DRUG INTERACTION

DRUG INTERACTION

Tramadol does not appear to induce its own metabolism in humans, since observed maximal plasma concentrations after multiple oral doses are higher than expected based on single-dose data. Tramadol is a mild inducer of selected drug metabolism pathways measured in animals.

Concomitant administration of Ultram (tramadol hydrochloride) with carbamazepine causes a significant increase in tramadol metabolism, presumably through metabolic induction by carbamazepine. Patients receiving chronic carbamazepine doses of up to 800 mg daily may require up to twice the recommended dose of Ultram.

Tramadol is metabolized to M1 by the CYP2D6 P-450 isoenzyme. Quinidine is a selective inhibitor of that isoenzyme; so that concomitant administration of quinidine and Ultram results in increased concentrations of tramadol and reduced concentrations of M1. The clinical consequences of this effect have not been fully investigated, and the effect on quinidine concentrations is unknown.

Concomitant administration of Ultram with cimetidine does not result in clinically significant changes in tramadol pharmacokinetics. Therefore, no alteration of the Ultram dosage regimen is recommended.

Interactions with MAO Inhibitors due to interference with detoxification mechanisms, have been reported for some centrally acting drugs (see WARNINGS).