Effect: Fluconazole may increase the plasma concentrations of sildenafil.
Clinical management: Caution should be exercised upon coadministration of these drugs. Monitor for increased sildenafil adverse events (e.g. headache, flushing, priapism, visual disturbance, hypotension). If prescribed for erectile dysfunction, consider a 25 mg starting dose of sildenafil.
Probable mechanism: Inhibition of the cytochrome P450 (CYP) 3A4-mediated biotransformation by fluconazole.
Summary: Although not studied for fluconazole, coadministration of erythromycin (500 mg BID for 5 days; a moderate CYP3A4-inhibitor) and sildenafil (100 mg single dose) increased the AUC of sildenafil by 182%. Coadministration of the strong CYP3A4-inhibitor saquinavir (1200 mg TID) and sildenafil (100 mg single dose) increased the AUC and Cmax of sildenafil by 210% and 140%, respectively. Coadministration with the CYP3A4 inhibitor fluconazole could result in similar effects.
QT effectFluconazole: QT risk
Substantial evidence reports that this drug prolongs the QT interval and has a risk of causing TdP (when used as directed in labeling).