Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The safety of Adempas has been evaluated in phase III studies of 681 patients with CTEPH and PAH receiving at least one dose of riociguat (see section 5.1). 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.

The most commonly reported adverse reactions, occurring in ≥10% of patients under Adempas treatment (up to 2.5 mg three times daily), were headache, dizziness, dyspepsia, peripheral oedema, nausea, diarrhoea and vomiting.

Serious haemoptysis and pulmonary haemorrhage, including cases with fatal outcome have been observed in patients with CTEPH or PAH treated with Adempas (see section 4.4).

The safety profile of Adempas 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 Adempas 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 Adempas in the phase III studies 
MedDRA                              Very common             Common                           Uncommon System Organ Class
Infections and infestations                                 Gastroenteritis Blood and lymphatic system                                  Anaemia (incl. respective disorders                                                   laboratory parameters) Nervous system disorders            Dizziness
Headache
Cardiac disorders                                           Palpitations Vascular disorders                                          Hypotension Respiratory, thoracic and                                   Haemoptysis                      Pulmonary mediastinal disorders                                       Epistaxis                        haemorrhage* Nasal congestion
Gastrointestinal disorders          Dyspepsia               Gastritis Diarrhoea               Gastro-oesophageal reflux
Nausea                  disease
Vomiting                Dysphagia
Gastrointestinal and abdominal pains
Constipation
Abdominal distension
General disorders and          Oedema peripheral administration site conditions
* fatal pulmonary haemorrhage was reported in uncontrolled long term extension studies 
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.

Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il