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Purpose: Recommendations for including drug-drug interactions (DDIs) in clinical decision support (CDS) are presented., Summary: A conference series was conducted to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information vendors, and healthcare organizations was convened to address (1) the process to use for developing and maintaining a standard set of DDIs, (2) the information that should be included in a knowledge base of standard DDIs, (3) whether a list of contraindicated drug pairs can or should be established, and (4) how to more intelligently filter DDI alerts. We recommend a transparent, systematic, and evidence-driven process with graded recommendations by a consensus panel of experts and oversight by a national organization. We outline key DDI information needed to help guide clinician decision-making. We recommend judicious classification of DDIs as contraindicated and more research to identify methods to safely reduce repetitive and less-relevant alerts., Conclusion: An expert panel with a centralized organizer or convener should be established to develop and maintain a standard set of DDIs for CDS in the United States. The process should be evidence driven, transparent, and systematic, with feedback from multiple stakeholders for continuous improvement. The scope of the expert panel's work should be carefully managed to ensure that the process is sustainable. Support for research to improve DDI alerting in the future is also needed. Adoption of these steps may lead to consistent and clinically relevant content for interruptive DDIs, thus reducing alert fatigue and improving patient safety., Competing Interests: and Conflict of Interest Statement: The other authors have no competing interests or conflicts of interest., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

The post-genomic era has been hallmarked by significant enthusiasm for therapeutic individualization through the use of pharmacogenomic and other biomarkers. This enthusiasm has been dampened by limited examples of widespread clinical adoption. The current clinical implementation paradigm may not be adequate to facilitate uptake of pharmacogenetics for a variety of reasons. This paper discusses certain limitations of the classical clinical implementation paradigm and describes the drug development paradigm as an additional, powerful mechanism to facilitate clinical implementation of individualized therapeutics.

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, what criteria should trigger follow-up clinical studies, and which clinical studies should be conducted if needed. In this article, we provide the recommendations of the International Transporter Consortium on these issues, and present decision trees that are intended to help guide clinical studies on the currently recognized most important drug transporter interactions. The recommendations are generally intended to support clinical development and filing of a new drug application. Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions (for example, exclusion and inclusion criteria), as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.

Both metabolizing enzymes and drug transporters play important roles in modulating drug absorption, distribution, metabolism and elimination. Acting alone or in concert with each other they can affect the pharmacokinetics and pharmacodynamics of a drug. This paper will present cases from recent reviews of new drug application (NDA) and literature that exemplify the role of metabolizing enzyme-transporter interplay in a drug's disposition, and discuss challenges in predicting drug interactions. Finally, the discussion will focus on the need to leverage current knowledge to obtain more meaningful drug interaction information.