Effects of Other Drugs on Viagra Citrate
In Vitro Studies: Viagra metabolism is principally mediated by the cytochrome P450 (CYP)
isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil
In Vivo Studies: Cimetidine (800 mg), a nonspecific CYP inhibitor, caused a 56% increase in plasma
sildenafil concentrations when coadministered with sildenafil citrate (50 mg) to healthy volunteers.
When a single 100 mg dose of sildenafil citrate was administered with erythromycin, a specific CYP3A4 inhibitor,
at steady state (500 mg bid for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC). In
addition, coadministration of the HIV protease inhibitor saquinavir, also a CYP3A4 inhibitor, at steady state (1200
mg tid) with sildenafil citrate (100 mg single dose) resulted in a 140% increase in sildenafil Cmax and a
210% increase in sildenafil AUC. Viagra citrate had no effect on saquinavir pharmacokinetics. Stronger CYP3A4
inhibitors such as ketoconazole or itraconazole would be expected to have still greater effects, and population data
from patients in clinical trials did indicate a reduction in sildenafil clearance when it was coadministered with
CYP3A4 inhibitors (such as ketoconazole, erythromycin, or cimetidine).
Coadministration with the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady
state (400 mg bid) with sildenafil citrate (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil
Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC. At 24 hours the plasma levels of sildenafil
were still approximately 200 ng/mL, compared to approximately 5 ng/mL when sildenafil was dosed alone. This is
consistent with ritonavirs marked effects on a broad range of P450 substrates. Viagra citrate had no effect on
It can be expected that concomitant administration of CYP3A4 inducers, such as rifampin, will decrease plasma
levels of sildenafil.
Single doses of antacid (magnesium hydroxide/aluminum hydroxide) did not affect the bioavailability of sildenafil
Pharmacokinetic data from patients in clinical trials showed no effect on sildenafil pharmacokinetics of CYP2C9
inhibitors (such as tolbutamide, warfarin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors,
tricyclic antidepressants), thiazide and related diuretics, ACE inhibitors, and calcium channel blockers. The AUC of
the active metabolite, N-desmethyl sildenafil, was increased 62% by loop and potassium-sparing diuretics and 102% by
nonspecific beta-blockers. These effects on the metabolite are not expected to be of clinical consequence.
Effects of Viagra Citrate on Other Drugs
In Vitro Studies: Viagra is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19,
2D6, 2E1 and 3A4 (IC50 >150 mM). Given sildenafil peak plasma concentrations of approximately 1 mcM after
recommended doses, it is unlikely that sildenafil citrate will alter the clearance of substrates of these
In Vivo Studies: When sildenafil citrate 100 mg oral was coadministered with amlodipine, 5 mg or 10
mg oral, to hypertensive patients, the mean additional reduction on supine blood pressure was 8 mmHg systolic and 7
No significant interactions were shown with tolbutamide (250 mg) or warfarin (40 mg), both of which are
metabolized by CYP2C9.
Viagra citrate (50 mg) did not potentiate the increase in bleeding time caused by aspirin (150 mg).
Viagra citrate (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean
maximum blood alcohol levels of 0.08%.
Viagra (100 mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir
and ritonavir, both of which are CYP3A4 substrates.