Mesalazine group. Reference book of medicines. Mesalazine and Crohn's disease

Rectal suppositories Mesalazole- antibacterial, anti-inflammatory drug with localization of action in the intestine.
Mesalazine has an anti-inflammatory effect at the level of the intestinal mucosa. Inhibits the activity of neutrophilic lipoxygenase and the synthesis of metabolites of arachidonic acid (prostaglandins and leukotrienes). It inhibits the formation of cytokines in the intestinal mucosa, inhibits migration, degranulation, phagocytosis of neutrophils, secretion of immunoglobulins by lymphocytes. It also has an antioxidant effect: it binds and destroys free oxygen radicals. Suppresses the activity of some intestinal bacteria, especially Escherichia coli (the antibacterial effect is manifested in the large intestine).

Pharmacokinetics

When using suppositories, the release and distribution of mesalazine occurs in the rectum and distal third of the colon. Absorption of the drug into the systemic circulation is low and is about 10%. It is metabolized in the intestinal mucosa and in the liver into an inactive metabolite - N-acetyl-5-aminosalicylic acid. The binding of mesalazine to plasma proteins is 43%, N-acetyl-5-aminosalicylic acid - 73-83%. The drug and its metabolite crosses the placental barrier and passes into breast milk. The half-life of mesalamine is 0.5-2 hours, N-acetyl-5-aminosalicylic acid is about 5-10 hours. Mesalazine and its metabolites are excreted by the kidneys (50%) in the urine (mainly in acetylated form) and through the intestines (40%) with feces. With rectal administration, 10-30% of the dose is found in daily urine. Cumulates in chronic renal failure.

Indications for use

Candles Mesalazole are used in the treatment of inflammatory diseases of the rectum and distal large intestine (ulcerative colitis, proctitis, proctosigmoiditis; Crohn's disease) in the acute stage and their prevention.

Mode of application

Candles Mesalazole applied rectally.
Adults. In mild and moderate forms in the acute stage, one suppository (500 mg) 3 times a day. The maximum daily dose is 1.5 g.
For the prevention of relapse, one suppository (250 mg) is prescribed 3 times a day, if necessary, for several years.
In severe forms, two suppositories (500 mg) 3 times a day. The maximum daily dose may be increased to 3-4 g (for a period not exceeding 8-12 weeks).
Children: during exacerbation 40-60 mg/kg of body weight per day, for the prevention of relapse - 20-30 mg/kg of body weight per day (reception frequency -3 times a day).
The duration of treatment is determined individually (average 8-10 weeks).

Side effects

From the digestive system: discomfort and pain in the abdomen, nausea, vomiting, flatulence, diarrhea, loss of appetite, increased activity of hepatic transaminases, hepatitis, pancreatitis;
From the side of the cardiovascular system: rarely - palpitations, tachycardia, arterial hyper- or hypotension, chest pain; shortness of breath, pericarditis, myocarditis;
From the urinary system: proteinuria, hematuria, oliguria, anuria, nephrotic syndrome, crystalluria;
On the part of the hematopoietic organs: anemia (hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, neutropenia, methemoglobinemia;
From the nervous system: asthenia, headache, dizziness; tinnitus, polyneuropathy, tremor, depression;
Allergic reactions: skin rash, itching, urticaria, dermatoses, bronchospasm, photosensitivity;
Other: weakness, mumps, alopecia, oligospermia, lupus-like syndrome, decreased production of lacrimal fluid.

Contraindications

:
Contraindications to the use of suppositories Mesalazole are: hypersensitivity to salicylates, severe renal and / or liver failure, blood diseases, gastric and duodenal ulcers, hemorrhagic diathesis, age up to 2 years, lactation, the last 2-4 weeks of pregnancy.
The drug is used with caution in hepatic and renal insufficiency of mild and moderate severity, deficiency of glucose-6-phosphate dehydrogenase, in patients with allergic diseases.

pregnancy:
The use of candles Mesalazole during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus.
The drug is contraindicated for use in the last 2-4 weeks of pregnancy and lactation.
Women planning a pregnancy need to choose a period when they can refuse treatment or take maintenance doses.

Interaction with other drugs

With the simultaneous use of the drug Mesalazole:
- enhances the effect of anticoagulants (risk of gastrointestinal bleeding);
- enhances the ulcerogenic effect of glucocorticoids on the gastric mucosa;
- enhances the toxicity of methotrexate;
- weakens the effect of rifampicin;
- weakens the effect of furosemide;
- enhances the hypoglycemic effect of sulfonylurea,
- slows down the absorption of cyanocobalamin.

Overdose

:
Symptoms of an overdose of suppositories Mesalazole: nausea, vomiting, abdominal pain, weakness, drowsiness.
Treatment: gastric lavage, the appointment of a laxative, symptomatic therapy.

