Mesalazine

Registered South African indications:

• Ulcerative colitis
• Proctitis
• Proctosigmoiditis

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Renal sensitivity to sulphasalazine
• Severe hepatic impairment
• Children below 2yrs

Cautions

• Pregnancy
• Breastfeeding 
• Severe renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Active peptic ulcer
• Pulmonary disease

Forms avail. in SA and covered in this monograph: tab, sup, ene, gra, prolonged release tab (PR tab)

Treatment and maintenance of remission in ulcerative colitis
Proctitis and proctosigmoiditis - Mild to moderate 

• Rectal: 500mg, 8hrly
  OR 
• Rectal: 2g, at night after defecation

Ulcerative colitis - Acute 

• Oral (gra): 1.5-3g/day, in 1-3 divided doses
• Rectal (sup): 1g, dly
• Rectal (ene): 2g, at night
• Oral (PR tab): 2.4-4.8g, dly; Max: 4.8g/24hrs; Treatment duration: 8 weeks
• Oral (tab): 2.4-4.8g, dly as single dose or in divided doses

Ulcerative colitis - Maintenance

• Oral (gra): 1.5g, dly in 1-3 divided doses
• Rectal (sup): 1g, 3 times weekly on non-consecutive days
• Oral (PR tab): 2.4g, dly
• Oral (tab): 1.6-2.4g, dly as single dose or in divided doses; Max: 4.8g/24hrs; Max single dose: 2.4g

Treatment of ulcerative proctosigmoiditis and left-sided colitis

• Rectal (ene): 1g, at night after defecation
• Rectal (sup): 500mg; 8hrly after defecation

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Enema should be inserted into the rectum and should not be taken by mouth

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Swallow granules without chewing, take regularly to achieve desired therapeutic effect

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Do not cut/crush/chew/dissolve tablets

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Tablets to be taken with food₈

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For immediate release tablets: swallow whole with a glass of water one hour before food intake

Doses above 2.4g should be given in divided doses

Not established for use in children 

Pregnancy

• Caution
• 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 mesalazine 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 newborns of mothers being treated with mesalazine. 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 should not be used during pregnancy 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

Breastfeeding

• Caution
• 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 of mesalazine use during breastfeeding have been carried out. Only limited experience during lactation in women after oral application is available to date. Hypersensitivity reactions like diarrhoea cannot be excluded. If the infant develops diarrhoea, breastfeeding should be discontinued
• Mesalazine should not be used during breastfeeding 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

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; dose adjustment recommended

eGFR (ml/min)	Dose
≥30- 89	No adjustment necessary
≥11- 29	Acute relapse: No adjustment necessary Maintenance of remission: Oral: Dosage should not exceed 1.5g daily Rectal: No adjustment necessary
<10	Oral: Avoid oral preparations Rectal: Dosage should not exceed 1g daily

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated 

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Headache
• Dizziness
• Peripheral neuropathy
• Benign intracranial hypertension in adolescents
• Peripheral neuropathy

Cardiovascular Disorders

• Myocarditis
• Pericarditis
• Pericardial effusion

Respiratory Disorders

• Allergic and fibrotic lung reactions
• Dyspnoea
• Cough
• Bronchospasm
• Allergic alveolitis
• Pulmonary eosinophilia
• Interstitial lung disease
• Lung infiltration
• Pneumonitis
• Pleurisy

Gastrointestinal Disorders

• Diarrhoea
• Abdominal pain
• Nausea and vomiting
• Acute pancreatitis
• Increased amylase
• Flatulence
• Colitis
• Anal irritation (ene)
• Colic

Hepatobiliary Disorders

• Increased liver enzymes
• Cholestasic jaundice
• Hepatotoxicity
• Pancreatitis

Genitourinary Disorders

• Oligospermia 
• Interstitial nephritis
• Nephrotic syndrome
• Renal failure
• Nephrotoxicity

Musculoskeletal Disorders

• Myalgia
• Arthralgia
• Lupus erythematous-like reactions

Skin and Subcutaneous Tissue Disorders

• Rash  
• Alopecia
• Quincke's oedema

Immune, Blood and Lymphatic System Disorders

• Eosinophilia 
• Altered blood counts  
• Thrombocytopenia
• Agranulocytosis
• Pancytopenia
• Hypersensitivity reactions
• Pancolitis
• Drug fever

• Preparations which lower stool pH  
• Lactulose
• Non-steroidal anti-inflammatory drugs
• Azathioprine
• 6-Mercaptopurine
• Thioguanine
• Warfarin

• Renal function

Specific cases may require

• Full blood count
• Respiratory function
• Hepatic function

Mesalazine suppositories - EML (Tertiary)

Mesalazine is an anti-inflammatory agent, structurally related to the salicylates, which is active in inflammatory bowel disease. It diminishes inflammation by blocking cyclo-oxygenase and inhibiting prostaglandin production in the colon.

Tablet 400mg

• Asacol ect (Equity) originator

Tablet 500mg

• Pentasa (Ferring) originator

Tablet 800mg

• Asacol ect (Equity) originator

Tablet 1200mg

• Mezavant (Takeda) originator

Enema (per 100ml) 1g

• Pentasa (Ferring) originator

Enema (per 50ml) 2g

• Asacol (Equity) originator

Suppositories 500mg

• Asacol (Equity) originator

Suppositories 1g

• Pentasa (Ferring) originator

Granules (per sachet) 500mg

• Salofalk (Cipla Medpro) originator

Granules (per sachet) 1g

• Salofalk (Cipla Medpro) originator
• Pentasa (Ferring) originator

Granules (per sachet) 2g

• Pentasa (Ferring) originator