Drug Interaction Report

GENERALLY AVOID: Phenytoin may induce the metabolism of meperidine to normeperidine, the latter of which has been associated with adverse effects such as lethargy, agitation, and seizures. The interaction may decrease the therapeutic effects of meperidine while increasing its adverse effects. In four healthy volunteers, phenytoin (300 mg daily for 10 days) increased the systemic clearance of meperidine by 26%, decreased its elimination half-life by 33%, and decreased its oral bioavailability by 30%. Systemic exposure (AUC) of normeperidine from intravenous and oral meperidine increased by 53% and 25%, respectively, during coadministration with phenytoin.

MANAGEMENT: Meperidine product labeling recommends that the combination of meperidine and phenytoin be avoided. The same precaution may be applicable to other hydantoins, although clinical data are lacking.

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.