Dosing and uses of Sabril (vigabatrin)
Adult dosage forms and strengths
tablet
- 500mg
powder for oral solution
- 500mg/packet
Complex Seizures
Indicated for adjunctive therapy in adults with refractory complex partial seizures
500 mg PO q12hr initially, THEN increase by 500-mg increments qWeek to target dose of 1.5 g q12hr
No additional benefit shown with 6 g daily compared with 3 g daily; higher incidence of adverse effects associated with 6 g daily
Renal Impairment
CrCl >50-80 mL/min: Decrease dose by 25%
CrCl >30-50 mL/min: Decrease dose by 50%
CrCl >10 to <30 mL/min: Decrease dose by 75%
Hemodialysis: Clearance not adequately studied
Administration
Oral solution preparation: Dissolve powder content from each 500 mg packet in 10 mL cold or room temp water (final concentration 50 mg/mL); prepare immediately before use
May take with or without food
Discontinuing: Taper by decreasing daily dose 1000 mg/day on a weekly basis until discontinued
Pediatric dosage forms and strengths
tablet
- 500mg
powder for oral solution
- 500mg/packet
Partial Seizures
Indicated for adjunctive therapy in children 10-16 years of age with refractory complex partial seizures
<10 years: Safety and efficacy not established
10-16 years
- 25-60 kg: 250 mg PO q12hr initially, THEN increase qWeek to total maintenance dose of 1000 mg q12hr
- >60 kg: 500 mg PO q12hr initially, THEN increase by 500-mg increments qWeek to target dose of 1.5 g q12hr
>16 years
- 500 mg PO q12hr initially, THEN increase by 500-mg increments qWeek to target dose of 1.5 g q12hr
Infantile Spasms
Indicated as monotherapy for pediatric patients with infantile spasms aged 1 month to 2 years for whom the potential benefits outweigh the potential risk of vision loss
<1 month: Not established
1 month to 2 years: 50 mg/kg/day PO divided q12hr initially; if needed, may increase dose by 25-50 mg/kg/day increments every 3 days; not to exceed 150 mg/kg/day
Renal Impairment
Infants: Information about how to adjust dose not available
≥10 years
- CrCl >50-80 mL/min: Decrease dose by 25%
- CrCl >30-50 mL/min: Decrease dose by 50%
- CrCl >10 to <30 mL/min: Decrease dose by 75%
- Hemodialysis: Clearance not adequately studied
Administration
Oral solution preparation: Dissolve powder content from each 500 mg packet in 10 mL cold or room temp water (final concentration 50 mg/mL); prepare immediately before use
May take with or without food
Discontinuing
- Infantile spasms: Taper by decreasing daily dose at a rate of 25-50 mg/kg q3-4 days
- Pediatric patients aged 10-16 yr with complex partial seizures: Taper by decreasing daily dose by one-third qWeek for 3 wk
- Pediatric patients >16 yr with complex partial seizures: Taper by decreasing daily dose 1000 mg/day on a weekly basis until discontinued
Geriatric dosage forms and strengths
Initiate at low end of dosing range and consider dose adjustment with renal impairment
Refractory Complex Seizures
500 mg PO q12hr initially, THEN increase by 500-mg increments qWeek to target dose of 1.5 g q12hr
No additional benefit shown with 6 g daily compared with 3 g daily; higher incidence of adverse effects associated with 6 g daily
Sabril (vigabatrin) adverse (side) effects
>10%
Weight gain, children (47%)
Permanent bilateral concentric visual field constriction (>30%)
Fatigue (28%)
Somnolence (24%)
Headache (18%)
Weight gain, adults (17%)
Dizziness (15%)
Convulsion (11%)
Hyperactivity, in children (11%)
1-10%
Nasopharyngitis (10%)
Weight increased (10%)
Upper respiratory tract infection (10%)
Visual field defect (9%)
Depression (8%)
Tremor (7%)
Nystagmus (7%)
Nausea (7%)
Diarrhea (7%)
Memory impairment (7%)
Insomnia (7%)
Irritability (7%)
Coordination abnormal (7%)
Vision blurred (6%)
Diplopia (6%)
Vomiting (6%)
Influenza (6%)
Pyrexia (6%)
Rash (6%)
Postmarketing Reports
Birth defects: Congenital cardiac defects, congenital external ear anomaly, congenital hemangioma, congenital hydronephrosis, congenital male genital malformation, congenital oral malformation, congenital vesicoureteric reflux, dentofacial anomaly, dysmorphism, fetal anticonvulsant syndrome, hamartomas, hip dysplasia, limb malformation, limb reduction defect, low set ears, renal aplasia, retinitis pigmentosa, supernumerary nipple, talipes
