Sildenafil CYP3A4 inducers

Although the manufacturer of vardenafii does not mention CYP3A4 inducers, like tadalafil and sildenafil, vardenafii is principally metabolised by CYP3A4, and its levels are markedly raised by CYP3A4 inhibitors such as ketoconazole , (p. 1270). It is therefore very likely that vardenafii levels will be reduced by rifampicin and similar drugs, and concurrent use should be monitored. 

Sildenafil is contraindicated in patients who are taking organic nitrates, for their metabolism is blocked and severe and acute hypotension result. Patients with recent stroke or myocardial infarction or whose blood pressure is known to be < 90/50 mmHg should not use it. Sildenafil is a substrate for the P450 isoenzyme CYP3A4 (and to a lesser extent CYP2C9) which gives scope for interaction with inhibitors or inducers of this system. The metabolic inhibitors erythromycin, saquinavir and ritonavir (protease inhibitors used for AIDS), and cimetidine, for example, produce substantial rises in the plasma concentration of sildenafil. 

On the basis of the 63% reduction in AUC seen with the moderate CYP3A4 indueer bosentan , (p.l274), the US manufacturer of sildenafil says that concurrent use with potent inducers of CYP3A4 such as rifampicin is predicted to cause a greater reduction in sildenafil levels. ... 

Rifampicin induces the activity of the cytochrome P450 isoenzyme CYP3A4, the principal enzyme concerned with the metabolism of sildenafil, tadalafil and vardenafii. 

Bosentan induces the cytochrome P450 isoenzyme CYP3A4 and CYP2C9, by which sildenafil is metabolised. 

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