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  • CLASSES

    Muscle Relaxants, Centrally Acting, Plain

    BOXED WARNING

    Abrupt discontinuation, priapism

    Avoid abrupt discontinuation of intrathecal baclofen therapy. Abrupt discontinuation of intrathecal baclofen, regardless of cause, has resulted in severe reactions including high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multi-system organ failure, and death. Priapism may also develop or recur if intrathecal therapy is interrupted. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to at-risk patients (e.g., spinal cord injuries at T6 or above, communication difficulties, or history of withdrawal symptoms from oral or intrathecal baclofen). Rapid, accurate diagnosis and treatment are important to prevent potentially life-threatening central nervous system and systemic effects of intrathecal baclofen withdrawal. When appropriate, oral baclofen and/or oral or intravenous benzodiazepines may be considered for emergency use.[42609] [42610] Also avoid sudden discontinuation of oral baclofen after chronic use; abrupt discontinuation is associated with confusion, hallucinations, other psychiatric disturbances, seizure(s), and exacerbations of spasticity or other neurologic events. Gradual reduction of the oral dosage over a period of 2 weeks or more is recommended. Use baclofen with caution in patients with a history of autonomic dysreflexia (e.g., spinal cord injuries at T6 or above), as abrupt withdrawal or nociceptive stimuli may cause autonomic dysreflexic episodes.

    DEA CLASS

    Rx

    DESCRIPTION

    Orally and intrathecally administered skeletal muscle relaxant; derivative of the inhibitory neurotransmitter GABA
    Used to treat spasticity in patients with MS and other spinal cord lesions; may improve bowel and bladder function in some patients
    Abrupt discontinuation may cause serious and fatal adverse reactions; avoid rapid drug withdrawal

    COMMON BRAND NAMES

    ED Baclofen, FLEQSUVY, Gablofen, Lioresal, Lioresal Intrathecal, LYVISPAH, OZOBAX

    HOW SUPPLIED

    Baclofen/ED Baclofen/Lioresal Oral Tab: 5mg, 10mg, 20mg
    Baclofen/Gablofen/Lioresal/Lioresal Intrathecal Intrathecal Inj Sol: 0.05mg, 0.5mg, 1mL, 2mg, 1000mcg
    Baclofen/OZOBAX Oral Sol: 5mg, 5mL
    FLEQSUVY Oral Susp: 1mL, 5mg
    Gablofen Intrathecal Sol: 1mL, 50mcg, 500mcg, 1000mcg, 2000mcg
    LYVISPAH Oral Gran: 5mg, 10mg, 20mg

    DOSAGE & INDICATIONS

    For the treatment of spasticity, muscle spasm (not due to rheumatic conditions), myoclonus, and muscle rigidity in multiple sclerosis and spinal cord injury or diseases.
    For severe spasticity due to multiple sclerosis, cerebral palsy, spinal cord injury, or traumatic brain injury; or in patients unresponsive to oral baclofen therapy or those who experience intolerable side effects at effective oral doses.
    NOTE: Intrathecal baclofen has been designated an orphan drug by the FDA for this indication.
    Intrathecal dosage (Screening dose)
    Adults

    Dosage requires special procedures, patient screening, and dosage techniques; consult specialized resources. Recommended initial screening dose is 50 mcg intrathecally by barbotage over a period of at least 1 minute. The patient is observed over 4 to 8 hours. A positive response consists of significant decrease in muscle tone and/or frequency and/or severity of spasms. If the initial response is less than desired, a second bolus of 75 mcg intrathecally may be given 24 hours after the first dose, and observe for 4 to 8 hours. If the response is still inadequate, a final bolus of 100 mcg intrathecally may be given 24 hours later. Patients who do not respond to the 100 mcg dose should not be considered candidates for an implanted pump for chronic infusion.

    Children 4 years and older

    Dosage requires special procedures, patient screening, and dosage techniques; consult specialized resources. The initial screening dose and procedure is the same as in adults, 50 mcg intrathecally initially. However, for very small patients, a screening dose of 25 mcg intrathecally may be tried first.

    Intrathecal dosage (Dose titration)
    Adults

    Dosage requires special dosage techniques and monitoring; consult specialized resources. The screening dose that gave a positive response should be doubled and administered as a continuous intrathecal infusion over a 24-hour period, unless the efficacy of the screening bolus dose was maintained for 8 hours or longer. In this case, the starting daily dose should be the screening dose delivered intrathecally over a 24-hour period. No dose increases should be given in the first 24 hours. After the first 24 hours, the daily dosage should be increased slowly by 10% to 30% increments for spasticity of spinal cord origin or 5% to 15% increments for spasticity of cerebral origin per 24-hour period, until a desired clinical effect is achieved.

    Children 4 years and older

    Dosage requires special dosage techniques and monitoring; consult specialized resources. The screening dose that gave a positive response should be doubled and administered as a continuous intrathecal infusion over a 24-hour period, unless the efficacy of the screening bolus dose was maintained for 8 hours or longer. In this case, the starting daily dose should be the screening dose delivered intrathecally over a 24-hour period. No dose increases should be given in the first 24 hours. After the first 24 hours, the daily dosage should be increased slowly 5% to 15% increments per 24-hour period, until a desired clinical effect is achieved.