Storage conditions

Store in a dry and dark place, at a temperature of 15-25?C.
Keep out of the reach of children.

Release form

Mesalazole - rectal suppositories.
7 suppositories in a PVC / PE film blister.
2 blisters with instructions for use in a cardboard box.

Composition

:
1 suppository Mesalazole 250 mg contains: active ingredient: mesalazine 250 mg. Excipients: semi-synthetic glycerides - up to 2.08 g.
1 suppository Mesalazole 500 mg contains: active substance: mesalazine 500 mg. Excipients: cetyl alcohol, sodium docusate, semi-synthetic glycerides up to 2.2 g.

Additionally

:
Before using suppositories Mesalazole bowel needs to be emptied.
It is necessary to monitor the picture of peripheral blood, liver function and excretory function of the kidneys (the level of urea and creatinine in the blood) before treatment, 14 days after the start of treatment, then 1 time per month for 3 months, after - with normal results - 1 time per three months, and also at the end of therapy.
Against the background of the use of the drug, staining of urine and tears in yellow-orange color, staining of soft contact lenses can be observed.

main parameters

Name:	MESALAZOLE SUPPLEMENTS
ATX code:	A07EC02 -

Formula: C7H7NO3, chemical name: 5-amino-2-hydroxybenzoic acid.
Pharmacological group: non-narcotic analgesics, including non-steroidal and other anti-inflammatory drugs / NSAIDs - derivatives of salicylic acid.
Pharmachologic effect: anti-inflammatory.

Pharmacological properties

Mesalazine is the active ingredient in sulfasalazine. Mesalazine inhibits phagocytosis and degranulation of neutrophils, chemotaxis, secretion of immunoglobulins by lymphocytes, inhibits the synthesis of prostaglandins, has antioxidant properties, and reduces the formation of free radicals in inflamed intestinal tissue. Mesalazine in relation to some cocci and Escherichia coli has an antibacterial effect, which manifests itself in the large intestine. The therapeutic effect of mesalazine is determined to a greater extent by a local effect on the inflamed intestinal tissue than by a systemic effect.
The release of mesalazine depends on the route of administration and dosage form and occurs in the colon and terminal small intestine (tablets) or colon and rectum (enemas, suppositories). Enteric tablets begin to dissolve at a pH greater than 6 in the small intestine after 110-170 minutes, and after 165-225 minutes after administration, they dissolve completely. During passage through the intestines, the drug is released from the tablets gradually (15-30% of mesalazine is released in the ileum, 60-75% in the colon). Up to 50% of the drug is absorbed into the blood, mainly in the small intestine. With a single dose of 250 mg of the drug, the maximum plasma concentration is 0.5 - 1.5 μg / ml. Mesalazine is determined in the blood plasma already 15 minutes after ingestion, the maximum concentration is reached after 1 hour and lasts up to 4 hours, gradually decreasing over 12 hours. When administered rectally, high concentrations of mesalazine are created in the distal part of the intestine. In patients with exacerbation of ulcerative colitis, the degree of absorption is markedly lower than in patients with the disease in remission. Mesalazine in the liver and intestinal mucosa is metabolized (by acetylation) with the formation of N-acetyl-5-aminosalicylic acid. To a small extent, the drug can be metabolized by enterobacteria. Mesalazine binds to plasma proteins by about 40%, N-acetyl-5-aminosalicylic acid - by 75 - 83%. In the form of a metabolite, mesalazine passes into breast milk (0.1% of the dose). Mesalazine and its metabolite do not cross the blood-brain barrier. When taking high doses, the drug may accumulate. With rectal use, 10-30% of the dose is found in daily urine. Mesalazine clearance is 18 l/hour. The half-life of mesalazine is 30 - 90 minutes, N-acetyl-5-aminosalicylic acid - 5 - 10 hours. Mesalazine and its metabolites are excreted from the body with feces and urine.
Mesalazine is effective in the treatment of ileitis in Crohn's disease, colitis, for the prevention of exacerbations of ulcerative colitis in patients with hypersensitivity to sulfasalazine. Mesalazine is well tolerated (even at a dose of 4.8 g per day, the tolerability of the drug is comparable to that of placebo). Mesalazine reduces the risk of relapse in Crohn's disease, especially in patients with ileitis and a long duration of the disease.

Indications

Exacerbation of inflammatory bowel diseases (Crohn's disease, ulcerative colitis), as well as prevention of their recurrence.

