What is the role of oxcarbazepine (OXC) in the treatment of epilepsy?

Updated: Jan 28, 2020
  • Author: Juan G Ochoa, MD; Chief Editor: Selim R Benbadis, MD  more...
  • Print
Answer

Answer

Oxcarbazepine (OXC) is a recently developed analogue of CBZ. It was developed in an attempt to maintain the benefits of CBZ while avoiding its auto-induction and drug interaction properties. Licensed in over 50 countries, including the United States, OXC now is considered a first-line therapy in some countries. [9, 10, 11, 12]

OXC does not produce the epoxide metabolite, which is largely responsible for the adverse effects reported with CBZ. Like CBZ, OXC blocks the neuronal sodium channel during sustained rapid repetitive firing.

OXC is absorbed almost completely on oral administration and can be taken with food. It is metabolized to the active 10-monohydroxy metabolite (MHD), 10,11-dihydro-10-hydroxy-5H-dibenz[b,f]azepine-5-carboxamide. MHD is the active compound that is responsible for the pharmacologic effects of OXC.

Volume of distribution is 0.3-0.8 L/kg. Protein binding is 38%. The drug readily crosses the blood-brain barrier. Metabolism takes place in the liver; no epoxide is formed, accounting for the better tolerability of this drug than of CBZ. It induces some cytochrome P-450 enzymes, including CYP3A4, CYP3A5, and CYP2C19, but other cytochrome enzymes appear to be unaffected. Excretion is via the kidneys; peak levels are reached in 4 hours. The half-life is 8-10 hours.

OXC interacts with oral contraceptives, thereby reducing their efficacy. It does not increase the metabolism of warfarin, cimetidine, erythromycin, verapamil, or dextropropoxyphene.

OXC is approved for monotherapy or adjunctive therapy in patients with partial and secondary generalized seizures. It is an effective drug for partial seizures but may aggravate myoclonic or absence seizures. Four randomized, double-blind trials of this agent as monotherapy demonstrated effectiveness superior to that of placebo in patients with refractory epilepsy and in candidates for epilepsy surgery.

OXC is better tolerated and has fewer drug interactions than CBZ. Retrospective studies have reported worsening of seizures caused by oxcarbazepine in juvenile idiopathic generalized epilepsies. Substitution for CBZ can be made abruptly with an OXC-to-CBZ ratio of 300:200. Comparison studies of tolerability between slow-release CBZ and OXC are not available.

Available formulations are tablets (150 mg, 300 mg, 600 mg), and the recommended frequency of administration is twice a day. The initial dose in children is 10 mg/kg/d, with titration up to a maximum of 30 mg/kg. In adults, the dose is 600 mg/d up to a maximum of 2400 mg/d. Some patients require low starting doses (300 mg/d) and slower titration for better tolerability.

Somnolence, headache, dizziness, rash, hyponatremia, weight gain, gastrointestinal (GI) disturbances, and alopecia are the most commonly reported adverse effects. The allergic rash is similar to the one caused by CBZ. Dose-related adverse effects include fatigue, headache, dizziness, and ataxia. Hyponatremia is mild and can be corrected by fluid restriction. Hyponatremia is uncommon in children younger than 17 years, but it occurs in 2.5% of adults and 7.4% of the elderly. Idiosyncratic reactions appear to be less common than with CBZ.


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!