    Intrathecal maintenance dosage (Spasticity of spinal origin)
    Adults

    Maintenance dosage for long-term continuous intrathecal infusion has ranged from 12 mcg/day to 2,003 mcg/day, with most patients maintained on dosages of 300 to 800 mcg/day. There is limited experience with doses more than 1,000 mcg/day. Doses are titrated to response with the lowest possible effective dose utilized. During periodic pump refills, the daily dose may be increased by 10% to 40%, but no more than 40%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

    Children 4 years and older

    For children younger than 12 years, the average dose was 274 mcg/day intrathecally (24 to 1,199 mcg/day). Dosage requirements for children older than 12 years are not significantly different from adults. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

    Intrathecal maintenance dosage (Spasticity of cerebral origin)
    Adults

    Maintenance dosage for long-term continuous intrathecal infusion has ranged from 22 mcg/day to 1,400 mcg/day, with most patients maintained on dosages of 90 to 703 mcg/day. There is limited experience with doses more than 1,000 mcg/day. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

    Children 4 years and older

    For children younger than 12 years, the average dose was 274 mcg/day intrathecally (24 to 1,199 mcg/day). Dosage requirements for children older than 12 years are not significantly different from adults. During periodic pump refills, the daily dose may be increased by 5% to 20%, but no more than 20%, to maintain adequate symptom control. The daily dose may be decreased by 10% to 20% if patients experience side effects. A sudden large requirement for dose escalation suggests a catheter complication (i.e., catheter kink or dislodgement).

    Oral dosage (tablets, oral solution, concentrated oral suspension, oral granules)
    Adults

    Optimal dosing requires careful titration. Initially, 5 mg PO 3 times daily, increase slowly every 3 days by 5 mg PO 3 times/day up to 40 to 80 mg/day given in 3 to 4 divided doses. Adverse reactions can be minimized by slowly increasing the dosage. A 4-times per day regimen may provide better control in some patients. Some patients require 1 to 2 months of treatment for full benefit. Avoid abrupt discontinuation of therapy. The maximum dose recommended by the manufacturers is 80 mg/day, however some clinicians suggest that higher doses are well tolerated and offer a therapeutic advantage. Mean doses of 140 to 160 mg/day PO have been used during clinical experience. Some patients have required up to 240 mg/day.

    Children and Adolescents 12 years and older

    Optimal dosing requires careful titration. Initially, 5 mg PO 3 times daily, increase slowly every 3 days by 5 mg PO 3 times/day up to 40 to 80 mg/day given in 3 to 4 divided doses. Adverse reactions can be minimized by slowly increasing the dosage. A 4-times per day regimen may provide better control in some patients. Some patients require 1 to 2 months of treatment for full benefit. Avoid abrupt discontinuation of therapy. The maximum dose recommended by the manufacturers is 80 mg/day, however some clinicians suggest that doses up to 160 mg/day are well tolerated and offer a therapeutic advantage.

    Children 8 to 11 years†

    Initially, 10 to 15 mg/day PO in 3 divided doses. Titrate slowly every 3 days in 5 to 15 mg increments to a maximum dose of 60 mg/day.

    Children 2 to 7 years†

    Initially, 10 to 15 mg/day PO in 3 divided doses. Titrate slowly every 3 days in 5 to 15 mg increments to a maximum dose of 40 mg/day.

    For the treatment of persistent singultus (hiccups)†.
    Oral dosage
    Adults

    Baclofen may be just as effective as other agents already in use. A dose of 10 mg PO 4 times per day has been used.

    For the treatment of trigeminal neuralgia†.
    Oral dosage
    Adults

    10 mg PO 3 times daily for 1 week, initially. Increase the dose by 10 mg/day every other day as needed. Usual dose: 40 to 80 mg/day divided in 3 to 4 doses. Max: 80 mg/day.

    For the treatment of central vestibular nystagmus†.
    Oral dosage
    Adults

    Initially, 5 mg PO 3 times per day. Increase dosage by 5 mg per week not to exceed 80 mg/day. It is advisable to individualize the dosage based upon clinical response and tolerability.

    For prevention of stuttering priapism† (i.e., recurrent priapism).
    Oral dosage
    Adults

    Two case reports suggest 40 mg PO at bedtime is effective. Complete resolution of priapism occurred in 2 patients with idiopathic priapism. In both patients, baclofen was initiated at 10 mg PO at bedtime and titrated to effect; priapism was eliminated at a dosage of 40 mg/day. Priapism has not recurred with chronic administration (longer than 5 months in 1 patient and longer than 12 months in the other); sexual function has remained intact.

    For the adjunct treatment of symptomatic gastroesophageal reflux disease (GERD)† in refractory patients.
    Oral dosage
    Adults

    5 to 20 mg PO 3 times daily may be considered in patients with objective documentation of continued symptomatic GERD despite optimal PPI therapy. Limited data from uncontrolled, short-term studies suggests benefits such as a reduction in transient LES relaxation, reflux episodes, postprandial acid and non-acid reflux events, nocturnal reflux activity, and belching episodes. Long-term efficacy and safety data are not available.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    80 mg/day PO is the labeled maximum; however, up to 240 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

    Geriatric

    80 mg/day PO is the labeled maximum; however, up to 240 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

    Adolescents

    80 mg/day PO is the labeled maximum; however, up to 160 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.

    Children

    12 years: 80 mg/day PO is the labeled maximum; however, up to 160 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.
    8 to 11 years: 60 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen.
    2 to 7 years: 40 mg/day PO has been reported off-label. Maximum dosage information is not available for intrathecal baclofen. Safe and effective use of intrathecal baclofen has not been established for children less than 4 years.
    Less than 2 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment necessary.

    Renal Impairment

    CrCl more than 80 mL/minute: No dosage adjustment necessary.
    CrCl 50 to 80 mL/minute: Reduce PO dosage by one-third.
    CrCl 30 to 50 mL/minute: Reduce PO dosage by one-half.
    CrCl less than 30 mL/minute and not on dialysis: Reduce PO dosage by two-thirds.
     
