Adverse reactions : תופעות לוואי

4.8 Undesirable effects

The overall safety profile of Ilomedin is based on data from post-marketing surveillance and on pooled clinical trial data. The crude incidences were based on the cumulative database of 3325 patients having received iloprost either in controlled or uncontrolled clinical trials or in a compassionate use program from generally elderly and multimorbid patients with peripheral arterial occlusive disease (PAOD) in its advanced stages III and IV and patients with thromboangitis obliterans (TAO), for details see table 1.

The most frequently observed adverse drug reactions (≥ 10%) in patients receiving iloprost in clinical trials are headache, flushing, nausea, vomiting and hyperhidrosis. These are likely to occur while the dose is titrated at the start of treatment to identify the best tolerable dose for the individual patient. However, all these side effects usually disappear quickly with dose reduction.

Overall, the most serious adverse drug reactions in patients receiving iloprost are cerebrovascular accident, myocardial infarction, pulmonary embolism, cardiac failure, convulsion, hypotension, tachycardia, asthma, angina pectoris, dyspnea and pulmonary edema.

Another group of side effects is related to local infusion site reactions. For example, infusion site redness and infusion site pain may occur or a cutaneous vasodilation may give rise to streaky erythema above the infusion vein.

The adverse drug reactions observed with Ilomedin are represented in the table below. They are classified according to System Organ Class. The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.

Adverse drug reactions from clinical trials are classified according to their frequencies. Frequency groupings are defined according to the following convention: very common ≥1/10, common ≥1/100 to <1/10, uncommon ≥ 1/1,000 to <1/100 and rare ≥1/10,000 to <1/1,000.


Table 1: Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with Ilomedin
System Organ      Very common         Common                 Uncommon                     Rare Class
(MedDRA)
Blood and                                                    Thrombocytopenia lymphatic system disorders
Immune                                                       Hypersensitivity system disorders
Metabolism                            Decreased and nutrition                         appetite disorders
Psychiatric                           Apathy,              Anxiety,
disorders                             Confusional state    Depression, Hallucinations
Nervous           Headache            Dizziness/ Vertigo,  Convulsion*, system                                Paresthesia/         Syncope,
disorders                             Throbbing sensation/ Tremor,
Hyperesthesia/       Migraine
Burning sensation,
Restlessness/
Agitation,
Sedation,
Drowsiness
Eye disorders                                              Vision blurred, Eye irritation,
Eye pain
Ear and                                                                                   Vestibular labyrinth                                                                                 disorder disorders
Cardiac                               Tachycardia*,          Myocardial infarction* disorders                             Bradycardia,           Cardiac failure*, Angina pectoris*       Arrhythmia/
Extrasystoles
Vascular          Flushing            Hypotension *,         Cerebrovascular accident*/ disorders                             Blood pressure         Cerebral ischemia, increased              Pulmonary embolism*,
Deep vein thrombosis

Respiratory,                          Dyspnea*               Asthma*,                     Cough thoracic and                                                 Pulmonary edema* mediastinal disorders


Very             Common                       Uncommon             Rare System Organ       common
Class
(MedDRA)
Gastrointestinal   Nausea,          Diarrhea,                    Diarrhea             Proctitis disorders          Vomiting         Abdominal                    hemorrhagic, discomfort/                  Rectal hemorrhage,
Abdominal pain               Dyspepsia,
Rectal tenesmus,
Constipation,
Eructation,
Dysphagia,
Dry mouth/
Dysgeusia


Hepato-biliary                                                   Jaundice disorders
Skin and           Hyperhidrosis                                 Pruritus Subcutaneous tissue disorders
Musculoskeletal                     Pain in jaw .                Tetany.
and connective                      Trismus.                     muscular tissue disorders                    Myalgia.                     spasms.
Arthralgia.                  Hypertonia.
Renal and                                                        Kidney Urinary                                                          pain.
disorders                                                        Vesical tenesmus.
urine abnormality,
Dysuria,
Urinary tract disorders
General                             Pain,
disorders and                       Pyrexia.
administration                      Body temperature site conditions                     increased.
feeling hot.
Asthenia. Malaise.
Chills.
Fatigue / Tiredness.
Thirst.
Infusion site reactions
(Infusion site erythema,
Infusion site pain,
Infusion site phlebitis) .

* life-threatening and/or fatal cases have been reported

Iloprost may provoke angina pectoris, especially in patients with coronary artery disease.

The risk of bleeding is increased in patients when inhibitors of platelet aggregation, heparin or anticoagulants of the coumarin-type are given concomitantly.

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/