Source: Health Products Regulatory Authority (IE) Revision Year: 2021 Publisher: Ferring Ireland Ltd, United Drug House, Magna Drive, Magna Business Park, Citywest Road, Dublin 24, Ireland
Hypersensitivity to mesalazine, any of the excipients listed in section 6.1, or salicylates.
Severe liver and/or renal impairment.
Caution is recommended when treating patients allergic to sulphasalazine (risk of allergy to salicylates). Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment. In case of acute symptoms of intolerance, i.e. abdominal cramps, abdominal pain, fever and severe headache, and/or the first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other signs of hypersensitivity, the treatment should be discontinued immediately.
Caution is recommended in patients with impaired liver function. Liver function parameters like ALT or AST should be assessed prior to and during treatment, at the discretion of the treating physician.
The drug is not recommended for use in patients with impaired renal function and in patients with haemorrhagic diathesis. The renal function should be regularly monitored (e.g. serum creatinine), especially during the initial phase of treatment. Urinary status (dip sticks) should be determined prior to and during treatment at the discretion of the treating physician. Mesalazine induced nephrotoxicity should be suspected in patients developing renal dysfunction during treatment. The concurrent use of other known nephrotoxic agents, such as NSAIDs and azathioprine, may increase the risk of renal reactions.
Caution is recommended in patients with active peptic ulcer.
Patients with pulmonary disease, in particular asthma, should be very carefully monitored during a course of treatment; please refer to section 4.8.
Mesalazine-induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported rarely. Serious blood dyscrasias have been reported very rarely with mesalazine (see section 4.5). Blood tests for differential blood counts is recommended prior to and during treatment, at the discretion of the treating physician. Treatment should be discontinued on suspicion or evidence of these adverse reactions.
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.
As a guideline, follow-up tests are recommended 14 days after commencement of treatment, then a further two to three tests at intervals of 4 weeks. If the findings are normal, follow-up tests should be carried out every three months. If additional symptoms occur, these tests should be performed immediately.
No interaction studies have been performed. Combination therapy with Pentasa and azathioprine or 6-mercaptopurine or thioguanine have shown a higher frequency of myelosuppressive effects, and an interaction cannot be ruled out, however, the mechanism behind the interaction is not established. Regular monitoring of white blood cells is recommended and the dosage regimen of thiopurine should be adjusted accordingly.
There is weak evidence that mesalazine might decrease the anticoagulant effect of warfarin.
Pentasa Sachet should not be used during pregnancy and lactation except when the potential benefits of the treatment outweigh the possible hazards in the opinion of the physician. The underlying condition itself (Inflammatory bowel disease (IBD)) may increase risks for adverse pregnancy outcome.
Mesalazine is known to cross the placental barrier and its concentration in umbilical cord plasma is lower than the concentration in maternal plasma. The metabolite acetyl-mesalazine is found at similar concentrations in umbilical cord and maternal plasma. Animal studies on oral mesalazine do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/foetal development, parturition or postnatal development. There are no adequate and well controlled studies of Pentasa use in pregnant women. Limited published human data on mesalazine show no increase in the overall rate of congenital malformations. Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. Blood disorders (leucopenia, thrombocytopenia, anaemia) have been reported in new-borns of mothers being treated with Pentasa Sachet.
In one single case after long-term use of a high dose of mesalazine (2-4g, orally) during pregnancy, renal failure in a neonate was reported.
Mesalazine is excreted in breast milk. The mesalazine concentration in breast milk is lower than in maternal blood, whereas the metabolite – acetyl-mesalazine – appears in similar or increased concentrations. No controlled studies with Pentasa Sachet during breast-feeding have been carried out. Only limited experience during lactation in women after oral application is available to date.
Hypersensitivity reactions like diarrhoea can not be excluded. If the infant develops diarrhoea, breast-feeding should be discontinued.
Animal data on Mesalazine show no effect on male and female fertility.
Pentasa Sachet has no or negligible influence on the ability to drive or use machines.
The most frequent adverse reactions seen in clinical trials are diarrhoea, nausea, abdominal pain, headache, vomiting and rash. Hypersensitivity reactions and drug fevermay occasionally occur, and severe cutaneous adverse reactions, including SJS and 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:
| SOC | Common ≥1/100 to <1/10 | Rare ≥1/10,000 to ≤1/1,000 | Very rare ≤1/10,000 | Not known (cannot be estimated from the available data) |
|---|---|---|---|---|
| Blood and the lymphatic system disorders | Altered blood counts (anaemia, aplastic anaemia, agranulocytosis, neutropenia, leukopenia (incl. granulocytopenia), pancytopenia, thrombocytopenia, and eosinophilia (as part of an allergic reaction)). | |||
| Immune system disorders | Hypersensitivity reaction including anaphylactic reaction, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) | |||
| Nervous system disorders | Headache | Dizziness | Peripheral neuropathy Benign intracranial hypertension in adolescents | |
| Cardiac disorders | Myocarditis* Pericarditis* | Pericardial effusion | ||
| Respiratory, thoracic and mediastinal disorders | Allergic alveolitis, allergic and fibrotic lung reactions (incl. dyspnoea, coughing, bronchospasm, pulmonary eosinophilia, interstitial lung disease, pulmonary infiltration, pneumonitis) | |||
| Gastrointestinal disorders | Diarrhoea Abdominal pain Nausea Vomiting Flatulence | Acute pancreatitis* Increased amylase (blood and/or urine) | Pancolitis | |
| Hepato-biliary disorders | Increased liver enzymes, cholestasis parameters and bilirubin, hepatotoxicity (incl. hepatitis*, cholestatic hepatitis, cirrhosis, hepatic failure) | |||
| Skin and subcutaneous tissue disorders | Rash (incl. urticaria, erythematous rash) | Photosensitivity** | alopecia Quincke’s oedema, dermatitis allergic, Erythema multiforme | Stevens-Johnson Syndrome(SJS)/ Toxic epidermal necrolysis (TEN) |
| Musculoskeletal and connective tissue disorders | Myalgia Arthralgia Lupus erythematosus-like reactions | |||
| Renal and urinary disorders | Renal function impairment (incl. interstitial nephritis* (acute and chronic), nephrotic syndrome, renal insufficiency (acute/chronic) Urine discolouration. | Nephrolithiasis*** | ||
| Reproductive system and breast disorders | Oligospermia (reversible) | |||
| General disorders and administration site conditions | Drug Fever |
* 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.
*** SeeSection 4.4 for further information.
It is important to note that several of these disorders can also be attributed to the inflammatory bowel disease itself.
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 HPRA Pharmacovigilance, Website: www.hpra.ie.
Not applicable.
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