    Use intrathecal baclofen with caution in patients with renal impairment. A dosage reduction may be necessary. Specific guidelines for dosage adjustments in renal impairment are not available.
     
    Intermittent hemodialysis
    Alternative therapies should be considered due to the potential for serious adverse effects. The pharmacokinetic properties of baclofen (i.e., low protein binding and volume of distribution) and low molecular weight (213 daltons) suggest that hemodialysis should be useful in removing baclofen from the blood in cases of clinical toxicity; although, efficacy of hemodialysis for this purpose has not been established.

    ADMINISTRATION

    Oral Administration

    Baclofen may be administered with food or milk to minimize gastric irritation.
    Whenever baclofen is discontinued, the daily dosage should be gradually decreased; abrupt discontinuation may result in adverse reactions.

    Oral Solid Formulations

    Oral granules (Lyvispah)
    Empty the entire contents of the packet into the mouth. The granules will dissolve in the mouth or can be swallowed. The granules can be administered with liquids or soft foods if needed.
    Alternatively, the granules may be mixed with up to 15 mL of liquid or soft food (such as apple sauce, yogurt, or pudding), and administered within 2 hours following mixing. When using multiple packets, mix each packet with a separate volume of liquid or soft food.
     
    Oral granules (Lyvispah) Feeding Tube Administration
    Oral granules can be administered via enteral feeding tubes including nasogastric (NG) tubes at sizes 8 French (FR) or higher, gastrostomy tubes at sizes 12 FR or higher, percutaneous endoscopic gastrostomy (PEG) tubes at sizes 14 FR or higher, and gastrojejunostomy (GJ) tubes at sizes 16 FR or higher.
    Flush the feeding tube with up to 15 mL of water using a catheter tip syringe.
    Mix each packet of granules with 15 mL of a preferred liquid (e.g., apple juice or milk) in a clean container; ensure the granules are wetted. Draw up the suspension into an oral dosing syringe administer within 2 hours following mixing. Invert the syringe 3 times to ensure mixing if the suspension stands for 15 minutes or more.
    Flush the feeding tube with 15 mL or water following administration.
    When using multiple packets, mix each packet with a separate volume of liquid.

    Oral Liquid Formulations

    Oral Solution (Ozobax)
    Measure using a calibrated oral dosing cup, spoon, syringe, or other oral device to ensure accurate dosage.
    Must keep refrigerated.
     
    Oral Suspension (Fleqsuvy)
    Verify strength and dosage of the product prior to administration. The suspension is a concentrated formulation.
    Shake well before each administration.
    Measure using a calibrated oral dosing cup, spoon, syringe, or other oral device to ensure accurate dosage.
    Storage: Store at room temperature. Discard any unused suspension 2 months after opening.

    Injectable Administration

    For intrathecal administration only via injection or continuous infusion; do not give parenterally or by epidural routes.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intrathecal Administration

    Only use implantable pumps FDA-approved for the administration of continuous intrathecal baclofen infusions. Refer to the implantable pump manual for the specific instructions and precautions regarding pump programming and filling the reservoir.
    Before pump implantation and initiation of chronic intrathecal baclofen therapy, patients must demonstrate a positive response to a baclofen intrathecal dose in a screening trial.
    IMPORTANT: Avoid use of baclofen prefilled syringes for intrathecal injection (Gablofen) in an aseptic setting (e.g., operating room) to fill sterile intrathecal pumps before implantation in patients due to the non-sterile external surface of the syringe and the potential for contamination. Baclofen injection in vials may be used with conventional aseptic technique to fill intrathecal pumps before implantation. If prefilled syringes are used to fill intrathecal pumps before implantation, the external surface of the syringe must be treated to ensure sterility.
    Procedures should also be in place to avoid contamination of sterile surfaces through contact with the non-sterile external surface of prefilled syringes when refilling implantable intrathecal pumps in the outpatient setting.[42610] [42609]
     
    Dilution:
    Dilution of baclofen injection is not required prior to use. However, if a baclofen concentration that is not commercially available is needed, dilute only with sterile, preservative-free 0.9% Sodium Chloride Injection.
    The specific concentration that should be used depends upon the total daily dose required as well as the delivery rate of the pump. Baclofen intrathecal injection may require dilution when used in certain pumps. Consult the manufacturer's manual for specific recommendations.[42609] [42610]
     
    Intrathecal Administration:
    Administer screening test dose intrathecally over at least 1 minute using barbotage. Following determination of patient response, baclofen may be administered by continuous intrathecal infusion using an implantable controlled-infusion pump.
    If patients require multiple infusion rates for optimal symptom control, changes in flow rate should be programmed to start 2 hours before the time of the desired clinical effect.
    ALERT: Avoid abrupt discontinuation of intrathecal baclofen therapy as serious, and potential fatal sequela may result. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms.
    ALERT: Over-infusion of more drug volume than the programmed rate can result in unexpected overdose or withdrawal caused by early emptying of the reservoir. If over-infusion is suspected, refer to the manufacturer's pump instructions for refilling the reservoir and contact the pump manufacturer. Reducing the dose and concentration is not recommended as a solution for over-infusion. Multiple factors may increase the risk for over-infusion, including the use of nonindicated drug formulations, overfilling of the pump reservoir, operation of the pump with no fluid in the reservoir, catheter occlusion, and pump stops or motor stalls lasting 48 hours or more.[42609] [42610]

    STORAGE

    Generic:
    - Keep away from heat and flame
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a cool, well ventilated, dry place
    ED Baclofen:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    FLEQSUVY:
    - Avoid extreme temperatures
    - Product should be used within 2 months after opening
    - Protect from direct sunlight
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a cool, dry place
    Gablofen:
    - Avoid temperatures above 86 degrees F
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not autoclave
    - Do not freeze
    - Refrigeration is not needed
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Lioresal:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Lioresal Intrathecal:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not autoclave
    - Do not freeze
    - Refrigeration is not needed
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    LYVISPAH:
    - Avoid extreme temperatures
    - Keep away from heat and flame
    - Protect from direct sunlight
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in a dry, well ventilated place
    OZOBAX:
    - Refrigerate (between 36 and 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Baclofen is contraindicated in patients with baclofen hypersensitivity.

