Riociguat

VERBATIM SPC 4.2 STARTING DOSE: 'The recommended starting dose is 1 mg 3 times daily for 2 weeks. Tablets should be taken 3 times daily approximately 6 to 8 hours apart.' TITRATION (adults): 'Dose should be increased in 2-week intervals by 0.5 mg 3 times daily to a maximum of 2.5 mg 3 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 3 times a day. 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 3 times daily.' MAINTENANCE: 'The established individual dose should be maintained unless signs and symptoms of hypotension occur.' MISSED DOSE: '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.' INTERRUPTION: 'In case treatment has to be interrupted for 3 days or more, treatment should be restarted with 1 mg 3 times daily for 2 weeks, and continued with the dose titration regimen as described above.' STRONG MULTI-PATHWAY CYP AND P-gp/BCRP INHIBITORS (azole antimycotics such as ketoconazole or itraconazole, HIV protease inhibitors such as ritonavir): 'consider a starting dose of 0.5 mg 3 times a day to mitigate the risk of hypotension... Consider a dose reduction for patients on riociguat doses higher than or equal to 1.0 mg if the patient develops signs or symptoms of hypotension.' SMOKERS: 'A dose increase to the maximum daily dose of 2.5 mg 3 times daily may be required in patients who are smoking or start smoking during treatment. A dose decrease may be required in patients who stop smoking.' PDE5-INHIBITOR TRANSITION: 'Sildenafil must be discontinued in adults and children at least 24 hours prior to administration of riociguat. Tadalafil must be discontinued at least 48 hours in adults and 72 hours in children prior to administration of riociguat. Riociguat must be discontinued in adults and children at least 24 hours prior to administration of a PDE5 inhibitor.' ELDERLY: '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.' INITIATION: 'Treatment should only be initiated and monitored by a physician experienced in the treatment of CTEPH or PAH.'

WEIGHT-BANDED AND BLOOD-PRESSURE-TITRATED, NOT PER-KILOGRAM - so no per-kg figure is published and the weight calculator is deliberately left inactive. Licensed paediatric population is PAH only, aged 6 to under 18 years; CTEPH in under-18s is explicitly not recommended. SPC 4.2 verbatim, 'Paediatric PAH patients aged 6 to < 18 years with body weight >= 50 kg': 'Adempas is available for paediatric use as a tablet for those with body weight >= 50 kg. Titration of riociguat dose is to be performed based on the patient's systolic blood pressure and general tolerability at the discretion of the treating physician/healthcare provider. If the patient has no signs or symptoms of hypotension and systolic blood pressure is >= 90 mmHg for the 6 to < 12 year age group or >= 95 mmHg for the 12 to < 18 year age group, the dose should be increased in 2-week intervals by 0.5 mg 3 times daily to a maximum daily dose of 3 times 2.5 mg. If systolic blood pressure falls below these specified levels the dosage should be maintained as long as 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 the specified levels, and the patient shows signs or symptoms of hypotension the current dose should be decreased by 0.5 mg 3 times daily.' UNDER 50 KG: 'Adempas is available as granules for oral suspension to treat paediatric PAH patients at least 6 years of age and weighing less than 50 kg - see Summary of Product Characteristics for Adempas granules for oral suspension for further direction.' That granules SPC was NOT fetched in this bundle, so no dose for children under 50 kg is published here. NOT ESTABLISHED IN: children aged under 6 years (safety concerns; non-clinical data show undesirable effects on growing bone); children with PAH aged 6 to <12 years with systolic BP <90 mmHg at initiation; children and adolescents with PAH aged 12 to <18 years with systolic BP <95 mmHg at initiation; children and adolescents with CTEPH aged <18 years. No clinical data are available in under-18s with hepatic impairment, with renal impairment, or receiving strong CYP/P-gp and BCRP inhibitors. Confirm every paediatric figure against a children's formulary and specialist paediatric pulmonary hypertension advice before use.