Enhancement of Warfarin Anticoagulant Reaction in Patients with Repeated Oral Tolvaptan Administration

Biological & Pharmaceutical Bulletin
Masayuki SaitoTadashi Suzuki

Abstract

The pharmacokinetics and pharmacodynamics of warfarin remained unaffected by tolvaptan during clinical trials. However, tolvaptan prolonged the prothrombin time-international normalized ratio (PT-INR) level of patients with cardiovascular disease taking warfarin. Tolvaptan was prescribed to 576 patients from December 2010 to December 2015. Of these patients, 37 underwent anticoagulant therapy. We investigated PT-INR fluctuation immediately before tolvaptan therapy was initiated. PT-INR remained unchanged in the control group and in groups administered with less than 7.5 mg/d tolvaptan, whereas it was significantly increased (p=0.03) in the group administered with more than 7.5 mg/d tolvaptan. This result indicates the possibility that tolvaptan affects the pharmacodynamics of warfarin in vivo. However, further research is necessary to clarify the mechanism of this phenomenon.

References

Jul 1, 1970·Clinical Pharmacology and Therapeutics·E M Sellers, J Koch-Weser
Jul 7, 1967·Biochemical Pharmacology·H M Solomon, J J Schrogie
Jan 22, 2014·JAMA Internal Medicine·Nathan P ClarkUNKNOWN Warfarin-Associated Research Projects and Other Endeavors Consortium
Apr 1, 2012·Clinical Pharmacology in Drug Development·Susan E Shoaf, Suresh Mallikaarjun

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Citations

Jul 21, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masayuki SaitoTadashi Suzuki

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