    Abrupt discontinuation, priapism

    Avoid abrupt discontinuation of intrathecal baclofen therapy. Abrupt discontinuation of intrathecal baclofen, regardless of cause, has resulted in severe reactions including high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, that in rare cases has advanced to rhabdomyolysis, multi-system organ failure, and death. Priapism may also develop or recur if intrathecal therapy is interrupted. Prevention of abrupt discontinuation of intrathecal baclofen requires careful attention to programming and monitoring of the infusion system, refill scheduling and procedures, and pump alarms. Patients and caregivers should be advised of the importance of keeping scheduled refill visits and should be educated on the early symptoms of baclofen withdrawal. Special attention should be given to at-risk patients (e.g., spinal cord injuries at T6 or above, communication difficulties, or history of withdrawal symptoms from oral or intrathecal baclofen). Rapid, accurate diagnosis and treatment are important to prevent potentially life-threatening central nervous system and systemic effects of intrathecal baclofen withdrawal. When appropriate, oral baclofen and/or oral or intravenous benzodiazepines may be considered for emergency use.[42609] [42610] Also avoid sudden discontinuation of oral baclofen after chronic use; abrupt discontinuation is associated with confusion, hallucinations, other psychiatric disturbances, seizure(s), and exacerbations of spasticity or other neurologic events. Gradual reduction of the oral dosage over a period of 2 weeks or more is recommended. Use baclofen with caution in patients with a history of autonomic dysreflexia (e.g., spinal cord injuries at T6 or above), as abrupt withdrawal or nociceptive stimuli may cause autonomic dysreflexic episodes.

    Cerebral palsy, head trauma, intracranial bleeding, stroke

    Baclofen should not be used in patients who require spasticity to maintain upright posture and balance. Although intrathecal use of baclofen is indicated in patients with spasticity of cerebral origin, oral baclofen is not recommended in patients with trauma-induced cerebral lesions, cerebral palsy, intracranial bleeding, parkinsonism, or a prior cerebrovascular accident (stroke). Efficacy of oral baclofen in such patients has not been established. Oral baclofen only crosses the blood-brain barrier in small amounts. In high doses, oral baclofen therapy may be successful in some patients with severe spasticity. In patients who do not respond adequately or do not tolerate oral therapy, a trial of intrathecal baclofen therapy may be appropriate. Manufacturers of intrathecal baclofen recommend that patients with spasticity secondary to head trauma wait at least 1 year before considering long-term intrathecal baclofen therapy; some clinicians recommend beginning treatment sooner.

    Geriatric

    Geriatric patients or patients with cerebral lesions as opposed to spinal lesions may experience increased toxicity to baclofen. Elderly patients require lower initial doses and slow dose titration. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. According to the OBRA guidelines, most muscle relaxants are poorly tolerated by older adults due to anticholinergic side effects, sedation, and/or weakness. However, periodic use (e.g., once every 3 months) for no more than 7 days may be appropriate when other interventions or alternative medications are not effective or indicated. Chronic use in individuals with complications due to multiple sclerosis, spinal cord injuries, cerebral palsy, and other select conditions may be indicated, although close monitoring is warranted. Abrupt discontinuation of some muscle relaxants may cause or predispose individuals to seizures or hallucinations.

    Bipolar disorder, depression, psychosis, schizophrenia

    Patients with pre-existing psychiatric disorders (e.g., bipolar disorder, depression, psychosis, schizophrenia) are at increased risk for baclofen-induced psychiatric adverse reactions.

    Diabetes mellitus

    Hyperglycemia is associated with oral and intrathecal baclofen use. Use with appropriate caution in patients with diabetes mellitus.

    Seizure disorder, seizures

    Baclofen has caused deterioration in the control of seizures and EEG changes in patients with epilepsy. Baclofen should be prescribed cautiously to patients with a history of a seizure disorder or a history of seizures.

    Dialysis, renal failure, renal impairment

    Cases of baclofen toxicity (manifesting as encephalopathy, abdominal pain, and in some cases, seizures and respiratory depression) have been reported in patients with severe renal impairment (e.g., serum creatinine more than 2 mg/dL) and renal failure who received oral baclofen. Most patients who became toxic received low oral doses of baclofen (e.g., 15 to 30 mg/day) for a short duration. Baclofen toxicity can occur with relatively low doses within 24 to 48 hours of initiation of oral therapy. In renal failure patients receiving dialysis, doses not exceeding 5 mg/day orally have been suggested; although toxicity may still occur. Therefore, in patients with severe renal impairment or renal failure, alternative therapies should be considered. If a patient develops baclofen toxicity, hemodialysis may be a useful treatment to alleviate clinical symptoms. Similar toxicity is not expected with intrathecal use of baclofen as resultant drug plasma concentrations are 100-fold lower than those experienced with oral use.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion

    Patients should be warned that baclofen may impair the ability to perform certain tasks that require mental alertness or physical coordination such as driving or operating machinery. Patients should also be cautioned that the central nervous system (CNS) depressant effects of baclofen may be additive to those of ethanol ingestion and coadministration with other CNS depressants.

