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  • vigabatrin - Drug Summary

  • CLASSES

    Anticonvulsants, GABA-T Inhibitors

    BOXED WARNING

    Requires an experienced clinician, visual impairment

    Vigabatrin causes permanent bilateral concentric visual field constriction in 30% or more of adult patients; the incidence in pediatric patients is not well defined, but is estimated at 20%. The visual field defect and resultant visual impairment can range in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation. Vigabatrin can also cause decreased visual acuity due to central retina damage. The onset of the vision disturbance can occur at any time during therapy, even after months or years. The risk increases with increasing dose and duration; there is no known risk-free exposure. Vision may worsen after vigabatrin discontinuation. Vigabatrin should be used at the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should not be used in patients with other risk factors for irreversible vision loss unless the benefits outweigh the risks. Vigabatrin also should not be used in patients taking other drugs that may cause serious ophthalmic adverse effects. Due to the risk for irreversible vision damage, vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation for complex partial seizures, within 2 to 4 weeks of initiation for infantile spasms, or if clinical failure is obvious at any time point. Vision loss is difficult to detect in pediatric patients and may not be detected until it is severe. Vision assessment at baseline (no later than 4 weeks after vigabatrin initiation), at least every 3 months during therapy, and approximately 3 to 6 months after vigabatrin discontinuation is recommended; assessment should include both acuity and visual fields whenever possible. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Vision assessment requires an experienced clinician, specifically an ophthalmic professional with expertise in visual field interpretation and the ability to perform a dilated indirect ophthalmoscopy of the retina.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral anticonvulsant designed to inhibit GABA metabolism
    Used for complex partial seizures and infantile spasms
    Risk of permanent vision loss; only available through restricted distribution

    COMMON BRAND NAMES

    Sabril, VIGADRONE

    HOW SUPPLIED

    Sabril/Vigabatrin Oral Tab: 500mg
    Sabril/Vigabatrin/VIGADRONE Oral Pwd F/Recon: 500mg

    DOSAGE & INDICATIONS

    For the treatment of infantile spasms.
    Oral dosage
    Infants and Children 1 month to 2 years

    50 mg/kg/day PO given in 2 divided doses initially. Titrate in 25 to 50 mg/kg/day increments every 3 days as needed based on patient response. Max: 150 mg/kg/day. Discontinue therapy if significant clinical benefit is not achieved within 2 to 4 weeks of initiation, or earlier if clinical failure is evident. To withdraw, decrease daily dose by 25 to 50 mg/kg every 3 to 4 days. Rapid discontinuation may be considered for serious adverse reactions. A post hoc analysis of a Canadian Pediatric Epilepsy Network study suggests a total duration of 6 months is adequate for treatment of infantile spasms; however, use clinical judgment regarding appropriate length of therapy.[36250]

    For the adjunctive treatment of refractory complex partial seizures.
    Oral dosage
    Adults

    500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.[36250]

    Adolescents 17 years

    500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.[36250]

    Children and Adolescents 2 to 16 years weighing more than 60 kg

    500 mg PO twice daily initially. Titrate in 500 mg/day increments at weekly intervals based on patient response. Recommended dose: 1,500 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by 1,000 mg/day at weekly intervals. Rapid discontinuation may be considered for serious adverse events.[36250]

    Children and Adolescents 2 to 16 years weighing 26 to 60 kg

    250 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 1,000 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.[36250]

    Children and Adolescents 2 to 16 years weighing 21 to 25 kg

    250 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 750 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.[36250]

    Children and Adolescents 2 to 16 years weighing 16 to 20 kg

    225 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 650 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.[36250]

    Children and Adolescents 2 to 16 years weighing 10 to 15 kg

    175 mg PO twice daily initially. Titrate in weekly intervals based on patient response. Recommended maintenance dose: 525 mg PO twice daily. Discontinue therapy if significant clinical benefit is not achieved within 3 months of initiation, or earlier if clinical failure is evident. To withdraw, decrease dose by one-third every week. Rapid discontinuation may be considered for serious adverse events.[36250]

