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Vigabatrin

Medically reviewed by Drugs.com. Last updated on Sep 23, 2020.

Pronunciation

(vye GA ba trin)

Dosage Forms

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)

Generic: 500 mg (1 ea, 50 ea)

Tablet, Oral:

Sabril: 500 mg [scored]

Generic: 500 mg

Brand Names: U.S.

  • Sabril
  • Vigadrone

Pharmacologic Category

  • Anticonvulsant, Miscellaneous

Pharmacology

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.

Absorption

Rapid, complete

Distribution

Vd: 1.1 L/kg

Metabolism

Insignificant

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.

Time to Peak

Infants and Children 5 months to 2 years: 2.5 hours; Children and Adolescents 3 to 16 years and Adults: 1 hour (2 hours with food).

Duration of Action

Resynthesis of GABA-T dependent: Variable (not strictly correlated to serum concentrations)

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.

Protein Binding

Does not bind to plasma proteins

Special Populations: Renal Function Impairment

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.

Special Populations: Elderly

Renal clearance was 36% lower in elderly patients compared with younger patients.

Special Populations: Race

Renal clearance was 25% higher in white patients compared with Japanese patients.

Use: Labeled Indications

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.

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Canadian labeling: Hypersensitivity to vigabatrin or any component of the formulation; pregnancy; breastfeeding

Dosing: Adult

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.

Dosing: Geriatric

Refractory complex partial seizures: Refer to adult dosing. Initiate at low end of dosage range; monitor closely for sedation and confusion.

Dosing: Pediatric

Note: Use the lowest effective and shortest exposure consistent with therapeutic objectives. Therapeutic drug monitoring is not useful with vigabatrin therapy.

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.

Refractory complex partial seizures; adjunctive treatment: 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.

Reconstitution

Powder for oral solution: Dissolve each 500 mg powder packet in 10 mL of cold or room temperature water to make a 50 mg/mL solution. Alternatively, the powder may be dissolved with 10 mL of fruit juice, milk, or infant formula (Sabril Canadian product monograph). After reconstitution, use immediately; discard any unused portion or if the resulting solution is not free of particles or colorless.

Administration

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).

Storage

Store at 20°C to 25°C (68°F to 77°F).

Drug Interactions

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

ClonazePAM: Vigabatrin may enhance the CNS depressant effect of ClonazePAM. Vigabatrin may increase the serum concentration of ClonazePAM. Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. 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. Exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Consider therapy modification

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

Fosphenytoin: Vigabatrin may decrease the serum concentration of Fosphenytoin. Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mefloquine: May diminish the therapeutic effect of Anticonvulsants. Mefloquine may decrease the serum concentration of Anticonvulsants. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of convulsions. If anticonvulsants are being used for another indication, monitor anticonvulsant concentrations and treatment response closely with concurrent use. Consider therapy modification

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. 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. Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

Mianserin: May diminish the therapeutic effect of Anticonvulsants. Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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. Consider therapy modification

Orlistat: May decrease the serum concentration of Anticonvulsants. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. 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. Interupt oxybate salt treatment during short-term opioid use. 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. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Phenytoin: Vigabatrin may decrease the serum concentration of Phenytoin. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. 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. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Test Interactions

Vigabatrin has been reported to decrease AST and ALT activity in the plasma in up to 90% of patients, causing the enzymes to become undetectable in some patients; this may preclude use of AST and ALT as markers for hepatic injury. Vigabatrin may increase amino acids in the urine leading to false-positive tests for rare genetic metabolic disorders

Adverse Reactions

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

ALERT: U.S. Boxed Warning

Permanent vision loss:

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.

Warnings/Precautions

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 antiepileptics (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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: 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: Anticonvulsants 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.

Monitoring Parameters

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

Pregnancy Considerations

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 anticonvulsant 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.

Patient Education

What is this drug used for?

• It is used to help control certain kinds of seizures.

• It is used to treat infantile spasms.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Fatigue

• Constipation

• Abdominal pain

• Cough

• Sore throat

• Stuffy nose

• Common cold symptoms

• Headache

• Trouble sleeping

• Joint pain

• Diarrhea

• Nausea

• Vomiting

• Lack of appetite

• Weight gain

• Tooth pain

• Back pain

• Increased appetite

• Tremors

• Flu-like symptoms

• Anxiety

• Nightmares

• Twitching

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain

• Burning or numbness feeling

• Chest pain

• Change in balance

• Severe dizziness

• Passing out

• Confusion

• Trouble focusing

• Behavioral changes

• Ear pain

• Seizures

• Severe loss of strength and energy

• Vision changes

• Blurred vision

• Trouble controlling eye movements

• Clumsiness

• Blindness

• Severe muscle pain

• Severe muscle weakness

• Swelling

• Trouble with memory

• Abnormal gait

• Sexual dysfunction

• Painful periods

• Depression like thoughts of suicide, anxiety, emotional instability, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.