Version July 2025
Vigabatrin can cause permanent bilateral concentric visual field constriction, including tunnel vision that can result in disability. In some cases, vigabatrin also can damage the central retina and may decrease visual acuity.
The onset of vision loss from vigabatrin is unpredictable and can occur within weeks of starting treatment or sooner, or at any time after starting treatment, even after months or years.
Symptoms of vision loss from vigabatrin are unlikely to be recognized by the patients or caregivers before vision loss is severe. Vision loss of milder severity, while often unrecognized by the patient or caregiver, can still adversely affect function.
The risk of vision loss increases with increasing dose and cumulative exposure, but there is no dose or exposure known to be free of risk of vision loss.
Vision assessment is recommended at baseline (no later than 4 weeks after starting vigabatrin), at least every 3 months during therapy, and about 3 to 6 months after the discontinuation of therapy. Once detected, vision loss caused by vigabatrin is not reversible. It is expected that, even with frequent monitoring, some patients will develop severe vision loss.
Consider drug discontinuation, balancing benefit and risk, if vision loss is documented.
Risk of new or worsening vision loss continues as long as vigabatrin is used. It is possible that vision loss can worsen despite discontinuation of vigabatrin.
Because of the risk of vision loss, vigabatrin should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2 to 4 weeks of initiation for patients with infantile spasms, or sooner if treatment failure becomes obvious. Patient response to and continued need for vigabatrin should be periodically reassessed.
Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss unless the benefits of treatment clearly outweigh the risks.
Vigabatrin should not be used with other drugs associated with serious adverse ophthalmic effects such as retinopathy or glaucoma unless the benefits clearly outweigh the risks.
Use the lowest dosage and shortest exposure to vigabatrin that is consistent with clinical objectives.
Because of the risk of permanent vision loss, vigabatrin is available only through a restricted program under a risk evaluation and mitigation strategy (REMS) called the Vigabatrin REMS program. Further information is available at http://www.vigabatrinREMS.com or by calling 1-866-244-8175.
Dosage guidance:
Safety: Multiple concentrations of oral liquid formulations (ready-to-use concentrated oral solution [100 mg/mL] and powder for oral solution [50 mg/mL prepared]) exist; verify strength and dose prior to prescribing, dispensing, and administering vigabatrin; incorrect selection or substitution of one vigabatrin product for another without proper dosage volume adjustment may result in serious over- or underdosing.
Dosing: Use the lowest effective and shortest exposure consistent with therapeutic objectives dependent upon indication. If the decision is made to discontinue therapy, it should be done gradually. Therapeutic drug monitoring is not generally useful with vigabatrin therapy; however, it could be considered in patients with kidney impairment or malabsorption or adherence/suspected overdose (Ref).
Infantile spasms: Note: Withdraw therapy in 2 to 4 weeks if a substantial clinical benefit is not observed or discontinue treatment if evidence of treatment failure becomes obvious earlier than 2 to 4 weeks.
Sabril, Vigadrone, Vigafyde, Vigpoder (and associated generics):
Infants and Children 1 month to 2 years: Oral: Initial: 25 mg/kg/dose twice daily; may titrate upwards by 25 to 50 mg/kg/day increments every 3 days based on response and tolerability; maximum daily dose: 75 mg/kg/dose twice daily (150 mg/kg/day).
Discontinuation of therapy: To taper, decrease dose by 25 to 50 mg/kg/day every 3 to 4 days.
Seizure disorder, adjunctive therapy for complex partial onset seizures: Note: Dose dependent upon weight and/or age. Withdraw therapy if a substantial clinical benefit is not observed within 3 months of treatment initiation; discontinue therapy if evidence of treatment failure becomes obvious earlier than 3 months.
Sabril, Vigadrone, Vigpoder (and associated generics):
Children ≥2 years and Adolescents ≤16 years and weighing ≤60 kg: Note: Dosing based on population dose-response analysis of 3 pediatric trials (Ref).
10 to 15 kg: Oral: Initial: 175 mg twice daily; titrate upwards at weekly intervals based on response and tolerability; recommended maintenance dose: 525 mg twice daily (1,050 mg/day).
>15 to 20 kg: Oral: Initial: 225 mg twice daily; titrate upwards at weekly intervals based on response and tolerability; recommended maintenance dose: 650 mg twice daily (1,300 mg/day).
>20 to 25 kg: Oral: Initial: 250 mg twice daily; titrate upwards at weekly intervals based on response and tolerability; recommended maintenance dose: 750 mg twice daily (1,500 mg/day).