    Infants† and Children younger than 2 years†

    Limited data suggest that vigabatrin may be effective; however, dosage recommendations have not been clearly defined. An initial dose of 40 to 50 mg/kg/day PO given in 2 divided doses, gradually titrated to a maintenance dose of 40 to 150 mg/kg/day has been suggested.[52185] [56573] [56574] However, initial doses ranging from 10 to 85 mg/kg/day (reported mean: 50 to 70 mg/kg/day) have been used with a reported mean maintenance dose of 50 to 80 mg/kg/day.[36346] [36348] [56571] [56572] In 1 review, doses up to 200 mg/kg/day were used in children with incomplete control after 2 weeks of vigabatrin therapy.[56499] A mean dose of 83.4 mg/kg/day PO (range: 10 to 150 mg/kg/day) for a mean duration of 21.75 months (range: 1 to 144 months) has been described in a retrospective review of 73 patients (mean age: 8.5 years; range: 1 month to 21 years) with various seizure disorders.[36346]

    MAXIMUM DOSAGE

    Adults

    3,000 mg/day PO.

    Geriatric

    3,000 mg/day PO.

    Adolescents

    17 years: 3,000 mg/day PO.
    13 to 16 years weighing more than 60 kg: 3,000 mg/day PO.
    13 to 16 years weighing 26 to 60 kg: 2,000 mg/day PO.
    13 to 16 years weighing 21 to 25 kg: 1,500 mg/day PO.

    Children

    2 to 12 years weighing more than 60 kg: 3,000 mg/day PO.
    2 to 12 years weighing 26 to 60 kg: 2,000 mg/day PO.
    2 to 12 years weighing 21 to 25 kg: 1,500 mg/day PO.
    2 to 12 years weighing 16 to 20 kg: 1,300 mg/day PO.
    2 to 12 years weighing 10 to 15 kg: 1,050 mg/day PO.
    1 year: 150 mg/kg/day PO for infantile spasms. Safety and efficacy have not been established for other seizure types.

    Infants

    150 mg/kg/day PO for infantile spasms. Safety and efficacy have not been established for other seizure types.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    NOTE: Although dosage adjustment is recommended for pediatric patients with renal impairment, specific guidelines are not available for infants and children younger than 2 years.
     
    Based on estimated CrCl, the following dosage adjustments are recommended for patients 2 years and older:[36250]
    CrCl more than 80 mL/minute: No dosage adjustment necessary.
    CrCl 51 to 80 mL/minute: Reduce dose by 25%.
    CrCl 31 to 50 mL/minute: Reduce dose by 50%.
    CrCl 11 to 30 mL/minute: Reduce dose by 75%.
     
    Intermittent hemodialysis
    The effect of dialysis on vigabatrin elimination has not been determined. In case reports of patients with renal failure receiving therapeutic doses of vigabatrin, hemodialysis reduced vigabatrin plasma concentrations by 40% to 60%. Dosing recommendations are not available.[36250]

    ADMINISTRATION

    Hazardous Drugs Classification
    NIOSH 2016 List: Group 3
    NIOSH (Draft) 2020 List: Table 2
    Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
    Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure and require additional protective equipment. Eye/face and respiratory protection may be needed during preparation and administration.

    Oral Administration

    Vigabatrin may be administered with or without food.

    Oral Liquid Formulations

    Powder for Oral Solution
    Each packet contains vigabatrin 500 mg.
    Reconstitute dose immediately before administration.
    Empty the entire contents of the appropriate number of packets into an empty clean cup.
    For each packet, dissolve the powder with 10 mL cold or room temperature water (i.e., use 10 mL for 1 packet, 20 mL for 2 packets, or 30 mL for 3 packets). The final solution concentration will be 50 mg/mL. Do not use any other liquid to reconstitute.
    Using a clean spoon or stirring device, carefully stir the contents of the cup until all of the powder has dissolved leaving a clear solution.
    Measure the appropriate dose using a calibrated oral syringe, and administer immediately. For infants and small children, place the tip of the oral syringe between the cheek and gum and slowly administer the solution in small increments.
    Discard remaining solution. Each dose must be reconstituted immediately before administration.

