Pharmacokinetic Drug Interactions of Synthetic Opiate Analgesics

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.