Drug Interactions and Medication Errors

Sheldon H. Preskorn, MD
David Flockhart, MD, PhD

Dr. Preskorn is Professor, Chair, Department of Psychiatry and Behavioral Sciences, University of Kansas School of Medicine, CEO, Clinical Research Institute
Dr. Flockhart is Professor of Medicine, Genetics, and Pharmacology; Chief, Division of Clinical Pharmacology, Indiana University School of Medicine

DDIs are a serious cause of concern for the US healthcare system. They are so numerous that the dictum to “do no harm” is seriously challenged. This situation is in part due to the large number of new prescription drugs available to prescribers.

An ignorance of important interactions threatens trust in physicians and other prescribers. Over the past 20 years possible drug interactions have increased to the point where prescribers universally find it impossible to remember all conceivable interactions and are forced to rely on electronic media.

The importance to the public health of a mechanistic understanding of adverse drug events, and of a system to prevent them, cannot be understated. DDIs are not the entire cause of adverse drug events, but they are a significant contributor, as indicated by the number of medicines withdrawn from the market because of drug interactions in the last 6 years, and by a growing number of significant interactions that result from comedication with herbal nutritional supplements, a market on which the US public spends more than they do on prescription medicines. Lastly, the population is aging. It has been clear for many years that adverse events experienced by the elderly are markedly increased in those who take more than four medications at once.

The convergence of these multiple complicating influences makes clear that the simple medication history that all physicians are taught to take, consisting of the question “What medications do you take and do you have any allergies to drugs?” has not evolved to accommodate the complexity of these concerns. Therefore, we propose a more detailed series of questions using the acronym “AVOID”.

DDIs are of paramount importance to health professionals who practice in the pharmaceutical industry. This is because the number of prescription medicines that were initially approved by the FDA as safe and effective but which then had to be removed from the market due to unacceptable DDIs, is considerable. The financial impact of such withdrawals on companies conservatively involves billions of dollars, but the harm to patients may also be substantial.

Disclosures: Dr. Preskorn is a consultant to Bristol-Myers Squibb, Cyberonics, Eli Lilly, Johnson & Johnson, Memory, Otsuka, Pfizer, Shire, Somerset, and Wyeth; is on the speaker’s bureaus of Bristol-Myers Squibb, Cyberonics, Forest, Otsuka, and Pfizer; and receives grant support from Brtistol-Myers Squibb, Cyberonics, Johnson & Johnson, Memory, Merck, the National Instute of Mental Health, Novartis, Organon, Otsuka, Pfizer, Predix, Sepracor, and Somerset. Dr. Flockhart is a consultant to Hoffman-La Roche.