Mesalazine: Formula, Presentation, Indications, Mechanism of Action, Dosage, Side Effects and Interactions

It is an anti-inflammatory drug used to treat inflammation in the digestive tract.

Mesalazine is also known as mesalamine or 5-aminosalicylic acid (5-ASA).

Chemical formula of mesalazine

  • C7H7NO3.

Presentation

The active ingredient is mesalazine with excipients such as povidone (E1201), ethylcellulose.

It is offered for commercialization in various presentations:

  • Rectal suspension, in a box of 5 vials of 100 ml of 1 g per 100 ml.
  • 250 and 500 mg tablets.
  • Suppository, 1 gr.
  • Granules in sachets and sachets of 1 gr.

Indications of mesalazine

It is recommended in the attack treatment for mild to moderate flare-ups and maintenance treatment of ulcerative colitis .

It is also indicated in the treatment of attacks for mild to moderate flare-ups and prevention of acute relapses for frequent recurrent forms of Crohn’s disease .

Mechanism of action of mesalazine

The mechanism of action of mesalazine is not completely clarified, although mechanisms such as activation of the peroxisome proliferator receptor γ (PPAR-γ) and inhibition of nuclear factor kappa B (NF-kB) in the intestinal mucosa are involved.

When mesalazine reaches the inflamed area of ​​the intestine (terminal ileum, colon, rectum) it has an anti-inflammatory effect.

The production in the mucosa of arachidonic acid metabolites, both through the cyclooxygenase pathways (the prostanoids) and through the lipoxygenase pathways (the leukotrienes and hydroxyoicosatetraenoic acids), increases in patients with intestinal disease chronic inflammatory disease, and mesalazine may decrease inflammation by blocking.

As orally administered mesalazine is generally absorbed before it reaches the desired site of action, it must be administered rectally in a special galenic form or as a ‘prodrug’ (olsalazine, sulfasalazine).

Mesalazine’s mechanism of action appears to be topical rather than systemic.

Dose

Treatment of attack of ulcerative colitis and Crohn’s disease by mouth

In adults

Take 2 to 4 g per day, taken in 1 or 2 doses during a meal.

The dosage will be adapted according to the response to the treatment.

The recommended duration of attack treatment is 4 to 8 weeks.

In children

In children 6 years of age and older: the daily dose should be determined individually, starting with 30 to 50 mg per kg per day to be divided into several doses.

The maximum dose is 75 mg per kg per day to be divided into several doses. The total dose should not exceed 4 g per day (maximum dose in adults).

Maintenance treatment of Crohn’s disease and ulcerative colitis

In adults

Take 1 to 2 g per day, during meals.

In children

In children 6 years of age and older: the daily dose should be determined individually, starting with 15 to 30 mg per kg per day to be divided into several doses.

The total dose should not exceed 2 g per day (recommended dose for an adult).

As a general rule, for children weighing up to 40 kg, the recommended dose is half that of adults, and for children who weigh more than 40 kg, the recommended dose is adult usual.

Swallow the contents of the sachet without chewing with a little water.

It should be divided into 1 to several doses per day during meals.

Mesalazine side effects

Hematologic and lymphatic system effects

Changes in blood count values: anemia , aplastic anemia, agranulocytosis , neutropenia , leukopenia (including granulocytopenia), pancytopenia, thrombocytopenia, and eosinophilia , due to an allergic reaction.

Immune system effects

Hypersensitivity reactions including anaphylactic reaction, drug reaction with eosinophilia, and systemic symptoms.

Nervous system effects

Peripheral neuropathy, dizziness and headache.

Allergic reactions and pulmonary fibrosis (including dyspnea, cough, bronchospasm, allergic alveolitis, pulmonary eosinophilia, interstitial lung disease, lung infiltration, pneumonia ).

Gastrointestinal effects

Diarrhea , abdominal pain, nausea, vomiting, flatulence, increased amylases, acute pancreatitis, colitis, increased transaminases, and increased cholestasis parameters such as alkaline phosphatase, gamma-glutamyl transferase, and bilirubin.

Hepatobiliary effects

Hepatitis, cholestatic hepatitis, liver failure.

Effects of the skin and subcutaneous tissue

Rash (including urticaria , erythematous rash), tenderness, alopecia, allergic dermatitis, erythema multiforme, Stevens-Johnson syndrome .

Musculoskeletal and systemic effects

Myalgia , arthralgia, lupus erythematosus syndrome.

Kidney and urinary duct effects

Impaired kidney function, including acute and chronic interstitial nephritis, kidney failure , nephrotic syndrome, urine discoloration.

General effects and anomalies in the administration site

Abdominal distention, anal discomfort, irritation at the application site, itching (anal), rectal urgency (only with the rectal form), fever of medicinal origin.

Effects on reproductive organs

Oligospermia (reversible).

Photosensitivity

More serious reactions have been reported in patients with pre-existing skin conditions, such as atopic dermatitis and atopic eczema.

Warnings and Contraindications

This medicine is contraindicated in:

Children under 6 years of age

Even data on the use of mesalazine in children 6 to 18 years of age are still limited.

Patients with known hypersensitivity

Patients with a history of adverse reactions to the active ingredient mesalazine or to some of the excipients listed in the composition should be kept under close medical supervision at the start of treatment.

Patients with kidney failure and severe liver failure

Blood tests (blood count, liver function parameters such as aspartate amino transferase and alanine amino transferase tests, calculation of creatinine clearance and proteinuria 2 times a year) should be performed before and during treatment.

As an indication, a follow-up report is recommended 14 days after the start of treatment, after two to three tests 4 weeks apart.

If the results are normal, a check can be done every three months. If other symptoms occur, this check should be done immediately.

Mesalazine-induced nephrotoxicity should be suspected in patients who develop renal impairment during treatment.

Nephropathies (tubulo-interstitial nephritis or nephrotic syndromes) (exceptionally in the rectal form) have been reported.

Hypovolemia is a risk factor for the appearance of these nephropathies; reversibility seems to depend on the duration of treatment.

Patients with pulmonary pathology

Patients with lung diseases, such as asthma, should be strictly monitored during treatment.

Interactions of mesalazine

Associations to consider:

Azathioprine

Risk of an increase in the myelosuppressive effect of azathioprine due to the inhibition of its hepatic metabolism by the derivative ASA, especially in subjects with partial deficiency of thiopurine methyltransferase.

Mercaptopurina

Risk of increased myelosuppressive effect of mercaptopurine due to inhibition of its metabolism by mesalazine, particularly in subjects with partial thiopurine methyltransferase (TPMT) deficiency.

Warfarin

The risk or severity of bleeding may be increased when mesalazine is combined with warfarin .