Drug interactions with carbamazepine: a case study of influence on anticoagulation treatment with warfarin

Abstract

Background: Drug interactions are an important segment of drug related problems. Therefore their evaluation should be an integral component of patient management, especially in elderly patients who often receive multiple medications. In this manuscript drug interactions with emphasis on their relevance and mechanism are reviewed. Additionally, as an example a detailed analysis of induction of warfarin metabolism during co-treatment with carbamazepine is presented.Patients and methods: We searched MEDLINE and tertiary sources. 188 patients on warfarin therapy in the maintenance phase were retrospectively analysed to study the interaction of carbamazepine with warfarin. Blood plasma concentrations of warfarin enantiomers and their metabolites were measured by high performance liquid chromatography.Results: In patients co-treated with carbamazepine daily warfarin dose necessary to maintain INR in the range between 2.0 in 3.0 was significantly higher (9.00 versus 4.07 mg/day). Despite the difference in daily dose requirement plasma concentrations of warfarin enantiomers were similar, due to the enhanced metabolism of predominantly R-warfarin by cytochrome P450 (CYP) 3A4. Consequently, the concentration of 10-hydroxywarfarin, which is formed by CYP3A4 was 9-times higher.Conclusions: With this study relevance and mechanism of carbamazepine interaction with warfarin was assessed. The study confirmed that the need for warfarin dosage adjustment during initiation and discontinuation of carbamazepine treatment is caused by induction of warfarin metabolism, predominantly by CYP3A4.

Keywords

• drug interactions
• drug related problems
• warfarin
• carbamazepine
• metabolism
• induction