Cisapride, an oral GI prokinetic agent, was reported with serious cardiac arrhythmia in patients who received imidazole antifungals, macrolide antibiotics, or protease inhibitors. Several label changes and dear Dr. letters were sent to prescribers in February and October 1995, and June 1998. OBJECTIVE: To quantify the effectiveness of label changes and dear Dr. letters on patient medication with cisapride and contraindicated drugs. METHODS: Using a managed care database, a total of 38,757 patients with cisapride prescriptions from July 1993 to December 1998 were selected. The outcomes measured are proportions of overlapping cisapride prescriptions and coexposed therapy days dispensed with contraindicated drugs per month/year. Poisson regression analyses were conducted to evaluate changes in the proportion of overlapping contraindicated prescriptions after each intervention. RESULTS: About 3.7% cisapride prescriptions were overlapped with contraindicated drugs. Of those, 51% were prescribed by the same physician; 17% were dispensed on the same day; and 97% were dispensed by the same pharmacy. After controlling for seasonal variation, both interventions in October 1995 and June 1998 significantly reduced the proportion of overlapping contraindicated prescriptions. We found a 15% reduction (p=0.0357) following the October 1995 intervention and a subsequent 30% reduction (p=0.0002) following the June 1998 intervention. No significant decline was found for the February 1995 intervention. The proportion of overlapping with antibiotics shows a seasonal pattern with peaks in the winter. Young and middle-aged patients were more likely to get overlapping contraindicated prescriptions than children and elderly patients (p=0.0001). CONCLUSIONS: Decreases in the proportions of overlapping medications were observed after product label changes accompanied by dear Dr. letters and associated information.