| Antiepileptic drugs: oxcarbazepine |
Oxcarbazepine is chemically related to carbamazepine and, like carbamazepine, its primary mechanism of action is thought to be blockade of voltage-sensitive sodium channels. Although oxcarbazepine itself is active, most of its activity in humans comes from a 10-monohydroxy metabolite. The drug has a broad spectrum of action, with Australian marketing approval for treatment as monotherapy or adjunctive therapy of partial seizures and generalised tonic-clonic seizures.
Upon oral administration, the drug is completely absorbed and is unaffected by food. It is quickly and extensively metabolised to the 10-monohydroxy derivative and steady state is achieved after 2 to 3 days of twice-daily dosing. The monohydroxy derivative is excreted in urine both unchanged and as a glucuronide conjugate, accounting for about 80% of the total dose. Dose reduction is recommended in moderate to severe renal failure and the usual initial dose should be halved when the glomerular filtration rate (GFR) is less than 30 mL/min with the dose being subsequently titrated as needed. Dose reduction is not required for mild to moderate hepatic impairment.
Interactions: Oxcarbazepine has been found to inhibit CYP2C19 of the cytochrome P450 group of human oxidative liver enzymes and to induce both CYP3A4 and CYP3A5, giving rise to a number of clinically significant interactions with other drugs metabolised by these systems. Notably, components of oral contraceptives studied had average serum concentrations reduced by 32% to 52%. Female patients taking hormonal contraceptives should be warned to use additional nonhormonal contraception
. For further information on drug interactions with oxcarbazepine, see Table 7.19.
Adverse effects: Common adverse reactions are somnolence, headache, dizziness, diplopia, nausea, vomiting and fatigue. As with carbamazepine, asymptomatic hyponatraemia occurs in about 2.7% of patients. Because of this, monitoring may be required in patients on sodium-lowering drugs or in those who may be predisposed to fluid retention. More serious but rare adverse reactions include Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, multi-organ hypersensitivity and hepatitis. With respect to the above immune-mediated reactions, it should be noted that there is a cross-reactivity with carbamazepine of about 30%. Oxcarbazepine is associated with the anticonvulsant hypersensitivity syndrome, with cross-reactivity with phenytoin having been reported. The absolute incidence of anticonvulsant hypersensitivity syndrome for oxcarbazepine is thought to be much less than for carbamazepine.
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