    STORAGE

    Sabril:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    VIGADRONE:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Requires an experienced clinician, visual impairment

    Vigabatrin causes permanent bilateral concentric visual field constriction in 30% or more of adult patients; the incidence in pediatric patients is not well defined, but is estimated at 20%. The visual field defect and resultant visual impairment can range in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation. Vigabatrin can also cause decreased visual acuity due to central retina damage. The onset of the vision disturbance can occur at any time during therapy, even after months or years. The risk increases with increasing dose and duration; there is no known risk-free exposure. Vision may worsen after vigabatrin discontinuation. Vigabatrin should be used at the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should not be used in patients with other risk factors for irreversible vision loss unless the benefits outweigh the risks. Vigabatrin also should not be used in patients taking other drugs that may cause serious ophthalmic adverse effects. Due to the risk for irreversible vision damage, vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation for complex partial seizures, within 2 to 4 weeks of initiation for infantile spasms, or if clinical failure is obvious at any time point. Vision loss is difficult to detect in pediatric patients and may not be detected until it is severe. Vision assessment at baseline (no later than 4 weeks after vigabatrin initiation), at least every 3 months during therapy, and approximately 3 to 6 months after vigabatrin discontinuation is recommended; assessment should include both acuity and visual fields whenever possible. In patients who cannot be tested, treatment may continue according to clinical judgment, with appropriate patient counseling. Vision assessment requires an experienced clinician, specifically an ophthalmic professional with expertise in visual field interpretation and the ability to perform a dilated indirect ophthalmoscopy of the retina.

    Depression, suicidal ideation

    In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (5 years of age and older). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation (0.43%) as patients receiving placebo (0.24%), corresponding to an estimated 2.1 per 1,000 (95% CI: 0.7 to 4.2) more patients in the drug treatment groups who developed suicidal behavior or ideation. The relative risk for suicidality was higher in patients with epilepsy compared to those with other conditions; however, the absolute risk differences were similar in trials for epilepsy and psychiatric indications. Age was not a determining factor. The increased risk of suicidal ideation and behavior was observed between 1 and 24 weeks after therapy initiation. However, a longer duration of therapy should not preclude the possibility of an association to the drug since most studies included in the analysis did not continue beyond 24 weeks. Data were analyzed from drugs with adequately designed clinical trials including carbamazepine, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, valproate, and zonisamide. However, this risk is considered to be a class effect. All patients beginning treatment with vigabatrin should be closely monitored for emerging or worsening depression or suicidal thoughts/behavior. Patients and caregivers should be informed of the increased risk of suicidal thoughts and behaviors and should be advised to immediately report the emergence or worsening of depression, the emergence of suicidal thoughts or behavior, thoughts of self-harm, or other unusual changes in mood or behavior. Anticonvulsants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    Abrupt discontinuation

    Abrupt discontinuation of vigabatrin should not be undertaken. If discontinuation becomes necessary, vigabatrin should be withdrawn gradually.

    Driving or operating machinery

    Vigabatrin may cause somnolence and fatigue. Patients should be advised to avoid driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether vigabatrin adversely affects their cognitive and/or motor performance. Patients should also be informed of the possibility for enhanced drowsiness or dizziness with concurrent use of alcohol.

