults

    590 mg inhalation by nebulizer once daily as part of combination therapy in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. Reserve for use in patients with limited or no alternative treatment options.[63608]

    Intravenous or Intramuscular dosage†
    Adults

    25 mg/kg/dose IV 3 times weekly for first 2 to 3 months or 8 to 10 mg/kg/dose IV or IM 2 to 3 times weekly for long-term (6 months or more) as part of a multiple drug regimen for cavitary, previously treated, or advanced disease.[34696] Alternately, 10 to 15 mg/kg/dose IV once daily (Max: 1.5 g/day) plus clarithromycin or azithromycin and ethambutol for HIV-infected patients. May consider addition of amikacin as a third or fourth drug (or rifabutin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Adolescents

    10 to 15 mg/kg/dose IV once daily (Max: 1.5 g/day) plus clarithromycin or azithromycin and ethambutol for HIV-infected patients. May consider addition of amikacin as a third or fourth drug (or rifabutin, streptomycin, levofloxacin, or moxifloxacin) for patients with high mycobacterial loads (more than 2 log CFU/mL of blood) or in the absence of effective antiretroviral therapy. Duration of treatment depends on clinical response but should continue for at least 12 months.[34362]

    Infants and Children

    15 to 30 mg/kg/day IV divided every 12 to 24 hours (Max: 1.5 g/day) plus clarithromycin or azithromycin and ethambutol for HIV-infected patients. May consider addition of amikacin if rifabutin cannot be administered for severe disease or if a fourth drug is needed for patients with more severe symptoms or disseminated disease. Duration of treatment depends on clinical response but should continue for at least 12 months.[34361]

    For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP) and nosocomial pneumonia.
    For the treatment of nonspecific LRTIs.
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM every 24 hours.[34207] [34208] [54262]

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 11 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 10 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).[29874]

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours. This dosing does not account for gestational age or birthweight.

    For the treatment of nosocomial pneumonia.
    Intravenous dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV every 24 hours for 7 days as part of combination therapy.[61215]

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous dosage (conventional dosing)
    Adults living with HIV

    15 mg/kg/day IV divided every 8 to 12 hours (Max: 1.5 g/day) for 5 to 7 days as an alternative as part of combination therapy.[29874] [34362]

    Adolescents living with HIV

    15 to 22.5 mg/kg/day IV divided every 8 to 12 hours (Max: 1.5 g/day) for 5 to 7 days as an alternative as part of combination therapy.[29874] [34362] [54262] [54266]

    Intravenous dosage (extended-interval dosing)†
    Adults living with HIV

    15 to 20 mg/kg/dose IV every 24 hours for 5 to 7 days as an alternative as part of combination therapy.[34207] [34208] [54262]

    Adolescents living with HIV

    15 to 22.5 mg/kg/dose IV every 24 hours for 5 to 7 days as an alternative as part of combination therapy.

    For the treatment of bacteremia and sepsis, including infections with difficult-to-treat resistance.
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM every 24 hours.[34207] [34208] [54262] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Neonates 30 to 34 weeks gestation and 11 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 10 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day (Max: 1.5 g/day) IV or IM divided every 8 to 12 hours.[29874] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day (Max: 1.5 g/day) IV or IM divided every 8 to 12 hours.[29874] [41183] [54262] [54266] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose; however, this dosing does not account for gestational age or birthweight.[29874] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    For the treatment of intraabdominal infections (i.e., peritonitis).
    For the treatment of peritoneal dialysis-associated peritonitis in patients with end-stage renal disease.
    Intraperitoneal dosage†
    Adults

    25 mg/L intraperitoneal (IP) loading dose followed by a maintenance dose of 12 mg/L of peritoneal dialysate. Alternatively, 2 mg/kg IP once daily in the long dwell as intermittent therapy. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.[54203]

    Infants, Children, and Adolescents

    25 mg/L intraperitoneal (IP) loading dose followed by a maintenance dose of 12 mg/L of peritoneal dialysate. Treat for 2 to 3 weeks depending on infecting organism and the patient's clinical status.

    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.  

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 11 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 10 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose; however, this dosing does not account for gestational age or birthweight.

    For the treatment of complicated urinary tract infection (UTI) and pyelonephritis.
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary. For pyelonephritis, guidelines recommend an aminoglycoside alone or in combination with ampicillin or with an extended-spectrum cephalosporin or penicillin. A one-time extended-interval dose of an aminoglycoside may also be used prior to oral therapy for patients who do not require hospitalization.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day). For pyelonephritis, guidelines recommend an aminoglycoside alone or in combination with ampicillin or with an extended-spectrum cephalosporin or penicillin.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day). 

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose; however, this dosing does not account for gestational age or birthweight.

    For the treatment of bone and joint infections (i.e., osteomyelitis, infectious arthritis).
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose; however, this dosing does not account for gestational age or birthweight.

    For the treatment of skin and skin structure infections (e.g., cellulitis, burn wound infection).
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates 30 to 34 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 36 hours.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day).

    Neonates

    10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose; however, this dosing does not account for gestational age or birthweight.

    For the treatment of meningitis and ventriculitis†.
    Intravenous or Intramuscular dosage (extended-interval dosing)†
    Adults

    15 to 20 mg/kg/dose IV or IM. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.[23521] [34207] [34208] [54262] The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.[32690]

    Infants, Children, and Adolescents

    15 to 22.5 mg/kg/dose IV or IM every 24 hours.[51960] [54170] [54171] [54261] [54262] [54264] [54266] [63245] The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.[32690]

    Neonates 35 weeks gestation and older and 8 days and older

    18 mg/kg/dose IV or IM every 24 hours.[63245] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]

    Neonates 35 weeks gestation and older and 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.

    Neonates 30 to 34 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.

    Neonates 30 to 34 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 36 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.

    Neonates younger than 30 weeks gestation and 15 days and older

    15 mg/kg/dose IV or IM every 24 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.

    Neonates younger than 30 weeks gestation and 0 to 14 days

    15 mg/kg/dose IV or IM every 48 hours. An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day). The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.

