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  • 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

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    For use as monotherapy in the treatment of infantile spasms in pediatric patients for whom the potential benefits outweigh the potential risk of vision loss.
    NOTE: Vision loss in infants and children may not be detected until it is severe. Vision assessment is recommended 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.
    Oral dosage
    Infants and Children younger than 2 years

    Initially, 50 mg/kg/day PO given in 2 divided doses. Titrate in 25 to 50 mg/kg/day increments every 3 days as needed for clinical response. Max: 150 mg/kg/day. Use the lowest dose and shortest duration necessary to achieve clinical goals. A post hoc analysis of a Canadian Pediatric Epilepsy Network study suggests vigabatrin therapy for a total duration of 6 months is adequate for treatment of infantile spasms; however, clinicians should use their clinical judgement regarding appropriate length of therapy. Vigabatrin should be discontinued if a significant clinical response is not achieved within 2 to 4 weeks of initiation or if clinical failure is obvious earlier. If drug discontinuation is necessary, withdraw vigabatrin gradually (e.g., reduce the total daily dose by 25 mg/kg to 50 mg/kg every 3 to 4 days). If withdrawal is needed because of a serious adverse event, rapid discontinuation may be considered. The manufacturer recommends the following initial and maximum doses of the 50 mg/mL oral solution based on patient weight:
    16 kg: 8 mL PO twice daily initially; maximum: 24 mL PO twice daily.
    15 kg: 7.5 mL PO twice daily initially; maximum: 22.5 mL PO twice daily.
    14 kg: 7 mL PO twice daily initially; maximum: 21 mL PO twice daily.
    13 kg: 6.5 mL PO twice daily initially; maximum: 19.5 mL PO twice daily.
    12 kg: 6 mL PO twice daily initially; maximum: 18 mL PO twice daily.
    11 kg: 5.5 mL PO twice daily initially; maximum: 16.5 mL PO twice daily.
    10 kg: 5 mL PO twice daily initially; maximum: 15 mL PO twice daily.
    9 kg: 4.5 mL PO twice daily initially; maximum: 13.5 mL PO twice daily.
    8 kg: 4 mL PO twice daily initially; maximum: 12 mL PO twice daily.
    7 kg: 3.5 mL PO twice daily initially; maximum: 10.5 mL PO twice daily.
    6 kg: 3 mL PO twice daily initially; maximum: 9 mL PO twice daily.
    5 kg: 2.5 mL PO twice daily initially; maximum: 7.5 mL PO twice daily.
    4 kg: 2 mL PO twice daily initially; maximum: 6 mL PO twice daily.
    3 kg: 1.5 mL PO twice daily initially; maximum: 4.5 mL PO twice daily.

    For the adjunctive treatment of refractory complex partial seizures.
    NOTE: Vision assessment is recommended 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.
    Oral dosage
    Adults and Adolescents 17 years and older

    Initially, 500 mg PO twice daily. Titrate in 500 mg/day increments at weekly intervals depending on patient response; the recommended dose is 1,500 mg PO twice daily. A dose of 3,000 mg PO twice daily has not been shown to provide additional benefit and has been associated with increased adverse events. Use the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation or if clinical failure is obvious earlier. If drug discontinuation is necessary, withdraw vigabatrin gradually (e.g., reduce daily dose by 1,000 mg/day at weekly intervals). If withdrawal is needed because of a serious adverse event, rapid discontinuation may be considered.

    Children and Adolescents 10 to 16 years weighing more than 60 kg

    Initially, 500 mg PO twice daily. Titrate in 500 mg/day increments at weekly intervals depending on patient response; the recommended dose is 1,500 mg PO twice daily. Use the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation or if clinical failure is obvious earlier. If drug discontinuation is necessary, withdraw vigabatrin gradually (e.g., reduce daily dose by 1,000 mg/day at weekly intervals). If withdrawal is needed because of a serious adverse event, rapid discontinuation may be considered.

    Children and Adolescents 10 to 16 years weighing 25 to 60 kg

    Initially, 250 mg PO twice daily. Titrate in 500 mg/day increments at weekly intervals depending on patient response; the recommended maintenance dose is 1,000 mg PO twice daily. Use the lowest dose and shortest duration necessary to achieve clinical goals. Vigabatrin should be discontinued if a significant clinical response is not achieved within 3 months of initiation or if clinical failure is obvious earlier. If drug discontinuation is necessary, withdraw vigabatrin gradually (e.g., reduce daily dose by one-third every week for 3 weeks). If withdrawal is needed because of a serious adverse event, rapid discontinuation may be considered.

