indication

For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.

pharmacology

Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.

mechanism of action

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.

toxicity

Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.

biotransformation

Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). MHD is metabolized further by conjugation with glucuronic acid.

absorption

Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine.

half life

The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity.

route of elimination

Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. Fecal excretion accounts for less than 4% of the administered dose.

drug interactions

Cyclosporine: Oxcarbazepine decreases the effect of cyclosporine

Ethinyl Estradiol: Oxcarbazepine may decrease the contraceptive effect of ethinyl estradiol. Hormonal contraception should not be solely relied upon during concomitant therapy with oxcarbazepine.

Ethotoin: Oxcarbazepine increases the effect of hydantoin

Felodipine: Oxcarbazepine decreases the levels of felodipine

Fosphenytoin: Oxcarbazepine increases the effect of hydantoin

Mephenytoin: Oxcarbazepine increases the effect of hydantoin

Mestranol: Oxcarbazepine decreases the effect of the contraceptive

Phenytoin: Oxcarbazepine increases the effect of hydantoin

Telithromycin: Oxcarbazepine may decrease the plasma concentration of Telithromycin. Consider alternate therapy.

Temsirolimus: Oxcarbamazepine may increase the metabolism of Temsirolimus decreasing its efficacy. Concomitant therapy should be avoided.

Tramadol: Oxcarbazepine may decrease the effect of Tramadol by increasing Tramadol metabolism and clearance.

Trazodone: The CYP3A4 inducer, Oxcarbazepine, may decrease Trazodone efficacy by increasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Oxcarbazepine is initiated, discontinued or dose changed.