MESASAL Enteric-coated tablet Ref.[50305] Active ingredients: Mesalazine

Caution should be exercised when administering mesalazine to patients with:

• a history of hypersensitivity to sulfasalazine; although in general, hypersensitivity reactions to mesalazine appear to be less frequent than those observed for sulfasalazine

Do not administer mesalazine with preparations which lower stool pH, such as lactulose.

If toxic or hypersensitivity reactions occur, MESASAL should be discontinued.

Although rare, blood dyscrasias may develop during therapy. Practitioners should be aware of the possibility of their occurrence and be prepared to cease treatment immediately.

Keratoconjunctivitis sicca has been observed rarely in dogs chronically dosed with mesalazine. There have been no spontaneous clinical reports of keratoconjunctivitis sicca in man.

Long-term administration (>1 year) of 5-aminosalicylic acid (up to 320 mg/kg/day) to rats resulted in renal nephropathy, gastric ulceration and increased plasma levels of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid. The clinical significance of these findings to man has not been determined.

Use in Pulmonary Function Impairment

MESASAL should be used with caution in patients with pulmonary function impairment, particularly asthma and in patients with known hypersensitivity to sulfasalazine containing preparations. Treatment in the latter patients should be instituted with careful medical supervision. Treatment should be discontinued immediately if symptoms of acute intolerance e.g. cramps, acute abdominal pain, fever, severe headache and skin rash occur.

Nephrolithiasis

Cases of nephrolithiasis have been reported with the use of mesalazine, including stones with mesalazine content. Ensure adequate fluid intake during treatment.

Severe Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCARs), including Steven-Johnsons 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 reaction, such as skin rash, mucosal lesions, or any other signs of hypersensitivity.

Special Instructions to Patients

MESASAL tablets should be taken with plenty of fluid. The tablets should not be crushed or chewed but swallowed whole.

Use in Hepatic Impairment

Caution should be exercised when administering mesalazine to patients with:

• hepatic impairment, as mesalazine is metabolised in the liver
• mesalazine might cause blood dyscrasias, although rarely reported, and hepatic impairment due to hypersensitivity reactions. Blood parameters, like blood counts and liver function and cholestasis parameters (e.g. ALT, AST, alkaline phosphatase, γGT) may be monitored like the renal parameters. Epigastric pain, also commonly associated with inflammatory bowel disease and prednisone or sulfasalazine therapy, should be investigated in order to exclude pericarditis, hepatitis and pancreatitis either as adverse drug reactions to 5-ASA or secondary manifestations or inflammatory bowel disease.

Use in Renal Impairment

Caution should be exercised when administering mesalazine to patients with:

• renal failure, elevated blood urea nitrogen (BUN) and proteinuria.
• renal impairment (given that 5-ASA is primarily eliminated through acetylation and subsequent urinary excretion). Interstitial nephritis has been reported following treatment with mesalazine. Hence, patients with compromised renal function, impaired renal reserve or individuals with an increased risk of developing renal dysfunction due to use of nephrotoxic drugs or other co-morbid conditions should be carefully monitored throughout the duration of therapy, and especially during the early months of treatment. Treatment with mesalazine should be discontinued promptly if renal function significantly deteriorates. Care should be taken to ensure adequate hydration in patients with compromised renal function during exacerbations of inflammatory bowel disease

In view of the rare risk of interstitial nephritis associated with mesalazine treatment, it is recommended that all patients have their renal function monitored (with serum creatinine levels measured) prior to treatment start. Renal function should then be periodically monitored during chronic treatment, based on individual patient history. Treatment with mesalazine should be discontinued promptly if renal function deteriorates.

Use in the Elderly

Regular monitoring of renal function in the elderly is essential as renal function deteriorates with age (see Section 4.3 CONTRAINDICATIONS).

Paediatric Use

Administration in children is not recommended.

Effects on Laboratory Tests

False-positive liquid chromatography assay results for urinary normetanephrine have been reported in patients receiving sulfasalazine or its metabolite, mesalazine.

There have been no specific studies on interactions of mesalazine with other drugs that may be co-administered.

