An exaggerated hypotensive response may be seen if antihypertensive agents are administered to patients receiving opiate analgesics. Caution should also be observed when using meperidine with carbamazepine, phenytoin, or rifampin. Despite changes in meperidine pharmacokinetics, however, phenytoin did not affect the analgesic action of meperidine. Opiate antagonists, such as naloxone, naltrexone, and nalmefene, are pharmacologic opposites of meperidine. There is some in vitro data that suggest cimetidine can inhibit the hepatic metabolism of meperidine, however, the clinical implications of this pharmacokinetic interaction have not been determined.
Meperidine appears to block the neuronal reuptake of serotonin.
Meperidine should be used cautiously, if at all, in patients receiving MAOIs, especially selegeline. Clomipramine, fluoxetine, paroxetine, sertraline, and sumatriptan are other drugs that can potentiate the effects of serotonin. Although no reports of interactions with meperidine are known, these drugs should nevertheless be used carefully with meperidine. The most significant adverse effect associated with opiate agonist use is the potential for respiratory depression. When used in therapeutic doses, the risk is generally small.