    Children, infants

    Safety has not been established for oral baclofen in infants and children younger than 12 years or for intrathecal baclofen in children younger than 4 years. Children undergoing intrathecal pump implantation for intrathecal baclofen therapy should have sufficient body mass to accommodate the pump.

    Epidural administration, intramuscular administration, intravenous administration, subcutaneous administration

    Baclofen intrathecal is for administration via FDA-approved infusion devices or as single intrathecal injections. Baclofen is not for intravenous administration, intramuscular administration, subcutaneous administration, or epidural administration. Physicians must be trained in intrathecal pump therapy due to the possibility of CNS depression, cardiovascular collapse, or respiratory failure. The pump should not be implanted until the patient's response to the screening process is evaluated; patients who do not respond to a 100 mcg intrathecal bolus should not be considered candidates for an implanted pump for chronic infusion. Patients should be closely monitored until the patient's initial response is stable and following each adjustment. Concurrent oral antispasmodic drugs should be discontinued prior to implantation of the infusion device to avoid drug interactions or toxicity. Avoid abrupt discontinuation of any antispasmodic agent.

    Anticoagulant therapy, coagulopathy, infection

    A patient who is a candidate for intrathecal baclofen infusion must have no contraindications to the insertion of an intrathecal catheter. Thus, patients should be free from the following conditions prior to pump insertion and prior to the screening trial and treatment with baclofen intrathecal injection: infection (local at site of pump implantation or systemic), coagulopathy, anatomical abnormality of the spine, anticoagulant therapy, and any other drug therapy or medical condition that might contraindicate administration of baclofen by this route.

    Neonates, pregnancy

    There are no adequate and well controlled studies of baclofen use during human pregnancy. Based on animal data, baclofen may cause fetal harm; oral administration of baclofen to pregnant rats resulted in an increased incidence of fetal structural abnormalities at a dose which was also associated with maternal toxicity. Baclofen should only be used during pregnancy when the potential benefit to the mother outweighs the potential risk to the fetus. Human data are limited. In 3 cases, healthy infants were delivered by C-section after in utero exposure to intrathecal baclofen infusions (doses of 140 to 1,400 mcg/day). Follow up in 2 of the cases revealed normal development at 12 months and 24 months of age, respectively. The effects of baclofen use during labor and obstetric delivery are unknown. There are adverse outcomes in neonates associated with neonatal withdrawal from baclofen after delivery. A neonatal abstinence syndrome (NAS) may occur shortly after birth in neonates following intrauterine baclofen exposure. Symptoms may include increased muscle tone, tremor, jitteriness, and seizure. Gradually reduce the maternal baclofen dosage and discontinue the drug before delivery if baclofen is used during pregnancy. In 1 case report, a woman received 80 mg of oral baclofen daily during pregnancy and post-partum. In order to prevent NAS, the neonate was placed on oral baclofen at initial dosage of 0.1 mg/kg/day for 4 days, followed by a daily decrease of 0.01 mg/kg/day until the drug was discontinued after 13 days. Of note, the neonate received approximately one-third of the total daily dose of baclofen from breast milk. Daily assessments for NAS were done using the modified Finnegan scoring system. Additional pharmacological intervention was not needed, and the neonate was discharged 3 days after the taper ended.

    Breast-feeding

    At therapeutic oral doses, baclofen is excreted in human milk; caution is recommended when using the drug during breast-feeding. Withdrawal symptoms in the infant may occur if breast-feeding is stopped or oral baclofen is discontinued. It is not known if baclofen is detectable in breast milk after intrathecal administration; the labeling for intrathecal products recommends that a decision be made whether to discontinue breast-feeding or to discontinue intrathecal baclofen injection, considering the importance of intrathecal baclofen therapy to the mother. Limited information indicates that oral baclofen to the lactating mother appears in low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Low intrathecal doses and topical application are unlikely to affect the nursing infant. If baclofen is continued, monitor the infant for signs of sedation. In one report in a woman given a single 20 mg oral dose of baclofen 14 days postpartum, the highest serum concentration of the drug occurred at 3 hours and the highest milk level was obtained at 4 hours. The total amount of drug recovered from the milk during the 26-hour sampling period was about 0.1% of the maternally ingested dose.

    Ovarian cyst

    A dose-related increase in the incidence of ovarian cyst and a less marked increase in enlarged and/or hemorrhagic adrenal glands was observed in female rats treated chronically with baclofen. Ovarian cysts have been found by palpation in about 4% of the multiple sclerosis female patients that were treated with baclofen for up to 1 year. In most cases these cysts disappeared spontaneously while patients continued to receive the drug. Ovarian cysts are estimated to occur spontaneously in approximately 1% to 5% of the normal female population.

