Interactions between ramelteon and Amiodarone (amiodarone)
amiodarone and ramelteon (Moderate Drug-Drug)
MONITOR: Coadministration with potent inhibitors of CYP450 3A4 and/or 2C9 may increase the plasma concentrations and pharmacologic effects of ramelteon, which is partially metabolized by these isoenzymes. In healthy volunteers, pretreatment with the potent CYP450 3A4 inhibitor ketoconazole (200 mg orally twice daily for 4 days) increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of ramelteon (16 mg single oral dose on day 4) by 36% and 84%, respectively, compared to administration of ramelteon alone. Likewise, coadministration with fluconazole, a potent CYP450 2C9 inhibitor, resulted in an increase of approximately 150% in the Cmax and AUC of ramelteon following a single 16 mg oral dose. Similar pharmacokinetic changes were also observed with its biologically active metabolite, known as M-II.
MANAGEMENT: Caution is advised if ramelteon is prescribed with potent inhibitors of CYP450 3A4 (e.g., itraconazole, ketoconazole, voriconazole, nefazodone, delavirdine, protease inhibitors, ketolide and certain macrolide antibiotics) and/or CYP450 2C9 (e.g., fluconazole, gemfibrozil, imatinib, metronidazole, miconazole, sulfonamides). A reduction in the ramelteon dosage may be necessary in patients who experience excessive sedation.
