Drugs List

Therapeutic Indications

Uses

Treatment of acute exacerbations of mild to moderate ulcerative colitis, especially in the rectum, sigmoid colon and also in the descending colon.

Maintenance of remission in mild to moderate ulcerative colitis.

Treatment of acute ulcerative proctitis.

Maintenance of remission of ulcerative proctitis.

Not all formulations are licensed for all indications.

Administration

For rectal administration.

The action of mesalazine enemas and suppositories is enhanced if the patient lies on the left side when introducing the enema.

If more than one dose of foam is necessary and the patient has difficulty in holding it then it can be administered in divided doses: one at bedtime and the other during the night (after evacuation of the first dose) or in the early morning.

Contraindications

Severe hepatic impairment (see 'Hepatic impairment' section).

Severe renal impairment (GFR <20ml/min) (see 'Renal impairment' section).

Active gastrointestinal ulcers.

Children under 12 years.

Hypersensitivity to salicylates.

Precautions and Warnings

Not all brands or formulations are licensed for all indications.

Mesalazine should be used with caution in patients with:
Mild to moderate hepatic impairment
Asthma or chronic pulmonary disease
Mild to moderate renal impairment (see 'Dosage; Renal Impairment' section)
Pregnancy (see 'Pregnancy' section)
Breastfeeding (see 'Lactation' section)
Children under 18 years; not all formulations are licensed for use in children under 18 years (see 'Dosage; Adolescent' section)

Mesalazine should be used with caution in the elderly.

Serious blood dyscrasias have been reported rarely with mesalazine. Haematological investigations, including a full blood count, should be performed prior to initiation of therapy and periodically during treatment. Such tests are generally recommended within 14 days of initiation of therapy and with 2-3 repeat tests at 4 week intervals. If the results are normal, tests are recommended every three months.
Haematological investigations should be performed if the patient develops any symptoms suggestive of a blood dyscrasia. Discontinue treatment if there is suspicion or evidence of blood dyscrasia.
Advise patient to report any signs of unexplained bruising, rash, sore throat, fever or malaise that occurs during treatment.

Renal and hepatic function should be monitored regularly. Mesalazine-induced nephrotoxicity should be suspected in patients developing renal impairment during treatment. Discontinue if renal function deteriorates during treatment.

Restore fluid and electrolyte balance as soon as possible in case of dehydration.

Mesalazine induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported rarely. Caution should be exercised in patients with conditions predisposing to the development of myocarditis or pericarditis. Discontinue treatment if there is suspicion or evidence of these reactions.

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been associated with mesalazine treatment. At the first signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity then mesalazine should be discontinued.

Patients who are allergic to sulfasalazine should be treated with caution, due to the potential risk of a cross sensitivity reaction between sulfasalazine and mesalazine. Discontinue if intolerability reactions occur such as cramps, acute abdominal pain, fever, severe headaches or rash.

The enemas may contain disodium edetate and sodium metabisulfite.

The suppositories may contain cetyl alcohol.

The foam enemas may contain cetostearyl alcohol, disodium edetate, propylene glycol, polysorbate 20 and sodium metabisulfite.

Mesalazine may cause dizziness. If affected patients should be advised not to drive or operate machinery.

Pregnancy and Lactation

Pregnancy

Mesalazine should be used with caution during pregnancy. Although mesalazine acts within the gastrointestinal tract, systemic absorption occurs with up to 50% of the dose being absorbed after oral administration. Animal studies on rats and rabbits have shown no foetal toxicity or teratogenicity although it is known to cross the placenta in humans and animals. In inflammatory bowel disease, symptoms and activity are linked to pregnancy outcomes, active disease being associated with low birth weights, higher rates of spontaneous abortion, prematurity and perinatal complications. Most authors conclude that mesalazine does not further increase the risk of adverse pregnancy outcomes. There is one report of renal insufficiency in an infant exposed during week 13 to week 30 of pregnancy. One manufacturer states that blood disorders (leucopenia, thrombocytopenia, anaemia) have been reported in neonates of mothers being treated with mesalazine and recommends use with caution. There have been a small number of abnormalities reported with mesalazine including rare reports of increased preterm delivery, low birth weight, ectopic pregnancies and abortions. However, many sources recommend the use of mesalazine during pregnancy, as the potential risk from untreated inflammatory bowel disorder outweighs the potential risk from mesalazine. Schaefer states that mesalazine is the drug of choice for chronic inflammatory bowel disease during pregnancy. They also agree with Lee that the priority is to obtain optimal and stable control with the lowest dose regimen. Inflammatory markers and haematology should be monitored regularly. Dosage should be as required for optimal disease control.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).

Licensed in pregnancy? - Manufacturer recommends mesalazine should be used with caution in pregnancy.