    Hepatic decompensation, hepatic disease, laboratory test interference

    Vigabatrin can cause laboratory test interference. Use caution in interpreting liver function tests in patients with hepatic disease. Vigabatrin decreases alanine transaminase (ALT) and aspartate transaminase (AST) plasma activity in up to 90% of patients; these enzymes may become undetectable in some patients. AST and ALT reductions may invalidate the use of these markers to detect hepatic decompensation and early hepatic disease. Also, vigabatrin may increase the amount of amino acids in the urine, which could result in a false positive test for certain rare genetic metabolic diseases (e.g., alpha aminoadipic aciduria).[36250]

    Renal impairment

    Vigabatrin is primarily renally eliminated. A dosage adjustment is required for patients with any degree of renal impairment.

    Geriatric

    Clinical studies of vigabatrin did not include enough geriatric patients aged 65 years and older to determine whether they responded differently from younger adults. Vigabatrin is primarily eliminated via the kidney, and elderly patients are more likely to have decreased renal function. Care should be taken in dose selection based on the degree of renal impairment, and it may be useful to monitor renal function. In one small study, 4 out of 5 geriatric patients with reduced renal function (CrCl less than 50 mL/minute) experienced moderate to severe sedation and confusion after receiving a single dose of vigabatrin 1.5 grams PO; the adverse effects lasted up to 5 days. Other reported clinical experience has not identified differences in responses between the elderly and younger adults.[36250] According to the Beers Criteria, anticonvulsants are considered potentially inappropriate medications in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, except for treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If vigabatrin must be used, consider reducing the use of other CNS-active medications that increase the risk of falls and fractures and implement strategies to reduce fall risk.[63923] The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities; the use of any anticonvulsant for any condition should be based on confirmation of the condition and its potential cause(s). Determine effectiveness and tolerability by evaluating symptoms, and use these as the basis for dosage adjustment for most patients. Therapeutic drug monitoring is not required or available for most anticonvulsants. Serum medication concentrations (when available) may assist in identifying toxicity. Monitor the treated patient for drug efficacy and side effects. Anticonvulsants can cause a variety of side effects; some adverse reactions can increase the risk of falls. When an anticonvulsant is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity as outlined in the OBRA guidelines.[60742]

    Children, infants, neonates

    Pediatric patients, particularly those with pre-existing myelin abnormalities, should be monitored closely for neurotoxicity during vigabatrin therapy. Abnormal magnetic resonance imaging (MRI) signal changes have been observed in infants receiving vigabatrin for infantile spasms. MRI abnormalities tend to peak after 3 to 6 months of vigabatrin exposure and typically resolve, even with continued use of the drug. Simultaneous motor abnormalities have been reported in some infants; however, a causal relationship has not been established. MRI abnormalities affect infants and children 6 years and younger and are associated with high dose therapy. Some investigators believe MRI changes are associated with developmental changes in myelination or an unknown underlying metabolic disorder. The clinical significance of MRI changes is unknown and the potential for long-term clinical sequelae has not been adequately studied. Animal models have suggested neurotoxicity may be more prevalent in neonates, infants, and children compared to adults. Neurotoxicity has been observed in rats with vigabatrin exposure during late gestation and the neonatal and juvenile periods of development, and in dogs exposed to vigabatrin during the juvenile period. Neurohistopathological (brain vacuolation, hypomyelination, retinal dysplasia) and neurobehavioral (seizures, neuromotor impairment, learning deficits) abnormalities occurred in young rats at vigabatrin doses lower than those producing neurotoxicity in adult animals and were associated with drug plasma concentrations substantially lower than those achieved clinically in human infants and children. Although neurobehavioral effects were not assessed, similar neurohistopathological abnormalities were observed in juvenile dogs. White matter vacuolation and intramyelinic edema (IME) have been associated with vigabatrin in animal studies involving several species. Although these findings have never been observed in pediatric or adult human studies, there is a single case report of vigabatrin-induced white matter vacuolation, IME, and subsequent encephalopathy in an infant with pre-existing white matter abnormalities due to prematurity. A relationship between MRI abnormalities in infants and neurotoxicity has not been established.

    Substance abuse

    Vigabatrin is not classified as a controlled substance; however, the manufacturer advises caution in patients with a history of substance abuse since the drug has CNS active properties and has not been formally evaluated for its abuse, tolerance, or physical dependence potential.

