Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
In addition to local effects resulting from administration of iloprost by inhalation such as cough, adverse reactions with iloprost are related to the pharmacological properties of prostacyclins.

The most frequently observed adverse reactions (≥ 20 %) in clinical trials include vasodilatation (including hypotension), headache and cough. The most serious adverse reactions were hypotension, bleeding events, and bronchospasm.


Tabulated list of adverse reactions
The adverse reactions reported below are based on pooled clinical trial data from phase II and III clinical trials involving 131 patients taking the medicinal product and on data from post-marketing surveillance. The frequencies of adverse reactions are defined as very common (≥1/10) and common (≥1/100 to <1/10). The adverse reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated from clinical trial data, are listed under "Frequency not known".

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Not known (cannot
System organ class         Very common                Common be estimated from
(MedDRA)                    (≥ 1/10)          (≥ 1/100 to < 1/10) the available data)
Blood and lymphatic       Bleeding events*§                               Thrombocytopenia system disorders
Not known (cannot
System organ class         Very common               Common be estimated from
(MedDRA)                    (≥ 1/10)          (≥ 1/100 to < 1/10) the available data)
Immune system                                                             Hypersensitivity disorders
Nervous system            Headache               Dizziness disorders
Cardiac disorders                                Tachycardia,
Palpitations
Vascular disorders        Vasodilatation         Syncope§ (see
Flushing               section 4.4)
Hypotension*
Respiratory, thoracic Chest discomfort           Dyspnoea                 Bronchospasm* (see and mediastinal       /chest pain                Pharyngolaryngeal        section 4.4) / disorders             Cough                      pain                     Wheezing Throat irritation
Gastrointestinal          Nausea                 Diarrhoea                Dysgeusia disorders                                        Vomiting
Mouth and tongue irritation including pain
Skin and                                         Rash subcutaneous tissue disorders
Musculoskeletal and       Pain in jaw/trismus connective tissue disorders
General disorders         Peripheral oedema§ and administration site condition

* Life-threatening and/or fatal cases have been reported
§ see section "Description of selected adverse reactions"

Description of selected adverse reactions
Bleeding events (mostly epistaxis and haemoptysis) were very common as expected in this patient population with a high proportion of patients taking anticoagulant co- medication. The risk of bleeding may be increased in patients when potential inhibitors of platelet aggregation or anticoagulants are given concomitantly (see section 4.5). Fatal cases included cerebral and intracranial haemorrhage.

Syncope is a common symptom of the disease itself, but can also occur under therapy.
The increased occurrence of syncope can be related to the deterioration of the disease or insufficient effectiveness of the product (see section 4.4).

In clinical trials peripheral oedema was reported in 12.2% of patients on iloprost and 16.2% of patients on placebo. Peripheral oedema is a very common symptom of the disease itself, but can also occur under therapy. The occurrence of peripheral oedema can be related to the deterioration of the disease or insufficient effectiveness of the product.
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/