Method of administration of mesalazine and dosage

Mesalazine is taken orally, administered rectally. The choice of dosage form is determined by the extent and localization of the intestinal lesion. With common forms, oral forms are used, with distal lesions, rectal forms are used (combined use is possible).
Rectally (after emptying the rectum): with proctosigmoiditis, proctitis, left-sided ulcerative colitis adults - 500 mg (1 suppository) 3 times a day. In the form of microclysters - 1 time per day, at bedtime 2-4 g of mesalazine (30-60 ml of suspension), depending on the extent of the lesion.
Inside, drinking plenty of water, without chewing: adults with exacerbation of diseases - 3 times a day, 400-500 mg, maintenance doses are 4 times a day, 1 g for Crohn's disease and 3 times a day, 500 mg for nonspecific ulcerative colitis; children over 2 years old - 20 - 30 mg / kg per day in divided doses. The daily dose can be increased to 3-4 g in severe cases of the disease, but not more than 8-12 weeks.
Mesalazine should be discontinued if an acute intolerance syndrome is suspected (muscle cramps, abdominal pain, fever, severe headache, skin rashes). But the syndrome of acute intolerance in some cases is difficult to differentiate from a severe exacerbation of inflammatory bowel disease.
Before starting, during (1-2 times a month) and after treatment (every 3 months), it is necessary to control the composition of peripheral blood, urinalysis, creatinine, urea levels.
There may be staining of the lacrimal fluid, soft contact lenses, urine in a yellow-orange color.
Use mesalazine with caution for drivers of vehicles and people whose professions are associated with increased concentration of attention and speed of psychomotor reactions.

Contraindications for use

Hypersensitivity, including to other derivatives of salicylic acid (when using enemas, including hypersensitivity to propyl- and methylparaben), blood diseases, severe renal and / or liver dysfunction, peptic ulcer of the stomach and duodenum, hemorrhagic diathesis, breast-feeding, the last 2 – 4 weeks of pregnancy, age up to 2 years.

Application restrictions

Dysfunction of the lungs (including bronchial asthma), kidneys and / or liver, deficiency of glucose-6-phosphate dehydrogenase, the presence of possible hypersensitivity to sulfasalazine, pregnancy.

Use during pregnancy and lactation

The use of mesalazine during pregnancy is possible only when the expected benefit to the mother is higher than the possible risk to the fetus; in the last 2-4 weeks of pregnancy, the drug should be discontinued. During therapy with mesalazine, breastfeeding should be discontinued.

side effects of mesalazine

Digestive system: nausea, heartburn, vomiting, loss of appetite, diarrhea, abdominal pain, flatulence, hepatitis, increased levels of hepatic transaminases and bilirubin, parotitis, pancreatitis, increased amylase, exacerbation of colitis symptoms, hepatosis, cirrhosis, liver failure.
Cardiovascular system and blood: palpitations, increase or decrease in blood pressure, tachycardia, myocarditis, pericarditis, shortness of breath, chest pain, anemia (megaloblastic, hemolytic, aplastic), leukopenia, thrombocytopenia, agranulocytosis, granulocytopenia, eosinophilia, pancytopenia, hypoprothrombinemia.
Nervous system and sense organs: dizziness, headache, sleep disturbance, peripheral neuropathy, malaise, depression, paresthesia, tremor, benign intracranial hypertension, convulsions, tinnitus.
Urogenital system: hematuria, proteinuria, crystalluria, anuria, nephrotic syndrome, oliguria, interstitial nephritis, urine color changes, transient renal failure, oligospermia.
Allergic reactions: itching, skin rash, bronchospasm, urticaria, erythema, hypersensitivity reactions, angioedema, drug fever.
Respiratory system: shortness of breath, cough, allergic alveolitis, lung infiltration, pulmonary eosinophilia, pneumonia, interstitial lung disease, bronchospasm.
Others: photosensitivity, fever, lupus-like syndrome, decreased production of lacrimal fluid, myalgia, arthralgia, alopecia, possibly increased levels of methemoglobin, pain and irritation in the anus.

Interaction of mesalazine with other substances

Mesalazine enhances the toxicity of methotrexate (the risk of kidney damage increases), the ulcerogenicity of glucocorticoids, the hypoprothrombinemic effect of anticoagulants, the hypoglycemic effect of sulfonylurea derivatives.
Mesalazine weakens the activity of spironolactone, furosemide, sulfonamides, probenecid, sulfinpyrazone, rifampicin.
Mesalazine inhibits the absorption of cyanocobalamin.
Mesalazine should be used with caution in conjunction with azathioprine or 6-mercaptopurine, as the risk of bone marrow suppression (thrombocytopenia, leukopenia, anemia, erythrocytopenia, pancytopenia) increases.
The combined use of mesalazine with other drugs that have nephrotoxicity (for example, non-steroidal anti-inflammatory drugs azathioprine), increases the risk of side effects from the kidneys.
Mesalazine increases the effectiveness of uricosuric drugs.
Mesalazine reduces the absorption of digoxin.