>25 to 60 kg: Oral: Initial: 250 mg twice daily; titrate upwards at weekly intervals based on response and tolerability; recommended maintenance dose: 1,000 mg twice daily (2,000 mg/day).
Discontinuation of therapy: In trials, doses were tapered by decreasing the daily dose by 1/3 every third week until discontinuation.
Children ≥2 years and Adolescents ≤16 years and weighing >60 kg and Adolescents ≥17 years: Oral: Initial: 500 mg twice daily; titrate upwards in 500 mg increments at weekly intervals based on response and tolerability; the target dose in adults is 1,500 mg twice daily (3,000 mg/day). Note: In clinical trials, higher doses (6 g/day) did not provide additional benefit and increased the incidence of adverse effects.
Discontinuation of therapy: In trials, doses were tapered in 1,000 mg/day increments at weekly intervals until discontinued.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants and Children <2 years: There are no dosage adjustments provided in US manufacturer's labeling; data is not available; vigabatrin is primarily eliminated through the kidney; use with caution; consider dosage reduction in patients with any degree of renal impairment (Ref).
Children ≥2 years and Adolescents: Oral:
CrCl >80 mL/minute: No dosage adjustment necessary.
CrCl >50 to 80 mL/minute: Decrease dose by 25%.
CrCl >30 to 50 mL/minute: Decrease dose by 50%.
CrCl >10 to 30 mL/minute: Decrease dose by 75%.
Hemodialysis: Reduces vigabatrin plasma concentration by 40% to 60%.
There are no dosage adjustments provided in manufacturer's labeling; has not been studied; however, does not undergo appreciable hepatic metabolism.
(For additional information see "Vigabatrin: Drug information")
Refractory complex partial seizures: Oral: Initial: 500 mg twice daily; increase daily dose by 500 mg increments at weekly intervals based on response and tolerability. Recommended dose: 1.5 g twice daily. Note: To taper, decrease dose by 1 g daily on a weekly basis. Withdraw therapy if a substantial clinical benefit is not observed within 3 months of treatment initiation; discontinue therapy if evidence of treatment failure becomes obvious earlier than 3 months.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function (Ref):
Renal function for the following dose adjustments may be estimated using the Cockcroft-Gault formula.
CrCl >80 mL/minute: No dosage adjustment necessary.
CrCl >50 to 80 mL/minute: Initial: 750 mg/day administered in 2 divided doses; may increase dose no more frequently than at weekly intervals based on response and tolerability. Target dose: 2.25 g/day.
CrCl >30 to 50 mL/minute: Initial: 500 mg/day administered in 2 divided doses; may increase dose no more frequently than at weekly intervals based on response and tolerability. Target dose: 1.5 g/day.
CrCl ≤30 mL/minute: Initial: 250 mg/day administered in 1 or 2 divided doses; may increase dose no more frequently than at weekly intervals based on response and tolerability. Target dose: 750 mg once daily.
Hemodialysis, intermittent (thrice weekly): Dialyzable (40% to 60%): Initial: 250 mg once daily; administer after dialysis on dialysis days; may increase dose no more frequently than at weekly intervals based on response and tolerability (Target dose: 750 mg once daily) (Ref). If dose administered prior to dialysis on a dialysis day, then may consider 50% supplemental postdialysis dose (Ref). Note: Some patients may respond to lower maintenance doses: (eg, 500 mg every 3 days was described as effective in a single case report) (Ref).
Peritoneal dialysis: Initial: 250 mg once daily; may increase dose no more frequently than at weekly intervals based on response and tolerability. Target dose: 750 mg once daily (Ref).
CRRT: Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
No pharmacokinetic data available; however, given low protein binding and clearance by intermittent hemodialysis, some removal is expected. May consider initial doses of 500 mg/day administered in 2 divided doses (may increase dose no more frequently than at weekly intervals based on response and tolerability). Target dose: 1.5 g/day (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of response and adverse reactions (eg, CNS effects) due to drug accumulation is important.
No pharmacokinetic data available; however, given low protein binding and clearance by intermittent hemodialysis, some removal is expected. May consider initial doses of 250 mg once daily; may increase dose no more frequently than at weekly intervals based on response and tolerability (Ref). Target dose: 750 mg/day. When scheduled dose falls on a PIRRT day, administer a 25% to 50% supplemental dose (depending on duration of treatment and effluent rates used) after PIRRT treatment (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied. However, does not undergo appreciable hepatic metabolism.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are adjunctive use except in infants for infantile spasms.