In common with other salicylates, mesalazine may potentiate the effect of coumarin anticoagulants and the blood sugar reducing effect of sulphonylureas. Mesalazine may delay the excretion of methotrexate and may antagonise the effects of probenecid and sulphinpyrazone. There is also the theoretical possibility that mesalazine may decrease the diuretic effect of furosemide (frusemide) and spironolactone and may affect the action of rifampicin. Lactulose or similar preparations may cause a possible reduction of mesalazine release from tablets due to decreased pH caused by bacterial metabolism.

There is in vitro evidence that mesalazine is a weak inhibitor of the azathioprine metabolising enzyme thiopurine methyltransferase (TPMT). Enhancement of the myelosuppressive effects of azathioprine or 6-mercaptopurine may occur rarely in patients who are treated concomitantly with mesalazine.

Effects on Fertility

Decreased sperm count and impaired sperm motility, which may affect male fertility, have been reported with mesalazine. This effect may be reversible when treatment is discontinued (see Section 4.8 ADVERSE EFFECTS (UNDESIRABLE EFFECTS)).

Use in Pregnancy

Pregnancy category: C.

Adequate human data on use during pregnancy are not available. There is a small theoretical risk that, in common with other non-steroidal anti-inflammatory agents, mesalazine may produce premature closure of the ductus arteriosus; may cause fetal renal impairment; and may, if given at term, prolong labour and delay parturition. The intake of aspirin (acetylsalicylic acid) increases the bleeding tendency both in the newborn child and in the mother.

Mesalazine is a salicylate and therefore is not recommended during pregnancy unless in the physician’s opinion, benefits outweigh the potential risk in the first stages of pregnancy. MESASAL is contraindicated in the last weeks of pregnancy.

Use in Lactation

It is recommended that breast-feeding be discontinued during maternal use of mesalazine. While adequate human data on use during lactation and adequate animal reproduction studies are not available, there are reports of mesalazine and its acetylated metabolite being excreted in human breast milk.

The effects of this medicine on a person’s ability to drive and use machines were not assessed as part of its registration.

In clinical trials totalling 2,164 patients, adverse reactions related to treatment with mesalazine occurred in 5.3% of patients; these were severe enough to lead to withdrawal in 1.4% of patients. A further 1.5% of patients had adverse reactions that were possibly drug related. The incidence of adverse reactions was lower amongst patients receiving mesalazine than the comparator drug (sulfasalazine).

Reproductive system and breast disorder: decreased sperm count and impaired sperm motility (see Section 4.6 FERTILITY, PREGNANCY AND LACTATION – Effects on Fertility)

Gastro-Intestinal System

Common nausea, abdominal pain and diarrhoea have been reported. Acute, reversible pancreatitis and exacerbation of the symptoms of colitis have been reported rarely.

Nervous System

Headache, neuropathy.

Skin and Appendages

Rash (including pruritis and urticaria).

Renal

There have been rare reports of renal disorders including cases of acute and chronic interstitial nephritis and renal failure with various mesalazine formulations. Cases of nephrolithiasis have also been reported.

Hepatobiliary

In common with other salicylates, transitory abnormal liver function tests or hepatitis may occur rarely.

Haematological Effects

Alterations in peripheral blood counts (e.g., leucopenia, neutropenia, thrombocytopenia, aplastic anaemia, agranulocytosis) have been reported rarely for various mesalazine formulations.

Reproductive System Disorders

Oligospermia (reversible).

Hypersensitivity

In common with other salicylates, hypersensitivity reactions including pulmonary and cardiac changes may occur rarely. These reactions include fever, myalgia, arthralgia, alveolitis, myocarditis and pericarditis although these have also been reported as extra-intestinal manifestations of the underlying bowel disease.

Skin and Subcutaneous Tissue Disorders

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnsons syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported in association with mesalazine treatment (see Section 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE). Mesalazine should be discontinued, at the first appearance of signs and symptoms of severe skin reaction, such as skin rash, mucosal lesions, or any other signs of hypersensitivity.

Reporting Suspected Adverse Effects

Reporting suspected adverse reactions after registration 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 at www.tga.gov.au/reporting-problems.

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.