- USES: Oxcarbazepine is an antiepileptic drug, indicated for use as adjunctive therapy in the treatment of partial seizures in adults and children 2 years and older and as monotherapy in the treatment of partial seizures in adults and children 4 years and older. PHARMACOLOGY: Oxcarbazepine is the 10-keto analogue of carbamazepine. Oxcarbazepine is a prodrug, with its primary metabolite, 10-hydroxycarbazepine (MHD), being the active agent. The exact mechanism by which oxcarbazepine exerts its anticonvulsant effect is unknown. It is known that the pharmacological activity of oxcarbazepine occurs primarily through its 10–monohydroxy metabolite (MHD). In vitro studies indicate an MHD-induced blockade of voltage-sensitive sodium channels, resulting in stabilization of hyperexcited neuronal membranes, inhibition of repetitive neuronal discharges, and diminution of propagation of synaptic impulses. EPIDEMIOLOGY: Overdose is rare. OVERDOSE: Overdose data are limited. Clinical manifestations following overdose have included vomiting, bradycardia, hypotension, tinnitus, vertigo, diplopia, somnolence, and lethargy. Hyponatremia, which is dose-related, has been reported at a higher frequency than with carbamazepine and may lead to seizures and coma, particularly in an overdose setting. ADVERSE EFFECTS: Oxcarbazepine has a similar therapeutic profile to carbamazepine, but is reported to have lower toxicity. COMMON: Headache, dizziness, somnolence, diplopia, fatigue, nausea, vomiting, ataxia, abnormal vision, abdominal pain, tremor, dyspepsia, nystagmus, fatigue, and abnormal gait. OTHER EFFECTS: Asthenia, amnesia, vertigo, insomnia, nervousness, confusion, diarrhea, constipation, upper respiratory tract infection, and cough. RARE: Oculogyric crisis, tardive dyskinesia, rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, thrombocytopenia, thrombocytopenic purpura, leukopenia, elevated liver enzymes, acute hepatitis, and acute allergic reactions. Significant hyponatremia (sodium less than 125 mmol/L) generally occurs during the first 3 months of therapy, but may occur more than 1 year after therapy initiation. In patients who discontinued therapy in clinical trials, sodium levels normalized within a few days without further treatment.
Range of Toxicity:
- TOXICITY: Adults have survived ingestions up to 42 g with supportive care. A 13-year-old boy developed vomiting and somnolence after ingesting 250 mL (15 g) of oxcarbazepine suspension. He recovered following supportive care. THERAPEUTIC DOSES: ADULTS: Varies by indication: 300 mg twice daily increased to 1200 mg/day or 2400 mg/day in patients converted from other antiepileptic drug therapy to oxcarbazepine monotherapy. CHILDREN: ADJUNCTIVE THERAPY: 4 TO 16 YEARS OLD: initial, 8 to 10 mg/kg/day orally in 2 divided doses; MAX: 600 mg/day. Maintenance: 900 mg/day for 20 to 29 kg children; 1200 mg/day for 29.1 to 39 kg; and 1800 mg/day for greater than 39 kg. 2 TO LESS THAN 4 YEARS OLD: Initial, 8 to 10 mg/kg/day orally in 2 divided doses; MAX: 600 mg/day; patients under 20 kg, may use an initial dose of 16 to 20 mg/kg/day in 2 divided doses; MAX: 60 mg/kg/day in 2 divided doses. MONOTHERAPY: 4 TO 16 YEAR OLD, initiation of monotherapy, 8 to 10 mg/kg/day orally in 2 divided doses; maintenance, 600 to 900 mg/day for 20 kg children; 900 to 1200 mg/day for 25 to 30 kg; 900 to 1500 mg/day for 35 to 40 kg; 1200 to 1500 mg/day for 45 kg; 1200 to 1800 mg/day for 50 to 55 kg; 1200 to 2100 mg/day for 60 to 70 kg.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids. Treat mild hyponatremia with water restriction and/or 0.9% sodium chloride. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Treat severe hypotension with IV fluids, dopamine, or norepinephrine. Treat seizures with IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required. Manage severe hyponatremia with 0.9% sodium chloride; 3% sodium chloride may be considered with severe symptomatic hyponatremia.
- Decontamination: PREHOSPITAL: Prehospital gastrointestinal decontamination is not recommended because of the potential for CNS depression and subsequent aspiration. HOSPITAL: Administer activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
- Airway management: Ensure adequate ventilation and perform endotracheal intubation early in patients with significant CNS depression, seizures, or severe allergic reactions.
- Antidote: None.
- Hypotensive episode: Administer IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids.
- Hyponatremia: Evaluate for hyponatremia and associated symptoms. Patients with mild symptoms can be managed with water restriction. Patients with moderate to severe symptoms should receive 0.9% sodium chloride (rarely 3% NaCl in patients with very severe symptoms). The goal is slow correction; the serum sodium should not increase more than 2 mEq/L/hour in any 4-hour period or more than 15 mEq/L per day. Rapid correction may cause central pontine myelinolysis. Monitor serum electrolytes, fluid intake and output, and urine volume and electrolytes.
- Seizure: Administer IV benzodiazepines; barbiturates or propofol may be needed if seizures persist or recur.
- Drug-induced dystonia: ADULTS: Benztropine 1 to 2 mg IV or diphenhydramine 1 mg/kg/dose IV over 2 minutes. CHILDREN: Diphenhydramine 1 mg/kg/dose IV over 2 minutes (maximum 5 mg/kg/day or 50 mg/m(2)/day).
- Hypersensitivity reaction: MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
- Monitoring of patient: Monitor vital signs, mental status, CBC with differential with platelet count, and liver enzymes in symptomatic patients. Monitor serum electrolytes. Hyponatremia has been reported following exposures to oxcarbazepine more frequently than following exposures to carbamazepine.
- Enhanced elimination procedure: Hemodialysis might significantly enhance elimination of the active metabolite, and may be considered following overdoses with potentially life threatening toxic effects not responsive to other therapy.
- Patient disposition: HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home. OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored for several hours to assess serum electrolyte and fluid balance. Patients that remain asymptomatic can be discharged. ADMISSION CRITERIA: Patients with a deliberate ingestions demonstrating seizure activity or other persistent neurotoxicity should be admitted. Patients should also be admitted for severe vomiting, profuse diarrhea, and electrolyte abnormalities. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.