quinidine and Clotrimazole Interactions

Interactions between quinidine and Clotrimazole (clotrimazole)

quinidine and clotrimazole (Major Drug-Drug)

GENERALLY AVOID: Coadministration with azole antifungal agents may significantly increase the plasma concentrations of quinidine. The mechanism is azole inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of quinidine. The use of quinidine has been associated with prolongation of the QT interval, thus elevated plasma levels of the drug may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death. Ketoconazole and itraconazole are considered potent inhibitors of 3A4, while fluconazole is comparatively weak and generally causes clinically significant interactions with 3A4 substrates only at dosages of 200 mg/day or more.

MANAGEMENT: Given the potential for serious and life-threatening adverse cardiac events associated with increased plasma levels of quinidine, concomitant use with azole antifungal agents (including fluconazole at multiple doses of 200 mg or higher) should be avoided whenever possible. If coadministration is necessary, pharmacologic response and quinidine plasma levels should be monitored more closely following initiation or discontinuation of the azole, and the quinidine dosage adjusted as necessary. Patients should be advised to notify their physician if they experience potential signs and symptoms of quinidine toxicity such as tinnitus, hearing loss, visual disturbances, diarrhea, dizziness, weakness, headache, syncope, and rapid or irregular heartbeats. Product labelings for itraconazole and voriconazole state that use with quinidine is contraindicated.