    Pregnancy

    There are no adequate data on the developmental risk associated with the use of vigabatrin during human pregnancy. Limited data from case reports and cohort studies have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, animal data suggest vigabatrin use may result in fetal harm. Vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (hippocampal vacuolation, decreased myelination, retinal dysplasia) abnormalities, when administered to pregnant animals at clinically relevant doses during organogenesis and the latter part of pregnancy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to vigabatrin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.[36250]

    Breast-feeding

    Breast-feeding is not recommended because of the potential for serious adverse reactions in the nursing infant. If a breast-fed infant is exposed to vigabatrin, observe for potential adverse effects. Vigabatrin is excreted in human milk. The effects of vigabatrin on the breast-fed infant and on milk production are unknown.[36250]

    ADVERSE REACTIONS

    Severe

    toxic epidermal necrolysis / Delayed / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    visual impairment / Early / 30.0
    optic neuritis / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known
    GI bleeding / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    hearing loss / Delayed / Incidence not known

    Moderate

    blurred vision / Early / 2.0-16.0
    depression / Delayed / 6.0-14.0
    confusion / Early / 4.0-14.0
    constipation / Delayed / 2.0-14.0
    candidiasis / Delayed / 3.0-8.0
    anemia / Delayed / 5.7-5.7
    conjunctivitis / Delayed / 2.0-5.0
    chest pain (unspecified) / Early / 1.0-5.0
    impotence (erectile dysfunction) / Delayed / 0-5.0
    peripheral neuropathy / Delayed / 4.2-4.2
    peripheral edema / Delayed / 2.0-2.0
    edema / Delayed / 1.0-1.0
    hallucinations / Early / 0-1.0
    hepatitis / Delayed / 0-1.0
    psychosis / Early / Incidence not known
    delirium / Early / Incidence not known
    esophagitis / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known

