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

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 pati...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2018/07/01, Vol.41(7), pp.1014-1016
Main Authors: Saito, Masayuki, Ajioka, Masayoshi, Iwao, Takahiro, Suzuki, Tadashi
Format: Article
Language:English
Subjects:
Anticoagulants
Cardiovascular diseases
Clinical trials
phamacodynamics
pharmacist
Pharmacodynamics
Pharmacokinetics
Prothrombin
tolvaptan
Variation
Warfarin
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b17-01008