Adverse reactions : תופעות לוואי

4.8 Undesirable effects
 a) Summary of the safety profile
Asacol 800 mg enteric coated Tablets have been evaluated in 140 patients with mild to moderate active ulcerative colitis in one controlled study lasting for 10 weeks comparing safety and efficacy versus another 141 patients treated with placebo. Treatment related undesirable effects in the Asacol group with the highest reporting rate were worsening of ulcerative colitis (3.6%), haematuria (2.9%), and ketonuria (2.1%). All undesirable effects with Asacol 800 mg enteric coated Tablets were of mild to moderate severity.
Discontinuations due to adverse reactions occurred in 8.6% of patients in the Asacol group and in 21.3% of patients in the placebo group. Most of the drug related reactions that led to study drug discontinuation were related to worsening of ulcerative colitis.
Organ specific adverse drug reactions affecting the heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue have been reported.

Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment
(see section 4.4).
 b)   Tabulated summary of adverse reactions

In addition to the undesirable effects reported above in a clinical trial with Asacol 800 mg enteric coated Tablets, undesirable effects relevant for the labeling reported from eight (8) double-blind and five (5) open clinical studies with 739 patients treated with Asacol 400 mg MR Tablets are listed below.

Common       Uncommon       Rare               Very rare               Frequency not System      Organ
(≥ 1/100      (≥ 1/1,000    (≥ 1/10,000 to <   (< 1/10,000)            known Class to < 1/10)   to < 1/100)    1/1,000)
Blood and                        eosinophilia                      altered blood lymphatic                        (as part of                       counts (aplastic system                           an allergic                       anemia, disorders                        reaction)                         agranulocytosis, pancytopenia,
neutropenia,
leucopenia,
thrombocytopenia)
Immune system                                                      hypersensitivity disorders                                                          reactions such as allergic exanthema,
drug fever, lupus erythematosus syndrome,
pancolitis
Nervous system                   paresthesia    headache,          peripheral disorders                                       dizziness          neuropathy Cardiac                                         myocarditis,
disorders                                       pericarditis
Respiratory,                                                       allergic and fibrotic   pleurisy thoracic and                                                       lung reactions mediastinal                                                        (including disorders                                                          dyspnoea, cough bronchospasm,
alveolitis,
pulmonary
eosinophilia, lung infiltration,
pneumonitis),
interstitial pneumonia,
eosinophilic pneumonia, lung disorder
Gastrointestinal   dyspepsia                 abdominal pain,     acute pancreatitis disorders                                    diarrhoea,
flatulence,
nausea, vomiting
Hepato-biliary                                                   changes in liver disorders                                                        function parameters
(increase in transaminases and cholestasis parameters),
hepatitis,
cholestatic hepatitis
Skin and           rash        urticaria,    photosensitivity*   alopecia                Stevens- subcutaneous                   pruritus                                                  Johnson tissue disorders                                                                         syndrome (SJS),
toxic epidermal necrolysis
(TEN)
Musculoskeletal,                                                 myalgia, arthralgia     lupus-like connective                                                                               syndrome with tissue and bone                                                                          pericarditis and disorders                                                                                pleuropericarditis as prominent symptoms as well as rash and arthralgia
Renal and                                                        Impairment of renal     Nephrolithiasis** urinary                                                          function including disorders                                                        acute and chronic interstitial nephritis, renal insufficiency,
nephrotic syndrome and renal failure which may be reversible on early withdrawal
Reproductive                                                     oligospermia system and                                                       (reversible) breast disorders
General                        pyrexia,                                                  intolerance to disorders and                  chest pain,                                               mesalazine with administration                                                                           C-reactive site conditions                                                                          protein increased and/or exacerbation of symptoms of underlying disease
Investigations                                                                        blood creatinine increased,
weight decreased,
creatinine clearance decreased,
amylase increased, red blood cell sedimentation rate increased,
lipase increased, BUN increased
*see section c)
**see section 4.4 for further information
 c) Description of selected adverse reactions

An unknown number of the above mentioned undesirable effects are probably associated to the underlying IBD rather than Asacol/mesalazine medication. This holds true especially for gastrointestinal undesirable effects, arthralgia, and alopecia.

To avoid blood dyscrasia resulting from developing bone marrow depression patients should be monitored with care, see section 4.4.

Under co-administration of mesalazine with immunosuppressive drugs, such as azathioprine or 6-MP or thioguanine, life-threatening infection can occur, see section 4.5.

Photosensitivity
More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.
 d) Paediatric population

There is only limited safety experience with the use of Asacol tablets in the paediatric population. It is expected that the target organs of possible adverse reactions in the paediatric population are the same as for adults (heart, lungs, liver, kidneys, pancreas, skin and subcutaneous tissue).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization 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/