Lakozamid (Vimpat)

Clinical Effects:

LACOSAMIDE
  • USES: An antiepileptic agent used as adjunctive therapy to treat partial-onset seizures in epileptic patients aged 17 years and older. PHARMACOLOGY: Targets the slow inactivation of voltage-gated sodium channels and binding of the phosphoprotein collapsin response mediator protein-2 (CRMP-2). EPIDEMIOLOGY: Overdose is rare. MILD TO MODERATE TOXICITY: The signs and symptoms of an acute overdose are expected to be similar to adverse effects seen at therapeutic doses. At the time of this review, limited overdose information was available. SEVERE: QRS prolongation, AV blocks and cardiac arrest have been reported. Coma and epileptic waveforms on EEG were reported in a patient with a mixed overdose (lacosamide, zonisamide, topiramate, and gabapentin). AV block was observed in one case of IV overdose. ADVERSE EFFECTS: COMMON: Headache, dizziness, ataxia, nausea, vomiting, diplopia, and blurred vision. RARE: Cardiac rhythm and conduction abnormalities as well as syncope have been reported infrequently in controlled trials. Paranoid behavior and psychotic symptoms developed in one patient after 7 days of lacosamide therapy.

Range of Toxicity:

LACOSAMIDE
  • TOXICITY: A specific toxic dose has not been established. Doses of 600 mg/day were no more effective and demonstrated a higher rate of adverse events when compared to 400 mg/day. In clinical trials, the inadvertent administration of lacosamide 1200 mg/day resulted in adverse effects similar to effects experienced by patients exposed to supratherapeutic doses. One case of an intentional overdose of 12 grams lacosamide (co-ingested with zonisamide, topiramate and gabapentin) resulted in coma and generalized tonic-clonic seizures. The patient recovered in 2 days with supportive care. An adult died after ingesting 7 grams of lacosamide. Despite supportive care, he died 14 hours after presentation. THERAPEUTIC DOSES: ADULT: PARTIAL-ONSET SEIZURE; ADJUNCT: IV AND ORAL: Initial, 100 to 200 mg/day in divided doses, increased weekly, up to the MAX dose of 200 mg twice daily (400 mg/day). IV dose: preferably infuse over 30 to 60 minutes; may infuse over 15 minutes if needed. MONOTHERAPY: Initial, 200 mg/day in divided doses, increased weekly, up to the MAX dose of 150 to 200 mg twice daily (300 to 400 mg/day). IV dose: preferably infuse over 30 to 60 minutes; may infuse over 15 minutes if needed. CHILD: Safety and efficacy of lacosamide in the pediatric population aged less than 17 years have not been established.

Treatment:

LACOSAMIDE
  • Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Patients may require airway management. Closely monitor neurologic function. Treat QRS prolongation with sodium bicarbonate; an initial dose of 1 to 2 mEq/kg is reasonable. Monitor ECG and arterial blood gases.
  • Decontamination: PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended because of the potential for CNS depression and subsequent aspiration. HOSPITAL: Consider activated charcoal after a potentially toxic ingestion of lacosamide if the patient is able to maintain airway or in whom airway is protected, or if coningestants dictate it.
  • Airway management: Most likely unnecessary, but perform early if life-threatening cardiac dysrhythmias or significant CNS depression develop.
  • Antidote: None
  • Monitoring of patient: Monitor fluid and electrolyte status in patients with severe vomiting and/or diarrhea. Monitor liver enzymes after significant overdose. Monitor ECG in symptomatic patients. Monitor vital signs and mental status.
  • Enhanced elimination procedure: Theoretically, hemodialysis may be effective following a significant exposure or in cases of significant renal impairment. Lacosamide is approximately 50% removed following a standard four hour hemodialysis session. Hemodialysis is unlikely to be necessary, but should be considered in patients with severe toxicity not responding to supportive care.
  • Patient disposition: OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions who are symptomatic should be observed in a healthcare facility. ADMISSION CRITERIA: Patients with a deliberate ingestions demonstrating cardiotoxicity, or persistent neurotoxicity should be admitted. CONSULT CRITERIA: Call a Poison Center for assistance in managing patients with severe toxicity or in whom the diagnosis is unclear.
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