    ADVERSE REACTIONS

    Severe

    coma / Early / 0-1.5
    seizures / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    stroke / Early / Incidence not known
    ileus / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    oliguria / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known
    thrombosis / Delayed / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    apnea / Delayed / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    neuroleptic malignant syndrome / Delayed / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known
    rhabdomyolysis / Delayed / Incidence not known
    disseminated intravascular coagulation (DIC) / Delayed / Incidence not known

    Moderate

    hypotonia / Delayed / 2.4-34.7
    confusion / Early / 0.5-11.0
    hypotension / Rapid / 0-9.0
    urinary retention / Early / 0.7-8.0
    hypertonia / Delayed / 0-6.0
    constipation / Delayed / 0.2-6.0
    hypoventilation / Rapid / 0.2-4.0
    peripheral edema / Delayed / 0-3.3
    amblyopia / Delayed / 0.2-2.3
    urinary incontinence / Early / 0-2.0
    depression / Delayed / 0-1.6
    impotence (erectile dysfunction) / Delayed / 0.2-1.6
    impaired cognition / Early / 0.5-1.3
    dyspnea / Early / 0-1.2
    hypertension / Early / 0.2-0.6
    hallucinations / Early / 0.3-0.5
    dystonic reaction / Delayed / Incidence not known
    dyskinesia / Delayed / Incidence not known
    amnesia / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    euphoria / Early / Incidence not known
    respiratory depression / Rapid / Incidence not known
    psychological dependence / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    dysarthria / Delayed / Incidence not known
    akathisia / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    psychosis / Early / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    dysuria / Early / Incidence not known
    hematuria / Delayed / Incidence not known
    vaginitis / Delayed / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    skin ulcer / Delayed / Incidence not known
    palpitations / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    meningitis / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    withdrawal / Early / Incidence not known
    priapism / Early / Incidence not known

