Interactions between ergotamine and Diflucan (fluconazole)
fluconazole and ergotamine (Major Drug-Drug)
CONTRAINDICATED: Coadministration with azole antifungal agents may significantly increase the plasma concentrations and pharmacologic effects of ergot derivatives. The mechanism is azole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of ergotamine and related drugs. Although the interaction has not been specifically reported with azole antifungal agents, clinical ergotism has occurred in patients receiving ergotamine or dihydroergotamine with other potent CYP450 3A4 inhibitors such as macrolide antibiotics and protease inhibitors. Within the azole class, ketoconazole and itraconazole are considered the most potent inhibitors, while fluconazole is comparatively weak and generally causes clinically significant interactions with CYP450 3A4 substrates only at dosages of 200 mg/day or more.
MANAGEMENT: Given the potential for ergot toxicity characterized by peripheral vasospasm, ischemia, thrombosis, tachycardia and hypertension, concomitant use of ergot derivatives with itraconazole, ketoconazole, posaconazole, or voriconazole is considered contraindicated. Use with other azole antifungal agents, including fluconazole at high multiple doses, should probably be avoided if possible.
