Outcomes of Other Prescription drugs on VIAGRA Sildenafil metabolism is principally mediated by CYP3A4 (key route) and CYP2C9 (insignificant route). For that reason, inhibitors of such isoenzymes might decrease sildenafil clearance and inducers of these isoenzymes may well increase sildenafil clearance.Sildenafil operates by blocking an enzyme in y