    Mild

    drowsiness / Early / 5.7-63.0
    weakness / Early / 5.0-15.0
    dizziness / Early / 1.7-15.0
    nausea / Early / 1.4-12.0
    headache / Early / 1.6-10.7
    vomiting / Early / 1.6-10.5
    insomnia / Early / 0-7.0
    paresthesias / Delayed / 0.7-6.7
    increased urinary frequency / Early / 0-6.0
    pruritus / Rapid / 0-4.0
    fatigue / Early / 2.0-4.0
    xerostomia / Early / 0-3.3
    hypersalivation / Early / 0-2.7
    diarrhea / Early / 0-2.3
    asthenia / Delayed / 0-2.0
    back pain / Delayed / 0.7-2.0
    agitation / Early / 0.5-1.3
    tremor / Early / 0-1.3
    chills / Rapid / 0-1.3
    urticaria / Rapid / 0.2-1.2
    abdominal pain / Early / 0-1.0
    anxiety / Delayed / 0.2-0.9
    diplopia / Early / 0-0.9
    anorexia / Delayed / 0-0.9
    musculoskeletal pain / Early / Incidence not known
    hyporeflexia / Delayed / Incidence not known
    emotional lability / Early / Incidence not known
    miosis / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    paranoia / Early / Incidence not known
    mydriasis / Early / Incidence not known
    flatulence / Early / Incidence not known
    weight gain / Delayed / Incidence not known
    dysgeusia / Early / Incidence not known
    dyspepsia / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    nocturia / Early / Incidence not known
    orgasm dysfunction / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    alopecia / Delayed / Incidence not known
    rash / Early / Incidence not known
    premature atrial contractions (PACs) / Early / Incidence not known
    malaise / Early / Incidence not known
    hypothermia / Delayed / Incidence not known
    influenza / Delayed / Incidence not known
    petechiae / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known
    nasal congestion / Early / Incidence not known
    rhinitis / Early / Incidence not known
    hyperventilation / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression is possible if skeletal muscle relaxants are used concomitantly with other CNS depressants. Dosage adjustments of one or both medications may be necessary.
    Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
    Acetaminophen; Pentazocine: (Major) Concomitant use of pentazocine with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
    Alfentanil: (Major) Concomitant use of alfentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aliskiren; Amlodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Alprazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Amiloride: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Atorvastatin: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Benazepril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Celecoxib: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Olmesartan: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Valsartan: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Amobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Amoxapine: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive CNS depressant effects. Skeletal muscle relaxants may produce additive CNS depression or other additive effects when combined with tricyclic antidepressants. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
    Angiotensin II receptor antagonists: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Angiotensin-converting enzyme inhibitors: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
    Atenolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Atenolol; Chlorthalidone: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with baclofen can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
    Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
    Barbiturates: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Belladonna; Opium: (Major) Concomitant use of opioid agonists with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of opioid agonists with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
    Benazepril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Bendroflumethiazide; Nadolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzodiazepines: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Beta-adrenergic blockers: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Betaxolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Bisoprolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Botulinum Toxins: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
    Brimonidine; Timolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Buprenorphine: (Major) Reserve concomitant prescribing of buprenorphine and baclofen for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
    Buprenorphine; Naloxone: (Major) Reserve concomitant prescribing of buprenorphine and baclofen for use in patients in whom alternate treatment options are inadequate. Limit dosages and durations to the minimum required and monitor patients closely for respiratory depression and sedation. Gradually tapering a patient off other CNS depressants or decreasing to the lowest effective dose is preferred in most cases of patients being treated for opioid use disorder. If concomitant use is necessary, consider prescribing naloxone for the emergency treatment of opioid overdose. Concomitant use can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
    Butabarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Butalbital; Acetaminophen: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as baclofen, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
    Calcium-channel blockers: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and baclofen. CNS depressants can potentiate the effects of cannabidiol.
    Captopril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including skeletal muscle relaxants.
    Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Carteolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Carvedilol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and baclofen. Concurrent use may result in additive CNS depression.
    Central-acting adrenergic agents: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
    Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
    Chlordiazepoxide: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Chlorpromazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Clevidipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Clonazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Clorazepate: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Clozapine: (Moderate) Skeletal muscle relaxants should be combined cautiously with clozapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
    Codeine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Codeine; Promethazine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as baclofen, may have additive effects and worsen drowsiness or sedation.
    Dexmedetomidine: (Moderate) Due to the anesthetic effects of dexmedetomidine, concurrent use with other CNS depressants, such as skeletal muscle relaxants, could result in additive sedative effects and possibly prolong recovery from anesthesia. Dosage adjustments of either or both medications may be necessary.
    Diazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
    Diltiazem: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with baclofen can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Dorzolamide; Timolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Doxazosin: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Dronabinol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
    Droperidol: (Moderate) Concomitant use of baclofen with other CNS depressants like droperidol can result in additive CNS depression.
    Enalapril, Enalaprilat: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Enalapril; Felodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Eplerenone: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Epoprostenol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Esketamine: (Major) Closely monitor patients receiving esketamine and skeletal muscle relaxants for sedation and other CNS depressant effects. Patients who receive a dose of esketamine should not drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Esmolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Estazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Eszopiclone: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
    Etomidate: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Felodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and baclofen. Concurrent use may result in additive CNS depression.
    Fentanyl: (Major) Concomitant use of fentanyl with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Fluphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Flurazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
    Fosinopril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and baclofen. Concomitant use of gabapentin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    General anesthetics: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Hydrocodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking baclofen.
    Hydromorphone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
    Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
    Iloprost: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Isoflurane: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Isradipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Ketamine: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Labetalol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and baclofen. Concurrent use may result in additive CNS depression.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and baclofen. Dosage adjustments of lemborexant and baclofen may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Levamlodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Levobetaxolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Levobunolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
    Levorphanol: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial levorphanol dosage by 50% or more.
    Lisinopril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Lofexidine: (Moderate) Monitor for additive sedation during coadministration of lofexidine and baclofen. Lofexidine can potentiate the effects of CNS depressants. Patients should be advised to avoid driving or performing any other tasks requiring mental alertness until the effects of the combination are known. In the use of intrathecal baclofen, hypotension is possible, so the additive effects of lofexidine on blood pressure should be considered. Carefully monitor blood pressure and heart rate in such patients.
    Loop diuretics: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Lorazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Loxapine: (Moderate) Loxapine is a central nervous system (CNS) depressant. The concurrent use of loxapine with other CNS depressants (e.g., muscle relaxants such as baclofen) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with loxapine.
    Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
    Maprotiline: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
    Mecamylamine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Meperidine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
    Meperidine; Promethazine: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Meprobamate: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Methadone: (Major) Concomitant use of methadone with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Methocarbamol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of baclofen and methocarbamol. Concurrent use may result in additive CNS depression.
    Methohexital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Methscopolamine: (Moderate) CNS depression can be increased when methscopolamine is combined with other CNS depressants such as skeletal muscle relaxants.
    Metoprolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Midazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Mirtazapine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and mirtazapine due to the risk for additive CNS depression.
    Moexipril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Molindone: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as molindone, can increase CNS depression. In addition, antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Morphine: (Major) Concomitant use of morphine with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Morphine; Naltrexone: (Major) Concomitant use of morphine with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Nabilone: (Major) Avoid use together if possible. Use of nabilone with skeletal muscle relaxants can potentiate the CNS depressant effects of nabilone on sedation, dizziness and other side effects, which can impair the ability to undertake tasks requiring mental alertness.
    Nadolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nalbuphine: (Major) Concomitant use of nalbuphine with baclofen may cause excessive sedation and somnolence. Limit the use of nalbuphine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
    Nebivolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nebivolol; Valsartan: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nicardipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nifedipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nimodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Nisoldipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Oliceridine: (Major) Concomitant use of oliceridine with baclofen may cause excessive sedation and somnolence. Limit the use of oliceridine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Oxazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Oxycodone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
    Oxymorphone: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half.
    Penbutolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Pentazocine: (Major) Concomitant use of pentazocine with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
    Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with baclofen may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
    Pentobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Perindopril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Perindopril; Amlodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Perphenazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Perphenazine; Amitriptyline: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Phenobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Phenothiazines: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Phenoxybenzamine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Phentolamine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Pindolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Potassium-sparing diuretics: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Prazosin: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and baclofen. Concomitant use of pregabalin with baclofen may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
    Primidone: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Prochlorperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Promethazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Promethazine; Dextromethorphan: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Promethazine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Propofol: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Propranolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Quazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Quinapril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Ramipril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Remifentanil: (Major) Concomitant use of remifentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Remimazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Reserpine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Secobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
    Sedating H1-blockers: (Moderate) An enhanced CNS depressant effect may occur when sedating H1-blockers are combined with other CNS depressants including skeletal muscle relaxants, such as baclofen.
    Sevoflurane: (Moderate) Concomitant use of skeletal muscle relaxants with other CNS depressants like general anesthetics can result in additive CNS depression.
    Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
    Spironolactone: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Sufentanil: (Major) Concomitant use of sufentanil with baclofen may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tapentadol: (Major) Concomitant use of opioid agonists with baclofen may cause excessive sedation and somnolence. Limit the use of opioid pain medications with baclofen to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
    Telmisartan; Amlodipine: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Temazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Terazosin: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as skeletal muscle relaxants due to the potential for additive sedative effects.
    Thiazide diuretics: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Thiethylperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Thioridazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
    Timolol: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Tizanidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of baclofen and tizanidine. Concurrent use may result in additive CNS depression.
    Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
    Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Trandolapril: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required
    Trandolapril; Verapamil: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Trazodone: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and trazodone due to the risk for additive CNS depression.
    Treprostinil: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Triamterene: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Triazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
    Tricyclic antidepressants: (Moderate) Monitor for unusual drowsiness and excess sedation during coadministration of baclofen and tricyclic antidepressants due to the risk for additive CNS depression.
    Trifluoperazine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of baclofen and phenothiazines due to the risk for additive CNS depression.
    Valerian, Valeriana officinalis: (Moderate) Concomitant use of baclofen with the phytomedicinals valerian, Valeriana officinalis can result in additive CNS depression.
    Vasodilators: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Verapamil: (Moderate) Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension. Dosage adjustments of the antihypertensive medication may be required.
    Zaleplon: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
    Ziprasidone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including baclofen.
    Zolpidem: (Moderate) Concurrent use of baclofen and CNS depressants such as certain sedatives or hypnotics can cause additive CNS depression. A reduction in the dose of these medications may be considered to minimize additive sedative effects, if they occur. With hypnotic medications, the risk of next-day psychomotor impairment is increased during coadministration of other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.

