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Concomitant use of riociguat with PDE5 inhibitors, together with sildenafil, is contraindicated (see part four.3). In medical studies, riociguat has been shown to augment the hypotensive results of PDE5 inhibitors. Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not have an result on the bioavailability of sildenafil. Cimetidine (800mg), a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor, caused a 56% improve in plasma sildenafil concentrations when co-administered with sildenafil (50mg) to wholesome volunteers. In regular healthy male volunteers, there was no proof of an effect of azithromycin (500mg daily for three days) on the AUC, Cmax, Tmax, elimination rate fixed, or subsequent half-life of sildenafil or its principal circulating metabolite.