>10%:
Dermatologic: Skin rash (infants: 8% to 11%)
Endocrine & metabolic: Weight gain (children, adolescents: 47%; adults: 6% to 17%)
Gastrointestinal: Constipation (infants: 12% to 14%; adults: 8%), diarrhea (10% to 13%), vomiting (infants: 14% to 20%; adults: 7%)
Infection: Viral infection (infants: 19% to 20%)
Nervous system: Dizziness (adults: 24%), drowsiness (infants: 17% to 45%; adults: 22% to 24%; children, adolescents: 6%), fatigue (adults: 23% to 28%; children, adolescents: 10%), headache (adults: 33%), insomnia (infants: 10% to 12%), irritability (infants: 16% to 23%), sedated state (infants: 17% to 19%; adults: 4%)
Neuromuscular & skeletal: Tremor (adults: 15%)
Ophthalmic: Blurred vision (13%), nystagmus disorder (adults: 13%), visual field loss (adults: ≥30%)
Otic: Otic infection (infants: 7% to 14%), otitis media (infants: 10% to 44%)
Respiratory: Bronchitis (infants: 30%), nasal congestion (infants: 4% to 13%), nasopharyngitis (adults: 14%), pneumonia (infants: 11% to 13%), upper respiratory tract infection (infants: 46% to 51%; adults: 7%)
Miscellaneous: Fever (infants: 19% to 29%; adults: 4%)
1% to 10%:
Cardiovascular: Edema (adults: 1%), peripheral edema (adults: 2% to 5%)
Endocrine & metabolic: Increased thirst (adults: 2%)
Gastrointestinal: Abdominal distention (adults: 2%), abdominal pain (adults: 3%), decreased appetite (infants: 7% to 9%), dyspepsia (adults: 4%), nausea (adults: 10%), stomach discomfort (adults: 4%), upper abdominal pain (adults: 5%), viral gastroenteritis (infants: 5% to 6%)
Genitourinary: Dysmenorrhea (adults: 9%), urinary tract infection (4% to 6%)
Hematologic & oncologic: Anemia (adults: 6%), bruise (adults: 3%), decreased hemoglobin (adults: 3%)
Infection: Candidiasis (infants: 3% to 8%), influenza (3% to 5%)
Nervous system: Abnormal sensory symptoms (adults: 4%), anxiety (adults: 4%), asthenia (adults: 5%), ataxia (adults: 7%), behavioral changes (adults: 3%), changes in thinking (adults: 3%), confusion (adults: 4%), depressed mood (adults: 5%), depression (adults: 6%), disturbance in attention (adults: 9%), dysarthria (adults: 2%), hyperreflexia (adults: 4%), hypoesthesia (adults: 4%), hyporeflexia (adults: 4%), hypotonia (≤6%), impaired consciousness (adults: 2%), lethargy (4% to 7%), memory impairment (adults: 7%), paresthesia (adults: 7%), peripheral neuropathy (adults: 1%), seizure (infants: 4% to 7%), status epilepticus (infants: 4% to 6%; adults: 2%), vertigo (adults: 2%)
Neuromuscular & skeletal: Arthralgia (adults: 10%), back pain (adults: 4%), limb pain (adults: 6%), muscle spasm (adults: 3%), myalgia (adults: 3%)
Ophthalmic: Asthenopia (adults: 2%), conjunctivitis (infants: 2% to 5%), diplopia (adults: 7%), strabismus (infants: 5%)
Otic: Tinnitus (adults: 2%)
Respiratory: Cough (infants: 3% to 8%), croup (infants: 1% to 5%), pharyngolaryngeal pain (adults: 7%), sinus headache (adults: 6%), sinusitis (infants: 5% to 9%)
Frequency not defined:
Nervous system: Suicidal ideation, suicidal tendencies
Ophthalmic: Decreased visual acuity, permanent vision loss, tunnel vision, visual field defect (bilateral concentric visual field constriction; may be permanent)
Postmarketing:
Cardiovascular: Pulmonary embolism
Dermatologic: Alopecia, maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis
Gastrointestinal: Cholestasis, esophagitis, gastrointestinal hemorrhage
Genitourinary: Sexual disorder (delayed puberty)
Hypersensitivity: Angioedema, facial edema
Nervous system: Acute psychosis, agitation (neonates), apathy, brain edema (infants: intramyelinic), delirium, developmental delay, encephalopathy, hypertonia, hypomania, hypotonia, myoclonus, psychosis
Neuromuscular & skeletal: Dyskinesia, dystonia, muscle spasticity
Ophthalmic: Optic neuritis
Otic: Deafness
Respiratory: Laryngeal edema, respiratory failure, stridor
Miscellaneous: Malignant hyperthermia, multi-organ failure
There are no contraindications listed in the US manufacturer’s labeling.
