Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Trileptal (Novartis)
300 mg film-coated tablets
Approved indication: epilepsy
Australian Medicines Handbook Section 16.1.3
Carbamazepine is efficacious in the treatment of partial seizures and generalized tonic-clonic seizures. Its effectiveness is limited by its toxicity and interactions. Oxcarbazepine is an analogue of carbamazepine which has been developed to overcome some of these problems. It has been available in some parts of Europe for several years.
Oxcarbazepine is taken twice a day. The dose can be increased at weekly intervals. This is a more rapid titration than with carbamazepine. Each dose is well absorbed and then converted to an active metabolite. This metabolite has a half-life of nine hours, whereas the half-life of oxcarbazepine is two hours. Less than1% of the dose is eliminated unchanged with most of the metabolites being excreted in the urine. Renal clearance is increased in children and reduced in the elderly.
Like other recently marketed antiepileptic drugs1 oxcarbazepine has been used as an adjunct to other treatments. It is efficacious in adults and children with partial seizures uncontrolled by other drugs.2
Oxcarbazepine has also been studied as monotherapy. It is more effective than placebo at controlling partial seizures. In patients with previously untreated partial or generalised tonic-clonic seizures, oxcarbazepine was as efficacious as sodium valproate and phenytoin.
Fatigue, dizziness, drowsiness, nausea and vomiting are common adverse reactions. Hyponatraemia can develop particularly during the first three months of treatment. The product information recommends that patients with renal problems, or those taking medications such as diuretics or non-steroidal anti-inflammatory drugs, should have their serum sodium measured frequently at the start of therapy.
If patients have a history of hypersensitivity reactions to carbamazepine, there is a 25-30% chance that they will react to oxcarbazepine.
Unlike carbamazepine, the metabolism of oxcarbazepine is not affected by drugs, such as erythromycin, which inhibit CYP3A4. Oxcarbazepine can inhibit CYP2C19 so there is a potential for interactions with phenytoin. There are also interactions with calcium channel blockers and oral contraceptives because oxcarbazepine induces CYP3A4 and CYP3A5.
Although oxcarbazepine may have some advantages over carbamazepine, there is less information about its long-term safety. Oxcarbazepine is also likely to be more expensive.
