Metformin use decreases the anticoagulant effect of phenprocoumon.
BACKGROUND
Anticoagulant therapy with vitamin K antagonists (VKAs) is affected by interaction of the VKAs with a large number of other drugs. Although metformin is generally not considered to interact with VKAs, we observed a decrease in INR after starting metformin treatment in patients using the VKA phenprocoumon.


OBJECTIVE
To investigate the influence of metformin use on the dosage of phenprocoumon and INR in stably anticoagulated patients.


METHODS
We used the database of the Anticoagulation Clinic Leiden for this study. In a population of 369 patients screened, 27 consecutive patients using phenprocoumon were prescribed metformin during the study period (1 January 2007 to 1 March 2009), without use of other concomitant medications or medical interventions that could influence the INR.


RESULTS
The mean phenprocoumon dosage increased from 2.13 to 2.37 mg per day within 6 weeks (mean increase, 0.23 mg; 95% CI, 0.12-0.34) and 2.49 mg per day within 3 months (mean increase, 0.36 mg; 95% CI, 0.24-0.48) after starting metformin. The mean INR decreased from 2.88 to 2.26 (mean decrease, 0.63; 95% CI, 0.41-0.85) within 6 weeks and 2.54 (mean decrease, 0.35; 95% CI, 0.24-0.48) within 3 months after starting metformin.


CONCLUSIONS
This study shows that clinicians should be aware that metformin treatment may lead to an increased optimal dosage of phenprocoumon.
Anticoagulation Clinic, Leiden University Medical Center, Leiden, the Netherlands.
J C F
JC
Wijnen
I R
IR
van de Riet
W M
WM
Lijfering
F J M
FJ
van der Meer
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D019934:International Normalized Ratio; D008297:Male; D008687:Metformin / Q000009:adverse effects*; D008875:Middle Aged; D009426:Netherlands; D010644:Phenprocoumon / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors
D000925:Anticoagulants; D007004:Hypoglycemic Agents; D008687:Metformin; D010644:Phenprocoumon
diabetes mellitus, type 2; drug interactions; metformin; phenprocoumon; warfarin