Ear disorders: Deafness
Endocrine disorders: Delayed puberty
Gastrointestinal disorders: Gastrointestinal hemorrhage, esophagitis
General disorders: Developmental delay, facial edema, malignant hyperthermia, multiorgan failure
Hepatobiliary disorders: Cholestasis
Nervous system disorders: Dystonia, encephalopathy, hypertonia, hypotonia, muscle spasticity, myoclonus, optic neuritis
Psychiatric disorders: Acute psychosis, apathy, delirium, hypomania, neonatal agitation, psychotic disorder
Respiratory disorders: Laryngeal edema, pulmonary embolism, respiratory failure, stridor
Skin and subcutaneous tissue disorders: Angioedema, maculopapular rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis
Vision disorders: Permanent vision loss
Warnings
Black box warnings
Causes permanent vision loss in infants, children, and adults and includes progressive and permanent bilateral concentric visual field constriction in >30% of patients and ranges in severity from mild to severe, including tunnel vision to within 10 degrees of visual fixation, and can result in disability
May damage the central retina and decrease visual acuity
Vision loss onset is unpredictable and can occur within weeks of starting treatment, or sooner, or at any time during treatment (even after months or years), and possibly after vigabatrin is discontinued
Vision assessment is recommended at baseline (no later than 4 weeks after initiating therapy), at least every 3 months during therapy, and about 3-6 months after discontinuation of therapy
Consider drug discontinuation, balancing benefit and risk, if vision loss documented
Symptoms of vision loss are unlikely to be recognized by patients or caregivers before vision loss is severe
Risk of new or worsening vision loss continues throughout therapy; it is possible that vision loss can worsen despite discontinuation of therapy
Therapy should not be administered to patients with, or at high risk of, other types of irreversible vision loss unless benefits of treatment clearly outweigh risks
Use lowest dosage and shortest exposure to therapy
Because of risk of permanent vision loss, therapy is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the SABRIL REMS Program; 1-888-457-4273
Contraindications
Hypersensitivity
Cautions
P450 CYP2C inducer; coadministration with CYP2C substrates (eg, phenytoin) result in decreased plasma levels, phenytoin levels decreased 16-20% when coadministered and therefore may require dosage adjustments
When coadministration with other AEDs, serum concentration of phenobarbital was reduced 8-16% and sodium valproate concentration was reduced by 8%
Vigabatrin increased clonazepam Cmax by 30% and decreased Tmax by 45%
May cause severe visual changes requiring regular ophthalmic monitoring (see Black box warnings)
May cause somnolence and fatigue
Abnormal MRI signal changes reported in some infants
Antiepileptic drugs may increase risk of suicidal thoughts and behavior
Taper dose gradually when discontinuing to avoid withdrawal seizures; if withdrawal needed because of serious adverse event, rapid discontinuation can be considered
Anemia reported
Peripheral neuropathy reported
Weight gain reported in adults and children
Edema reported in adults
Pregnancy and lactation
Pregnancy category: C; Based on animal data, may cause fetal harm
Lactation: excreted in breast milk, do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sabril (vigabatrin)
Mechanism of action
Irreversible inhibitor of gamma aminobutyric acid (GABA) transaminase, thereby increases the level of the inhibitory neurotransmitter GABA within the brain
Pharmacokinetics
Half-Life: 5.7 hr in infants; 5-8 hr in young adults; 7.5 hr in adults; 12-14 hr in geriatric patients
Absorption: 100% (solution and tablets are bioequivalent to one another and may be interchanged)
Vd: 1.1 L/kg
Peak Plasma Time: [fasting] 2.5 hr; [with food] 2 hr
Protein Bound: Negligible
Metabolism: Not extensively metabolized
Clearance: [adults] 7 L/hr; [infants] 2.4 L/hr; [children] 5.7 L/hr
Excretion: Urine: 95%
