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Fluconazole

Interaction with Tadalafil

Monitor therapy
QT risk: Fluconazole Tadalafil

Effect: Fluconazole may increase the plasma concentrations of tadalafil.

Clinical management: Caution should be exercised upon coadministration of these drugs. Monitor for increased tadalafil adverse events (e.g. headache, flushing, priapism, visual disturbance, hypotension) and adjust dose of tadalafil if necessary.

Probable mechanism: Inhibition of the cytochrome P450 (CYP) 3A4-mediated biotransformation by fluconazole.

Summary: Coadministration of fluconazole (300 mg/day, once weekly) and tadalafil (20 mg, before intercourse) resulted in sclerosing lymphangitis of the penis ~24 hours after tadalafil intake (3 days after fluconazole intake), as described in a case report. Sexual and pharmacological abstinence were recommended, resulting in resolved symptoms after 4 weeks. It was concluded that fluconazole and tadalafil should be coadministered with caution. In addition, ketoconazole (200 mg/day; strong CYP3A4-inhibitor) significantly increased tadalafil (10 mg) AUC and Cmax by 107% and 15%. Ketoconazole (400 mg/day) significantly increased tadalafil (20 mg) AUC and Cmax by 312% and 22%. Coadministration with the CYP3A4 inhibitor fluconazole could result in similar effects. 

QT effect

Fluconazole: 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).

References

Tadalafil: QT risk not available