Ketoconazole Darifenacin

Coadministration with CYP450 inhibitors- Nhen coadministered with potent CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, nefazodone), do not exceed a daily dose of darifenacin 7.5 mg. 

ANTIMUSCARINICS ANTIFUNGALS -ITRACONAZOLE, KETOCONAZOLE 1. i ketoconazole levels. 2. t darifenacin, solifenacin and tolterodine levels 1. 1 absorption 2. Inhibited metabolism 1. Watch for poor response to keto-conazole 2. Avoid co-administration of itraconazole, ketoconazole and these antimuscarinics. The US manufacturer of darifenacin recommends that its dose should not exceed 7.5 mg/day... 

Ketoconazole markedly increases darifenacin levels, whereas erythromycin and fluconazoie have only a modest effect on darifenacin ieveis. 

The manufacturers note that, in a study in 16 healthy subjects, ketoconazole 400 mg daily for 6 days markedly increased the steady-state AUC of darifenacin 30 mg once daily by about tenfold. The UK manufacturers also note that ketoconazole 400 mg caused a fivefold increase in the AUC of a 7.5-mg dose of darifenacin. ... 

Darifenacin is principally metabolised by the cytochrome P450 isoenzyme CYP3A4, of which ketoconazole is a potent inhibitor, and erythromycin and fluconazole are moderate inhibitors. 

---