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Cimetidine (800 mg), a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor, caused a 56% improve in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to wholesome volunteers. In regular wholesome male volunteers, there was no proof of an effect of azithromycin (500 mg every day for 3 days) on the AUC, Cmax, tmax, elimination fee constant, or subsequent half-life of sildenafil or its principal circulating metabolite. Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady state (1 200 mg thrice a day) with sildenafil (100 mg single dose) resulted in a 140% improve in sildenafil Cmax and a 210% improve in sildenafil AUC. Primarily Based on these pharmacokinetic results co-administration of sildenafil with ritonavir is not suggested (see section four.4) and in any event the maximum dose of sildenafil should by no means exceed 25 mg within forty eight hours. Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg twice daily) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1 000% (11-fold) improve in plasma AUC.
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