Interactions between vaprisol(conivaptan) and D h e 45 (dihydroergotamine)
dihydroergotamine and conivaptan (Major Drug-Drug)
GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of ergot derivatives. The mechanism is conivaptan inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of ergotamine and related drugs. Although the interaction has not been specifically studied with conivaptan, clinical ergotism has occurred in patients receiving ergotamine or dihydroergotamine with other potent 3A4 inhibitors such as macrolide antibiotics and protease inhibitors. Even small, single doses of ergotamine have resulted in clinically significant interactions, occasionally resulting in surgical amputation or death. In pharmacokinetic studies with other drugs that are primarily metabolized by CYP450 3A4 such as midazolam, simvastatin, and amlodipine, conivaptan has increased systemic exposure (AUC) by 2- to 3-fold.
MANAGEMENT: Given the potential for ergot toxicity characterized by peripheral vasospasm, ischemia, thrombosis, tachycardia and hypertension, concomitant use of ergot derivatives with conivaptan should be avoided if possible. Patients currently receiving ergot derivatives should consider an interruption during administration of conivaptan, and allow an appropriate amount of time following completion of conivaptan therapy before resuming these medications.
