Oxcarbazepine drug interactions

Oxcarbazepine has mood-stabilizing effects similar to those of carbamaz-epine, but with milder side effects, no autoinduction of metabolizing enzymes, and potentially fewer drug interactions. There are fewer data supporting its efficacy than there are for carbamazepine s efficacy. 

Oxcarbazepine is a derivative of carbamazepine and although its precise mechanism of action is unknown it has similar properties as carbamazepine and is also used for the treatment of primary generalized tonic-clonic seizures and partial seizures. Also the adverse effects are similar to those of carbamazepine. However the drug interaction profile is different as oxcarbazepine has hardly any enzyme-inducing capacity. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Geriatric Considerations - Summary Well-tolerated in older adults. Adjust dose based on creatinine clearance. Autoinduction of metabolism does not occur as seen with carbamazepine, but drug interactions are still an issue. Many of the CNS effects occur early in treatment and are transitory. One-third of patients with hypersensitivity reactions to carbamazepine will experience cross-sensitivity to oxcarbazepine. 

Oxcarbazepine is less potent than carbamazepine, both in animal models of epilepsy and in epileptic patients clinical doses of oxcarbazepine may need to be 50% higher than those of carbamazepine to obtain equivalent seizure control. Some studies report fewer hypersensitivity reactions to oxcarbazepine, and cross-reactivity with carbamazepine does not always occur. Furthermore, the drug appears to induce hepatic enzymes to a lesser extent than carbamazepine, minimizing drug interactions. Although hyponatremia may occur more commonly with oxcarbazepine than with carbamazepine, most adverse effects that occur with oxcarbazepine are similar in character to reactions reported with carbamazepine. 

Oxcarbazepine has much less prominent actions on CYP 450 enzyme systems than carbamazepine, and thus fewer drug-drug interactions... 

Oxcarbazepine. Oxcarbazepine (10,11-dihydro-10-oxo-5i -dibenz [6,/] azepine-5-car-boxamide or 10,ll,dihydro-10-oxo carbamazepine, 12) was designed to avoid the dose-dependent side effects noted in some patients (e.g., nausea, headache, dizziness, ataxia, diplopia) and to minimize enzyme induction and drug-drug interactions displayed by carbamazepine (195,196). As shown previously (Fig. 6.3), the change in structure results in a difference in metabolism. Although both carbamazepine and oxcarbazepine are ultimately converted to the inactive trans diol, oxcarbazepine does not form the active 10,11-epoxide intermediate, but does form the active 10-hydroxy metabolite MHD (197). The mechanism of action of oxcarbazepine is very similar... 

W. M. Sallas, S. Milosavljev, J. D souza, and M. Hossain, Pharmacokinetic drug interactions in children taking oxcarbazepine. Clin Pharmacol Ther 74 138-149 (2003). 

Enzyme-inducing drugs increase the clearance of the active MHD. The replacement of carbamazepine with oxcarbazepine may result in a drug interaction because an enzyme-inducing drug is being removed. 

Drug-Drug Interactions. Oxcarbazepine, a cytochrome P450 2C19 enzyme inhibitor and a 3A3/4 enzyme inducer, has the potential for causing drug interactions. Oxcarbazepine induces the metabolism of oral contraceptives, thus alternative contraceptive measures are required. ... 

Kramer G, Dorn T, Etter H. Oxcarbazepine clinically relevant drug interaction witii lamotrigine. Epilepsia (2003) 44 (Suppl 9), 95-6. 

Drug-drug interactions A case of fatal serotonin syndrome was reported in a patient taking oxcarbazepine in combination with sertraline. It was thought that long-term use of a selective serotonin reuptake inhibitor may have predisposed the patient to serotonin s5mdrome [114 ]. 

Viloxazine Carbamazepine Phenytoin Oxcarbazepine Risk of phenytoin and carbamazepine toxicity interaction with oxcarbazepine probably of little clinical significance Inhibition of metabolism of the object drugs... 

Citalopram, sertraline and possibly paroxetine serum levels may be reduced because carbamazepine induces their metabolism by CYP3A4, which results in lower levels of these SSRIs. Oxcarbazepine appears not to interact. Both carbamazepine and paroxetine may cause hyponatraemia so the reduced sodium levels could be due to the effects of both drugs. ... 

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