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). CASE SUMMARY: 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. DISCUSSION: 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.

Using serum creatinine concentrations to screen for inappropriate dosage of renally eliminated drugs.

The impact on drug therapy and costs of a program to identify and correct unadjusted dosage in renally impaired patients is described. The program was instituted in May 1988 by the clinical pharmacy staff at a 272-bed hospital. Each day the clinical pharmacist uses laboratory data to list patients with serum creatinine concentrations greater than 1.5 mg/dL. The pharmacist screens the pharmacy profiles of listed patients and calculates creatinine clearance for patients receiving renally eliminated drugs. If, after reviewing the patient's medical record, the pharmacist judges that a dosage adjustment may be appropriate, he writes a confidential note to the physician. From May 1988 through June 1989, 2341 patients with elevated serum creatinine were monitored. During that period, 162 notes were left; recommendations from 142 (88%) of the notes were accepted by physicians. Most of the notes were written for patients receiving antimicrobials or histamine H2-receptor antagonists. The program, which requires 20-30 minutes of pharmacist time per day, avoided $5003 in drug acquisition costs and cost $2700 to administer during the one-year period. When the costs associated with drug preparation and administration are considered, net cost avoidance was $5040. An intervention program in which notes to physicians are written when patients with abnormal serum creatinine values are receiving drugs for which a dosage adjustment appears indicated (1) has medical staff acceptance, (2) helps to satisfy standards of the Joint Commission on Accreditation of Healthcare Organizations, and (3) saves money.