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JOHN E. MURPHY, PHARM.D., is Professor and Associate Dean; and DANIEL C. MALONE, PH.D., is Professor, College of Pharmacy, The University of Arizona, Tucson. BRIDGET M. OLSON, PHARM.D., M.S., is Vice President, Dymaxium Inc., San Diego, CA. AMY J. GRIZZLE, PHARM.D., is Assistant Director, Center for Health Outcomes and PharmacoEconomic Research; EDWARD P. ARMSTRONG, PHARM.D., is Professor; and GRANT H. SKREPNEK, PH.D., is Assistant Professor, College of Pharmacy, The University of Arizona.

Address correspondence to Dr. Murphy at the College of Pharmacy, The University of Arizona, P.O. Box 210202, Tucson, AZ 85721-0202 (murphy{at}pharmacy.arizona.edu).

Purpose. The development of computerized alerts with management strategies for 25 drug–drug interactions (DDIs) is described. Summary. To ensure that clinicians, when confronted with any of 25 serious DDIs in the ambulatory care setting, can avoid these DDIs while treating patients with appropriate medications, management strategies were developed using a consensus approach. Several methods were used to ensure that the recommended alternatives were truly safe. Four well-established drug-interaction compendia were screened, and any potential alternative agent that was listed as having an interaction (moderate or serious in nature) was excluded from the list of alternative agents. Case reports, case series, and clinical studies that focused on the alternative combinations were reviewed to determine if the alternative posed interaction risks. If an interaction for the alternative combination had not been identified in the compendia or in the literature search, other potential mechanisms for drug interactions were explored such as alterations in absorption, distribution, metabolism, or excretion. Pharmacology and therapeutics textbooks and other drug information sources also served as resources. In general, the strategies included alternatives to both medications, changing dosage or increasing monitoring of one of the agents, situations where one of the medications had no alternative but alternatives were available for the other medication, and alternative methods of birth control. In some situations the two drugs were contraindicated, while in others the two drugs should be avoided if at all possible and alternatives used. Conclusion. Consensus-based management strategies for 25 serious DDIs were developed for inclusion in computerized alert messages. Index terms: Ambulatory care; Computers; Drug interactions; Quality assurance