Adempas

Treatment should only be initiated and monitored by a physician experienced in the treatment of CTEPH or PAH. Posology Starting dose The recommended starting dose is 1 mg 3 times daily for 2 weeks. 2). 5 mg 3 times daily, if systolic blood pressure is ≥95 mmHg and the patient has no signs or symptoms of hypotension.

1). 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. 5 mg 3 times daily. 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. 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.

5 mg 3 times daily. Maintenance dose The established individual dose should be maintained unless signs and symptoms of hypotension occur. 5 mg 3 times daily) for adults and paediatric patients with body weight of at least 50 kg. 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. Paediatric PAH patients weighing less than 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.

Patients may switch between tablets and oral suspension during therapy due to body weight changes. Treatment discontinuation 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.

Transitioning between phosphodiesterase-5 (PDE5) inhibitors and riociguat 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.

1). With longer observation in 11 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 1).

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 1:

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. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

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). In chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy is the treatment of choice as it is a potentially curative option.

According to standard medical practice, expert assessment of operability should be done prior to treatment with riociguat. 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.

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 years with systolic blood pressure < 95 mmHg.

1).