Sabril

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Sabril

Classes

Anticonvulsants, GABA-T Inhibitors

Administration

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

Oral Administration

Vigabatrin may be administered with or without food.

Oral Liquid Formulations

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

Adverse Reactions
Severe

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

Moderate

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

Mild

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

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.

Common Brand Names

Sabril, VIGADRONE

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

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

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

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

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

Adolescents 17 years

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

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

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

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

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

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

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

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

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

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

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

Infants† and Children younger than 2 years†

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

Dosing Considerations
Hepatic Impairment

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

Renal Impairment

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

Drug Interactions

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

zed; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as sulfamethoxazole, may occur during concurrent use of vigabatrin.
Sumatriptan; Naproxen: (Minor) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as naproxen, may occur during concurrent use of vigabatrin.
Tapentadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Temazepam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Thiothixene: (Major) Vigabatrin should not be used with thiothixene, which is associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Tramadol: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Tramadol; Acetaminophen: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with opiate agonists.
Triamcinolone: (Major) Vigabatrin should not be used with corticosteroids, which are associated with serious ophthalmic effects (e.g., retinopathy or glaucoma) unless the benefit of treatment clearly outweighs the risks.
Triazolam: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given in combination with benzodiazepines.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs), when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Triprolidine: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with sedating H1-blockers.
Warfarin: (Moderate) Vigabatrin is not significantly metabolized; however, it is an inducer of CYP2C9. In theory, decreased exposure of drugs that are extensively metabolized by CYP2C9, such as warfarin, may occur during concurrent use of vigabatrin.
Zaleplon: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.
Zolpidem: (Moderate) Vigabatrin may cause somnolence and fatigue. Drugs that can cause CNS depression, if used concomitantly with vigabatrin, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when vigabatrin is given with anxiolytics, sedatives, and hypnotics.

How Supplied

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

Maximum Dosage
Adults

3,000 mg/day PO.

Geriatric

3,000 mg/day PO.

Adolescents

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

Children

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

Infants

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

Neonates

Safety and efficacy have not been established.

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.

Pregnancy And Lactation
Pregnancy

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

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