ADEMPAS FILM-COATED TABLET 2.0mg

TABLET, FILM COATED

**4.2 Dosage and method of administration** **4.2.1 Method of administration** Oral use. **4.2.2 Dosage regimen** _Adults_ _Treatment initiation_ The recommended starting dose is 1.0 mg three times daily for 2 weeks. Tablets should be taken three times daily approximately 6 to 8 hours apart with or without food. Dosage should be increased in 2-week intervals by 0.5 mg increments 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 1.5mg three times a day (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). If systolic blood pressure falls below 95 mmHg dosage 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 a day. _Maintenance dose_ The established individual dose should be maintained unless signs and symptoms of hypotension occur. The maximum total daily dose of Adempas is 7.5 mg. If a dose is missed, treatment should be continued with the next dose as planned. If not tolerated, dose reduction might be considered at any time. _Crushed tablets_ For patients who are unable to swallow whole tablets, Adempas tablet may be crushed and mixed with water or soft foods such as applesauce immediately prior to use and administered orally _(see section ‘Pharmacokinetic properties’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)_. _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 described above. **4.2.3 Additional information on special populations** Individual dose titration at treatment initiation allows to adjust the dose to the patient's needs. **4.2.3.1 Transitioning to and from Adempas** Discontinue sildenafil at least 24 hours prior to administering Adempas. It is recommended to monitor for signs and symptoms of hypotension on initiation (see section _‘Contraindications_’, _‘Pharmacodynamic Interaction’_ and _‘Clinical efficacy’_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Discontinue tadalafil at least 48 hours prior to administering Adempas. It is recommended to monitor for signs and symptoms of hypotension on initiation (see section _‘Contraindications_’, _‘Pharmacodynamic Interaction’_ and _‘Clinical efficacy’_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Discontinue Adempas at least 24 hours prior to administering a PDE5 inhibitor. It is recommended to monitor for signs and symptoms of hypotension on initiation (see section _‘Contraindications_’, _‘Pharmacodynamic Interaction’_ and _‘Clinical efficacy’_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.2.3.2 Pediatric patients** The safety and efficacy of Adempas have not yet been tested in patients below 18 years. No data are available. Non-clinical data show an adverse effect on growing bone. Until more is known about the implication of these findings, the use of riociguat in children and in adolescents should be avoided. **4.2.3.3 Geriatric patients** In elderly (≥65 years), particular care should be exercised during individual dose titration. **4.2.3.4 Patients with hepatic impairment** Patients with moderate hepatic impairment (Child Pugh B) showed a higher exposure to Adempas. Particular care should be exercised during individual dose titration. Patients with severe hepatic impairment (Child Pugh C) have not been studied and therefore use of Adempas is not recommended in these patients _(see Section ‘special warnings and precautions for use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)_. **4.2.3.5 Patients with renal impairment** Patients with mild, moderate or severe renal impairment (creatinine clearance 80–15 mL/min) showed a higher exposure to Adempas. Particular care should be exercised during individual dose titration. Patients with creatinine clearance <15 mL/min or on dialysis have not been studied and therefore use of Adempas is not recommended in these patients _(see section ‘special warnings and precautions for use’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)_. There is a higher risk of hypotension in patients with renal impairment; therefore particular care should be exercised during individual dose titration. **4.2.3.6 Patients on stable doses of strong multi pathway CYP / P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitors 20** Coadministration of Adempas with strong multi pathway CYP and P-gp/BCRP inhibitors such as azole antimycotics (e.g. ketoconazole, itraconazole) or HIV protease inhibitors (e.g. ritonavir) increases exposure to Adempas ( _see section ‘Interaction with other medicinal products and other forms of interaction’_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). When initiating Adempas in patients on stable doses of strong multi pathway CYP and P-gp/BCRP inhibitors, consider a starting dose of 0.5 mg, three times a day to mitigate the risk of hypotension. Monitor for signs and symptoms of hypotension on initiation and on treatment. Consider a dose reduction for patients on Adempas doses higher than or equal to 1.0 mg if the patient develops signs or symptoms of hypotension (see sections _‘Dosage regimen’, ‘Special warnings and precautions for use’_ and _‘Interaction with other medicinal products and other forms of interaction’_ – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **4.2.3.7 Smoking status** Current smokers should be advised to stop smoking. Plasma concentrations of riociguat in smokers are reduced compared to non-smokers. Dose adjustment of riociguat may be required in patients who stop or start smoking during treatment _(see section ‘Interaction with other medicinal products and other forms of interaction’ – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information)_.