    Infants† and Children younger than 10 years† or weighing less than 25 kg†

    Limited data suggest that vigabatrin may be effective; however, dosage recommendations have not been clearly defined. One retrospective review described vigabatrin use in 73 patients aged 1 month to 21 years. The mean dose was 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). Sixty patients received vigabatrin for the treatment of partial seizures or mixed seizure types that included partial seizures; 84% of patients were also taking other antiepileptic drugs (AEDs). Of the 44 patients with refractory epilepsy who failed treatment with at least 3 AEDs in combination, 18 (41%) experienced more than 90% reduction in seizure frequency, 1 (2%) had a 50 to 90% reduction in seizure frequency, and vigabatrin was considered to be ineffective in 25 (57%). Of the 18 patients with partial simple or partial complex seizures, 10 (56%) experienced more than 90% reduction in seizure frequency and vigabatrin was considered to be ineffective in 8 (44%). In another retrospective chart review of 43 patients aged 1 to 16 years with various intractable seizure types, those with complex partial seizures (n = 20) had the best response to vigabatrin therapy. All patients continued to receive other AEDs, but the patient’s usual AED regimen was not altered during the 6 month evaluation. Vigabatrin was initiated at a dose of 55 to 85 mg/kg/day PO given in 2 divided doses, and the dose was increased to 100 mg/kg/day PO in 10 patients (seizure type not defined). Of those patients with complex partial seizures or complex partial with secondary generalization, 60% experienced a greater than 50% reduction in seizure frequency.

    MAXIMUM DOSAGE

    Adults

    3000 mg/day PO.

    Geriatric

    3000 mg/day PO.

    Adolescents

    17 years and older: 3000 mg/day PO.
    16 years and younger weighing 60 kg or more: 3000 mg/day PO.
    16 years and younger weighing less than 60 kg: 2000 mg/day PO.

    Children

    10 years and older weighing 60 kg or more: 3000 mg/day PO.
    10 years and older weighing 25 to 59 kg: 2000 mg/day PO.
    10 years and older weighing less than 25 kg: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day PO have been used off-label for refractory partial seizures.
    2 through 9 years: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day PO have been used off-label for refractory partial seizures.
    Younger than 2 years: 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 children < 10 years. The following is recommended for adult and pediatric patients >= 10 years:
    CrCl > 80 ml/min: No dosage adjustment necessary.
    CrCl > 50 to 80 ml/min: Reduce dose by 25%.
    CrCl > 30 to 50 ml/min: Reduce dose by 50%.
    CrCl > 10 to < 30 ml/min: 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.

    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:
    - Reconstituted product should be used immediately. Discard unused portion
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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).

    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

    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.

    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 renally eliminated, 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. 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, with the exception of treating seizure and mood disorders, since anticonvulsants can produce ataxia, impaired psychomotor function, syncope, and additional falls. If vigabatrin must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to the OBRA guidelines, some anticonvulsants may be used to treat disorders other than seizures (e.g., bipolar disorder, schizoaffective disorder, chronic neuropathic pain, migraine prevention). The need for indefinite continuation in treating any condition should be based on confirmation of the condition and its potential cause(s). Determining effectiveness and tolerability through evaluation of symptoms should be used to adjust doses. Therapeutic drug monitoring is not required or available for most anticonvulsants. In addition, significant signs and symptoms of toxicity can occur at normal or low serum concentrations, and symptom control for seizures or behavior can occur at subtherapeutic serum concentrations. Obtaining serum medication concentrations may assist in identifying toxicity. High or toxic serum concentrations should become a consideration for dosage adjustments. Anticonvulsants may cause liver dysfunction, blood dyscrasias, and serious skin rashes requiring treatment discontinuation. Anticonvulsants may also cause nausea/vomiting, dizziness, ataxia, somnolence/lethargy, incoordination, blurred or double vision, restlessness, toxic encephalopathy, anorexia, and headaches; these effects can increase the risk for 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 in accordance with OBRA guidelines.