Recommended for use in pregnancy? - Yes, by Schaefer

Animal data - Studies in rats and rabbits have shown no foetal toxicity or teratogenicity

Crosses placenta? - Yes

Lactation

Mesalazine should be used with caution while breastfeeding. Mesalazine is excreted into breast milk in small quantities while its metabolite N-acetyl-5-aminosalicyclic acid is excreted in larger amounts. This metabolite is considered responsible for the effects on the infant. There have been a number of reported cases of diarrhoea in the nursing infant which were considered to be due to a possible hypersensitivity reaction. Briggs state that the infant should be closely observed for changes in stool consistency. Schaefer state that mesalazine is their drug of choice in patients with inflammatory bowel disease who are breastfeeding. However, caution is advised and the infant stools should be monitored closely for changes in consistency.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1 .

Drug excreted in breast milk? - Yes, in small quantities but its metabolite N-acetyl-5-aminosalicyclic acid is excreted in larger quantities.

Considered suitable or recommended by manufacturer? - The manufacturer advises the use of mesalazine with caution while breastfeeding.

UK Drugs in Lactation Advisory Service Classification - Minor adverse effects have been described, this drug should be administered where the mother and infant can be monitored.

Drug substance licensed in infants? - No.

Effects on breastfeed infant - Diarrhoea has been reported.

Side Effects

Exacerbation of colitis
Nausea
Vomiting
Diarrhoea
Abdominal pain
Constipation
Rash
Urticaria
Headache
Leucopenia
Granulocytopenia
Neutropenia
Agranulocytosis
Aplastic anaemia
Thrombocytopenia
Myocarditis
Pericarditis
Dyspnoea
Cough
Allergic alveolitis
Pulmonary eosinophilia
Pulmonary infiltration
Pancreatitis
Elevated amylase levels
Hepatotoxicity
Hepatitis
Cirrhosis
Hepatic failure
Renal impairment
Interstitial nephritis
Nephrotic syndrome
Renal failure
Nephrotoxicity
Lupus erythematosus-like syndrome
Anaemia
Eosinophilia
Pancytopenia
Elevation of liver enzymes
Alopecia
Myalgia
Arthralgia
Hypersensitivity reactions
Drug fever
Pruritus
Rectal discomfort
Faecal urgency
Serum bilirubin increased
Flatulence
Dizziness
Bronchospasm
Pancolitis
Peripheral neuropathy
Malaise
Paraesthesia
Erythematous rash
Bullous reactions
Stevens-Johnson syndrome
Exanthema
Diarrhoea - bloody
Pneumonitis
Discolouration of urine
Erythema multiforme
Allergic lung reactions
Methaemoglobinaemia
Fibrosing alveolitis
Irritation (localised)
Oligospermia (reversible)
Abdominal distension
Cholestatic hepatitis
Changes in hepatic function
Tenesmus
Toxic epidermal necrolysis
Photosensitivity
Nephrolithiasis

Presentation

Suppository containing 500mg mesalazine
Suppository containing 1g mesalazine
Enema containing mesalazine 1g per 100ml
Enema containing mesalazine 2g per 59ml
Foam enema containing mesalazine 1g per metered dose

Drugs List

Therapeutic Indications

Uses

Treatment of acute exacerbations of mild to moderate ulcerative colitis, especially in the rectum, sigmoid colon and also in the descending colon.

Maintenance of remission in mild to moderate ulcerative colitis.

Treatment of acute ulcerative proctitis.

Maintenance of remission of ulcerative proctitis.

Not all formulations are licensed for all indications.

Dosage

Dosage should be adjusted to suit the progress of the condition. Do not discontinue treatment suddenly.

Not all brands are licensed for all indications and dose recommendations vary according to brand; refer to product literature for further information.

Adults

Children

Adolescents

Patients with Renal Impairment

Patients with Hepatic Impairment

Administration

For rectal administration.

The action of mesalazine enemas and suppositories is enhanced if the patient lies on the left side when introducing the enema.

If more than one dose of foam is necessary and the patient has difficulty in holding it then it can be administered in divided doses: one at bedtime and the other during the night (after evacuation of the first dose) or in the early morning.

Contraindications

Severe hepatic impairment (see 'Hepatic impairment' section).

Severe renal impairment (GFR <20ml/min) (see 'Renal impairment' section).

Active gastrointestinal ulcers.

Children under 12 years.

Hypersensitivity to salicylates.

Precautions and Warnings

Not all brands or formulations are licensed for all indications.

