Trade Names:Sabril- Tablets 500 mg- Powder for oral solution 500 mg
Precise mechanism unknown. Possibly inhibition of GABA transaminase, resulting in increased levels of GABA in the CNS.
Completely absorbed. T max is 1 h (2.5 h in infants). Food decreased C max by 33% and T max increased to 2 h; AUC was unchanged.
Widely distributed throughout the body; no plasma protein binding. Mean Vd is 1.1 L/kg.
Not significantly metabolized.
Half-life is 7.5 h in adults and 5.7 h in infants. Eliminated primarily through renal excretion; 80% recovered in the urine as parent drug.
AUC increased by 30% and half-life increased by 55% in patients with mild renal impairment (CrCl greater than 50 to 80 mL/min). AUC and half-life increased 2-fold in patients with moderate renal impairment (CrCl greater than 30 to 50 mL/min). In patients with severe renal impairment (CrCl greater than 10 to 30 mL/min), AUC increased 4.5-fold and half-life increased 3.5-fold.Hepatic Function Impairment
Pharmacokinetics have not been studied.Elderly
Renal Cl was 36% lower in elderly patients compared with younger patients.Children
The Cl was 2.4 and 5.7 L/h in infants and children, respectively, compared with 7 L/h in adults.Gender
No pharmacokinetic differences were observed.Race
Renal Cl was 25% lower in Japanese patients compared with white patients.
Adjunctive therapy for adults with refractory complex partial seizures who have inadequately responded to several alternative treatments (tablets only); monotherapy for children with infantile spasms (oral solution only).
PO 500 mg twice daily, initially. May increase total daily dose in increments of 500 mg at weekly intervals, depending on patient response. Maintenance dose, 1,500 mg twice daily.Infantile SpasmsChildren 1 mo to 2 yr of age
PO Initially, 50 mg/kg twice daily. Titrate by 25 to 50 mg/kg/day every 3 days (max, 150 mg/kg/day).Renal Function ImpairmentCrCl greater than 50 to 80 mL/min
Decrease dose by 25%.CrCl greater than 30 to 50 mL/min
Decrease dose by 50%.CrCl greater than 10 to 30 mL/min
Decrease dose by 75%.
Store at 68° to 77°F.
Clonazepam plasma concentrations may be increased while the T max may be reduced, increasing the pharmacologic effects and risk of adverse reactions. Monitor the patient when starting or stopping vigabatrin. Adjust the clonazepam dose as needed.Drugs associated with serious adverse ophthalmic effects, such as retinopathy (eg, hydroxychloroquine) or glaucoma (corticosteroids [open-angle], tricyclic antidepressants [closed-angle])
Risk of serious adverse ophthalmic effects may be increased. Avoid coadministration unless the benefits clearly outweigh the risks.Hydantoins (eg, phenytoin)
Coadministration has been reported to decrease phenytoin plasma concentrations 16% to 20%. Monitor the patient when starting or stopping vigabatrin. Be prepared to adjust the hydantoin dose if an interaction is suspected.Phenobarbital, primidone
On average, phenobarbital plasma concentrations may be reduced 8% to 16%. This change is not likely to be clinically important.Valproic acid
On average, valproate plasma concentrations may be reduced 8%. This change is not likely to be clinically important.
ALT and AST enzyme activity is suppressed in up to 90% of patients; false positive test for certain rare genetic metabolic diseases (eg, alpha aminoadipic aciduria).
Somnolence (45%); fatigue (40%); headache (33%); dizziness (26%); irritability (23%); sedation (19%); abnormal coordination, memory impairment, tremor (16%); confusional state, depression (14%); gait disturbance, insomnia (12%); convulsion (11%); disturbance in attention (9%); abnormal thinking, asthenia, expressive language disorder, lethargy, paresthesia, sensory disturbance (7%); hypotonia, status epilepticus (6%); abnormal behavior, abnormal dreams, depressed mood, hypoesthesia, hyporeflexia, malaise, nervousness, sensory disturbance, sensory loss, vertigo (5%); anxiety, hyperreflexia, peripheral neuropathy (4%); aggression, dysarthria, postictal state (2%); acute psychosis, apathy, delirium, dystonia, encephalopathy, hypertonia, hypomania, hypotonia, muscle spasticity, myoclonus, neonatal agitation, optic neuritis, psychotic disorder (postmarketing).
Rash (11%); maculopapular rash, pruritus (postmarketing).
