The pharmacokinetics of oral riociguat are characterized by rapid absorption, almost complete bioavailability, and dose-proportional exposure, which correlates with its pharmacodynamic effects. Riociguat exposure varies substantially between patients; this has been addressed by use of an individual dose-adjustment scheme at treatment initiation, which has been proven to be safe and efficacious in phase III studies in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, and appears to be practical and straightforward in clinical practice.

Most intrinsic and extrinsic factors that influence riociguat pharmacokinetics or pharmacodynamics do not warrant further dose adjustment beyond the individual dose-adjustment scheme; however, particular care should be exercised during individual dose adjustment in elderly patients and those with moderate hepatic impairment or mild to severe renal impairment. Concomitant use of riociguat with strong multipathway cytochrome P450 and P-glycoprotein/breast cancer resistance protein inhibitors should be avoided or approached with caution because of the risk of hypotension; a reduced starting dose of 0.5 mg three times daily might be considered. Smoking decreases riociguat exposure, and dose adjustments may be necessary in patients who start or stop smoking during treatment.