    Infants, Children, and Adolescents

    20 to 30 mg/kg/day IV or IM divided every 8 hours is recommended by guidelines.  15 mg/kg/day IV or IM divided every 8 to 12 hours (Max: 1.5 g/day) is the FDA-approved dosage. The IDSA recommends an aminoglycoside in combination with ampicillin as a treatment option for meningitis due to Streptococcus agalactiae (group B streptococcus), Listeria monocytogenes, and Enterococcus species. An aminoglycoside in combination with a third-generation cephalosporin is also recommended for meningitis due to Pseudomonas aeruginosa. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis and at least 3 weeks for meningitis due to Listeria monocytogenes or Pseudomonas aeruginosa.

    Neonates 8 days and older

    30 mg/kg/day IV or IM divided every 8 hours is recommended by guidelines, with a smaller dose and longer dosing interval recommended in low birth-weight neonates (less than 2 kg).[32690] 10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose.[29874] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]

    Neonates 0 to 7 days

    15 to 20 mg/kg/day IV or IM divided every 12 hours is recommended by guidelines, with a smaller dose and longer dosing interval recommended in low birth-weight neonates (less than 2 kg).[32690] 10 mg/kg IV or IM loading dose, followed by 7.5 mg/kg/dose IV or IM every 12 hours is the FDA-approved dose.[29874] An aminoglycoside plus ampicillin is recommended as a treatment option for initial empiric therapy for neonatal meningitis. The recommended duration of therapy is 14 to 21 days for group B streptococcal meningitis or meningitis due to Listeria monocytogenes and a duration of at least 21 days is recommended for meningitis due to gram-negative bacilli.[32690] [51871]

    Intrathecal† or Intraventricular dosage† (preservative-free formulations only)
    Adults

    5 to 50 mg (with a usual dose of 30 mg) intraventricularly into the CSF once daily in combination with parenteral therapy is recommended in guidelines.  Doses should be adjusted to maintain adequate CSF concentrations depending on the susceptibility of the infecting organism.

    Infants, Children, and Adolescents

    5 to 50 mg (with a usual dose of 30 mg) intraventricularly into the CSF once daily in combination with systemic therapy has been recommended in general without specific pediatric qualifications.  Doses should be adjusted to maintain adequate CSF concentrations depending on the susceptibility of the infecting organism.

    Neonates

    1 to 5 mg administered intraventricularly into the CSF has been studied in a small case series (n = 8) with the goal of maintaining a drug concentration at least 10 times the MIC of the infecting organism. In general, a 5 mg intraventricular dose achieved this goal in all patients studied.

    For the treatment of pulmonary exacerbations in patients with cystic fibrosis† (CF).
    Intravenous dosage
    Adults

    30 to 35 mg/kg/dose IV every 24 hours.[53709] [58126] Amikacin has traditionally been administered as a 2 to 3 times daily regimen such as 30 mg/kg/day IV divided every 8 to 12 hours; however, high dose extended-interval aminoglycoside regimens are now preferred.[42096] [42097] [42098] [58126] [54292] Amikacin and tobramycin have comparable efficacy for the treatment of acute pulmonary exacerbations in CF patients and either agent is recommended as first-line therapy in conjunction with an antipseudomonal beta-lactam agent.[51725] [58129]

    Infants, Children, and Adolescents

    30 to 35 mg/kg/dose IV every 24 hours.[53709] [58126] Amikacin has traditionally been administered as a 2 to 3 times daily regimen such as 30 mg/kg/day IV divided every 8 to 12 hours; however, high dose extended-interval aminoglycoside regimens are now preferred.[42096] [42097] [42098] [58126] [54292] Amikacin and tobramycin have comparable efficacy for the treatment of acute pulmonary exacerbations in CF patients and either agent is recommended as first-line therapy in conjunction with an antipseudomonal beta-lactam agent.[51725] [58129]

    For the empiric treatment of febrile neutropenia†.
    For the treatment of febrile neutropenia in adults.
    Intravenous dosage (extended-interval)
    Adults

    Typical extended-interval doses are 15 to 20 mg/kg/dose IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 or 72 hours may be necessary. Amikacin may be added to antipseudomonal beta-lactams in febrile neutropenia patients with complications or those with suspected or documented resistance.

    Intravenous dosage (conventional dosing)
    Adults

    15 mg/kg/day IV or IM divided every 8 to 12 hours has been used in studies. The FDA-approved maximum daily dose is 1.5 g/day. Amikacin may be added to antipseudomonal beta-lactams in febrile neutropenia patients with complications or those with suspected or documented resistance.

    For the treatment of febrile neutropenia in pediatric patients.
    Intravenous dosage (extended-interval dosing)
    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose IV every 24 hours. The efficacy of once daily amikacin for febrile neutropenia has been established in several studies in pediatric patients. A maximum single dose of 750 mg was reported in 1 study. The FDA-approved maximum daily dose is 1.5 g/day. Amikacin, in combination with an antipseudomonal penicillin or cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia in children. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

    Intravenous dosage (conventional dosing)
    Infants, Children, and Adolescents

    15 to 20 mg/kg/day IV, divided every 8 to 12 hours.[53160] [57884] [54172] [54291] The FDA-approved maximum daily dose is 1.5 g/day.[29874] Amikacin, in combination with an antipseudomonal penicillin or cephalosporin, has been successfully used for the empiric treatment of febrile neutropenia in children.[53160] [53163] [53587] [53589] [57850] [57851] Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.[49827] [53571]

    For the treatment of actinomycotic mycetoma† or nocardiosis† caused by Nocardia sp..
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/day IV or IM divided every 12 hours has been given as part of a multi-drug regimen. Combination therapy with amikacin and co-trimoxazole (sulfamethoxazole-trimethoprim), amikacin and cefotaxime, or amikacin and imipenem has been used. In patients with CNS disease, therapy should include drugs with favorable CNS penetration (e.g., co-trimoxazole and ceftriaxone). Patients with severe nocardiosis may benefit a third agent, such as linezolid. Amikacin is often a second-line treatment due to renal toxicity and its cost. Combination therapy should continue until clinical patient improvement occurs and organism identification and antimicrobial drug susceptibility are confirmed; single-drug therapy may be appropriate at that time. Prolonged treatment minimizes the risk of disease relapse. Immunocompetent patients with pulmonary or multifocal (non-CNS) disease may be successfully treated with 6 to 12 months of antimicrobial therapy. Immunosuppressed patients and those with CNS disease should receive at least 12 months of antimicrobial therapy and close clinical monitoring.[60679]

    For the treatment of infective endocarditis†.
    Intravenous dosage
    Adults

    15 mg/kg/day IV divided every 8 to 12 hours (Max: 1.5 g/day) is the general dosage recommended for adults. Clinical practice guidelines recommend an aminoglycoside in combination with a beta-lactam (i.e., penicillin, cephalosporin, carbapenem) for 6 weeks for endocarditis due to non-HACEK gram-negative microorganisms.

