Riociguat

eMC SPC 4.2 (Adempas 0.5 mg film-coated tablets). Treatment should only be initiated and monitored by a physician experienced in the treatment of CTEPH or PAH. TITRATION (adults): increase the dose only 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 may be reached at 1.5 mg three times a day. If systolic blood pressure falls below 95 mmHg, maintain the dose provided the patient shows no signs or symptoms of hypotension; if at any time during up-titration systolic blood pressure decreases below 95 mmHg AND the patient shows signs or symptoms of hypotension, decrease the current dose by 0.5 mg three times daily. MAINTENANCE: the established individual dose should be maintained unless signs and symptoms of hypotension occur; if a dose is missed, continue with the next dose as planned; if not tolerated, consider dose reduction at any time. INTERRUPTION: if treatment has to be interrupted for 3 days or more, restart at 1 mg three times daily for 2 weeks and continue with the dose titration regimen. TRANSITIONING WITH PDE5 INHIBITORS: sildenafil must be discontinued in adults and children at least 24 hours prior to riociguat; tadalafil must be discontinued at least 48 hours in adults and 72 hours in children prior to riociguat; riociguat must be discontinued in adults and children at least 24 hours prior to a PDE5 inhibitor; monitor for signs and symptoms of hypotension after any transition. STRONG MULTI-PATHWAY CYP AND P-gp/BCRP INHIBITORS (e.g. azole antimycotics such as ketoconazole or itraconazole, HIV protease inhibitors such as ritonavir): when initiating riociguat in patients on stable doses, consider a starting dose of 0.5 mg three times a day and monitor for hypotension; consider a dose reduction for patients on riociguat doses >= 1.0 mg who develop signs or symptoms of hypotension. ELDERLY (65 years or older): higher risk of hypotension - particular care during individual dose titration. HEPATIC IMPAIRMENT: contraindicated in severe impairment (Child Pugh C, not studied); higher exposure in moderate impairment (Child Pugh B) - particular care during titration. PAEDIATRIC (not a per-kg regimen, so not captured in paedDose): for paediatric PAH patients aged 6 to < 18 years with body weight >= 50 kg, tablets are used and the dose is increased in 2-week intervals by 0.5 mg three times daily to a maximum daily dose of 3 times 2.5 mg, provided 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; if systolic blood pressure falls below these levels the dose should be maintained as long as there are no signs or symptoms of hypotension, and if hypotension is symptomatic the current dose should be decreased by 0.5 mg three times daily. Paediatric PAH patients at least 6 years of age weighing less than 50 kg should receive the granules for oral suspension - see the separate SPC for that presentation; patients may switch between tablets and oral suspension during therapy due to body weight changes. Safety and efficacy have not been established in children aged < 6 years (safety concerns; non-clinical data show undesirable effects on growing bone) or in children with PAH aged 6 to < 12 years with systolic blood pressure < 90 mmHg at treatment initiation, and no paediatric data exist for hepatic or renal impairment or for concomitant strong CYP/P-gp/BCRP inhibitors. Verify all paediatric dosing against a children's formulary.