Canadian labeling: Hypersensitivity to vigabatrin or any component of the formulation; pregnancy; breastfeeding
Concerns related to adverse effects:
• Anemia: Use has been associated with decreased hemoglobin and hematocrit; cases of significantly reduced hemoglobin (<8 g/dL) and/or hematocrit (<24%) have been reported.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Edema: Peripheral edema and edema independent of hypertension, heart failure, weight gain, renal or hepatic dysfunction has been reported.
• Neurotoxicity: Intramyelinic edema has been reported (rarely) in infants. Patients must be closely monitored for potential neurotoxicity (observed in animal models but not established in adults).
• Peripheral neuropathy: Peripheral neuropathy manifesting as numbness or tingling in the toes or feet, reduced distal lower limb vibration or position sensation, or progressive loss of reflexes, starting at the ankles, has been reported in adult patients.
• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify healthcare provider immediately if symptoms occur.
• Vision loss: Vigabatrin can cause permanent vision loss in infants, children, and adults. If in the clinical judgment of the prescriber evidence of treatment failure becomes obvious earlier in treatment, vigabatrin should be discontinued at that time. Patient response to and continued need for treatment should be periodically assessed. Assessment of vision loss is difficult in children and the frequency and extent of vision loss in infants and children is poorly characterized. Most data are available in adult patients. Vigabatrin causes permanent bilateral concentric visual field constriction in >30% of patients ranging in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation, and can result in disability. In patients who cannot be tested, treatment may continue according to clinical judgement, with appropriate patient counseling. The interaction of other types of irreversible vision damage with vision damage from vigabatrin has not been well characterized, but is likely adverse. The possibility that vision loss from vigabatrin may be more common, more severe or have more severe functional consequences in infants and children than in adults cannot be excluded.
• Weight gain: Use has been associated with an average weight gain of 3.5 kg in adults and ≥7% of baseline body weight in pediatric patients.
Disease-related concerns:
• Psychiatric behavior: Use with caution in patients with a history of psychosis (psychotic/agitated reactions may occur more frequently), depression, or behavioral problems.
• Renal impairment: Use with caution in patients with renal impairment; modify dose in children and adults with renal impairment (CrCl <80 mL/minute).
• Seizures: May cause an increase in seizure frequency in some patients; use with particular caution in patients with myoclonic seizures, which may be more prone to this effect.
Special populations:
• Older adult: Use with caution in older adults as moderate to severe sedation and confusion have been reported; consider dose and/or frequency adjustments as renal clearance may be decreased.
Dosage form specific issues:
• Interchangeability: Ensure the correct volume for the correct dosage is prescribed, dispensed, and administered. The oral solution is concentrated (100 mg/mL) and requires a smaller volume compared to other vigabatrin products (50 mg/mL).
Other warnings/precautions:
• Appropriate use: Vigabatrin is not indicated as a first-line agent for complex partial seizures.
• MRI abnormalities: Abnormal MRI changes have been reported in some infants and children ≤6 years of age. Resolution of MRI changes usually occurs with discontinuation of therapy. MRI changes were not seen in older children (>6 years of age) and adult patients.
• REMS program: Under the Vigabatrin REMS program, only prescribers and pharmacies registered with the program are able to prescribe and distribute vigabatrin. Vigabatrin may only be dispensed to patients who are enrolled in and meet all conditions of the Vigabatrin REMS program. Call 866-244-8175 or visit http://www.vigabatrinREMS.com for further information.
• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.