    Children and Adolescents

    15 mg/kg/day IV divided every 8 to 12 hours. Clinical practice guidelines recommend an aminoglycoside, in combination with ampicillin, for 4 weeks as an alternative therapy for endocarditis due to HACEK organisms. An aminoglycoside in combination with a third or fourth generation cephalosporin (i.e., ceftazidime, cefepime, cefotaxime, ceftriaxone) for at least 6 weeks is recommended as preferred treatment for endocarditis due to other gram-negative microorganisms.

    For the treatment of drug-susceptible tuberculosis infection† as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    For the treatment of drug-susceptible tuberculosis infection† in persons without HIV as part of combination therapy.
    Intravenous and Intramuscular dosage
    Adults

    15 mg/kg/dose IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week.[61094] Daily dosing is preferred and is defined as 5- or 7 days/week.  Use adjusted body weight in obese patients. Amikacin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Infants, Children, and Adolescents

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 to 30 mg/kg/dose (Max: 1/dose) IV or IM twice weekly.[61094] [63245] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Use adjusted body weight in obese patients.[65744] Amikacin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Neonates

    15 to 30 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Amikacin is generally recommended as part of the initial 2-month intensive phase of treatment for susceptible infections.[53484]   

    For the treatment of drug-susceptible tuberculosis infection† in persons with HIV as part of combination therapy.
    Intravenous and Intramuscular dosage
    Adults

    15 mg/kg/dose IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week. [61094] Daily dosing is preferred and is defined as 5- or 7 days/week. Use adjusted body weight in obese patients. Amikacin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Adolescents

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week.[34362] [63245] [61094] Daily dosing is preferred and is defined as 5- or 7 days/week.[61094] [65619] Use adjusted body weight in obese patients.[65744] Amikacin is generally recommended as second-line therapy; duration is dependent on the site of involvement.[61094] [65619]

    Infants and Children

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week. [61094] Daily dosing is defined as 5- or 7 days/week. Use adjusted body weight in obese patients.[65744] Amikacin is generally recommended as second-line therapy; duration is dependent on the site of involvement.

    Neonates

    15 to 30 mg/kg/dose IV or IM once daily. Although tuberculosis is rare in neonates, congenital and postnatal cases have been successfully treated with antitubercular agents. Amikacin is generally recommended as part of the initial 2-month intensive phase of treatment for susceptible infections.[53484]   

    For the treatment of drug-resistant tuberculosis infection† as part of combination therapy.
    NOTE: Use adjusted body weight (i.e., ideal body weight plus 40% of excess weight) for dosing in patients with marked obesity.
    Intravenous or Intramuscular dosage
    Adults

    15 mg/kg/dose IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week.   Use adjusted body weight in obese patients. Daily dosing is preferred and is defined as 5- or 7 days/week.

    Adolescents

    15 to 30 mg/kg/dose (Max: 1 g/dose) IV or IM once daily or 5 days/week, or alternatively, 25 mg/kg/dose IV or IM 3 days/week.    Use adjusted body weight in obese patients. Daily dosing is preferred and is defined as 5- or 7 days/week.

    Infants and Children

    15 to 30 mg/kg/dose (Max: 1 g /dose) IV or IM once daily or 5 days/week.   Use adjusted body weight in obese patients. Daily dosing is defined as 5- or 7 days/week.

    For the treatment of bartonellosis†, including severe Oroya fever†.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    7.5 mg/kg/dose IV or IM every 12 hours for 7 to 10 days plus ciprofloxacin as second-line therapy.

    Pregnant or Breast-feeding Persons

    500 mg IV or IM every 12 hours for 7 to 10 days plus ceftriaxone or ceftazidime as second-line therapy.

    Infants, Children, and Adolescents

    7.5 mg/kg/dose IV or IM every 12 hours for 7 to 10 days plus ciprofloxacin as second-line therapy.

    For the treatment of plague† infection.
    For the treatment of bubonic or pharyngeal plague†.
    Intravenous or Intramuscular dosage
    Adults

    15 to 20 mg/kg/dose IV or IM every 24 hours 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients and patients infected after intentional release of Y. pestis.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Neonates 8 days and older

    17.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    Neonates 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.

    For the treatment of pneumonic or septicemic plague†.
    Intravenous or Intramuscular dosage
    Adults

    15 to 20 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment of naturally occurring plague in pregnant patients, patients with severe disease, and patients infected after intentional release of Y. pestis.

    Infants, Children, and Adolescents

    15 to 20 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Neonates 8 days and older

    17.5 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    Neonates 0 to 7 days

    15 mg/kg/dose IV or IM every 24 hours for 10 to 14 days as an alternative therapy. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum dose is 15 mg/kg/day IV/IM (Max: 1.5 g/day); however, doses up to 20 mg/kg/day IV/IM are used off-label, and up to 35 mg/kg/day is used off-label for cystic fibrosis patients. Liposome inhalation suspension maximum dose is 590 mg/day.

    Geriatric

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum dose is 15 mg/kg/day IV/IM (Max: 1.5 g/day); however, doses up to 20 mg/kg/day IV/IM are used off-label, and up to 35 mg/kg/day is used off-label for cystic fibrosis patients. Liposome inhalation suspension maximum dose is 590 mg/day.

    Adolescents

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum dose is 15 mg/kg/day IV/IM (Max: 1.5 g/day); however, doses up to 22.5 mg/kg/day IV/IM are used off-label, and up to 35 mg/kg/day is used off-label for cystic fibrosis patients. Safety and efficacy of liposome inhalation suspension have not been established.

    Children

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum dose is 15 mg/kg/day IV/IM (Max: 1.5 g/day); however, doses up to 22.5 mg/kg/day IV/IM are used off-label, and up to 35 mg/kg/day is used off-label for cystic fibrosis patients. Safety and efficacy of liposome inhalation suspension have not been established.

