In healthy subjects, tolterodine did not alter pharmacokinetics or pharmacodynamics of warfarin, but isolated cases of raisedINRs have been reported.
Clinical evidence,mechanism, importance and management
In a placebo-controlled study in healthy subjects, tolterodine 2mg twice daily for 7 days did not affect pharmacokinetics of R-or S-warfarin after a single 25mg dose of warfarin given on day 4, nor were pharmacokinetics of tolterodine altered by warfarin. In addition, prothrombin time and factor VII activity were not altered by tolterodine (See reference number 1).
However,a report describes two patients on stable warfarin doses who had elevated INRs shortly after tolterodine 2mg daily was started and stopped: one had an INR of 6.1 one day after stopping 13 days of tolterodine, and other had an INR of 7.4 two days after stopping 8 days of tolterodine. In both cases no bleeding occurred and warfarin was withheld for three doses and successfully reinstated at original dose (See reference number 2). Another case has been reported of a patient who required a 15 % reduction in warfarin dose while taking tolterodine 4mg daily. Her maximum INR had been 3.9. However, she had undergone several warfarin dose increases over previous 2 months and her INR had been fluctuating (See reference number 3).
The controlled study suggests that no warfarin dose adjustment would expected to be needed when tolterodine is added to warfarin therapy. However, 3 cases introduce a note of caution. Although additional monitoring would seem over-cautious on basis of these cases, bear them in mind in case of an unexpected response to warfarin.
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