    Mild

    weight gain / Delayed / 6.0-47.0
    fever / Early / 4.0-29.0
    irritability / Delayed / 7.0-23.0
    vomiting / Early / 7.0-20.0
    diplopia / Early / 3.0-16.0
    diarrhea / Early / 10.0-16.0
    pharyngitis / Delayed / 4.0-14.0
    cough / Delayed / 2.0-14.0
    nasal congestion / Early / 4.0-13.0
    rash / Early / 4.0-11.0
    nausea / Early / 2.0-10.0
    arthralgia / Delayed / 5.0-10.0
    sinusitis / Delayed / 5.0-9.0
    dysmenorrhea / Delayed / 3.0-9.0
    asthenia / Delayed / 5.0-7.0
    back pain / Delayed / 4.0-7.0
    influenza / Delayed / 3.0-7.0
    ocular pain / Early / 0-5.0
    malaise / Early / 0-5.0
    appetite stimulation / Delayed / 1.0-5.0
    abdominal pain / Early / 2.0-5.0
    dental pain / Delayed / 2.0-5.0
    dyspepsia / Early / 4.0-5.0
    myalgia / Early / 3.0-5.0
    vertigo / Early / 2.0-5.0
    anxiety / Delayed / 0-4.0
    acne vulgaris / Delayed / 3.0-3.0
    muscle cramps / Delayed / 0-3.0
    polydipsia / Early / 0-2.0
    tinnitus / Delayed / 0-2.0
    hyperkinesis / Delayed / Incidence not known
    abnormal magnetic resonance imaging (MRI) signal changes / Delayed / Incidence not known
    agitation / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    alopecia / Delayed / Incidence not known
    maculopapular rash / Early / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Acetaminophen; Caffeine; Pyrilamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Chlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with dichloralphenazone.
    Acetaminophen; Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Acetaminophen; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Acetaminophen; Pentazocine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with pentazocine.
    Acrivastine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Alfentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Alprazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Amobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Aspirin, ASA; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Azathioprine: (Major) Vigabatrin should not be used with other drugs like azathioprine that are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Azelastine; Fluticasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Barbiturates: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Beclomethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Belladonna; Opium: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Benzhydrocodone; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Benzodiazepines: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Betamethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Brompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Brompheniramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Brompheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Budesonide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Budesonide; Formoterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Budesonide; Glycopyrrolate; Formoterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Bupivacaine; Meloxicam: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as meloxicam, may occur during concurrent use of vigabatrin.
    Buprenorphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buprenorphine.
    Buprenorphine; Naloxone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buprenorphine.
    Buspirone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with buspirone.
    Butabarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Butalbital; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Butorphanol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with butorphanol.
    Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and vigabatrin. CNS depressants can potentiate the effects of cannabidiol.
    Carbinoxamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Carbinoxamine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Carbinoxamine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Celecoxib; Tramadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Chlophedianol; Dexbrompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorcyclizine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlordiazepoxide: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Chlordiazepoxide; Amitriptyline: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Chlordiazepoxide; Clidinium: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Chloroquine: (Major) Vigabatrin should not be used with chloroquine due to potential retinal toxicity associated with both drugs, unless the benefits of treatment clearly outweigh the risks.
    Chlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Dextromethorphan: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists. (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Ciclesonide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Clemastine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Clonazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Clorazepate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Codeine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Codeine; Guaifenesin: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Codeine; Phenylephrine; Promethazine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Codeine; Promethazine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Corticosteroids: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Cortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Cyclizine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Cyproheptadine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Deferoxamine: (Major) Vigabatrin should not be used with deferoxamine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Deflazacort: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as vigabatrin, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
    Dexamethasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Dexbrompheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Dexchlorpheniramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Diazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Diclofenac: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as diclofenac, may occur during concurrent use of vigabatrin.
    Diclofenac; Misoprostol: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as diclofenac, may occur during concurrent use of vigabatrin.
    Dimenhydrinate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Diphenhydramine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Diphenhydramine; Ibuprofen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Diphenhydramine; Naproxen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers. (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Diphenhydramine; Phenylephrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Doxylamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Doxylamine; Pyridoxine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Dronabinol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with dronabinol, THC.
    Droperidol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with droperidol.
    Estazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Eszopiclone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
    Ethambutol: (Major) Vigabatrin should not be used with ethambutol, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Fentanyl: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Fludrocortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Flunisolide: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Flurazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Fluticasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Fluticasone; Salmeterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Fluticasone; Umeclidinium; Vilanterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Fluticasone; Vilanterol: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Formoterol; Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Fosphenytoin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. Decreased exposure of drugs that are extensively metabolized by CYP2C9, such as phenytoin, may occur during concurrent use of vigabatrin. During clinical trials, average reductions in total phenytoin plasma levels of 16% to 20% were reported during concurrent use of vigabatrin. If combination therapy is indicated, determinations for dosage adjustments of phenytoin should be made on an individual basis. Because fosphenytoin is hydrolyzed to phenytoin, a change in phenytoin plasma levels would also be expected to occur during concurrent administration of vigabatrin and fosphenytoin.