    Infants

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum dose is 15 mg/kg/day IV/IM; however, doses up to 22.5 mg/kg/day are used off-label, and up to 35 mg/kg/day is used off-label for cystic fibrosis patients. Safety and efficacy of liposome inhalation suspension have not been established.

    Neonates

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA maximum dose is 15 mg/kg/day IV/IM; however, this dosing does not account for gestational age or birthweight and may be excessive in some patients. Usual maximum doses in neonates are as follows:
    35 weeks gestation and older: 15 to 18 mg/kg/dose IV/IM every 24 hours, depending on postnatal age.
    30 to 34 weeks gestation: 15 mg/kg/dose IV/IM every 24 to 36 hours, depending on postnatal age.
    Younger than 30 weeks gestation: 15 mg/kg/dose IV/IM every 24 to 48 hours, depending on postnatal age.
     
    Safety and efficacy of liposome inhalation suspension have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Amikacin does not undergo hepatic metabolism. Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    INJECTABLE CONVENTIONAL DOSING
    Adults
    Maintain the standard dose and increase the interval between doses or decrease the dose while maintaining an every 12 hour dosing interval. To increase the dosing interval, multiply the patient's serum creatinine (mg/100 mL) by 9 to determine the dosing interval (i.e., serum creatinine of 2 mg/100 mL would yield a dosing interval of 18 hours). To decrease the dose, divide the patient's standard dose by the serum creatinine (mg/100 mL) to determine the lower recommended dose. Measure amikacin serum concentrations and adjust the dose accordingly. Additionally, the status of the renal function may change throughout the course of therapy. Factors such as site of infection and organism susceptibility may alter the goals of therapy; thereby altering dosing in patients with renal impairment. Individualize the initial dosing interval based on specific patient and disease-state characteristics, serum concentrations goals, site of infection, organism susceptibility, weight, age, and degree and stability of renal impairment (acute vs. chronic). Guide further dosing by serum amikacin concentrations. Alternative dosing adjustments are listed below:
    CrCl more than 50 mL/minute: No initial adjustment; monitor serum concentrations.
    CrCl 10 to 50 mL/minute: Give usual dose every 24 to 72 hours; adjust doses based on serum concentrations.
    CrCl less than 10 mL/minute: Give usual dose every 48 to 72 hours; adjust doses based on serum concentrations.
     
    Pediatric patients
    Dosing adjustments are recommendations based on a usual dose of 5 to 7.5 mg/kg/dose IV/IM every 8 hours.
    CrCl more than 50 mL/minute/1.73 m2: No initial adjustment; monitor serum concentrations.
    CrCl 30 to 50 mL/minute/1.73 m2: 5 to 7.5 mg/kg/dose IV every 12 to 18 hours; monitor serum concentrations.
    CrCl 10 to 29 mL/minute/1.73 m2: 5 to 7.5 mg/kg/dose IV every 18 to 24 hours; monitor serum concentrations.
    CrCl less than 10 mL/minute/1.73 m2: 5 to 7.5 mg/kg/dose IV every 48 to 72 hours; monitor serum concentrations.
     
    INJECTABLE EXTENDED-INTERVAL DOSING† of 15 mg/kg - ADJUSTMENT of DOSING INTERVAL:
    CrCl 60 mL/minute or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
    CrCl 40 to 59 mL/minute: 15 mg/kg IV every 36 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 20 to 39 mL/minute: 15 mg/kg IV every 48 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl less than 20 mL/minute: Use traditional dosing. Adjust doses based on serum concentrations and organism MIC.
     
    INJECTABLE TUBERCULOSIS DOSING:
    Clinical guidelines recommend 12 to 15 mg/kg IV/IM given 2 to 3 times weekly or 25 mg/kg IV/IM 3 times weekly in patients with a CrCl less than 30 mL/minute with the doses adjusted based on serum concentrations.
     
    Intermittent hemodialysis
    Administer half of the dose IV/IM after dialysis for adult patients. For pediatric patients, give 5 mg/kg/dose IV/IM after dialysis. In tuberculosis patients, clinical guidelines recommend 12 to 15 mg/kg IV/IM given 2 to 3 times weekly or 25 mg/kg IV/IM 3 times weekly with the doses adjusted based on serum concentrations.
     
    Peritoneal dialysis
    Data are unavailable for intermittent IV/IM dosing in adult patients undergoing peritoneal dialysis. For pediatric patients, give 5 mg/kg/dose IV/IM as indicated by serum concentrations. For intraperitoneal dosing by population, refer to dosing guidelines for the treatment of peritonitis.
     
    Continuous renal replacement therapy (CRRT)
    For adult patients, give usual dose IV/IM every 24 to 72 hours; adjust doses based on serum concentrations. For pediatric patients, give 7.5 mg/kg/dose IV/IM every 12 hours; adjust doses based on serum concentrations.
     
    LIPOSOME INHALATION SUSPENSION
    Specific guidelines for dosage adjustment in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Dilution:
    Dilute amikacin vial with a compatible solution to a concentration of 2.5 to 5 mg/mL. A maximum concentration of 10 mg/mL has been suggested.
    Storage: The reconstituted solution is stable for 24 hours at room temperature even after 60 days refrigerated (4 degrees C) or after 30 days frozen (-15 degrees C).
     
    Intravenous injection:
    Infuse appropriate dose over 30 to 60 minutes.

    Intramuscular Administration

    Inject deeply into a large muscle mass.

