Interactions between wellbutrin-sr(buPROPion) and Anafranil (clomiPRAMINE)
buPROPion and clomiPRAMINE (Major Drug-Drug)
MONITOR CLOSELY: The concomitant use of bupropion and tricyclic antidepressants (TCAs) may potentiate the risk of seizures. These agents are individually epileptogenic and may have additive effects on the seizure threshold. Additionally, bupropion can increase the plasma concentrations of some TCAs due to inhibition of CYP450 2D6. 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. 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.
MANAGEMENT: The manufacturer advises extreme caution if bupropion is coadministered with TCAs. Low initial TCA dosages with gradual titration are recommended. In patients who are already stabilized on TCA therapy, plasma TCA levels and pharmacologic response should be monitored more closely whenever bupropion is added to or withdrawn from therapy, and the TCA dosage adjusted as necessary. Patients should be advised to notify their physician if they experience seizures or increased TCA adverse effects such as somnolence, dry mouth, urinary retention, orthostasis, tachycardia, or irregular heartbeats.
