Version May 2024
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Because of the risk of vision loss, vigabatrin should be withdrawn from patients with refractory complex partial seizures who fail to show substantial clinical benefit within 3 months of initiation and within 2 to 4 weeks of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.
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 (manufacturer’s labeling; expert opinion):
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) (Jacqz-Aigrain 1997; expert opinion). If dose administered prior to dialysis on a dialysis day, then may consider 50% supplemental postdialysis dose (Diaz 2012; Sazgar 2021). Note: Some patients may respond to lower maintenance doses: (eg, 500 mg every 3 days was described as effective in a single case report) (Bachmann 1996).
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 (expert opinion).
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 (expert opinion).
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 (expert opinion). 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 (expert opinion).
There are no dosage adjustments provided in the manufacturer’s labeling; has not been studied. However, does not undergo appreciable hepatic metabolism.
Refractory complex partial seizures: Refer to adult dosing. Initiate at low end of dosage range; monitor closely for sedation and confusion.
(For additional information see "Vigabatrin: Pediatric drug information")
Dosage guidance:
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 (ILAE [Patsalos 2018]).
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.
Infants and Children 1 month to 2 years of age: Oral: Powder for oral solution: 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.
Children ≥2 years and Adolescents ≤16 years and weighing ≤60 kg: Oral: Note: Dosing based on population dose-response analysis of 3 pediatric trials (Nielsen 2014).
Patient weight:
10 to 15 kg: 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 kg to 20 kg: 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 kg to 25 kg: 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: 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 (Sabril prescribing information [Canada] 2018).
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.
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 and 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 and adolescents: 6%), fatigue (adults: 23% to 28%; children and 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 behavior (adults: 3%), abnormality in thinking (adults: 3%), abnormal sensory symptoms (adults: 4%), anxiety (adults: 4%), ataxia (adults: 7%), 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%), asthenia (adults: 5%), 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: Facial edema, 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
Nervous system: Acute psychosis, agitation (neonates), apathy, brain edema (infants: intramyelinic), delirium, developmental delay, dystonia, encephalopathy, hypertonia, hypomania, hypotonia, malignant hyperthermia, myoclonus, psychosis
Neuromuscular & skeletal: Dyskinesia, muscle spasticity
Ophthalmic: Optic neuritis
Otic: Deafness
Respiratory: Laryngeal edema, respiratory failure, stridor
Miscellaneous: 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: [US Boxed Warning]: Vigabatrin can cause permanent vision loss in infants, children, and adults. Due to the risk of vision loss and because vigabatrin provides an observable symptomatic benefit when it is effective, the patient who fails to show substantial clinical benefit within a short period of time after initiation of treatment (2 to 4 weeks for infantile spasms; <3 months for refractory complex partial seizures), should be withdrawn from therapy. 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. The onset of vision loss is unpredictable, and can occur within weeks of starting treatment or sooner, or at any time during treatment, even after months or years. 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. It is possible that vision loss can worsen despite discontinuation. 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 some cases, vigabatrin can damage the central retina and may decrease visual acuity. Symptoms of vision loss are unlikely to be recognized by the patient or caregiver before loss is severe. Vision loss of milder severity, although potentially unrecognized by the patient or caregiver, may still adversely affect function. Vision should be assessed to the extent possible at baseline (no later than 4 weeks after initiation), at least every 3 months during therapy and at 3 to 6 months after discontinuation. Once detected, vision loss is not reversible; even with frequent monitoring, it is expected that some patients will develop severe vision loss. In patients who cannot be tested, treatment may continue according to clinical judgement, with appropriate patient counseling. 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. The interaction of other types of irreversible vision damage with vision damage from vigabatrin has not been well-characterized, but is likely adverse. 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. The lowest dose and shortest exposure should be used that is consistent with clinical objectives. 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 the elderly as moderate to severe sedation and confusion have been reported; consider dose and/or frequency adjustments as renal clearance may be decreased.
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: [US Boxed Warning]: Because of the risk of permanent vision loss, vigabatrin is only available through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (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)
Tablet, Oral:
Sabril: 500 mg [scored]
Vigadrone: 500 mg [scored]
Generic: 500 mg
Yes
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): $145.67
Pack (Vigpoder Oral)
500 mg (per each): $108.00
Tablets (Sabril Oral)
500 mg (per each): $242.18
Tablets (Vigabatrin Oral)
500 mg (per each): $151.57
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
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).
Oral: May be administered without regard to food.
Powder for oral solution: 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 |
Hazardous agent (NIOSH 2016 [group 3]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets or capsules. NIOSH recommends double gloving, a protective gown, and (if there is a potential for vomit or spit up) eye/face protection for administration of an oral liquid/feeding tube administration (NIOSH 2016). Assess risk to determine appropriate containment strategy (USP-NF 2017).
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.
Infantile spasms: As monotherapy for pediatric patients 1 month to 2 years of age with infantile spasms for whom the potential benefits outweigh the potential risk of vision loss.
Refractory complex partial seizures: As adjunctive therapy for adults and pediatric patients ≥2 years of age with refractory complex partial seizures who have inadequately responded to several alternative treatments and for whom the potential benefits outweigh the risk of vision loss.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect 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
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect 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 enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
ClonazePAM: Vigabatrin may enhance the CNS depressant effect of ClonazePAM. Vigabatrin may increase the serum concentration of ClonazePAM. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect 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 enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect 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
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect 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: Vigabatrin may decrease the serum concentration of Fosphenytoin. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect 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 enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect 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
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the 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
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect 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
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect 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
Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Phenytoin: Vigabatrin may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect 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 enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect 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 enhance the CNS depressant effect 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
Vigabatrin crosses the placenta (Tran 1998).
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. Time of exposure or maternal dosage was not reported and information is not available relating to the incidence or types of these outcomes in comparison to the general epilepsy population. Visual field examinations have been conducted following in utero exposure in a limited number of children tested at ≥6 years of age; no visual field loss was observed in 4 children and results were inconclusive in 2 others (Lawthom 2009; Sorri 2005).
Data collection to monitor pregnancy and infant outcomes following exposure to vigabatrin is ongoing. Healthcare providers are encouraged to enroll women exposed to vigabatrin during pregnancy in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling 1-888-233-2334. Additional information is available at www.aedpregnancyregistry.org.
Vigabatrin is present in breast milk
Based on data collected from 2 women taking vigabatrin 1,000 mg twice daily during pregnancy and postpartum, vigabatrin concentrations in breast milk are ≤4% of the weight-adjusted maternal dose. Breast milk was sampled 7 and 8 days postpartum (Tran 1998). Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
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; hemoglobin and hematocrit; suicidality (eg, suicidal thoughts, depression, behavioral changes); weight gain/edema
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 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.
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