    Inhalation Administration
    Oral Inhalation Administration

    Liposome inhalation suspension:
    Administer by nebulization only with the Lamira Nebulizer System.
    Consider pretreatment with short-acting beta-2 agonists for patients with known airway disease (i.e., chronic obstructive pulmonary disease, asthma, bronchospasm). Instruct patients who use a bronchodilator to first use the bronchodilator before using amikacin liposome inhalation suspension.
    Bring amikacin liposome inhalation suspension to room temperature by removing it from the refrigerator at least 45 minutes before use.
    Shake the vial well for at least 10 to 15 seconds until the contents appear uniform and well mixed.
    Open the vial by flipping up the plastic top and pulling downward to loosen the metal ring. Carefully remove the metal ring and rubber stopper.
    Pour the contents of the vial into the medication reservoir of the nebulizer handset, then attach the medication cap.
    Sit in a relaxed, upright position.
    Press and hold the on/off button for a few seconds to turn on the nebulizer. Mist will begin to flow.
    Insert the mouthpiece and take slow, deep breaths. Then, breathe normally through the mouthpiece until the treatment is complete (about 14 to 20 minutes). Be sure to hold the handset level throughout the treatment.
    When the treatment has ended, the nebulizer will beep and the LED light will flash red 2 times. A checkmark will briefly appear on the screen, and the controller will automatically shut off.
    Remove the medication cap, and check the medication reservoir to ensure that no more than a few drops of medication remain. If inhalation suspension remains, replace the medication cap; then press the on/off button, and complete the dose.
    Clean and disinfect the nebulizer handset and aerosol head after each use.
    Do not use other medication in the handset.
    Storage: If amikacin liposome inhalation suspension has been stored at room temperature, discard any unused medication at the end of 4 weeks.[63608]

    STORAGE

    Generic:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Amikin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Amikin Pediatric:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    ARIKAYCE:
    - Do not freeze
    - Product is stable until the expiration date on the label if refrigerated (36 to 46 degrees F)
    - Refrigerate (between 36 and 46 degrees F)
    - Unrefrigerated product can be stored at temperatures not exceeding 77 degrees F for 28 days

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Prescribing amikacin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of developing drug-resistant bacteria. Amikacin liposome inhalation suspension is only indicated for patients with refractory Mycobacterium avium complex (MAC) lung disease who have limited or no alternate treatment options and have failed to achieve negative sputum cultures after at least 6 consecutive months of a multidrug background regimen therapy.

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Closely monitor patients receiving systemic aminoglycosides, such as amikacin, for nephrotoxicity. Aminoglycosides are associated with major toxic effects on the renal tubules. In patients with preexisting renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine). When monitoring amikacin serum concentrations during use of conventional dose regimens, avoid peak concentrations above 35 mcg/mL and trough concentrations above 10 mcg/mL.[29874] However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted.[34173] [34175] [34186] [34172] Closely monitor renal function. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in amikacin removal in the event of overdose or toxic reactions, especially if renal function is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.[29874]

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Closely monitor patients receiving systemic aminoglycosides, such as amikacin, for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with preexisting renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring amikacin serum concentrations during use of conventional dose regimens, avoid peak concentrations above 35 mcg/mL and trough concentrations above 10 mcg/mL.[29874] However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted.[34173] [34175] [34186] [34172] Closely monitor eighth cranial nerve function. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Do not administer aminoglycosides concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended.[29874] [42984]

    Aminoglycoside hypersensitivity

    Amikacin is contraindicated in patients with known aminoglycoside hypersensitivity.[29874] [63608] Serious and potentially life-threatening hypersensitivity reactions, including anaphylaxis, have been reported in patients taking amikacin liposome inhalation suspension. Evaluate for previous hypersensitivity reactions to aminoglycosides before therapy with amikacin liposome inhalation suspension is instituted. If anaphylaxis or a hypersensitivity reaction occurs, discontinue amikacin liposome inhalation suspension and institute appropriate supportive measures.[63608]

    Botulism, electrolyte imbalance, myasthenia gravis, neuromuscular blockade, neuromuscular disease, parkinsonism, respiratory depression, respiratory insufficiency

    Systemic aminoglycosides, such as amikacin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled after local irrigation and after topical application during surgical procedures. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). Corrective therapy is required for any electrolyte imbalance, which may aggravate risk for neuromuscular/neurological symptoms. During or after aminoglycoside therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia. In infants, tetany and muscle weakness have been described. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including amikacin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    Neonates, premature neonates

    Use amikacin with caution in neonates and premature neonates due to renal immaturity and the prolongation of serum half-life of the drug, which increases the risk of amikacin-induced toxicity. When amikacin is used in the neonatal population, careful monitoring is warranted for signs and symptoms of toxicity including auditory, vestibular, and renal toxicity and neuromuscular blockade.[29874]

    Geriatric

    Geriatric patients may have reduced renal function which may not be evident on routine screening tests such as a serum creatinine. A creatinine clearance may be more useful. Monitoring of renal function during treatment with aminoglycosides is particularly important in the elderly since there is an age-related decrease in renal function thereby increasing the risk of auditory, vestibular, and renal toxicity and neuromuscular blockade. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral amikacin must be accompanied by monitoring of renal function tests, including a baseline value, and serum amikacin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. 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.

    Acute bronchospasm, asthma, chronic obstructive pulmonary disease (COPD), pulmonary disease

    Amikacin liposome inhalation suspension has been associated with an increased risk of respiratory adverse reactions, including exacerbation of underlying pulmonary disease with some cases requiring hospitalization. Consider pretreatment with a short-acting selective beta-2 agonist for patients with known hyperreactive airway disease, chronic obstructive pulmonary disease (COPD), asthma, or acute bronchospasm. Manage patients who develop a respiratory adverse reaction during amikacin liposome inhalation treatment as medically appropriate; discontinue amikacin liposome inhalation therapy if hypersensitivity pneumonitis develops.[63608]

    Pregnancy

    Aminoglycosides, including amikacin, may cause fetal harm when administered during pregnancy; the product labeling for other aminoglycosides carry a boxed warning regarding use in pregnancy for this reason. Aminoglycosides rapidly cross the placenta. Although serious side effects to the fetus or newborns have not been reported in the treatment of pregnant women with all aminoglycosides, there have been several reports of total irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. There are no well controlled studies in pregnant women, but investigational experience does not include any positive evidence of adverse effects to the fetus. Studies in patients undergoing elective abortions in the first and second trimesters indicate that amikacin distributes to most fetal tissues except the brain and cerebrospinal fluid, with the highest fetal concentrations found in the kidneys and urine. If amikacin is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to the fetus. 

    Breast-feeding

    Because of the potential for serious adverse reactions in breast-feeding infants, the manufacturer recommends discontinuing injectable amikacin or discontinuing breast-feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for amikacin liposome inhalation solution and any potential adverse effects on the breast-fed infant from amikacin liposome inhalation solution or the underlying maternal condition. Aminoglycosides are generally excreted into breast milk in low concentrations. However, amikacin and other aminoglycosides are poorly absorbed from the gastrointestinal tract are not likely to cause adverse events in nursing infants. Only trace amounts of amikacin have been reported in breast milk after intramuscular doses. Previous American Academy of Pediatrics (AAP) recommendations considered aminoglycosides as generally compatible with breast-feeding.