Otitis media (44%); nystagmus (19%); blurred vision, diplopia (16%); ear infection, nasopharyngitis, pharyngolaryngeal pain (14%); nasal congestion (13%); sinusitis, visual field defect (9%); conjunctivitis, eye pain, strabismus (5%); eye disorder other than field or acuity changes (3%); asthenopia, tinnitus (2%); deafness (postmarketing).
Vomiting (20%); diarrhea (16%); constipation (14%); nausea (10%); decreased appetite (9%); viral gastroenteritis (6%); dyspepsia, increased appetite, toothache, upper abdominal pain (5%); stomach discomfort (4%); abdominal pain (3%); abdominal distension, hemorrhoids (2%); esophagitis, GI hemorrhage (postmarketing).
Dysmenorrhea (9%); UTI (6%); erectile dysfunction (5%).
Weight increased (17%).
Arthralgia (10%); muscle twitching (9%); back pain (7%); pain in extremity (6%); myalgia (5%); joint swelling, muscle spasms (3%); joint sprain, muscle strain, shoulder pain (2%).
Upper respiratory tract infection (51%); bronchitis (30%); cough (14%); pneumonia (13%); sinus headache (6%); pulmonary congestion (5%); dyspnea (2%); laryngeal edema, pulmonary embolism, respiratory failure, stridor (postmarketing).
Fever (29%); MRI abnormalities (22%); viral infection (20%); candidiasis (8%); influenza, peripheral edema (7%); anemia (6%); chest pain, contusion, infectious croup (5%); fluid retention, thirst, wound secretion (2%); angioedema, cholestasis, delayed puberty, developmental delay, facial edema, malignant hyperthermia, multiorgan failure (postmarketing).
Vigabatrin causes permanent vision loss. 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 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 discontinuing vigabatrin. Vigabatrin should be withdrawn from patients with infantile spasms who fail to show substantial clinical benefit within 2 to 4 wk of initiation, within 3 mo of initiation in patients with complex partial seizures who fail to show substantial response, or sooner if treatment failure becomes obvious. Periodically reassess patient response to and continued need for vigabatrin. Once detected, vision loss due to vigabatrin is not reversible. Symptoms of vision loss from vigabatrin are unlikely to be recognized by the patient, parent, or caregiver before vision loss is severe. Vision loss of milder severity, although unrecognized by the caregiver, may still adversely affect function.
Vigabatrin should not be used in patients with, or at high risk of, other types of irreversible vision loss, or with other drugs associated with serious adverse ophthalmic effects, such as retinopathy or glaucoma, unless benefits clearly outweigh risks. The lowest dose and shortest exposure should be used.
Because of the risk of permanent vision loss, vigabatrin is only available through a special restricted distribution program called SHARE. Only prescribers and pharmacies registered with SHARE may prescribe and distribute vigabatrin. Vigabatrin may be dispensed only to patients who are enrolled in and meet all conditions of SHARE. Contact SHARE at 1-888-457-4273.
Assess vision at baseline (no later than 4 wk after starting vigabatrin), at least every 3 mo during therapy, and about 3 to 6 mo after discontinuation of therapy with vigabatrin. Assessment should include visual activity and visual field defect whenever possible. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Category C .
Excreted in breast milk.
For the treatment of refractory complex partial seizures, safety and efficacy not established for children younger than 16 yr of age. Safety and efficacy not established in patients younger than 1 mo of age or older than 2 yr of age with infantile spasms.
Adjustment of dose or frequency of administration should be considered. May respond to a lower maintenance dose.
Use with caution; adjust doses for patients with renal impairment.
May cause fatigue or somnolence.
Anemia and potentially clinically important changes in hemoglobin, hematocrit, or RBC indices have occurred.
Birth defects have occurred and include 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, and talipes.
Observed in some infants treated with vigabatrin. Changes generally resolved with discontinuation of therapy.
Manifestations of peripheral neuropathy, including numbness or tingling in the toes or feet and progressive loss of reflexes, have occurred.
Antiepileptic drugs, including vigabatrin, increase the risk of suicidal thoughts or behavior. Balance the risk of suicidal thoughts or behavior with the risk of untreated illness.
Abnormal behavior, agitation, apnea or respiratory depression, bradycardia, coma, confusion, drowsiness, headache, hypotension, increased seizure activity, irritability, psychosis, speech disorder, status epilepticus, unconsciousness, vertigo.
Copyright © 2009 Wolters Kluwer Health.