Effect: Voriconazole may increase the plasma concentrations of diclofenac.
Clinical management: Caution should be exercised upon coadministration of these drugs. Monitor for increased diclofenac toxicity and adjust dose if necessary. The SPC of diclofenac recommends not to exceed a diclofenac dose of 50 mg twice daily.
Probable mechanism: Inhibition of the cytochrome P450 (CYP) 2C9-mediated biotransformation by voriconazole. Of note, in vitro studies have shown that diclofenac is primarily metabolised by CYP2C9.
Summary: Coadministration of voriconazole (400 mg BID on day 1, 200 mg on day 2) and diclofenac (50 mg single dose after last dose of voriconazole on day 2) increased diclofenac AUC and Cmax by 178% and 214%, respectively, in 10 healthy male subjects. Although voriconazole pre-treatment was not associated with clinically relevant changes in absorption or half-life, diclofenac renal clearance was reduced by 47% (similar amounts of diclofenac were excreted in urine).
- SPC Diclofenac
QT effectVoriconazole: Conditional QT risk
Substantial evidence reports that this drug causes QT prolongation and has a risk of TdP, but only under certain known conditions (e.g. excessive dose, drug interaction, etc.).