Dose dependent, asymptomatic MRI abnormalities have been reported in infants treated with vigabatrin for infantile spasms; resolution of abnormalities generally occurs upon vigabatrin discontinuation; abnormalities resolved in a few infants, despite continued use; some infants displayed coincident motor abnormalities, but no causal relationship has been established; risk for long-term clinical sequelae has not been studied. A relationship between MRI abnormalities in infants and animal model findings has not been established. Somnolence and fatigue occur at a higher incidence in infants compared to adults (infants: ≤45%; adults: ≤24%). May cause fever; higher incidence reported in infants than adults (≤30% vs 6%). May cause vomiting; higher incidence in infants (up to 20%). Infants may experience a higher frequency of other adverse effects than adults, including vomiting and upper respiratory tract infections.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Sabril: 500 mg (50 ea)
Vigadrone: 500 mg (1 ea, 50 ea)
Vigpoder: 500 mg (1 ea, 50 ea)
Generic: 500 mg (1 ea, 50 ea)
Solution, Oral:
Vigafyde: 100 mg/mL (150 mL) [contains methylparaben, propylparaben; peppermint flavor]
Tablet, Oral:
Sabril: 500 mg [scored]
Vigadrone: 500 mg [scored]
Generic: 500 mg
May be product dependent
Pack (Sabril Oral)
500 mg (per each): $242.19
Pack (Vigabatrin Oral)
500 mg (per each): $126.65 - $189.19
Pack (Vigadrone Oral)
500 mg (per each): $154.41
Pack (Vigpoder Oral)
500 mg (per each): $108.00
Solution (Vigafyde Oral)
100 mg/mL (per mL): $28.44
Tablets (Sabril Oral)
500 mg (per each): $242.18
Tablets (Vigabatrin Oral)
500 mg (per each): $151.57 - $207.59
Tablets (Vigadrone Oral)
500 mg (per each): $201.74
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Sabril: 500 mg (1 ea)
Tablet, Oral:
Sabril: 500 mg
Oral: May be administered without regard to food.
Concentrated oral solution (eg, Vigafyde): Ready-to-use 100 mg/mL oral solution; no further dilution required. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose (overdosage may occur).
Powder for oral solution (eg, Sabril, Vigadrone, Vigpoder): Prior to administration, dissolve each 500 mg powder packet in 10 mL per packet of cold or room temperature water to make a 50 mg/mL solution; see table for number of packets and volume of water for dose. Discard solution if it is not clear (or free of particles) and colorless. Withdraw the appropriate dose aliquot using calibrated measuring device; administer dose immediately after reconstitution; use provided oral syringe, not a household spoon. Any remaining liquid should be discarded.
Canadian labeling: Dissolve each 500 mg powder packet in 10 mL of cold or room temperature water, fruit juice, milk, or infant formula to make a 50 mg/mL solution.
|
Dose range (mg) |
Number of packets |
Volume of water (10 mL per packet) |
|---|---|---|
|
0 to 500 mg |
1 packet |
10 mL |
|
501 to 1,000 mg |
2 packets |
20 mL |
|
1,001 to 1,500 mg |
3 packets |
30 mL |
Administer without regard to meals.
Oral solution: Mix with water immediately prior to administration. Use a calibrated measuring device to measure dose (household teaspoon or tablespoon is not an adequate measuring device).
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Oral solution: Store unopened bottles at 20°C to 25°C (68°F to 77°F); excursion permitted between 15°C to 30°C (59°F to 86°F). Once opened, store at 2°C to 30°C (36°F to 86°F); discard any unused portion after 90 days of first opening.
Packets, tablets: Store at 20°C to 25°C (68°F to 77°F).
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020427s020,022006s022lbl.pdf#page=26, must be dispensed with this medication.
Monotherapy for treatment of infantile spasms in patients for whom the potential benefits outweigh the potential risk of vision loss (Sabril, Vigadrone, Vigafyde, Vigpoder: FDA approved in ages 1 month to 2 years).
Adjunct therapy for refractory complex partial seizures in patients with inadequate response to several alternative treatments and for whom the potential benefits outweigh the potential risk of vision loss (Sabril, Vigadrone, Vigpoder: FDA approved in ages ≥2 years and adults).
Vigabatrin may be confused with dabigatran, Vibativ, vibegron.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification
Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification
Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
ClonazePAM: Vigabatrin may increase CNS depressant effects of ClonazePAM. Vigabatrin may increase serum concentration of ClonazePAM. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Desmopressin: Hyponatremia-Associated Agents may increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification
Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification
Fosphenytoin-Phenytoin: Vigabatrin may decrease serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider Therapy Modification
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider Therapy Modification
OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification
ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification
Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient’s reproductive lifespan (ACOG 2020; NICE 2022).
Obtain baseline concentrations of antiseizure medications prior to pregnancy and monitor adherence (NICE 2022).
