- USES: Lamotrigine is a phenyltriazine anticonvulsant with a pharmacological profile similar to phenytoin. It is currently used for the treatment of seizures and Bipolar I Disorder. PHARMACOLOGY: The exact mechanism of action of lamotrigine has not been fully elucidated. One proposed mechanism is that lamotrigine inhibits sodium channels, resulting in neuronal membrane stabilization and control of excitatory neurotransmitter release. EPIDEMIOLOGY: Overdose is rare. MILD TO MODERATE TOXICITY: Nausea, vomiting, anorexia, abdominal pain, somnolence, lethargy, slurred speech, xerostomia, blurred vision, diplopia, rash, confusion, nystagmus, ataxia, tremor, agitation, dyskinesia, hyperreflexia, and elevated liver enzymes. SEVERE TOXICITY: Tachycardia and conduction disturbances, hypokalemia, oculogyric crisis, seizures, rhabdomyolysis, encephalopathy, coma, and respiratory depression. ADVERSE EFFECTS: COMMON: Weight gain, amnesia, nervousness, and thought disturbances. LESS COMMON: Headache, dizziness, visual disturbances, gastrointestinal disturbances, hypotension, leukopenia, anemia, hematuria, elevated liver enzymes, and rashes. RARE: Disseminated intravascular coagulation, acute renal failure, aseptic meningitis, Stevens Johnson Syndrome, and toxic epidermal necrolysis. Premarketing studies have revealed slight increases in the PR interval in a small number of patients on therapeutic doses. Rhabdomyolysis may result from lamotrigine therapeutic dose. It should be noted that generalized seizures may be a cause of rhabdomyolysis.
Range of Toxicity:
- TOXICITY: Adults have survived overdoses of greater than 4000 mg with supportive therapy. A man developed generalized myoclonus status epilepticus and coma several hours after ingesting 6 g of lamotrigine. He recovered following supportive care. A 3-year-old girl survived an overdose of 1.15 g of lamotrigine. Another child, a 2-year-old, also survived an overdose of 800 mg. Fatalities have been reported following overdoses of up to 15 g. THERAPEUTIC: Adult maintenance doses of lamotrigine for bipolar disorder can be up to 400 mg/day and up to 500 mg/day for anti-seizure therapy. For children 2 to 12 years of age, the maintenance dose for the anti-seizure therapy can be up to 15 mg/kg/day (max 400 mg/day). For children over the age of 12, the maintenance dose for the anti-seizure therapy can be up to 500 mg/day.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Management will primarily be symptomatic and supportive. Manage mild hypotension with IV fluids. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Closely monitor neurologic function. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. Manage hypotension with IV fluids and pressors if needed. Treat hypokalemia with oral or IV potassium chloride. Consider intravenous lipid therapy early for patients with ventricular dysrhythmias or hypotension.
- 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 lamotrigine if the patient is able to maintain airway or in whom airway is protected, or if coingestants dictate it.
- Airway management: Endotracheal intubation may be necessary if life-threatening cardiac dysrhythmias, significant CNS, or respiratory depression develop.
- Antidote: None
- Seizure: Administer IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
- Hypotensive episode: IV 0.9% NaCl at 10 mL to 20 mL/kg, dopamine, norepinephrine.
- Ventricular arrhythmia: Institute continuous cardiac monitoring, obtain an ECG, and administer oxygen. Evaluate for hypoxia, acidosis, and electrolyte disorders. Lidocaine and amiodarone are generally first line agents for stable monomorphic ventricular tachycardia, particularly in patients with underlying impaired cardiac function. Amiodarone should be used with caution if a substance that prolongs the QT interval and/or causes torsades de pointes is involved in the overdose. Unstable rhythms require immediate cardioversion.
- Fat emulsion: Limited anecdotal evidence suggest that lipid emulsion my be useful in patients with severe cardiac or neurologic toxicity. Administer 1.5 mL/kg of 20% lipid emulsion over 2 to 3 minutes as an IV bolus, followed by an infusion of 0.25 mL/kg/min. If possible, discontinue after 30 to 60 minutes. Longer periods of lipid therapy should be considered if the patient’s hemodynamic stability is dependent on continued lipid infusion.
- Rhabdomyolysis: Administer sufficient 0.9% saline to maintain urine output of 2 to 3 mL/kg/hr. Monitor input and output, serum electrolytes, CK, and renal function. Diuretics may be necessary to maintain urine output. Urinary alkalinization is NOT routinely recommended.
- Monitoring of patient: The value of plasma lamotrigine monitoring has not been established. Monitor vital signs, serial CBC with differential, serum electrolytes, liver enzymes, and renal function in symptomatic patients. Obtain an ECG and institute continuous cardiac monitoring following significant exposures. Overdoses have resulted in ECG abnormalities, including widening QRS complex and PR prolongation. Monitor for CNS and respiratory depression. Monitor CPK levels in patients with prolonged coma or seizures.
- Enhanced elimination procedure: Hemodialysis has not been established as an effective means of removing lamotrigine from the blood. Approximately 20% (range, 5.6% to 35.1%) of the amount of lamotrigine present in the body was eliminated by hemodialysis during a 4-hour session. In 6 renal failure patients, approximately 17% of the amount of lamotrigine in the body was removed during 4 hours of hemodialysis.
- 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, seizure activity, or other 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.