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Pharmacokinetic Drug Interactions of Synthetic Opiate Analgesics

Dr. Wynn is Assistant Chief, Inpatient Psychiatry Services for the Department of Psychiatry, Walter Reed Army Medical Center, Washington, D.C., and is Assistant Professor of Psychiatry, Uniformed Services Univ. of Health Sciences, Bethesda, MD. Dr. Armstrong is the Medical Director, Center for Geriatric Psychiatry, Tuality Forest Grove Hospital, Forest Grove, Ore., and Associate Clinical Professor of Psychiatry, Oregon Health Sciences University, Portland, OR. Dr. Sandson is Clinical Associate Professor, Dept. of Psychiatry, Univ. of Maryland. Send correspondence and reprint requests to Gary H. Wynn, M.D., Dept of Psychiatry, Walter Reed Army Medical Center, Washington, DC. email: wynn.md{at}gmail.com
© 2009 The Academy of Psychosomatic Medicine

Earlier reviews have covered pharmacokinetic drug interactions of natural and semi-synthetic opioid analgesics. This review will focus on the pharmacokinetic drug–drug interactions of methadone, propoxyphene, levomethadyl, meperidine, other phenylpiperidines (such as fentanyl), pentazocine, diphenoxylate, loperimide, and tramadol. The authors present an extensive review of the current literature. These drugs, with a few exceptions, are, at least partially, if not primarily, metabolized by the cytochrome P450 isoenzyme system (CYP) 3A4, and the action/interaction of these enzymes can have an effect on outcome. Therefore, these drugs are likely to produce drug–drug interactions when the CYP3A4 system is inhibited or induced. Knowledge of these drug–drug interactions is important because such interactions may decrease drug efficacy or result in adverse effects.

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