Vigabatrin crosses the placenta (Tran 1998).
Outcome data following maternal use of vigabatrin during pregnancy are limited (Christensen 2024; Pack 2024). According to product labeling, birth defects have been reported following use in pregnancy and include cardiac defects, limb defects, male genital malformations, fetal antiseizure syndrome, renal and ear abnormalities. Data are insufficient to evaluate the risk of specific major congenital malformations or neurodevelopmental outcomes (IQ scores or autism spectrum disorder) in children following in utero exposure to vigabatrin. Screen for major congenital malformations and monitor fetal growth when antiseizure medications are used during pregnancy. Conduct age-appropriate developmental screening in children who had in utero exposure to antiseizure medications (Pack 2024).
Vigabatrin is associated with permanent vision loss, therefore availability is restricted through the Vigabatrin REMS program. Limited data are available from visual field examinations conducted in 5 mothers and their 6 children following vigabatrin exposure during pregnancy. Visual field abnormalities were observed in 3 mothers; no visual field loss was observed in 4 children and results were inconclusive in 2 children (Lawthom 2009; Sorri 2005). Vigabatrin is approved for use only as adjunctive therapy for patients with refractory complex partial seizures who have inadequately responded to several alternative treatments when the potential benefits outweigh the risk of vision loss.
Monitor concentrations of antiseizure medications during pregnancy and adjust doses based on decreasing concentrations and seizure control (Pack 2024). Formulate a plan to return to prepregnancy doses after delivery (NICE 2022).
Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).
Data collection to monitor pregnancy outcomes following exposure to antiepileptic drugs is ongoing. Encourage patients to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or www.aedpregnancyregistry.org).
Ophthalmologic examination by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina at baseline (no later than 4 weeks after therapy initiation), periodically during therapy (every 3 months), and 3 to 6 months after discontinuation of therapy; assessment should include visual acuity and visual field whenever possible including mydriatic peripheral fundus examination and visual field perimetry, preferably by automated threshold visual field testing. Observe patient for excessive sedation, especially when instituting or increasing therapy; frequency, duration, and severity of seizure episodes; hemoglobin and hematocrit; renal function; weight; signs and symptoms of suicidality (eg, anxiety, depression, behavior changes); neurotoxicity; peripheral neuropathy; and edema.
Although not routinely used to assess efficacy, assessment of vigabatrin plasma concentration may be considered in certain clinical situations (kidney impairment, malabsorption) or to assess adherence or a suspected overdose. Reported range: Plasma: 0.8 to 36 mg/L (ILEA [Patsalos 2018]).
Irreversibly inhibits gamma-aminobutyric acid transaminase (GABA-T), increasing the levels of the inhibitory compound gamma amino butyric acid (GABA) within the brain. Duration of effect is dependent upon rate of GABA-T resynthesis.
Note: A correlation between serum concentrations and efficacy has not been established.
Duration (rate of GABA-T resynthesis dependent): Variable (not strictly correlated to serum concentrations).
Absorption: Rapid, complete.
Distribution: Vd: 1.1 L/kg.
Protein binding: Does not bind to plasma proteins.
Metabolism: Insignificant.
Bioavailability: Oral: Tablet and powder for oral solution are bioequivalent.
Half-life elimination: Terminal: Prolonged in renal impairment.
Pediatric patients: 5 months to 2 years: ~5.7 hours; 3 to 9 years: ~6.8 hours; 10 to 16 years: ~9.5 hours.
Adult patients: ~10.5 hours.
Time to peak: Infants (5 months to 2 years): 2.5 hours; Children (3 to 16 years) and Adults: 1 hour (2 hours with food).
Excretion: Urine (80%, as unchanged drug).
Clearance:
Pediatric patients: 5 months to 2 years: 2.4 L/hour; 3 to 9 years: 5.1 L/hour; 10 to 16 years: 5.8 L/hour.
Adults: 7 L/hour.
Altered kidney function: AUC increased 30% and half-life increased 55% in patients with mild renal impairment (CrCl >50 to 80 mL/minute). AUC and half-life increased twofold in patients with moderate renal impairment (CrCl >30 to 50 mL/minute). In patients with severe renal impairment (CrCl >10 to 30 mL/minute), AUC increased 4.5-fold and half-life increased 3.5-fold.
Older adult: Renal clearance was 36% lower in elderly patients compared with younger patients.
Race/ethnicity: Renal clearance was 25% higher in white patients compared with Japanese patients.
