Adverse reactions : תופעות לוואי

         4.8     Undesirable effects
Summary of the safety profile
The most frequent adverse reactions seen in clinical trials are diarrhoea, nausea, abdominal pain, headache, vomiting and rash. Hypersensitivity reactions and drug fever may occasionally occur, and severe cutaneous adverse reactions (SCARs), including Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens- Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see section 4.4).

Frequency of adverse effects, based on clinical trials and reports from post-marketing surveillance


Common                                                                 Not Known Rare
≥1/100 to                                   Very rare                   (cannot be SOC                            ≥1/10,000 to
< 1/10                                     ≤1/10,000                estimated from ≤1/1,000 the available data)
Blood and the                                          Altered blood counts lymphatic                                              (anaemia,
system                                                 aplastic anaemia, disorders                                              agranulocytosis, neutropenia,
leucopenia (incl.
granulocytopenia) pancytopenia thrombocytopenia,and eosinophilia (as part of an allergic reaction).


Immune system                                          Hypersensitivity reaction disorders                                              including anaphylactic reaction,
Nervous system    Headache        dizziness            Peripheral neuropathy disorders                                              Benign intracranial hypertension in adolescents
Cardiac                           Myocarditis*         Pericardial effusion disorders                         Pericarditis*
Respiratory,                                           Allergic alveolitis, allergic thoracic and                                           and fibrotic lung reactions mediastinal                                            (incl. dyspnoea, coughing, disorders                                              bronchospasm, pulmonary eosinophilia, interstitial lung disease, pulmonary infiltration, pneumonitis)


Gastrointestinal   Diarrhoea,         Increased amylase Pancolitis disorders          abdominal          (blood and/or pain, nausea,      urine), acute vomiting,          pancreatitis* flatulence

Hepato-biliary                                     Increased liver enzymes, disorders                                          cholestatis parameters and bilirubin, Hepatotoxicity
(incl. hepatitis*, cholestatic hepatitis, cirrhosis, hepatic failure)
Skin and           Rash (incl.  Photosensitivity** Alopecia (Reversible)                           Stevens-Johnson subcutaneous       urticaria,                      Quincke's oedema,                               Syndrome tissue disorders   erythematous                    dermatitis allergic,                            (SJS)/Toxic rash)                           Erythema multiforme                             epidermal necrolysis (TEN).
Drug Reaction with Eosinophilia and Systemic
Symptoms
(DRESS)
Musculoskeletal                                                Myalgia, Arthralgia connective                                                     Lupus erythematosus-like tissue and bone                                                reactions disorders
Renal and                                                      Renal function impairment       Nephrolithiasis*** urinary                                                        (incl. interstitial nephritis*( disorders                                                      acute and chronic), nephrotic syndrome, renal insufficiency(acute/chronic),
Urine discolouration***
Reproductive                                                   Oligospermia (reversible) system disorders

General                                                        Drug fever disorders and administration site conditions

* The mechanism of mesalazine induced myo- and pericarditis, pancreatitis, nephritis and hepatitis is unknown, but it might be of allergic origin.
(**) Photosensitivity: More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.
(***) Nephrolithiasis; see section 4.4 for further information

It is important to note that several of these disorders can also be attributed to be the inflammatory bowel disease itself.
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 to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il/