Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Shire Pharmaceutical Contracts Ltd, 1 Kingdom Street, London, W2 6BD, United Kingdom
History of hypersensitivity to salicylates (including mesalazine) or any of the excipients of Mezavant XL.
Severe renal impairment (GFR <30ml/min/1.73m²) and/or severe hepatic impairment.
Reports of renal impairment, including minimal change nephropathy, acute/chronic interstitial nephritis and renal failure have been associated with preparations containing mesalazine and pro-drugs of mesalazine. Mezavant should be used with caution in patients with confirmed mild to moderate renal impairment. It is recommended that all patients have an evaluation of renal function prior to initiation of therapy and at least twice a year, while on treatment.
Patients with chronic lung function impairment, especially asthma, are at risk of hypersensitivity reactions and should be closely monitored.
Following mesalazine treatment, serious blood dyscrasias have been reported rarely. If the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat, haematological investigations should be performed. If there is suspicion of blood dyscrasia, treatment should be terminated. (See sections 4.5 and 4.8).
Mesalazine induced cardiac hypersensitivity reactions (myo- and pericarditis) have been reported rarely with Mezavant and with other mesalazine containing preparations. Caution should be used in prescribing this medication to patients with conditions predisposing to the development of myo- or pericarditis. If such hypersensitivity reaction is suspected, products containing mesalazine must not be reintroduced.
Mesalazine has been associated with an acute intolerance syndrome that may be difficult to distinguish from a flare of inflammatory bowel disease. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalazine or sulphasalazine. Symptoms include cramping, acute abdominal pain and bloody diarrhoea, sometimes fever, headache and rash. If acute intolerance syndrome is suspected, prompt withdrawal is required and products containing mesalazine must not be reintroduced.
There have been reports of increased liver enzyme levels in patients taking preparations containing mesalazine. Caution is recommended if Mezavant is administered to patients with hepatic impairment.
Caution should be exercised when treating patients allergic to sulphasalazine due to the potential risk of cross sensitivity reactions between sulphasalazine and mesalazine.
Organic or functional obstruction in the upper gastrointestinal tract may delay onset of action of the product.
Use of mesalazine may lead to falsely elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection, because of the similarity in the chromatograms of normetanephrine and mesalazine’s main metabolite, N-acetylaminosalicylic acid (N-Ac-5-ASA). An alternative, selective assay for normetanephrine should be considered.
Drug-drug interaction studies in healthy adult subjects have been conducted with Mezavant to investigate any effect of Mezavant on the pharmacokinetics and safety of three commonly used antibiotics. There were no clinically significant interactions of Mezavant with amoxicillin, metronidazole or sulfamethoxazole.
However, the following drug-drug interactions have been reported for products containing mesalazine.
Mezavant is recommended to be administered with food (see sections 4.2 and 5.2).
Limited experience with mesalazine in pregnancy does not indicate an increased risk of drug induced congenital malformations. Mesalazine crosses the placental barrier, but provides foetal concentrations much lower than those seen with adult therapeutic use. Animal studies do not indicate harmful effects of mesalazine in pregnancy, embryonal/foetal development, parturition or postnatal development. Mesalazine should be used during pregnancy only when clearly indicated. Caution should be exercised when using high doses of mesalazine.
Mesalazine is excreted in breast milk at low concentration. Acetylated form of mesalazine is excreted in breast milk at higher concentration. Caution should be exercised if using Mesalazine while breast-feeding and only if the benefit outweighs the risks. Sporadically acute diarrhoea has been reported in breast fed infants.
Data on mesalazine show no sustained effect on male fertility.
No studies on the effects on the ability to drive and use machines have been performed. Mezavant is considered to have negligible influence on these abilities.
The most frequently reported adverse drug reactions (ADRs)within the pooled safety analysis of clinical studies with Mezavant, including 3,611 patients, were colitis (including ulcerative colitis) 5.8%, abdominal pain 4.9%, headache 4.5%, liver function test abnormal, 2.1%, diarrhoea 2.0%, and nausea 1.9%.
Adverse reactions are listed by System Organ Class (see table below). Within each system organ class, adverse reactions are listed under headings of frequency using the categories: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); not known (cannot be estimated from the available data).
Uncommon: Thrombocytopenia*
Rare: Agranulocytosis*
Not known: Aplastic anaemia*, Leukopenia*, Neutropenia*, Pancytopenia*
Uncommon: Face oedema
Not known: Hypersensitivity*, Anaphylactic shock, Angioedema, Stevens-Johnson syndrome, Drug rash with eosinophilia and systemic symptoms (DRESS)
Common: Headache*
Uncommon: Dizziness, Somnolence, Tremor
Not known: Intracranial pressure increased, neuropathy
Uncommon: Ear pain
Uncommon: Tachycardia
Not known: Myocarditis*, Pericarditis*
Common: Hypertension
Uncommon: Hypotension
Uncommon: Pharyngolaryngeal pain*
Not known: Hypersensitivity pneumonitis (including interstitial Pneumonitis, allergic alveolitis, eosinophilic pneumonitis), Bronchospasm
Common: Abdominal distension, Abdominal pain*, Colitis, Diarrhoea*, Dyspepsia, Vomiting, Flatulence, Nausea
Uncommon: Pancreatitis, Rectal polyp
Common: Liver Function Test abnormal* (e.g. ALT; AST, Bilirubin)
Not known: Hepatitis, Cholelithiasis
Common: Pruritus, Rash*
Uncommon: Acne, Alopecia, Urticaria
Rare: Photosensitivity
Common: Arthralgia, Back pain
Uncommon: Myalgia
Not known: Systemic-lupus erythematosus-like syndrome, Lupus-like syndrome
Rare: Renal failure*
Not known: Interstitial nephritis*, Nephrotic syndrome*
Not known: Oligospermia (reversible)
Common: Asthenia, Fatigue, Pyrexia*
* See section 4.4.
Cases of increased intracranial pressure with papilledema (pseudotumor cerebri or benign intracranial hypertension) have been reported with the use of mesalamines. If undetected, this condition may result in restriction of the visual field and may progress to permanent loss of vision. Mesalamine should be discontinued, if this syndrome occurs.
More severe reactions are reported in patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema.
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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Not applicable.
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