    ADVERSE REACTIONS

    Severe

    aphonia / Delayed / 48.0-48.0
    bronchospasm / Rapid / 29.0-29.0
    ototoxicity / Delayed / 0-17.0
    pneumothorax / Early / 2.0-2.0
    hyposthenuria / Delayed / Incidence not known
    renal tubular acidosis (RTA) / Delayed / Incidence not known
    renal tubular necrosis / Delayed / Incidence not known
    nephrotoxicity / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    apnea / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known

    Moderate

    dysphonia / Delayed / 48.0-48.0
    dyspnea / Early / 29.0-29.0
    wheezing / Rapid / 29.0-29.0
    hemoptysis / Delayed / 18.0-18.0
    candidiasis / Delayed / 4.0-4.0
    pneumonitis / Delayed / 3.1-3.1
    interstitial lung disease / Delayed / 3.1-3.1
    peripheral neuropathy / Delayed / 1.0-1.0
    hypotension / Rapid / 0-1.0
    eosinophilia / Delayed / 0-1.0
    anemia / Delayed / 0-1.0
    pyuria / Delayed / Incidence not known
    tetany / Early / Incidence not known
    neurotoxicity / Early / Incidence not known
    myasthenia / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known

    Mild

    cough / Delayed / 40.0-40.0
    arthralgia / Delayed / 0-18.0
    myalgia / Early / 18.0-18.0
    back pain / Delayed / 18.0-18.0
    laryngitis / Delayed / 18.0-18.0
    throat irritation / Early / 18.0-18.0
    asthenia / Delayed / 16.0-16.0
    fatigue / Early / 16.0-16.0
    diarrhea / Early / 13.0-13.0
    nausea / Early / 0-12.0
    headache / Early / 0-10.0
    infection / Delayed / 9.0-9.0
    tinnitus / Delayed / 8.1-8.1
    fever / Early / 0-8.0
    vomiting / Early / 0-7.0
    weight loss / Delayed / 7.0-7.0
    dizziness / Early / 6.3-6.3
    maculopapular rash / Early / 6.0-6.0
    rash / Early / 0-6.0
    urticaria / Rapid / 6.0-6.0
    anxiety / Delayed / 5.0-5.0
    dysgeusia / Early / 3.0-3.0
    xerostomia / Early / 3.0-3.0
    epistaxis / Delayed / 3.0-3.0
    weakness / Early / 1.0-1.0
    cylindruria / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    paresthesias / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Aspirin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Aspirin; Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion. (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acyclovir: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
    Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
    Aminosalicylate sodium, Aminosalicylic acid: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Amlodipine; Celecoxib: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with aminoglycosides (e.g., gentamicin, tobramycin, or amikacin). Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aminoglycosides, as the risk of renal impairment may be increased.
    Aspirin, ASA: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Dipyridamole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Omeprazole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Oxycodone: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Pravastatin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bacillus Calmette-Guerin Vaccine, BCG: (Major) Urinary concentrations of amikacin could interfere with the therapeutic effectiveness of BCG. Postpone instillation of BCG if the patient is receiving antibiotics.
    Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as aminoglycosides (particularly kanamycin, streptomycin, and neomycin).Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, with aminoglycosides may have additive nephrotoxic potential.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Beractant: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
    Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Bismuth Subsalicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bleomycin: (Moderate) Previous treatment with nephrotoxic agents, like aminoglycosides, may result in decreased clearance of bleomycin if renal function has been impaired.
    Botulinum Toxins: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
    Bumetanide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Bupivacaine; Meloxicam: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Calfactant: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
    Capreomycin: (Major) The concomitant use of capreomycin and aminoglycosides may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including aminoglycosides may increase serum concentrations of either capreomycin or aminoglycosides. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Aminoglycosides have also been reported to interfere with nerve transmission at the neuromuscular junction. Concomitant administration of capreomycin with aminoglycosides should be avoided if possible; however, if they must be coadministered, use extreme caution.
    Carbetapentane; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carboplatin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely.
    Cefepime: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotetan: (Minor) Cefotetan's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefoxitin: (Minor) Cefoxitin's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefprozil: (Minor) Cefprozil's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime; Avibactam: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftizoxime: (Minor) Ceftizoxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefuroxime: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Celecoxib: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Celecoxib; Tramadol: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Codeine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin. (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpromazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Choline Salicylate; Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Cidofovir: (Contraindicated) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Cisplatin: (Moderate) Closely monitor renal function and hearing ability if concomitant use with cisplatin and aminoglycosides is necessary. Both cisplatin and aminoglycosides can cause nephrotoxicity and ototoxicity, which may be exacerbated with the use of other nephrotoxic and ototoxic drugs.
    Clindamycin: (Moderate) Concomitant use of aminoglycosides and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Clofarabine: (Major) Avoid the concurrent and/or sequential use of amikacin and other nephrotoxic drugs such as clofarabine; coadministration may result in additive nephrotoxicity.
    Codeine; Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Codeine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Colfosceril; Cetyl Alcohol; Tyloxapol: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
    Colistin: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Cyclizine: (Minor) Cyclizine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Cyclosporine: (Major) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as aminoglycosides.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diclofenac: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Diclofenac; Misoprostol: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Diflunisal: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Dimenhydrinate: (Minor) Dimenhydrinate and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity, including nausea secondary to vertigo.
    Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Ibuprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin. (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Naproxen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin. (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs.
    Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for changes in serum creatinine and adverse reactions, such as lactic acidosis or hepatotoxicity if emtricitabine is administered in combination with nephrotoxic agents, such as aminoglycosides. Consider the potential for drug interaction prior to and during concurrent use of these medications. Both emtricitabine and aminoglycosides are excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. While no drug interactions due to competition for renal excretion have been observed, coadministration of these medications may increase concentrations of both drugs. (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Enflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and aminoglycosides can affect renal function, concurrent administration with aminoglycosides may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ethacrynic Acid: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Ethiodized Oil: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Etodolac: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Etomidate: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Fenoprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Fluphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by aminoglycosides.
    Flurbiprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as aminoglycosides.
    Furosemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Gallium: (Contraindicated) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as aminoglycosides, may increase the risk for developing severe renal insufficiency. If use of an aminoglycoside is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of the aminoglycoside is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Ginger, Zingiber officinale: (Minor) Ginger may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Gold: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Hydrocodone; Ibuprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Ibuprofen lysine: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Ibuprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Ibuprofen; Famotidine: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Ibuprofen; Oxycodone: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Ibuprofen; Pseudoephedrine: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Indomethacin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and aminoglycosides due to the risk of glomerulonephritis and nephrotoxicity.
