Metformin use decreases the anticoagulant effect of phenprocoumon

J Thromb Haemost. 2014 Jun;12(6):887-90. doi: 10.1111/jth.12578.

Abstract

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.

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

Patients: 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.

Keywords: diabetes mellitus, type 2; drug interactions; metformin; phenprocoumon; warfarin.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects*
  • Drug Interactions
  • Drug Monitoring / methods
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects*
  • International Normalized Ratio
  • Male
  • Metformin / adverse effects*
  • Middle Aged
  • Netherlands
  • Phenprocoumon / therapeutic use*
  • Retrospective Studies
  • Time Factors

Substances

  • Anticoagulants
  • Hypoglycemic Agents
  • Metformin
  • Phenprocoumon