Drug Interactions between brexpiprazole and cimetidine

ADJUST DOSE: Coadministration with inhibitors of CYP450 3A4 and/or 2D6 may significantly increase the plasma concentrations of brexpiprazole, which is metabolized by these isoenzymes. According to product labeling, administration of brexpiprazole with a potent 3A4 inhibitor (ketoconazole) or a potent 2D6 inhibitor (quinidine) resulted in an approximately 2-fold increase in AUC.
The combination of brexpiprazole plus potent CYP450 3A4 inhibitors in poor 2D6 metabolizers is expected to result in a 4.8-fold increase in AUC. The combination of brexpiprazole plus potent CYP450 3A4 inhibitors plus potent CYP450 2D6 inhibitors in extensive 2D6 metabolizers is expected to result in a 5.1 increase in AUC.

MANAGEMENT: The manufacturer recommends that the brexpiprazole dosage be reduced as follows during concomitant administration of CYP450 inhibitors. The brexpiprazole dosage should be increased to the original level if these agents are discontinued. It is advisable to monitor patients for clinical response.

- Potent 3A4 inhibitor: One-half of the usual dose.
- Potent or moderate 3A4 inhibitor in known poor 2D6 metabolizers: One-fourth of the usual dose.
- Potent 2D6 inhibitor: One-half of the usual dose. No dosage adjustments are required for patients with major depressive disorder.
- Potent or moderate 3A4 inhibitor plus potent or moderate 2D6 inhibitor: One-fourth of the usual dose.

Potent CYP450 3A4 inhibitors: antiviral boosters, adagrasib, boceprevir, ceritinib, clarithromycin, conivaptan, delavirdine, idelalisib, indinavir, itraconazole, ketoconazole, lonafarnib, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole.

Moderate CYP450 3A4 inhibitors: aprepitant, atazanavir, ciprofloxacin, clotrimazole, crizotinib, dalfopristin, darunavir, diltiazem, dronedarone, erythromycin, fluconazole, fosamprenavir, fosaprepitant, imatinib, isavuconazonium, mifepristone, netupitant, nilotinib, ranolazine, stiripentol, verapamil.

Potent CYP450 2D6 inhibitors: bupropion, cinacalcet, fluoxetine, methotrimeprazine, paroxetine, quinidine, ritonavir.

Moderate CYP450 2D6 inhibitors: abiraterone, adagrasib, celecoxib, cimetidine, clobazam, darifenacin, diphenhydramine, duloxetine, eliglustat, givosiran, lorcaserin, mirabegron, panobinostat, ranolazine, sertraline, stiripentol.