    Iodixanol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iohexol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iomeprol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopromide: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ioversol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Isoflurane: (Moderate) Halogenated anesthetics may be associated with enhanced neuromuscular blocking effects. Aminoglycosides may potentiate this effect, however, it appears this is only seen when aminoglycosides are used to irrigate the abdominal cavity during surgery, a practice which has been discouraged. It is believed that this problem is less likely to occur with parenteral aminoglycoside therapy since patients are exposed to smaller amounts of drug.
    Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ketamine: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Ketoprofen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Ketorolac: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Lansoprazole; Naproxen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Mannitol: (Major) Avoid concomitant use of mannitol and aminoglycosides, if possible. Concomitant administration of systemic therapy may increase the risk of ototoxicity and nephrotoxicity. In addition, systemic mannitol may alter the serum and tissue concentrations of aminoglycosides and increase the risk for aminoglycoside toxicity. If use together is necessary, monitor renal function and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Meclizine: (Minor) Meclizine and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo).
    Meclofenamate Sodium: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Mefenamic Acid: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Meloxicam: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Meperidine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Mesoridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Methenamine; Sodium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Methohexital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Methotrexate: (Major) Avoid concomitant use of methotrexate with amikacin due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions. Amikacin and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with amikacin may result in decreased renal function as well as increased methotrexate plasma concentrations.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nabumetone: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Naproxen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Naproxen; Esomeprazole: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Naproxen; Pseudoephedrine: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Nonsteroidal antiinflammatory drugs: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    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.
    Oxaprozin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Pentamidine: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Perphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Perphenazine; Amitriptyline: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Piroxicam: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Polymyxin B: (Major) The concomitant use of systemic Polymyxin B with systemic aminoglycosides increases the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Poractant Alfa: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
    Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Promethazine; Dextromethorphan: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Promethazine; Phenylephrine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Propofol: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    Pyridostigmine: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rofecoxib: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Salsalate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Sevoflurane: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving amikacin.
    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.
    Streptozocin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sulindac: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Sumatriptan; Naproxen: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Surfactants: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
    Tacrolimus: (Moderate) Additive nephrotoxicity is possible if aminoglycosides are used with tacrolimus. Care should be taken in using tacrolimus with other nephrotoxic drugs. Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced
    Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs (e.g., systemic aminoglycosides) may lead to additive nephrotoxicity. Televancin is closely related to vancomycin. In one clinical study, vancomycin coadministration, high aminoglycoside trough levels, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Closely monitor renal function and adjust telavancin doses based on creatinine clearance/renal function, and aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Telbivudine: (Moderate) Drugs that alter renal function such as aminoglycosides may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment.
    Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
    Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Thioridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Tolmetin: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Torsemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Trifluoperazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Trimethobenzamide: (Minor) Because of trimethobenzamide's antiemetic pharmacology, the drug may effectively mask dizziness, tinnitus, or vertigo that are associated with ototoxicity induced by various medications, including the aminoglycosides. Clinicians should be aware of this potential interaction and take it into consideration when monitoring for aminoglycoside-induced side effects.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Urea: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including urea. In addition, urea may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Valacyclovir: (Moderate) Additive nephrotoxicity is possible if systemic aminoglycosides are used with valacyclovir. Carefully monitor renal function during concomitant therapy.
    Valdecoxib: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal antiinflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as amikacin.
    Valganciclovir: (Major) Concurrent use of nephrotoxic agents, such as aminoglycosides, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Vancomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and systemic aminoglycosides may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Voclosporin: (Moderate) Concomitant use of voclosporin and aminoglycosides may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zalcitabine, ddC: (Moderate) Drugs such as parenteral aminoglycosides may increase the risk of developing peripheral neuropathy or other zalcitabine-associated adverse events by interfering with the renal clearance of zalcitabine and thereby raising systemic drug exposure. Coadministration of these drugs with zalcitabine requires frequent clinical and laboratory monitoring, with dosage adjustment for any significant change in renal function.
    Zoledronic Acid: (Moderate) Since zoledronic acid is eliminated by the kidney, coadministration of zoledronic acid with other potentially nephrotoxic drugs may increase serum concentrations of either zoledronic acid and/or these coadministered drugs. Theoretically, the chronic coadministration of zoledronic acid with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Aminoglycosides, including amikacin, may cause fetal harm when administered during pregnancy; the product labeling for other aminoglycosides carry a boxed warning regarding use in pregnancy for this reason. Aminoglycosides rapidly cross the placenta. Although serious side effects to the fetus or newborns have not been reported in the treatment of pregnant women with all aminoglycosides, there have been several reports of total irreversible, bilateral congenital deafness in children whose mothers received streptomycin during pregnancy. There are no well controlled studies in pregnant women, but investigational experience does not include any positive evidence of adverse effects to the fetus. Studies in patients undergoing elective abortions in the first and second trimesters indicate that amikacin distributes to most fetal tissues except the brain and cerebrospinal fluid, with the highest fetal concentrations found in the kidneys and urine. If amikacin is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential hazard to the fetus. 

    Because of the potential for serious adverse reactions in breast-feeding infants, the manufacturer recommends discontinuing injectable amikacin or discontinuing breast-feeding. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for amikacin liposome inhalation solution and any potential adverse effects on the breast-fed infant from amikacin liposome inhalation solution or the underlying maternal condition. Aminoglycosides are generally excreted into breast milk in low concentrations. However, amikacin and other aminoglycosides are poorly absorbed from the gastrointestinal tract are not likely to cause adverse events in nursing infants. Only trace amounts of amikacin have been reported in breast milk after intramuscular doses. Previous American Academy of Pediatrics (AAP) recommendations considered aminoglycosides as generally compatible with breast-feeding.

