Increased liability of tramadol-warfarin interaction in individuals with mutations in the cytochrome P450 2D6 gene

Abstract

This study aimed to investigate the importance of cytochrome P(450) enzymes for the reported interaction between tramadol and warfarin.

Cases of suspected interaction between tramadol and warfarin resulting in International Normalised Ratios increases that were reported to the Swedish Adverse Drug Reactions Advisory Committee until March 2003 were included. Ten cases had been genotyped for known polymorphisms of CYP2D6, CYP2C9 and CYP2C19.

Seven of ten patients carried defective CYP2D6 alleles (population prevalence 42.2%) (one-sided binomial test, P=0.07). A further patient received concomitant drug treatments that may have resulted in CYP2D6 enzyme inhibition.

The liability to an interaction between tramadol and warfarin may be related to the CYP2D6 activity.