Riociguat

Source: UK SPC (eMC) for Adempas 0.5 mg film-coated tablets, §4.2 (https://www.medicines.org.uk/emc/product/5334/smpc). Indication context: chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH). Treatment should only be initiated and monitored by a physician experienced in the treatment of CTEPH or PAH. TITRATION RULES: in some PAH patients an adequate response on the 6-minute walk distance 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 up-titration 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: maintain the established individual dose 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 with 1 mg 3 times daily for 2 weeks and then continue the titration regimen. TRANSITIONING WITH PDE5 INHIBITORS: sildenafil must be discontinued in adults and children at least 24 hours prior to riociguat; tadalafil 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 hypotension after any transition. PATIENTS ON STABLE DOSES OF 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, monitor for signs and symptoms of hypotension, and consider a dose reduction for patients on riociguat doses higher than or equal to 1.0 mg who develop signs or symptoms of hypotension. SMOKERS: plasma concentrations of riociguat are reduced in smokers; the UK SPC states that a dose increase to the maximum daily dose of 2.5 mg 3 times daily may be required in patients who are smoking or who start smoking during treatment, and a dose decrease may be required in patients who stop. (The US FDA label §2.4 instead says to consider titrating above 2.5 mg three times a day in patients who smoke — that US divergence has NOT been adopted here; the UK ceiling above stands.) ELDERLY (65 years or older): higher risk of hypotension — exercise particular care during individual dose titration. HEPATIC IMPAIRMENT: contraindicated in severe hepatic impairment (Child Pugh C); higher exposure in Child Pugh B, so exercise particular care during titration; no clinical data in under-18s with hepatic impairment. ADMINISTRATION: may generally be taken with or without food, but for patients prone to hypotension switches between fed and fasted intake are not recommended; for patients unable to swallow whole tablets, Adempas tablets may be crushed and mixed with water or soft foods immediately prior to use. §4.5 was not retrieved — the interactions listed come from §4.2, §4.3 and the US FDA label §7; verify the full §4.5.

NOT A PER-KG DOSE — dosePerKg is deliberately null; do not compute a weight-based dose from this entry. UK SPC §4.2: the Adempas TABLET is for paediatric PAH patients aged 6 to less than 18 years with body weight 50 kg or more. Titration is performed on systolic blood pressure and general tolerability at the discretion of the treating physician: if the patient has no signs or symptoms of hypotension and systolic blood pressure is 90 mmHg or above (6 to less than 12 years) or 95 mmHg or above (12 to less than 18 years), increase 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 levels, maintain the dose as long as there are no signs or symptoms of hypotension; if it falls below these levels with signs or symptoms of hypotension, decrease the current dose by 0.5 mg 3 times daily. PAEDIATRIC PAH PATIENTS WEIGHING LESS THAN 50 KG must use Adempas granules for oral suspension — a different product with its own SPC, which is NOT in this bundle. Patients may switch between tablets and oral suspension during therapy due to body weight changes. Safety and efficacy have not been established, and use is not recommended, in children aged under 6 years, in children with PAH aged 6 to less than 12 years with systolic blood pressure below 90 mmHg at treatment initiation, in patients aged 12 to less than 18 years with systolic blood pressure below 95 mmHg at initiation, and in children and adolescents with CTEPH aged under 18 years. Verify any under-18 use against a children's formulary.