- USES: Topiramate is a sulfamate-substituted monosaccharide used as an anticonvulsant and for the prophylactic treatment of migraines. PHARMACOLOGY: The exact mechanism remains unknown. It may be able to block voltage-dependent sodium channels, augment the activity of the neurotransmitter gamma-aminobutyrate as some subtypes of GABA-A receptor, and antagonize the AMPA/kainate subtype of the glutamate receptor TOXICOLOGY: Inhibits carbonic anhydrase, causing renal tubular acidosis and a non-anion gap metabolic acidosis. EPIDEMIOLOGY: Overdose is rare. In most cases, acute exposure produced only minimal to moderate effects. Fatalities have occurred, but were the result of polydrug exposure. MILD TO MODERATE TOXICITY: Data limited. Drowsiness, dizziness, agitation, confusion, nausea, vomiting, ataxia, tremor, hypotension, depression, speech disturbances, impaired mentation, blurred vision and diplopia have occurred in overdose. SEVERE TOXICITY: Rarely, severe metabolic acidosis and coma have been reported after overdose. ADVERSE EVENTS: COMMON: The most common dose-dependent events associated with topiramate therapy include: paresthesia, fatigue, nausea, anorexia, dizziness, weight decrease, diarrhea, difficulty with memory and concentration and somnolence. Other events that occur less frequently but are likely dose-dependent include: anxiety, depression, hypoaesthesia, mood problems, dry mouth, confusion, involuntary muscle contractions, abnormal vision, and renal calculus.
Range of Toxicity:
- TOXICITY: Limited data. A toxic dose has not been established; doses up to 1600 mg/day have been well tolerated. A patient developed coma lasting up to 24 hours after ingesting between 96 and 110 g of topiramate; the patient made a complete recovery. THERAPEUTIC DOSE: ADULTS: EPILEPSY: Monotherapy: Recommended: 400 mg/day in 2 divided doses. Adjunctive: For patients with partial seizures: 200 to 400 mg/day in 2 divided doses, and 400 mg/day in 2 divided doses in patients with primary generalized tonic-clonic seizures. MIGRAINE: For the prophylactic treatment of migraine headache: 100 mg/day in 2 divided doses. PEDIATRIC: EPILEPSY: Monotherapy: Recommended: For children 10 years of age and older: 400 mg/day in 2 divided doses. Adjunctive: For patients with partial onset seizures or primary generalized tonic-clonic seizures: 5 to 9 mg/kg/day in 2 divided doses.
- Support: MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Monitor vital signs and serum electrolytes. SEVERE TOXICITY: Treatment is symptomatic and supportive. Non-anion gap metabolic acidosis has been reported in some cases of overdose and therapeutic use. Monitor serum electrolytes and ABGs. Administer fluids, sodium bicarbonate to correct acidosis. Monitor respiratory effort; intubation and mechanical ventilation may be necessary.
- Decontamination: PREHOSPITAL: Activated charcoal may be considered in patients who are alert or in whom the airway is protected. HOSPITAL: Activated charcoal may be considered in patients who are alert or in whom the airway is protected.
- Airway management: Assess airway. Airway protection may be indicated in patients who develop significant neurologic toxicity.
- Antidote: None.
- Hypotensive episode: Administer IV 0.9% NaCl, dopamine, norepinephrine.
- Seizure: IV benzodiazepines, barbiturates.
- Monitoring of patient: Monitor vital signs including blood pressure, cardiac monitoring as indicated, monitor serum electrolytes, obtain an arterial blood gas if significant metabolic acidosis is present. Monitor mental status following a significant overdose.
- Hemodialysis: Hemodialysis may be useful following a significant exposure because it is easily cleared by hemodialysis and minimally bound to plasma proteins.
- Patient disposition: OBSERVATION CRITERIA: All patients with a topiramate overdose should be evaluated and monitored until symptoms resolve. Monitor neurologic function and serum electrolytes. Patients can be discharged when neurologic function is normal and laboratory values are stable. ADMISSION CRITERIA: Patients with evidence of severe neurologic toxicity or metabolic acidosis should be admitted.