Vigabatrin (Sabril)

Clinical Effects:

VIGABATRIN
  • USES: Vigabatrin is used for the treatment of refractory complex partial seizures in adults. It is indicated as an adjunctive therapy in patients that fail to respond to other therapies. It is also used to treat infantile spasms in children 1 month to 2 years. PHARMACOLOGY: Although the exact mechanism for antiseizure activity is unknown, it is thought to be an irreversible inhibitor of the gamma-aminobutyric acid transaminase (GABA-T), the enzyme responsible for the metabolism of the inhibitory neurotransmitter GABA. This can increase the levels of GABA in the central nervous system. EPIDEMIOLOGY: Overdose is infrequent. Due to the risk of permanent vision loss, the drug is only available through a restricted distribution program called SHARE (1-888-45-SHARE). When overdose has occurred, it has often been combined with other agents. MILD TO MODERATE TOXICITY: Drowsiness and fatigue are likely to occur. Other symptoms may include: vertigo, irritability, agitation, headache, and increased seizure activity. SEVERE TOXICITY: Coma and unconsciousness may develop. Other events may include: seizures, acute psychosis, delirium, respiratory depression, hypotension and bradycardia. Although not reported in overdose, anemia has developed with therapy. ADVERSE EFFECTS: COMMON: Drowsiness and fatigue are the most common adverse events. Exacerbation of psychotic symptoms may develop during treatment with vigabatrin or withdrawal from vigabatrin. As with other antiepileptic drugs, vigabatrin may increase the risk of suicidal thoughts or behavior during therapeutic use. Other events include: fever, seizures, anemia, peripheral edema and neuropathy, weight gain, and headache. SEVERE EVENTS: Permanent vision loss can develop with therapy, which has led to its restricted use. In postmarketing experience, relatively serious events have included: gastrointestinal hemorrhage, acute psychosis, delirium, neonatal agitation, laryngeal edema, pulmonary embolism, respiratory failure, stridor, angioedema, malignant hyperthermia, dystonia, and multiorgan failure; the frequency of these events is unknown.

Range of Toxicity:

VIGABATRIN
  • TOXICITY: Based on limited data, most cases of vigabatrin overdose involved other agents; no overdoses resulted in death. Coma, unconsciousness or drowsiness have occurred in overdose. In a single case, a 25-year-old woman ingested 60 g and developed severe delirium; no other severe events were observed. An adult developed a psychotic episode (lasting 36 hours) after inadvertently ingesting 8 to 12 g of vigabatrin. THERAPEUTIC DOSE: ADULT: TABLET: INITIAL: 500 mg orally twice daily; MAINTENANCE: 1.5 g twice daily (3 g total). Maximum: 3 g/day. PEDIATRIC: ORAL SOLUTION: INITIAL DOSE: Children 1 month to 2 years: 50 mg/kg/day orally in 2 divided doses. The dose may be titrated by 25 to 50 mg/kg/day increments every 3 days up to a maximum dose of 150 mg/kg/day.

Treatment:

VIGABATRIN
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment of mild to moderate toxicity is largely supportive. Monitor neuro status and vital signs. Assess respiratory effort; monitor pulse oximetry. Airway protection and management may be indicated. Moderate to severe nausea and vomiting should be treated with antiemetics, as needed. MANAGEMENT OF SEVERE TOXICITY: Supportive care is the mainstay of treatment. Mental status or respiratory depression may require airway protection. Intubation and mechanical ventilation may be indicated. Coma should be treated with airway management and supportive care. Seizures should be treated with benzodiazepines as a first-line therapy. Agitation/delirium should be treated with benzodiazepines, large doses may be required. Treat hypotension initially with isotonic fluids; vasopressor agents, such as norepinephrine or phenylephrine may also be required.
  • Decontamination: PREHOSPITAL: Because of the risk of CNS depression and subsequent aspiration, prehospital decontamination should generally be avoided. HOSPITAL: Activated charcoal should be considered in an asymptomatic patient, if performed soon after exposure and the airway is protected. Airway protection is indicated prior to decontamination in symptomatic patients.
  • Airway management: A mild exposure is unlikely to necessitate airway management, however airway protection may be necessary in cases of prominent CNS depression, seizures or significant respiratory depression.
  • Antidote: There is no specific antidote.
  • Monitoring of patient: Monitor mental status. Monitor pulse oximetry, initiate cardiac monitoring and obtain an ECG upon initial evaluation and repeat as indicated following a significant overdose. Monitor fluid status, renal function and a basic metabolic panel as necessary. Obtain a CBC as indicated. ABGs should be obtained in patients with significant respiratory depression. Creatinine kinase should be measured in patients with prolonged coma or seizures.
  • Enhanced elimination procedure: Hemodialysis may be of value following a significant exposure because vigabatrin is not bound to plasma proteins. In limited cases, hemodialysis has reduced vigabatrin plasma concentration by 40% to 60% in patients with renal failure receiving therapeutic doses.
  • Patient disposition: HOME CRITERIA: Asymptomatic patients (adult) with a minor inadvertent ingestion of a therapeutic dose may be observed at home. An inadvertent exposure by a child may require evaluation in a healthcare facility due to the risk of CNS depression. Patients with an intentional exposure should be referred to a health care facility. OBSERVATION CRITERIA: Patients with a deliberate self-harm ingestion or a large ingestion should be evaluated in a healthcare facility and monitored until symptoms resolve. Patients may be discharged to home after 10 to 12 hours, if symptoms improve after treatment and laboratory studies remain normal. Patients who remain symptomatic or develop significant symptoms should be admitted. ADMISSION CRITERIA: Patients with persistent CNS or respiratory depression, despite adequate treatment should be admitted. CONSULT CRITERIA: Contact a medical toxicologist or Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
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