Oxcarbazepine

Oxcarbazepine is a keto analogue of carbamazepine used for focal seizures. It is a prodrug with weaker enzyme induction and a lower risk of haematological and hepatic toxicity, but hyponatraemia is more frequent.

Mechanism. Its active metabolite, a monohydroxy derivative (licarbazepine), blocks voltage-gated sodium channels.

Pharmacokinetics. Rapid reduction to the active metabolite, with a half-life of 8 to 10 hours. Absorption is complete and unaffected by food. Excretion is renal. It is a weak to moderate inducer of cytochrome P450 3A4, dose dependent, and inhibits cytochrome P450 2C19.

First-line use. Focal seizures, with or without secondary generalisation, in adults and children, as monotherapy or adjunct. Treatment is long term.

• Adults, oral oxcarbazepine: start 600 mg daily in two divided doses, increase by up to 600 mg each week to a usual maintenance of 600 to 2400 mg daily in two divided doses. Usual maximum 2400 mg daily. Many labels cap adjunctive therapy at 1200 mg daily when effective.

• Children 6 years and over (some labels from 4 years): 8 to 10 mg/kg daily in two doses (not over 600 mg daily at the start), increased weekly to a target of 30 to 46 mg/kg daily. Maximum 2400 mg daily.

Alternative use. Trigeminal neuralgia (off-label): 300 mg twice daily, titrated to 600 to 1200 mg daily when carbamazepine is not tolerated.

Kidney, liver, weight and age.

• Kidney: with creatinine clearance under 30 mL/min, start at half the usual dose (300 mg daily) and titrate slowly at intervals of at least one week.

• Liver: no change in mild to moderate impairment. Not studied in severe impairment.

• Older adults: dose by creatinine clearance, and monitor sodium closely.

Contraindications. Hypersensitivity to oxcarbazepine or eslicarbazepine. About 25 to 30% of people with carbamazepine hypersensitivity react to oxcarbazepine.

Serious adverse effects. Hyponatraemia (sometimes severe), Stevens-Johnson syndrome and toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, angioedema, leucopenia, and multi-organ hypersensitivity.

Common adverse effects. Dizziness, drowsiness, diplopia, headache, nausea, vomiting and ataxia.

Interactions.

• Strong enzyme inducers (carbamazepine, phenytoin, phenobarbital, rifampicin) lower the active metabolite.

• Oxcarbazepine raises phenytoin levels at doses over 1200 mg daily and phenobarbital levels, and lowers lamotrigine and some calcium channel blockers (felodipine).

• It reduces hormonal contraceptive efficacy, so use a copper device or levonorgestrel intrauterine system.

• Diuretics, desmopressin and NSAIDs add hyponatraemia risk.

Common prescribing errors. Not checking sodium. Assuming no cross-reactivity with carbamazepine. Relying on the contraceptive pill.

Special groups.

• Pregnancy: limited data; drug clearance rises and levels fall. Give folic acid 5 mg daily before conception. Avoid unless benefit outweighs risk.

• Breastfeeding: infant exposure is low to moderate; monitor for sedation and poor feeding.

• Ancestry: avoid in HLA-B*1502 carriers where testing is available and relevant.

Formulations. Tablets 150, 300 and 600 mg. Oral suspension 60 mg/mL. Take with or without food.

Monitoring.

• Baseline: sodium, creatinine and liver function.

• Ongoing: sodium at 2 weeks, then monthly for 3 months, then periodically, and with new diuretics. Reduce the dose or stop if sodium falls under 125 mmol/L with symptoms.

• Drug level monitoring is not routine; the active metabolite range is laboratory dependent (often quoted as 3 to 35 mg/L).

Stopping. Reduce by about 600 mg weekly, more slowly if seizures are frequent. Stop immediately for severe skin reactions.

Referral and escalation. Refer if seizures persist, in planned pregnancy, or if hyponatraemia is symptomatic or recurrent.