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Updated: Jun 19, 2026

Quadruple-Checkerboard: A Modification of the Three-Dimensional Checkerboard for Studying Drug Combinations
Published on: July 24, 2021
Coprescribing and codispensing of cisapride and contraindicated drugs
J K Jones1, D Fife, S Curkendall
1Director of Research, The Degge Group, Ltd, 1616 N Fort Myer Dr, No. 1430, Arlington, VA 22209, USA.
Context:
Cisapride, an oral prokinetic drug indicated for the symptomatic treatment of nocturnal heartburn due to gastroesophageal reflux disease, was approved by the US Food and Drug Administration in July 1993. After reports of serious cardiac arrhythmias and deaths during administration of cisapride, most involving concomitant exposure to another drug, a series of label changes and warnings were issued in February 1995, October 1995, June 1998, and June 1999. Cisapride was removed from general distribution in July 2000.
Objective:
To determine the frequency of contraindicted coprescribing and codispensings, in which cisapride and a contraindicated drug were prescribed or dispensed to the same patient for overlapping periods, and the proportion of contraindicated coprescribing by the same physicians and codispensing by the same pharmacies.
Design And Setting:
Retrospective study of prescription claims from a managed care organization database for all patients with cisapride prescriptions between July 1993 and December 1998.
Participants:
A total of 38 757 adult and pediatric patients who had a cisapride prescription immediately preceded by at least 60 days of insurance eligibility.
Main Outcome Measure:
Proportion of cisapride prescriptions or dispensing occurring during the same treatment period as a drug contraindicated at that time prescribed by the same physicians or dispensed by the same pharmacies.
Results:
Of 131 485 cisapride prescriptions dispensed after the warnings began, 4414 (3.4%) overlapped with at least 1 drug contraindicated in the labeling at the time of the prescription. Of all overlapping prescription pairs, 2190 (50%) were by the same physicians, 3908 (89%) were by the same pharmacies, and 765 (17%) were dispensed on the same day.
Conclusion:
Prescriptions dispensed by the same pharmacies accounted for a far higher proportion of contraindicated medication pairs than prescriptions from the same physicians. The pharmacy may be an important and underutilized intervention point to prevent contraindicated drugs from being used together.
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