Adverse reactions : תופעות לוואי

4.8 Undesirable effects
a) Summary of the safety profile
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, see section 4.4.

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
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 enteric coated 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
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)
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
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)
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/