    MECHANISM OF ACTION

    Amikacin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Amikacin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA). As a result, abnormal, nonfunctional proteins are formed due to a misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. The uptake of aminoglycosides may be facilitated by the presence of inhibitors of the bacterial cell wall (i.e., beta-lactams, vancomycin).[34041] [34163] [34173] [40042] [41225]
     
    Against gram-negative aerobic rods, aminoglycosides exhibit 'concentration-dependent killing' and a 'post-antibiotic effect' (PAE). 'Concentration-dependent killing' describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The post-antibiotic effect can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (less than 2 hours) and longer for gram-negative organisms (2 to 7 hours), such as E. coli, K. pneumoniae, and P. aeruginosa. Both these phenomena are being exploited in designing dosage regimens that employ higher doses administered at longer intervals. The major pharmacodynamic parameter that determines efficacy of aminoglycosides is the serum peak concentration to MIC ratio (peak:MIC). Both time-kill studies as well as studies in humans have shown that a peak:MIC of more than 8:1 to 12:1 is associated with successful regimens.[23947] [24566] [34142] [34143] [34144] [34145] [34191] [34192]
     
    The mechanism of renal toxicity with aminoglycosides is associated with accumulation in the renal tubule, which is a saturable process. Elevated serum trough concentrations are associated with an increased risk of toxicity.[34159] [34160] [41226]
     
    The mechanism of ototoxicity relates to the aminoglycoside-induced destruction of sensory hair cells of the inner ear. The cochlear sensory cells that are most vulnerable are in the basal end, thereby leading to high-frequency hearing loss first. As ototoxicity ascends toward the apex of the cochlea, the lower frequencies are affected. Sensory cells that deal with vestibular function may also be affected. Aminoglycosides may cause free-radical damage to sensory cells and neurons. Biochemically, aminoglycosides may bind to polyphosphoinositides, which are part of the transmembrane signaling system mediating physiological effects of hormones, neurotransmitters, and neuromodulators which may interfere with essential mechanisms of cell physiology. Neural destruction without any cochlear hair cell damage has also been described. There may also be a genetic mitochondrial RNA mutation that may predispose some patients to aminoglycoside ototoxicity. Aminoglycosides enter the inner ear rapidly, but it is suggested that concentrations do not correlate with the development of ototoxicity. Likely, the concentrations in the inner ear dissipate slowly, which is consistent with the possibility of developing ototoxicity days to weeks after drug discontinuation.[33555] [42984] [42985] [42986]
     
    The susceptibility interpretive criteria for amikacin are delineated by pathogen. The MICs are defined for S. aureus, Enterobacterales, non-Enterobacterales, P. aeruginosa, and Acinetobacter sp. as susceptible at 16 mcg/mL or less as susceptible, intermediate at 32 mcg/mL, and resistant at 64 mcg/mL or more.[63320] [63321]
     
    Aminoglycoside resistance is well documented. There are a variety of resistance mechanisms employed by different pathogens. Enzymatic inhibition by gram-negative pathogens and Enterococcus sp. via aminoglycoside-modifying enzymes is achieved by modification of the aminoglycoside as it is transported across the cytoplasmic membrane. Alterations in the inner membrane porin channels by P. aeruginosa decrease antimicrobial penetration to the site of activity within the bacterial cell. Some gram-negative organisms and Enterococcus sp. can alter the ribosomal target sites of the aminoglycosides to decrease binding, thereby decreasing antimicrobial activity.[34161] [34162] [34163] [41225]

    PHARMACOKINETICS

    Amikacin is administered intravenously, intramuscularly, and via nebulized inhalation. Amikacin distributes into extracellular fluid. The volume of distribution is approximately 0.25 L/kg. Volume of distribution approximates extracellular space; therefore, peak serum concentrations may be lower in patients with a large volume of extracellular fluid. The volume of distribution may be higher in patients with sepsis, fever, severe burns, congestive cardiac failure, and peritonitis which may result in lower peak concentrations. Protein binding ranges from 0% to 11%. After administration, amikacin can be detected in bone, heart, gallbladder, and lung tissues as well as in the urine, sputum, bronchial secretions, and interstitial fluid, pleural fluid, and synovial fluid.
     
    Amikacin is not metabolized. Elimination is almost exclusively via glomerular filtration. Thus, elimination half-life varies according to renal function. Reabsorption of a small amount of the drug by the proximal tubule results in accumulation in the renal cortex, which may be responsible for nephrotoxicity. Animal models suggest that amikacin and tobramycin have a diminished affinity for the proximal tubule. In patients with normal renal function, 94% to 98.2% of an intravenous dose is recovered in the urine within 24 hours, and the plasma elimination half-life is approximately 2 hours. However, on average 7.42% (range, 0.72% to 22.6%) of an amikacin liposome inhalation dose is excreted unchanged in the urine. The serum half-life of amikacin liposome inhalation suspension is approximately 5.9 to 19.5 hours. It is likely that the majority of unabsorbed amikacin after amikacin liposome inhalation is eliminated by cellular turnover and expectoration.[29874] [34173] [54300] [54301] [54303]
     
    Affected cytochrome P450 isoenzymes and drug transporters: none

    Intravenous Route

    After IV administration, there is an acute distribution phase, followed by a linear elimination phase.

    Intramuscular Route

    Amikacin is rapidly absorbed after intramuscular administration with peak serum concentrations occurring about 1 hour after administration.

    Inhalation Route

    Bioavailability of amikacin liposome inhalation suspension varies from patient to patient because of differences in nebulizer efficiency and airway pathology. After 590 mg inhaled once daily in Mycobacterium avium complex (MAC) patients, sputum concentrations at 1 to 4 hours postinhalation were 1720, 884, and 1300 mcg/g at 1, 3, and 6 months, respectively. High variability in amikacin concentrations was observed. At 48 to 72 hours postinhalation, amikacin sputum concentrations decreased to approximately 5% of those at 1 to 4 hours postinhalation. After 3 months of 590 mg inhaled once daily dosing, the mean serum AUC and mean maximum serum concentration (Cmax) were 23.5 mcg x hour/mL and 2.8 mcg/mL, respectively. These values are lower than the mean AUC (154 mcg x hour/mL) and Cmax (76 mcg/mL) observed with 15 mg/kg IV once daily.[63608]