Source: Health Products Regulatory Authority (IE) Revision Year: 2023 Publisher: Tillotts Pharma GmbH, Warmbacher Strasse 80, DE- 79618 Rheinfelden, Germany
Blood tests (differential blood count, liver function parameters such as ALT or AST; serum creatinine) and urinary status (dip sticks) should be determined prior to and during treatment, at the discretion of the treating physician. As a guideline, follow-up tests are recommended 14 days after commencement of treatment and then every 4 weeks for the following 12 weeks. If the findings are normal, follow-up tests should be carried out every three months. If additional signs appear, these tests should be performed immediately.
Asacolon should not be used in patients with impaired renal function.Caution should be exercised in patients with raised serum creatinine or proteinuria. The possibility of mesalazine-induced nephrotoxicity should be suspected in patients developing impairment of renal function during treatment.
Treatment with Asacolon should be stopped immediately if there is evidence of renal impairment and patients should seek immediate medical advice.
Cases of nephrolithiasis have been reported with the use of mesalazine including stones with a 100% mesalazine content. It is recommended to ensure adequate fluid intake during treatment.
Mesalazine may produce red-brown urine discoloration after contact with sodium hypochlorite bleach (e.g. in toilets cleaned with sodium hypochlorite contained in certain bleaches).
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.
Mesalazine should be discontinued, at the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.
Serious blood dyscrasia has very rarely been reported. Treatment with Asacolon should be stopped immediately if there is a suspicion or evidence of blood dyscrasia (signs of unexplained bleeding, haematoma, purpura, anaemia, persistent fever or sore throat) and patients should seek immediate medical advice.
There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Asacolon is administered to patients with liver impairment.
Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have rarely been reported with Asacolon. In case of a suspected mesalazine-induced cardiac hypersensitivity Asacolon must not be reintroduced. Caution should be taken in patients with previous myo- and pericarditis of allergic background regardless of its origin.
Patients with pulmonary disease, in particular asthma, should be very carefully monitored during treatment with Asacolon.
Patients with a history of adverse drug reactions to sulphasalazine therapy should be kept close under medical supervision. Treatment must be stopped immediately if acute symptoms of intolerance occur such as abdominal cramps, acute abdominal pain, fever, severe headache and rash.
In case of existing gastric or duodenal ulcers treatment should begin with caution based on theoretical grounds.
A limited number of reports of intact tablets in stool have been received. What appear to be intact tablets may in some cases represent largely empty shells of the coated tablets. If intact tablets are observed in the stool repeatedly, the patient should consult his/her physician.
Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Use in older patients should be handled with caution and the product should only be prescribed to patients having a normal or non-severely impaired liver and renal function, see 4.3.
There is only limited documentation for an effect in children (age 6-18 years), see section 4.2.
This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, i.e. is essentially “sodium-free”.
No interaction studies have been performed.
There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.
In patients who are concomitantly treated with azathioprine, or 6-mercaptopurine or thioguanine, a possible increase in the myelosuppressive effects of azathioprine, or 6-mercaptopurine or thioguanine should be taken into account.
As a result, life-threatening infection can occur.
Patients should be closely observed for signs of infection and myelosuppression. Haematological parameters, especially the leukocyte, thrombocyte and lymphocytecell counts should be monitored regularly (weekly), especially at initiation of such combination therapy(see section 4.4).
If white blood cells are stable after 1 month, testing every 4 weeks for the following 12 weeks followed by 3 monthly monitoring intervals appears to be justified.
There are no adequate data on the use of Asacolon in pregnant women. However, data from a limited number of exposed pregnancies indicate no adverse effect of mesalazine on the pregnancy or on the health of the fetus/newborn child. To date no other relevant epidemiologic data are available.
In one single case after long-term use of a high dose of mesalazine (2-4 g, orally) during pregnancy, renal failure in a neonate was reported.
Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/fetal development, parturition or postnatal development. Asacolon should only be used during pregnancy if the potential benefit outweighs the possible risk.
N-acetyl-5-aminosalicylic acid and to a lesser degree mesalazine are excreted in breast milk. The clinical significance of this has not been determined. Only limited experience during lactation in women is available to date. Hypersensitivity reactions such as diarrhoea in the infant cannot be excluded. Therefore, Asacolon should only be used during breast-feeding, if the potential benefit outweighs the possible risk. If the infant develops diarrhoea, breast-feeding should be discontinued.
No effects on fertility have been observed.
Asacolon has no or negligible influence on the ability to drive and use machines.
Asacolon 800 mg GR 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 Asacolon group with the highest reporting rate were worsening of ulcerative colitis (3.6%), haematuria (2.9%), and ketonuria (2.1%). All undesirable effects with Asacolon 800 mg GR Tablets were of mild to moderate severity. Discontinuations due to adverse reactions occurred in 8.6% of patients in the Asacolon 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 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).
Undesirable effects reported from clinical studies with patients treated with Asacolon 400 mg GR tablets and other sources are listed below.
| System Organ Class | 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) | Frequency not known |
|---|---|---|---|---|---|
| Blood and lymphatic system disorders | -- | eosinophilia (as part of an allergic | -- | altered blood counts (aplastic anemia, agranulocytosis, pancytopenia, neutropenia, leucopenia, thrombocytopenia). | -- |
| Immune system disorders | -- | -- | -- | hypersensitivity reactions such as allergic exanthema, drug fever, lupus erythematosus syndrome, pancolitis. | -- |
| Nervous system disorders | -- | paresthesia | headache, dizziness | peripheral neuropathy | -- |
| Cardiac disorders | -- | -- | myocarditis, pericarditis | -- | -- |
| Respiratory, thoracic and mediastinal disorders | -- | -- | -- | allergic and fibrotic lung reactions (including dyspnoea, cough, bronchospasm, alveolitis, pulmonary eosinophilia, lung infiltration, pneumonitis), interstitial pneumonia, eosinophilic pneumonia, lung disorder | pleurisy |
| Gastrointestinal disorders | dyspepsia | -- | abdominal pain, diarrhoea, flatulence, nausea, vomiting | acute pancreatitis | -- |
| Hepato-biliary disorders | -- | -- | -- | changes in liver function parameters (increase in transaminases and cholestasis parameters), hepatitis, cholestatic hepatitis | -- |
| Skin and subcutaneous tissue disorders | rash | urticaria, pruritus | photosensitivity* *see section c) | alopecia | Drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) |
| Musculoskeletal, connective tissue and bone disorders | -- | -- | -- | myalgia, arthralgia | lupus-like syndrome with pericarditis and pleuropericarditis as prominent symptoms as well as rash and arthralgia |
| Renal and urinary disorders | -- | -- | -- | impairment of renal function including acute and chronic interstitial nephritis and renal insufficiency, nephrotic syndrome, renal failure which may be reversible on early withdrawal. | Nephrolithiasis** ** see section 4.4 for further information |
| Reproductive system and breast disorders | -- | -- | -- | oligospermia (reversible) | -- |
| General disorders and administration site conditions | -- | pyrexia, chest pain | -- | -- | intolerance to mesalazine with C-reactive 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. |
An unknown number of the above mentioned undesirable effects are probably associated to the underlying IBD rather than Asacolon/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).
More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.
There is only limited safety experience with the use of Asacolon 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 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 via the HPRA Pharmacovigilance; Earlsfort Terrace IRL-Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
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