OXCARBAZEPINE - CLINICAL DEVELOPMENT PROGRAM

Oxcarbazepine (OCBZ, Trileptal) is registered in several countries and has been well received by patients and physicians. However, newer sta ndards in many other countries require additional data before registra tion can be achieved. For this reason, Ciba has implemented further cl inical studies. OCBZ has a chemical structure that is closely related to carbamazepine (CBZ). In humans, OCBZ is not oxidatively metabolized , therefore causing little, if any, induction of hepatic enzymes. Beca use of this, and because of low protein-binding properties, OCBZ cause s markedly fewer interactions with concomitant medications than most m arketed antiepileptic drugs. OCBZ has been shown to have significantly fewer limiting side effects (described as side effects leading to dis continuation of treatment) than CBZ, while showing comparable efficacy . Many patients who are hypersensitive to CBZ can be treated with OCBZ . The usually administered dosage of OCBZ is approximately 50% higher than that of CBZ. However, better tolerability of OCBZ makes it possib le to give higher dosages. The plasma concentration half-life of the a ctive metabolite (monohydroxy derivative; MHD) makes it possible to ad minister OCBZ twice daily. No changes in dosage are necessary in patie nts with impaired renal function unless creatinine clearance is below 30 ml/min. In patients with such severely reduced creatinine clearance , the dose of OCBZ should be halved. Specific questions e.g., such as whether OCBZ causes hepatic enzyme induction at higher doses and the e ffect of OCBZ on intrinsic sex hormones, will be answered in future st udies. In addition, the tolerability and pharmacokinetics of OCBZ in s pecific target populations such as the elderly, children, and hepatica lly impaired patients will be addressed. This will enable a more compl ete delineation of the clinical profile of OCBZ, thereby helping physi cians to decide how best to use OCBZ in their patients with epilepsy.