Tolterodine-warfarin drug interaction.
OBJECTIVE
To report two cases of warfarin therapy in which the addition of tolterodine resulted in prolonged international normalized ratios (INRs).


METHODS
Two patients, each receiving warfarin for stroke prophylaxis in association with chronic atrial fibrillation, developed adverse effects after the initiation of tolterodine for urinary disorders. Other medications for concurrent medical diagnoses had remained unchanged. One patient had an episode of prostatitis, which was treated with levofloxacin immediately prior to tolterodine initiation. The warfarin dosage had remained constant for many weeks in both patients prior to and during the tolterodine trials. In each patient, the initiation of tolterodine was associated with a significant increase in the patient's INR measured 10-14 days later. Thus, tolterodine was ineffective in both patients and was discontinued one to two days before the elevated INRs were determined during routine clinic visits. INRs determined approximately two weeks after tolterodine was discontinued were similar to those obtained during the period before the use of the drug; the warfarin dosage remained unchanged. Rechallenge with tolterodine was not attempted in either patient.


CONCLUSIONS
Several aspects of the reported cases support the validity of a proposed drug interaction when tolterodine is initiated in a patient stabilized on warfarin therapy. The temporal association of the course of tolterodine with an elevated INR, the return to the previous warfarin dose-INR response relationship after tolterodine discontinuation, and the absence of other causes for the elevated INR were factors found in both patients. Possible mechanisms to explain the suggested drug interaction are explored.


CONCLUSIONS
Until further data are available, clinicians should be vigilant for a possible drug interaction when tolterodine therapy is initiated in a patient maintained on warfarin therapy.
Colucci
V J
VJ
Pharmacy Practice, School of Pharmacy, University of Montana, Missoula 59812, USA. colucci@selway.umt.edu
Rivey
M P
MP
D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000627:therapeutic use; D003408:Cresols / Q000009:adverse effects* / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D018727:Muscarinic Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D010665:Phenylpropanolamine; D020521:Stroke / Q000517:prevention & control; D000068737:Tolterodine Tartrate; D014555:Urination Disorders / Q000188:drug therapy; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
D000925:Anticoagulants; D001559:Benzhydryl Compounds; D003408:Cresols; D018727:Muscarinic Antagonists; D010665:Phenylpropanolamine; D014859:Warfarin; D000068737:Tolterodine Tartrate