Mesalazine should be used with caution in patients with:
Mild to moderate hepatic impairment
Asthma or chronic pulmonary disease
Mild to moderate renal impairment (see 'Dosage; Renal Impairment' section)
Pregnancy (see 'Pregnancy' section)
Breastfeeding (see 'Lactation' section)
Children under 18 years; not all formulations are licensed for use in children under 18 years (see 'Dosage; Adolescent' section)

Mesalazine should be used with caution in the elderly.

Serious blood dyscrasias have been reported rarely with mesalazine. Haematological investigations, including a full blood count, should be performed prior to initiation of therapy and periodically during treatment. Such tests are generally recommended within 14 days of initiation of therapy and with 2-3 repeat tests at 4 week intervals. If the results are normal, tests are recommended every three months.
Haematological investigations should be performed if the patient develops any symptoms suggestive of a blood dyscrasia. Discontinue treatment if there is suspicion or evidence of blood dyscrasia.
Advise patient to report any signs of unexplained bruising, rash, sore throat, fever or malaise that occurs during treatment.

Renal and hepatic function should be monitored regularly. Mesalazine-induced nephrotoxicity should be suspected in patients developing renal impairment during treatment. Discontinue if renal function deteriorates during treatment.

Restore fluid and electrolyte balance as soon as possible in case of dehydration.

Mesalazine induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported rarely. Caution should be exercised in patients with conditions predisposing to the development of myocarditis or pericarditis. Discontinue treatment if there is suspicion or evidence of these reactions.

Severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been associated with mesalazine treatment. At the first signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity then mesalazine should be discontinued.

Patients who are allergic to sulfasalazine should be treated with caution, due to the potential risk of a cross sensitivity reaction between sulfasalazine and mesalazine. Discontinue if intolerability reactions occur such as cramps, acute abdominal pain, fever, severe headaches or rash.

The enemas may contain disodium edetate and sodium metabisulfite.

The suppositories may contain cetyl alcohol.

The foam enemas may contain cetostearyl alcohol, disodium edetate, propylene glycol, polysorbate 20 and sodium metabisulfite.

Mesalazine may cause dizziness. If affected patients should be advised not to drive or operate machinery.

Pregnancy and Lactation

Pregnancy

Mesalazine should be used with caution during pregnancy. Although mesalazine acts within the gastrointestinal tract, systemic absorption occurs with up to 50% of the dose being absorbed after oral administration. Animal studies on rats and rabbits have shown no foetal toxicity or teratogenicity although it is known to cross the placenta in humans and animals. In inflammatory bowel disease, symptoms and activity are linked to pregnancy outcomes, active disease being associated with low birth weights, higher rates of spontaneous abortion, prematurity and perinatal complications. Most authors conclude that mesalazine does not further increase the risk of adverse pregnancy outcomes. There is one report of renal insufficiency in an infant exposed during week 13 to week 30 of pregnancy. One manufacturer states that blood disorders (leucopenia, thrombocytopenia, anaemia) have been reported in neonates of mothers being treated with mesalazine and recommends use with caution. There have been a small number of abnormalities reported with mesalazine including rare reports of increased preterm delivery, low birth weight, ectopic pregnancies and abortions. However, many sources recommend the use of mesalazine during pregnancy, as the potential risk from untreated inflammatory bowel disorder outweighs the potential risk from mesalazine. Schaefer states that mesalazine is the drug of choice for chronic inflammatory bowel disease during pregnancy. They also agree with Lee that the priority is to obtain optimal and stable control with the lowest dose regimen. Inflammatory markers and haematology should be monitored regularly. Dosage should be as required for optimal disease control.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password at ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).

Licensed in pregnancy? - Manufacturer recommends mesalazine should be used with caution in pregnancy.

Recommended for use in pregnancy? - Yes, by Schaefer

Animal data - Studies in rats and rabbits have shown no foetal toxicity or teratogenicity

Crosses placenta? - Yes

Lactation

Mesalazine should be used with caution while breastfeeding. Mesalazine is excreted into breast milk in small quantities while its metabolite N-acetyl-5-aminosalicyclic acid is excreted in larger amounts. This metabolite is considered responsible for the effects on the infant. There have been a number of reported cases of diarrhoea in the nursing infant which were considered to be due to a possible hypersensitivity reaction. Briggs state that the infant should be closely observed for changes in stool consistency. Schaefer state that mesalazine is their drug of choice in patients with inflammatory bowel disease who are breastfeeding. However, caution is advised and the infant stools should be monitored closely for changes in consistency.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1 .

Drug excreted in breast milk? - Yes, in small quantities but its metabolite N-acetyl-5-aminosalicyclic acid is excreted in larger quantities.

Considered suitable or recommended by manufacturer? - The manufacturer advises the use of mesalazine with caution while breastfeeding.

UK Drugs in Lactation Advisory Service Classification - Minor adverse effects have been described, this drug should be administered where the mother and infant can be monitored.

