Table 2.

Drug Interactions.

Drug class	Interaction
Nitrates	Coadministration of riociguat with nitrates or nitric oxide donors in any form is contraindicated because of hypotension
PDE Inhibitors	Coadministration of riociguat with specific PDE-5i (eg, sildenafil, tadalafil, vardenafil) and nonspecific PDE inhibitors (eg, dipyridamole, theophylline) is contraindicated because of hypotension Do not administer within 24 hours of sildenafil Do not administer 24 hours before or within 48 hours after tadalafil
Strong CYP and P-gp/BCRP Inhibitors	Concomitant use of riociguat with strong CYP inhibitors and P-gp/BCRP inhibitors, such as azole antimycotics (eg, ketoconazole, itraconazole) or HIV protease inhibitors (eg, ritonavir), increases riociguat exposure and may result in hypotension Consider a starting dose of 0.5 mg TID when initiating riociguat and monitor for signs and symptoms of hypotension A dose reduction should be considered in patients who may not tolerate the hypotensive effect of riociguat
Strong CYP3A Inducers	Strong inducers of CYP3A (eg, rifampin, phenytoin, carbamazepine, phenobarbital, St. John’s wort) may significantly reduce riociguat exposure Data are not available to guide dosing of riociguat when strong CYP3A inducers are coadministered
Antacids	Antacids, such as aluminum hydroxide/magnesium hydroxide, decrease riociguat absorption and should not be taken within 1 hour of riociguat administration

Source: Adempas [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc; 2018. ⁴³