Increased liability of tramadol-warfarin interaction in individuals with mutations in the cytochrome P450 2D6 gene.
OBJECTIVE
This study aimed to investigate the importance of cytochrome P(450) enzymes for the reported interaction between tramadol and warfarin.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The liability to an interaction between tramadol and warfarin may be related to the CYP2D6 activity.
Hedenmalm
Karin
K
Drug Epidemiology Unit, Medical Products Agency, 75103 Uppsala, Sweden. karin.hedenmalm@mpa.se
Lindh
Jonatan D
JD
Säwe
Juliette
J
Rane
Anders
A
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004347:Drug Interactions / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D009294:Narcotics / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D013548:Sweden; D014147:Tramadol / Q000009:adverse effects*; D014859:Warfarin / Q000009:adverse effects*
D000925:Anticoagulants; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D009294:Narcotics; D014147:Tramadol; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D019389:Cytochrome P-450 CYP2D6