    Guaifenesin; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Homatropine; Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Hydrocodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Hydrocodone; Ibuprofen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Hydrocodone; Pseudoephedrine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Hydrocortisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Hydromorphone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Hydroxychloroquine: (Major) Vigabatrin should not be used with hydroxychloroquine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. Additionally, hydroxychloroquine can lower the seizure threshold; therefore, the activity of antiepileptic drugs may be impaired with concomitant use.
    Hydroxyzine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Ibuprofen; Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Interferons: (Major) Vigabatrin is associated with vision loss. The drug should not be used with interferons, which are associated with a potential for serious ophthalmic effects (e.g., retinopathy, optic neuritis, visual impairment), unless the benefit of treatment clearly outweighs the risks.
    Lansoprazole; Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Levorphanol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Lorazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Losartan: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as losartan, may occur during concurrent use of vigabatrin.
    Losartan; Hydrochlorothiazide, HCTZ: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as losartan, may occur during concurrent use of vigabatrin.
    Loxapine: (Major) Vigabatrin should not be used with loxapine, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Maprotiline: (Moderate) Maprotiline, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Monitor patients on anticonvulsants carefully when maprotiline is used concurrently. Because of the lowering of seizure threshold, an alternative antidepressant may be a more optimal choice for patients taking drugs for epilepsy.
    Mecasermin rinfabate: (Major) Vigabatrin should not be used with mecasermin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Mecasermin, Recombinant, rh-IGF-1: (Major) Vigabatrin should not be used with mecasermin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Meclizine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Mefloquine: (Moderate) Coadministration of mefloquine and anticonvulsants may result in lower than expected anticonvulsant concentrations and loss of seizure control. Monitoring of the anticonvulsant serum concentration, if the drug is monitored via therapeutic drug monitoring, is recommended. Mefloquine may cause CNS side effects that may cause seizures or alter moods or behaviors. Some, but not all anticonvulsants, induce CYP3A4 and may increase the metabolism of mefloquine. Use of enzyme-inducing anticonvulsants can reduce the clinical efficacy of mefloquine, increasing the risk of Plasmodium falciparum resistance during treatment of malaria.
    Meloxicam: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as meloxicam, may occur during concurrent use of vigabatrin.
    Meperidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Meperidine; Promethazine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Meprobamate: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
    Methadone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Methohexital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Methylprednisolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Midazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Mirtazapine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with mirtazapine.
    Molindone: (Moderate) Consistent with the pharmacology of molindone, additive effects may occur with other CNS active drugs such as anticonvulsants. In addition, seizures have been reported during the use of molindone, which is of particular significance in patients with a seizure disorder receiving anticonvulsants. Adequate dosages of anticonvulsants should be continued when molindone is added; patients should be monitored for clinical evidence of loss of seizure control or the need for dosage adjustments of either molindone or the anticonvulsant.
    Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Morphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Morphine; Naltrexone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Nabilone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with nabilone.
    Nalbuphine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with nalbuphine.
    Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Naproxen; Esomeprazole: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Naproxen; Pseudoephedrine: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Nateglinide: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as nateglinide, may occur during concurrent use of vigabatrin.
    Oliceridine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Olopatadine; Mometasone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Opiate Agonists: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Oxazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Oxycodone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Oxymorphone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Pentazocine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with pentazocine.
    Pentazocine; Naloxone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with pentazocine.
    Pentobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Pentostatin: (Major) Vigabatrin should not be used with pentostatin, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Phenobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Phenothiazines: (Major) Vigabatrin should not be used with phenothiazines, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Phenytoin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. Decreased exposure of drugs that are extensively metabolized by CYP2C9, such as phenytoin, may occur during concurrent use of vigabatrin. During clinical trials, average reductions in total phenytoin plasma levels of 16% to 20% were reported during concurrent use of vigabatrin. If combination therapy is indicated, determinations for dosage adjustments of phenytoin should be made on an individual basis.
    Phosphodiesterase inhibitors: (Major) Vigabatrin should not be used with phosphodiesterase inhibitors, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Prednisolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Prednisone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Primidone: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Pseudoephedrine; Triprolidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Pyrilamine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Quazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Ramelteon: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with ramelteon.
    Remifentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Remimazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Secobarbital: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with barbiturates.
    Sedating H1-blockers: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and vigabatrin. CNS depressants can potentiate the effects of stiripentol.
    Sufentanil: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as sulfamethoxazole, may occur during concurrent use of vigabatrin.
    Sumatriptan; Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
    Tapentadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Temazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Thiothixene: (Major) Vigabatrin should not be used with thiothixene, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Tramadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Tramadol; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
    Triamcinolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Triazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
    Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
    Triprolidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
    Warfarin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as warfarin, may occur during concurrent use of vigabatrin.
    Zaleplon: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
    Zolpidem: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate data on the developmental risk associated with the use of vigabatrin during human pregnancy. Limited data from case reports and cohort studies have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, animal data suggest vigabatrin use may result in fetal harm. Vigabatrin produced developmental toxicity, including an increase in fetal malformations and offspring neurobehavioral (convulsions, neuromotor impairment, learning deficits) and neurohistopathological (hippocampal vacuolation, decreased myelination, retinal dysplasia) abnormalities, when administered to pregnant animals at clinically relevant doses during organogenesis and the latter part of pregnancy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to vigabatrin; information about the registry can be obtained at www.aedpregnancyregistry.org or by calling 1-888-233-2334.[36250]