    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 appear to be specific to children with infantile spasms, affect younger infants and children, 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

    Vigabatrin is classified as FDA pregnancy category C. Use vigabatrin during pregnancy only if the potential benefit justifies the potential risk to the fetus.There are no adequate and well-controlled trials of vigabatrin use in pregnant women; however, in postmarketing experience, numerous birth defects have been reported, including congenital cardiac defects, congenital hemangioma, congenital hydronephrosis and vesicoureteric reflux, male genital malformation, dysmorphism, fetal anticonvulsant syndrome, hip dysplasia, limb malformations, and renal aplasia. In addition, developmental toxicity and teratogenic effects have occurred when vigabatrin was administered to pregnant animals during organogenesis and the latter part of pregnancy, including anatomical defects (unspecified), neurologic toxicities and neurobehavioral effects, cleft palate, and increased embryolethality at doses ranging from 50 mg/kg up to 200 mg/kg per day. The no-effect dose for teratogenicity and embryolethality in rabbits is approximately half the maximum recommended human dose (MRHD) of 3 g/day on a body surface area basis, and the no-effect dose for embryo-fetal toxicity in rats is approximately one-fifth the MRHD in adults on a body surface area basis. Physicians are advised to recommend that pregnant patients receiving vigabatrin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry.

    Breast-feeding

    Vigabatrin is excreted in human milk. Because of the potential for serious adverse reactions from vigabatrin in breast-feeding infants, discontinue breast-feeding or vigabatrin, taking into account the importance of the drug to the mother. When vigabatrin 50, 100, or 150 mg/kg was administered to rats from the latter part of pregnancy through weaning, neurological toxicity (e.g., hippocampal vacuolation and seizures) was noted in the offspring. In addition, special precautions apply to the use vigabatrin in infants, due to the potential for MRI changes and neurotoxicity, including vision loss.

    ADVERSE REACTIONS

    Severe

    Stevens-Johnson syndrome / Delayed / 0-1.0
    toxic epidermal necrolysis / 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 / 3.0-16.0
    confusion / Early / 4.0-14.0
    depression / Delayed / 6.0-14.0
    constipation / Delayed / 3.0-14.0
    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
    delirium / Early / Incidence not known
    psychosis / 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 / 5.0-16.0
    diarrhea / Early / 6.0-16.0
    pharyngitis / Delayed / 9.0-14.0
    cough / Delayed / 2.0-14.0
    nasal congestion / Early / 4.0-13.0
    rash (unspecified) / 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
    dyspepsia / Early / 4.0-5.0
    abdominal pain / Early / 2.0-5.0
    dental pain / Delayed / 2.0-5.0
    myalgia / Early / 3.0-5.0
    vertigo / Early / 2.0-5.0
    hyperactivity / Early / 4.0-4.0
    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
    maculopapular rash / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    infection / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; 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.
    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; Magnesium Salicylate; Phenyltoloxamine: (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; Phenyltoloxamine; Salicylamide: (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; Phenyltoloxamine: (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; 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.
    Acetaminophen; Propoxyphene: (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; Tramadol: (Moderate) Tramadol may decrease the seizure threshold and thus, interfere with the ability of anticonvulsants to control seizures. 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 tramadol.
    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.
    Amitriptyline; 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.
    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.
    Amoxapine: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Some anticonvulsants, such as phenobarbital or carbamazepine, may potentially induce the metabolism of amoxapine as well. Monitor patients for side effects or altered responses to drug therapy.
    Amphetamines: (Major) Patients who are taking anticonvulsants for epilepsy/seizure control should use amphetamines with caution. Amphetamines may decrease the seizure threshold and increase the risk of seizures. If seizures occur, amphetamine discontinuation may be necessary.
    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; 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.
    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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    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 Alkaloids; Ergotamine; 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.
    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.
    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; Carbetapentane; 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; 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; 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. (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; 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. (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.
    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.
    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.
    Bupropion: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin, as well as fosphenytoin and ethotoin.
    Bupropion; Naltrexone: (Moderate) Bupropion should not be used by patients with a preexisting seizure disorder because it may lower the seizure threshold. Bupropion may also interact pharmacokinetically with anticonvulsant drugs that induce hepatic microsomal isoenzyme function such as carbamazepine, barbiturates, or phenytoin, as well as fosphenytoin and ethotoin.
    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.
    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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; 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.
    Carbetapentane; Phenylephrine; 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.
    Carbetapentane; 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.
    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; Hydrocodone; 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.
    Carbinoxamine; 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. (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.
    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.
    Chloral Hydrate: (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.
    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; 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; 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; Dihydrocodeine; 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. (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; 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. (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; Hydrocodone; 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; 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. (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; 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.
    Corticotropin, ACTH: (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.
    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.
    Dihydrocodeine; 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.
    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; Hydrocodone; 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.
    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, THC: (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.
    Esomeprazole; 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.
    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.
    Ethanol: (Major) Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    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.
    Hydrochlorothiazide, HCTZ; 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.
    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; 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.
    Hydrocodone; Potassium Guaiacolsulfonate: (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; Potassium Guaiacolsulfonate; 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.
    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 should not be used with interferons, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
    Kava Kava, Piper methysticum: (Major) The German Commission E warns that any substances that act on the CNS, including anticonvulsants, may interact with kava kava. While the interactions can be pharmacodynamic in nature, kava kava has been reported to inhibit many CYP isozymes (i.e., CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A9/11) and important pharmacokinetic interactions with CNS-active agents that undergo oxidative metabolism via these CYP isozymes are also possible. Persons taking an anticonvulsant should discuss the use of herbal supplements with their health care professional prior to consuming them.
    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.
    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 is recommended. Dosage adjustments may be required during and after therapy with mefloquine.
    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.
    Mephobarbital: (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.
    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; 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.
    Naproxen; Sumatriptan: (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.
    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.
    Orlistat: (Moderate) Seizures have been reported in patients treated concomitantly with orlistat and anticonvulsants. Patients should be monitored for possible changes in the frequency and/or severity of convulsions. A mechanism for the potential interaction has not been stated.
    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.
    Pemoline: (Major) A reduction in seizure threshold has been reported following concomitant administration of pemoline with anticonvulsant agents. Dosage adjustments of anticonvulsants may be necessary during simultaneous use of these drugs.
    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.
    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.
    Propoxyphene: (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.
    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.
    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.
    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.
    Tamoxifen: (Major) Vigabatrin should not be used with other drugs associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks. Tamoxifen use has been associated with corneal changes, decrement in color vision perception (visual impairment), retinal thrombosis, and retinopathy. Additionally, vigabatrin is a CYP2C9 inducer. Tamoxifen is metabolized by CYP3A4 and CYP2D6, and to a lesser extent by CYP2C9, to other potent, active metabolites including endoxifen, which have up to 33 times more affinity for the estrogen receptor than tamoxifen. These metabolites are then inactivated by sulfotransferase 1A1 (SULT1A1). Theoretically, by inducing CYP2C9, vigabatrin may increase the concentrations of the active metabolites of tamoxifen, which may increase toxicity
    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.
    Thiopental: (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.
    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) Tramadol may decrease the seizure threshold and thus, interfere with the ability of anticonvulsants to control seizures. 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 tramadol.
    Trazodone: (Moderate) Trazodone can lower the seizure threshold of anticonvulsants, although the overall risk is low at therapeutic doses. Patients may require increased concentrations of anticonvulsants to achieve equivalent effects if trazodone is added. 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 trazodone.
    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

