ADEMPAS

Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. The child’s weight and systolic blood pressure must be monitored, and the dose be checked regularly. 0 mg 3 times daily). The oral suspension should be taken 3 times daily approximately 6 to 8 hours apart.

Titration Titration scheme Titration of riociguat dose is to be performed based on the patient’s systolic blood pressure, at the discretion of the treating healthcare professional. 5 mg 3 times daily, if the patient has no signs or symptoms of hypotension and if systolic blood pressure is - ≥ 90 mmHg for the 6 to < 12 year age group - ≥ 95 mmHg for the 12 to < 18 year age group.

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. 5 mg 3 times daily. Maintenance dose The established individual dose should be maintained unless signs and symptoms of hypotension occur.

The maximum dose depends on the body weight and is shown in Table 1. If not tolerated, dose reduction should be considered at any time. 0 * single dose (mL) to be given 3 times daily Missed dose If a dose is missed, treatment should be continued with the next dose as planned.

Treatment interruption In case treatment has to be interrupted for 3 days or more, treatment should be restarted with a body weight adjusted equivalent to 1 mg 3 times daily for 2 weeks and continued with the dose titration regimen as described above.

Transitioning between phosphodiesterase-5 (PDE5) inhibitors and riociguat Sildenafil must be discontinued at least 24 hours prior to administration of riociguat. Tadalafil must be discontinued at least 72 hours prior to administration of riociguat.

Riociguat must be discontinued at least 24 hours prior to administration of a PDE5 inhibitor. 1). PAH patients weighing 50 kg and more Adempas is also available as a tablet to treat paediatric patients weighing 50 kg and more – see Summary of Product Characteristics for Adempas tablets for further direction.

Patients may switch between tablets and oral suspension during therapy due to body weight changes. Special populations Individual dose titration at treatment initiation allows adjustment of the dose to the patient´s needs. 3). 2). Particular care should be exercised during individual dose titration.

No clinical data are available in children and adolescents less than 18 years of age with hepatic impairment. 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.

4). 2). There is a higher risk of hypotension in patients with renal impairment, therefore particular care should be exercised during individual dose titration. No clinical data are available in children and adolescents less than 18 years of age with renal impairment.

g. g. 5). 5 mg of the oral suspension 3 times daily (see Table 2) to mitigate the risk of hypotension. Monitor for signs and symptoms of hypotension on initiation and on treatment. 5). No clinical data are available in children and adolescents less than 18 years of age receiving concomitant systemic treatment with strong CYP/P-gp and BCRP inhibitors.

Table 2:

Body weight-adjusted […]

1). With longer observation in uncontrolled long term extension studies the safety profile was similar to that observed in the placebo controlled phase III trials. Most of the adverse reactions are caused by relaxation of smooth muscle cells in vasculature or the gastrointestinal tract.

5 mg 3 times daily), were headache, dizziness, dyspepsia, peripheral oedema, nausea, diarrhoea and vomiting. 4). The safety profile of riociguat in patients with CTEPH and PAH appeared to be similar, therefore adverse reactions identified from placebo controlled 12 and 16 weeks clinical studies are presented as pooled frequency in the table listed below (see table 3).

Tabulated list of adverse reactions The adverse reactions reported with riociguat are listed in the table below by MedDRA system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000) and not known (cannot be estimated from the available data).

Table 3:

Adverse reactions reported with riociguat in adult patients in phase III studies (pooled CHEST 1 and PATENT 1 data) MedDRA System Organ Class Very common Common Uncommon Infections and infestations Gastroenteritis Blood and lymphatic system disorders Anaemia (incl.

2), followed by an optional long-term extension phase. Most common adverse reactions including the long-term extension phase were hypotension and headache occurring in 4/24, and 2/24 patients, respectively. Overall, the safety data is consistent with the safety profile observed in adults.

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

In pulmonary arterial hypertension, studies with riociguat have been mainly performed in forms related to idiopathic or heritable PAH and PAH associated with connective tissue disease. 1). Pulmonary veno-occlusive disease Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD).

Therefore, administration of riociguat to such patients is not recommended. Should signs of pulmonary oedema occur, the possibility of associated PVOD should be considered and treatment with riociguat should be discontinued. Respiratory tract bleeding In pulmonary hypertension patients there is increased likelihood for respiratory tract bleeding, particularly among patients receiving anticoagulation therapy.

A careful monitoring of patients taking anticoagulants according to common medical practice is recommended. The risk of serious and fatal respiratory tract bleeding may be further increased under treatment with riociguat, especially in the presence of risk factors, such as recent episodes of serious haemoptysis including those managed by bronchial arterial embolisation.

Riociguat should be avoided in patients with a history of serious haemoptysis or who have previously undergone bronchial arterial embolisation. In case of respiratory tract bleeding, the prescriber should regularly assess the benefit- risk of treatment continuation.

4% (12/490) of patients taking riociguat compared to 0/214 of placebo patients. Serious haemoptysis occurred in 1% (5/490) patients taking riociguat compared to 0/214 patients taking placebo, including one event with fatal outcome. Serious haemorrhagic events also included 2 patients with vaginal haemorrhage, 2 with catheter site haemorrhage, and 1 each with subdural haematoma, haematemesis, and intra-abdominal haemorrhage.

Hypotension Riociguat has vasodilatory properties which may result in lowering of blood pressure. g. patients on antihypertensive therapy or with resting hypotension, hypovolaemia, severe left ventricular outflow obstruction or autonomic dysfunction).

3). Renal impairment Data in adult patients with severe renal impairment (creatinine clearance < 30 mL/min) are limited and there are no data for patients on dialysis, therefore riociguat is not recommended in these patients. Patients with mild and moderate renal impairment were included in the pivotal studies.

2). There is a higher risk of hypotension in these patients, particular care should be exercised during individual dose titration. 3). 2). Particular care should be exercised during individual dose titration. There is no clinical experience with riociguat in patients with elevated liver aminotransferases (> 3 x Upper Limit of Normal (ULN)) or with elevated direct bilirubin (> 2 x ULN) prior to initiation of treatment; riociguat is not recommended in these patients.

3). Therefore, female patients at potential risk of pregnancy must use an effective method of contraception. Monthly pregnancy tests are recommended. Smokers Plasma concentrations of riociguat in smokers are reduced compared to non-smokers.

2). 8 mg sodium benzoate (E 211) in each mL oral suspension. 5 mg sodium in each mL oral suspension. This medicinal product contains less than 1 mmol sodium (23 mg) per mL oral suspension, that is to say essentially “sodium free”.

5). - Severe hepatic impairment (Child Pugh C). 1. 6). 5). - Concomitant use with other soluble guanylate cyclase stimulators. - Treatment initiation for o children aged 6 to < 12 years with systolic blood pressure < 90 mmHg, o patients ≥ 12 to < 18 years with systolic blood pressure < 95 mmHg.

1).