    Breast-feeding is not recommended because of the potential for serious adverse reactions in the nursing infant. If a breast-fed infant is exposed to vigabatrin, observe for potential adverse effects. Vigabatrin is excreted in human milk. The effects of vigabatrin on the breast-fed infant and on milk production are unknown.[36250]

    MECHANISM OF ACTION

    The exact mechanism by which vigabatrin exerts its anticonvulsant effects is unknown; however, it is believed to be the result of increased GABA concentrations in the central nervous system (CNS). Vigabatrin is a structural analog of GABA and is an irreversible inhibitor of gamma-aminobutyric acid transaminase (GABA-T), which is the enzyme that metabolizes GABA. GABA is the major inhibitory neurotransmitter in the CNS and acts on postsynaptic membranes to open chloride channels, thereby leading to membrane hyperpolarization and preventing propagation of neural impulses. By inhibiting GABA metabolism, vigabatrin allows more GABA to be available for receptor binding on post-synaptic cells. There does not appear to be a direct correlation between plasma vigabatrin concentrations and efficacy; the duration of action is thought to be dependent on the rate of GABA synthesis rather than vigabatrin elimination.
     
    Another drug that is used for the treatment of partial seizures, tiagabine, also affects GABA CNS concentrations but by a different mechanism. Whereas vigabatrin inhibits the metabolism of GABA, tiagabine inhibits the reuptake of GABA. Unlike tiagabine and vigabatrin, the mechanisms of action of other drugs indicated for adjunctive treatment of partial seizures (e.g., lamotrigine, gabapentin, topiramate) are not primarily mediated through GABA transmission.

    PHARMACOKINETICS

    Vigabatrin is administered orally. Vigabatrin does not bind to plasma proteins and is widely distributed throughout the body. The mean steady state volume of distribution is 1.1 L/kg. Vigabatrin is not significantly metabolized. It is eliminated primarily through renal excretion. In healthy adult male volunteers who received radiolabeled vigabatrin, approximately 95% of the total radioactivity was recovered in the urine over 72 hours; approximately 80% was parent drug. Drug clearance is 7 L/hour in adult patients. The half-life in adults is approximately 10.5 hours. Of note, a direct correlation between plasma vigabatrin concentrations and efficacy has not been established; the duration of action is thought to be dependent on the rate of GABA synthesis rather than vigabatrin elimination.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP2C9
    Vigabatrin induces CYP2C9, but does not appear to induce other hepatic cytochrome P450 enzymes. Vigabatrin is not metabolized by hepatic enzymes.

    Oral Route

    Bioequivalence has been established between the oral solution and oral tablets. In adults, vigabatrin displays linear pharmacokinetics after single doses of 0.5 g to 4 g and after repeated doses of 0.5 g and 2 g twice daily. After oral administration, vigabatrin is completely and rapidly absorbed with a time to maximum plasma concentration (Tmax) in adults of approximately 1 hour after single or multiple doses; minimal accumulation occurs after multiple doses. In healthy volunteers, administration with food resulted in a 33% reduction in maximum plasma concentration (Cmax), an increase in Tmax to 2 hours, and unchanged AUC compared to administration under fasting conditions.