Interactions between dextromethorphan and Budeprion sr (buPROPion)
buPROPion and dextromethorphan (Moderate Drug-Drug)
ADJUST DOSE: Coadministration with bupropion may increase the plasma concentrations of drugs that are metabolized by CYP450 2D6 (e.g., selective serotonin reuptake inhibitors; tricyclic antidepressants; some beta blockers, antiarrhythmics, and antipsychotics). The mechanism is decreased clearance due to inhibition of CYP450 2D6 activity by bupropion. Approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent are extensive metabolizers of CYP450 2D6 and may be affected by this interaction. In a study of 15 male volunteers who were extensive metabolizers of CYP450 2D6, pretreatment with bupropion (150 mg twice daily) increased the peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and half-life of desipramine (50 mg single dose) by an average of 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. In one case report, plasma levels of imipramine and its metabolite, desipramine, increased approximately fourfold in a 64-year-old woman following the addition of bupropion 225 mg/day. Plasma levels of desipramine were increased twofold more than the imipramine levels, which is consistent with the fact that desipramine is primarily metabolized by CYP450 2D6 while imipramine is also metabolized by other CYP450 isoenzymes. Similarly, a 62-year-old woman with no history of seizures developed a generalized tonic-clonic seizure in association with toxic trimipramine plasma levels following the addition of bupropion. No further seizures occurred following dosage reductions of both drugs.
MANAGEMENT: Caution is advised if bupropion must be used concomitantly with medications that undergo metabolism by CYP450 2D6, particularly those with a narrow therapeutic range. Concomitant medications should be initiated at the lower end of the dose range. Clinical and laboratory monitoring may be appropriate for some drugs whenever bupropion is added to or withdrawn from therapy.
