Adverse reactions : תופעות לוואי

4.8    Undesirable effects
In this section frequencies of undesirable effects are defined as follows: 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); not known (cannot be estimated from the available data).

Commonly the occurrence of anaphylactoid and other hyperergic reactions have been reported, e.g. in some cases in connection with the reduction of the thrombocyte count, were reported after the use of mesna. This risk is approx. 3.5 times higher in patients with autoimmune disease than in patients with tumour disease (without autoimmune disease).

Skin and mucous membrane reactions, such as urticaria, itching, exanthema up to the formation of blisters, enanthema, Lyell’s syndrome, Stevens-Johnson syndrome, local tissue swellings, conjunctivitis as well as unspecific general symptoms such as fever, chills, face redness, cough, pharyngitis, fatigue, tiredness, headache, back pain, arthralgia, nausea and vomiting, flatulence, diarrhoea, constipation, colics (e.g. abdominal pain), anorexia, influenza-like symptoms occurred. Circulatory reactions such as a drop in blood pressure and tachycardia (pulse rate >100/min), tachypnoea, hypertension, ST-segment elevation and myalgia and also a transient increase of values of different liver function tests (such as e.g transaminases) were observed. Uncommonly, local oedema and venous irritation at the injection site occurred.

In a tolerability study with high intravenous or oral doses of mesna, nausea, vomiting, diarrhoea, headache, limb and joint pain, drop in blood pressure and tachycardia, skin reactions, exhaustion, weakness, depression, irritability and exanthema occurred, when a single dose of 60 mg/kg body weight was administered. During treatment, the undesirable effects mentioned above cannot always be distinguished from those of the oxazaphosphorines or other concomitant medication.

SOC                Common          Uncommon               Rare                Very rare Infections and                                                                  Pharyngitis infestations
Immune system         Hypersensitivity                    Anaphylactoid disorders             reactions,                          reactions, allergic hyperergic                          reactions reactions
Metabolism and                                                                  Anorexia nutrition disorders
Psychiatric                                                                     Irritability, disorders                                                                       depression Nervous system                                                                  Headache disorders
Eye disorders                                             Conjunctivitis Cardiac disorders                                                               Tachycardia Vascular disorders                                        Drop in blood pressure,
hypertension, face redness,
circulatory reactions
SOC               Common            Uncommon                 Rare                Very rare Respiratory,                                                                        Tachypnoea, thoracic and                                                                        cough mediastinal disorders
Gastrointestinal     Nausea, vomiting                        Diarrhoea              Flatulence, disorders                                                                           constipation, colics, abdominal pain
Skin and             Itching,            Urticaria                                  Stevens-Johnson subcutaneous         exanthema,                                                     syndrome, Lyell’s tissue disorders     enanthematous                                                  syndrome skin reactions
Musculoskeletal                          Local tissue        Back pain              Arthralgia, and connective                           swelling                                   Myalgia, limb tissue disorders                                                                    pain, joint pain General disorders    Fever               Local oedema,       Exhaustion,            Influenza-like and administration                       venous irritation   weakness,              symptoms site conditions                          at the injection    mucous skin site, chills        reactions, fatigue,
tiredness
Investigations                                               Increase of the        Reduction of the values of different    thrombocyte liver function tests   count, pulse rate
> 100/min, ST- segment elevation
Injury, poisoning                                                                   Toxic reactions and procedural complications

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