Drug substance licensed in infants? - No.

Effects on breastfeed infant - Diarrhoea has been reported.

Effects on Ability to Drive and Operate Machinery

Mesalazine may cause dizziness. If affected patients should be advised not to drive or operate machinery.

Counselling

Advise patient to report any signs of unexplained bruising, rash, sore throat, fever or malaise that occurs during treatment.

Advise patient to report signs and symptoms of severe skin reactions.

Mesalazine may cause dizziness. If affected patients should be advised not to drive or operate machinery.

Side Effects

Exacerbation of colitis
Nausea
Vomiting
Diarrhoea
Abdominal pain
Constipation
Rash
Urticaria
Headache
Leucopenia
Granulocytopenia
Neutropenia
Agranulocytosis
Aplastic anaemia
Thrombocytopenia
Myocarditis
Pericarditis
Dyspnoea
Cough
Allergic alveolitis
Pulmonary eosinophilia
Pulmonary infiltration
Pancreatitis
Elevated amylase levels
Hepatotoxicity
Hepatitis
Cirrhosis
Hepatic failure
Renal impairment
Interstitial nephritis
Nephrotic syndrome
Renal failure
Nephrotoxicity
Lupus erythematosus-like syndrome
Anaemia
Eosinophilia
Pancytopenia
Elevation of liver enzymes
Alopecia
Myalgia
Arthralgia
Hypersensitivity reactions
Drug fever
Pruritus
Rectal discomfort
Faecal urgency
Serum bilirubin increased
Flatulence
Dizziness
Bronchospasm
Pancolitis
Peripheral neuropathy
Malaise
Paraesthesia
Erythematous rash
Bullous reactions
Stevens-Johnson syndrome
Exanthema
Diarrhoea - bloody
Pneumonitis
Discolouration of urine
Erythema multiforme
Allergic lung reactions
Methaemoglobinaemia
Fibrosing alveolitis
Irritation (localised)
Oligospermia (reversible)
Abdominal distension
Cholestatic hepatitis
Changes in hepatic function
Tenesmus
Toxic epidermal necrolysis
Photosensitivity
Nephrolithiasis

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( https://www.toxbase.org/ ) or if this is unavailable at the backup site ( https://www.TOXBASEbackup.org/ ).

Shelf Life and Storage

Suppositories and enema: Storage conditions vary according to brand.

Foam enema: Do not store above 30 degrees C. The canister should not be refrigerated or frozen. The pressurised canister contains a flammable propellant. Store away from flames or sparks, including cigarettes. Protect from direct sunlight and temperatures over 50 degrees C and do not burn or pierce even when empty.

Further Information

Last Full Review Date: January 2011

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mother's Milk, 12th edition (2006) Hale, T.W. Hale Publishing, Amarillo, Texas.

Therapeutics in Pregnancy and Lactation (2000) Lee, A., Inch, S. and Finnigan, D. Radcliffe Medical Press, Abingdon.

The Renal Drug Handbook. 2nd edition. (2004) ed. Ashley, C and Currie, A. Radcliffe Medical Press, Abingdon.

Summary of Product Characteristics: Salofalk Enema 2g. Dr. Falk Pharma UK Ltd. Dated January 2021.
Summary of Product Characteristics: Salofalk Suppositories 500mg. Dr. Falk Pharma UK Ltd. Dated January 2021.
Summary of Product Characteristics: Salofalk Suppositories 1g. Dr. Falk Pharma UK Ltd. Dated January 2021.
Summary of Product Characteristics: Salofalk 1g/actuation Rectal Foam. Dr. Falk Pharma GmbH. Dated January 2021.
Summary of Product Characteristics: Octasa 1g suppositories. Tillotts Pharma UK Ltd. Dated February 2021.
Summary of Product Characteristics: Pentasa Mesalazine Enema. Ferring Pharmaceuticals Ltd. Dated February 2005.
Summary of Product Characteristics: Pentasa Suppositories 1g. Ferring Pharmaceuticals Ltd. Dated February 2005

(Summary of Product Characteristics: Pentasa Sachet 1g prolonged release granules. Ferring Pharmaceuticals Ltd. Revised November 2007.)
(Summary of Product Characteristics: Pentasa Sachet 2g prolonged release granules. Ferring Pharmaceuticals Ltd. Revised October 2007.)
(Summary of Product Characteristics, Pentasa Slow Release tablets, Ferring Pharmaceuticals, February 2005.)

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 April 2021.

UK Drugs in Lactation Advisory Service.
Available at: https://www.ukmicentral.nhs.uk/drugpreg/guide.htm
Last accessed: March 30, 2012.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Mesalamine (mesalazine) Last revised: December 27, 2007.
Last accessed: March 30, 2012