    PREGNANCY AND LACTATION

    Pregnancy

    At therapeutic oral doses, baclofen is excreted in human milk; caution is recommended when using the drug during breast-feeding. Withdrawal symptoms in the infant may occur if breast-feeding is stopped or oral baclofen is discontinued. It is not known if baclofen is detectable in breast milk after intrathecal administration; the labeling for intrathecal products recommends that a decision be made whether to discontinue breast-feeding or to discontinue intrathecal baclofen injection, considering the importance of intrathecal baclofen therapy to the mother. Limited information indicates that oral baclofen to the lactating mother appears in low levels in milk and would not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. Low intrathecal doses and topical application are unlikely to affect the nursing infant. If baclofen is continued, monitor the infant for signs of sedation. In one report in a woman given a single 20 mg oral dose of baclofen 14 days postpartum, the highest serum concentration of the drug occurred at 3 hours and the highest milk level was obtained at 4 hours. The total amount of drug recovered from the milk during the 26-hour sampling period was about 0.1% of the maternally ingested dose.

    MECHANISM OF ACTION

    The precise mechanism of action of baclofen as a muscle relaxant and antispasticity agent is not fully understood. Baclofen inhibits both monosynaptic and polysynaptic reflexes at the spinal level, possibly by decreasing excitatory neurotransmitter release from primary afferent terminals, although actions at supraspinal sites may also occur and contribute to its clinical effect. Baclofen is a structural analog of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and may exert its effects by stimulation of the GABA B receptor subtype. In people, as well as in animals, baclofen has been shown to have general CNS depressant properties as indicated by the production of sedation with tolerance, somnolence, ataxia, and respiratory and cardiovascular depression.

    PHARMACOKINETICS

    Baclofen is given orally or intrathecally. Baclofen crosses the placenta and is excreted into breast milk. Protein binding is low (roughly 30%). Approximately 15% of a baclofen dose is metabolized in the liver, mostly by deamination. The serum half-life ranges from 2.5 to 5.7 hours. The kidney excretes 70% to 85% of a dose as unchanged drug and metabolites, and the remainder is excreted via the feces.
     
    Affected cytochrome P450 enzymes and drug transporters: None

    Oral Route

    Following oral administration, baclofen is rapidly and almost completely absorbed, although bioavailability varies from patient to patient. Both the rate and extent of absorption is inversely proportional to the dose. Oral baclofen is distributed throughout the body (volume of distribution 2.4 L/kg), but only minimally crosses the blood-brain barrier. Bioavailability for oral solution, oral suspension, oral granules, and oral tablets is similar at the 20 mg dose level under fasting conditions. Maximum concentration occurred at approximately 0.75 hours (Tmax) for the oral solution. Bioavailability of the oral granule was not affected by administration with applesauce. Peak plasma concentrations are achieved within 1 hour following administration of the oral granules. Baclofen exposure following oral granule administration was dose proportional across the dose range of 5 mg, 10 mg, and 20 mg. A 10% decrease in AUC and a 29% decrease in Cmax compared to the fasted state occurred during administration of the oral granules with a high fat meal. Tmax occurred at approximately 1 hour following administration of the oral suspension in the fasted state. The apparent elimination half-life of baclofen in the oral suspension is approximately 5.6 hours. A 9% decrease in AUC and a 33% decrease in Cmax compared to the fasted state occurred during administration of the oral suspension with a high fat meal.

    Other Route(s)

    Intrathecal Route
    When baclofen is introduced directly into the intrathecal space, effective CSF concentrations are achieved with plasma concentrations 100-times less than those occurring with oral administration. The onset of action following intrathecal administration occurs within 0.5 to 1 hour and peak antispasmodic effect is seen approximately 4 hours after dosing and lasts 4 to 8 hours; although, there is considerable interpatient variability. With continuous intrathecal infusion, the initial antispasmodic effect is seen within 6 to 8 hours and peak effects are observed within 24 to 48 hours. CSF clearance of baclofen approximates CSF turnover, suggesting that elimination of the drug occurs via bulk-flow removal of CSF. Following an intrathecal dose of 50 or 100 mcg, the CSF elimination half-life over the first 4 hours is 1.51 hours and the average CSF clearance was approximately 30 mL/hour. The mean CSF clearance for LIORESAL INTRATHECAL (baclofen injection) was approximately 30 mL/hour in a study (n = 10 patients) of continuous intrathecal infusion. Concurrent plasma concentrations of baclofen during intrathecal administration are expected to be low (0 to 5 ng/mL). Limited pharmacokinetic data suggest that a lumbar-cisternal concentration gradient of about 4:1 is established along the neuroaxis during baclofen infusion. This is based upon simultaneous CSF sampling via cisternal and lumbar tap in 5 patients receiving continuous baclofen infusion at the lumbar level at doses associated with therapeutic efficacy; the interpatient variability was great. The gradient was not altered by position.