    Vigabatrin is classified as FDA pregnancy category C. Use vigabatrin during pregnancy only if the potential benefit justifies the potential risk to the fetus.There are no adequate and well-controlled trials of vigabatrin use in pregnant women; however, in postmarketing experience, numerous birth defects have been reported, including congenital cardiac defects, congenital hemangioma, congenital hydronephrosis and vesicoureteric reflux, male genital malformation, dysmorphism, fetal anticonvulsant syndrome, hip dysplasia, limb malformations, and renal aplasia. In addition, developmental toxicity and teratogenic effects have occurred when vigabatrin was administered to pregnant animals during organogenesis and the latter part of pregnancy, including anatomical defects (unspecified), neurologic toxicities and neurobehavioral effects, cleft palate, and increased embryolethality at doses ranging from 50 mg/kg up to 200 mg/kg per day. The no-effect dose for teratogenicity and embryolethality in rabbits is approximately half the maximum recommended human dose (MRHD) of 3 g/day on a body surface area basis, and the no-effect dose for embryo-fetal toxicity in rats is approximately one-fifth the MRHD in adults on a body surface area basis. Physicians are advised to recommend that pregnant patients receiving vigabatrin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to provide information about the effects of in utero exposure to the drug. Patients must call 1-888-233-2334 to enroll in the registry.

    Vigabatrin is excreted in human milk. Because of the potential for serious adverse reactions from vigabatrin in breast-feeding infants, discontinue breast-feeding or vigabatrin, taking into account the importance of the drug to the mother. When vigabatrin 50, 100, or 150 mg/kg was administered to rats from the latter part of pregnancy through weaning, neurological toxicity (e.g., hippocampal vacuolation and seizures) was noted in the offspring. In addition, special precautions apply to the use vigabatrin in infants, due to the potential for MRI changes and neurotoxicity, including vision loss.

    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.