The effect of other drugs on the pharmacokinetics of sildenafil The metabolism of sildenafil occurs mainly under the action of isoenzymes CYP3A4 (the main pathway) and CYP2C9 (a secondary pathway), so inhibitors of these isoenzymes can reduce the clearance of sildenafil.
Ritonavir increases the AUC of sildenafil 11 times, the combined use of these drugs is not recommended.
Simultaneous use of sildenafil (once in a dose of 100 mg) and an inhibitor of HIV protease saquinavir, which is an inhibitor of the isoenzyme CYP3A4,in conditions of equilibrium concentration (1200 mg 3 times a day) led to an increase in Cmax sildenafil by 140%, and AUC - by 210%.
Sildenafil did not influence the pharmacokinetics of saquinavir. More potent inhibitors of the CYP3A4 isoenzyme, such as
ketoconazole and
itraconazole, can cause more pronounced changes in the pharmacokinetics of sildenafil.
A single dose of sildenafil 100 mg together with erythromycin, a specific inhibitor of the isoenzyme CYP3A4, under the conditions of an equilibrium concentration of erythromycin in the blood (500 mg twice a day for 5 days) leads to an increase in the AUC of sildenafil by 182%.
Cimetidine (800 mg), a cytochrome P450 inhibitor and a non-specific inhibitor of the CYP3A4 isoenzyme, when co-administered with sildenafil (50 mg) in healthy volunteers, increased the concentration of sildenafil in blood plasma by 56%.
Grapefruit juice is a weak inhibitor of the isoenzyme CYP3A4 and can moderately increase the concentration of sildenafil in blood plasma.
Single application of antacids (magnesium hydroxide / aluminum hydroxide) does not affect the bioavailability of sildenafil.
Inhibitors of the isoenzyme CYP2C9 (such as tolbutamide,
warfarin,
phenytoin), CYP2D isoenzyme inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazides and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin converting enzyme inhibitors, beta blockers, calcium antagonists and inducers of CYP450 isoenzymes (for example,
rifampicin, barbiturates) have no effect on the pharmacokinetics of sildenafil.
Nicorandil is a hybrid of the activator of potassium channels and nitrate. Due to the nitrate component, it can enter into serious interactions with sildenafil. Effect of sildenafil on other drugs
Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. It is unlikely that syyafil can affect the clearance of the substrates of these isoenzymes.
Sildenafil enhances the hypotensive effect of nitrates, so its combined use with donators of nitric oxide or nitrates in any form is contraindicated. Simultaneous use of sildenafil and alpha-adrenoblockers can lead to symptomatic hypotension, especially in the first 4 hours after admission.
There were no significant interactions with the simultaneous use of sildenafil (50 mg) and tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by the isoenzyme CYP2C9.
Sildenafil (50 mg) did not cause an additional increase in bleeding time caused by acetylsalicylic acid (150 mg).
Sildenafil (50 mg) did not increase the hypotensive effect of ethanol in healthy volunteers with a maximum concentration of ethanol in the blood of 80 mg / dl.
In patients with hypertension, there was no evidence of interaction between sildenafil (100 mg) and amlodipine. The average additional decrease in blood pressure (BP) in the lying position is 8 mm Hg. Art. (systolic) and 7 mm Hg. Art. (diastolic).
Strengthens the antiplatelet effect of sodium nitroprusside in vitro.