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 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).


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
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)
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                Drug reaction subcutaneous                    pruritus                                                    with eosinophilia tissue disorders                                                                            and systemic symptoms
(DRESS),
Stevens-
Johnson
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
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)
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/