Treatment should only be initiated and monitored by a physician experienced in the treatment of CTEPH or PAH.
Posology: Dose titration: The recommended starting dose is 1 mg three times daily for 2 weeks. Tablets should be taken three times daily approximately 6 to 8 hours apart (see Pharmacology: Pharmacokinetics under Actions).
Dose should be increased by 0.5 mg three times daily every two weeks to a maximum of 2.5 mg three times daily, if systolic blood pressure is ≥95 mmHg and the patient has no signs or symptoms of hypotension. In some PAH patients, an adequate response on the 6-minute walk distance (6MWD) may be reached at a dose of 1.5 mg three times a day (see Pharmacology: Pharmacodynamics under Actions). If systolic blood pressure falls below 95 mmHg, the dose should be maintained provided the patient does not show any signs or symptoms of hypotension. If at any time during the up-titration phase systolic blood pressure decreases below 95 mmHg and the patient shows signs or symptoms of hypotension the current dose should be decreased by 0.5 mg three times daily.
Maintenance dose: The established individual dose should be maintained unless signs and symptoms of hypotension occur. The maximum total daily dose is 7.5 mg i.e., 2.5 mg 3 times daily. If a dose is missed, treatment should be continued with the next dose as planned.
If not tolerated, dose reduction should be considered at any time.
Food: Tablets can generally be taken with or without food. For patients prone to hypotension, as a precautionary measure, switches between fed and fasted Adempas intake are not recommended because of increased peak plasma levels of riociguat in the fasting compared to the fed state (see Pharmacology: Pharmacokinetics under Actions).
Treatment discontinuation: In case treatment has to be interrupted for 3 days or more, restart treatment at 1 mg three times daily for 2 weeks, and continue treatment with the dose titration regimen as previously described.
Transitioning between PDE5 inhibitors and riociguat: Discontinue sildenafil at least 24 hours or tadalafil at least 48 hours prior to administering riociguat. Discontinue riociguat at least 24 hours prior to administering a PDE5 inhibitor. It is recommended to monitor for signs and symptoms of hypotension after any transition (see Contraindications, Interactions, and Pharmacology: Pharmacodynamics under Actions).
Special populations: Individual dose titration at treatment initiation allows adjustment of the dose to the patient's needs.
Paediatric population: The safety and efficacy of riociguat in children and adolescents below 18 years have not been established. No clinical data are available. Non-clinical data show an adverse effect on growing bone (see Pharmacology: Toxicology: Preclinical safety data under Actions). Until more is known about the implications of these findings the use of riociguat in children and in growing adolescents should be avoided (see Precautions).
Elderly population: In elderly patients (65 years or older) there is a higher risk of hypotension and therefore particular care should be exercised during individual dose titration (see Pharmacology: Pharmacokinetics under Actions).
Hepatic impairment: Patients with severe hepatic impairment (Child Pugh C) have not been studied and therefore use of Adempas is contraindicated in these patients (see Contraindications). Patients with moderate hepatic impairment (Child Pugh B) showed a higher exposure to this medicine (see Pharmacology: Pharmacokinetics under Actions). Particular care should be exercised during individual dose titration.
Renal impairment: Data in patients with severe renal impairment (creatinine clearance <30 mL/min) are limited and there are no data for patients on dialysis. Therefore use of Adempas is not recommended in these patients (see Precautions).
Patients with moderate renal impairment (creatinine clearance <50 - 30 mL/min) showed a higher exposure to this medicine (see Pharmacology: Pharmacokinetics under Actions). There is a higher risk of hypotension in patients with renal impairment, therefore particular care should be exercised during individual dose titration.
Smokers: Current smokers should be advised to stop smoking due to a risk of a lower response. Plasma concentrations of riociguat in smokers are reduced compared to non-smokers. A dose increase to the maximum daily dose of 2.5 mg three times daily may be required in patients who are smoking or start smoking during treatment (see Interactions and Pharmacology: Pharmacokinetics under Actions).
A dose decrease may be required in patients who stop smoking.
Method of administration: For oral use.
Crushed tablets: For patients who are unable to swallow whole tablets, Adempas tablets may be crushed and mixed with water or soft foods such as applesauce immediately prior to use and administered orally (see Pharmacology: Pharmacokinetics under Actions).