Overdose

With an overdose of mesalazine, nausea, gastralgia, vomiting, drowsiness, weakness, and pulmonary edema develop. It is necessary: gastric lavage (when taken orally), laxative, increased diuresis, monitoring of liver and kidney function, symptomatic treatment, with the development of alkalosis, acidosis, dehydration, it is necessary to restore the water-electrolyte and acid-base balance, with signs of hypoglycemia, the introduction of dextrose is recommended. There is no specific antidote.

Inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the acute stage and prevention of their recurrence.

Mesalazine release form

tablets of the prolonged action of 500 mg; blister pack 10 in a carton pack of 3,5,6,9 and 10 pcs.;
tablets of the prolonged action of 500 mg; blister pack 15 in a carton pack of 2,4 and 6 pcs.;

Pharmacodynamics of Mesalazine

It inhibits the synthesis of PG, inhibits chemotaxis, degranulation and phagocytosis of neutrophils, the secretion of immunoglobulins by lymphocytes, and has antioxidant properties. It has an antibacterial effect against Escherichia coli and some cocci (manifested in the large intestine).
Effective in the treatment of colitis, ileitis in Crohn's disease, for the prevention of exacerbations of ulcerative colitis in patients with hypersensitivity to sulfasalazine, it is well tolerated (even at a dose of 4.8 g / day comparable to that of placebo). Reduces the risk of recurrence in Crohn's disease, especially in patients with ileitis and a long duration of the disease.

Pharmacokinetics of Mesalazine

Depending on the dosage form and route of administration, mesalazine is released in the rectum and colon (enemas, suppositories) or the terminal small intestine and colon (tablets). Tablets (enteric) begin to dissolve in the small intestine (at pH> 6) after 110-170 minutes, completely dissolve after 165-225 minutes after administration. During the passage through the intestines, mesalazine is released from the tablets gradually, with 15–30% in the ileum, 60–75% in the large intestine, and only 10% enters the bloodstream. Plasma concentration is low - after a single dose of 250 mg Cmax is 0.5–1.5 μg / ml. In the intestinal mucosa and liver forms N-acetyl-5-aminosalicylic acid. The binding of mesalazine to plasma proteins is about 40%, the metabolite is 75–83%. In breast milk penetrates (in the form of a metabolite) 0.1% of the dose. With rectal administration, 10–30% of the dose is found in daily urine. T1 / 2 mesalazine 0.5-1.5 hours, N-acetyl-5-aminosalicylic acid - 5-10 hours.

Use of Mesalazine during pregnancy

In the first trimester of pregnancy, the appointment of mesalazine is possible only under strict indications; in the last 2-4 weeks of pregnancy, the drug should be discontinued.

At the time of treatment, it is recommended to stop breastfeeding due to the lack of sufficient clinical experience during this period. If a breastfed newborn develops diarrhea, breastfeeding should be discontinued.

Contraindications to the use of the drug Mesalazine

Hypersensitivity, incl. to other derivatives of salicylic acid (when using enemas, including methyl- and propylparaben), severe violations of the liver and / or kidneys, blood diseases, hemorrhagic diathesis, peptic ulcer of the stomach and duodenum, the last 2-4 weeks of pregnancy, breastfeeding, children's age (up to 2 years).

Side effects of Mesalazine

On the part of the digestive tract: nausea, vomiting, heartburn, loss of appetite, abdominal pain, diarrhea, flatulence, increased levels of hepatic transaminases, hepatitis, pancreatitis, parotitis.

From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): palpitations, tachycardia, increased or decreased blood pressure, chest pain, shortness of breath, anemia (hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, hypoprothrombinemia.

From the nervous system and sensory organs: headache, dizziness, sleep disturbance, depression, malaise, paresthesia, convulsions, tremor, tinnitus.

From the genitourinary system: proteinuria, hematuria, crystalluria, oliguria, anuria, nephrotic syndrome, oligospermia.

Allergic reactions: skin rash, itching, erythema, bronchospasm.

Others: fever, photosensitivity, lupus-like syndrome, alopecia, decreased production of lacrimal fluid, possibly increased levels of methemoglobin.

Dosage and administration of Mesalazine

Inside, without chewing, drinking plenty of water: for adults with exacerbation - 400-500 mg 3 times a day, maintenance doses - 500 mg 3 times a day for ulcerative colitis and 1 g 4 times a day for Crohn's disease; children over 2 years old - 20-30 mg / kg / day in divided doses. In severe cases of the disease, the daily dose can be increased to 3-4 g, but not more than 8-12 weeks.

Overdose of mesalazine

Symptoms: nausea, vomiting, gastralgia, weakness, drowsiness.

Treatment: gastric lavage (when taken orally), the appointment of a laxative, symptomatic therapy.

Interactions of the drug Mesalazine with other drugs

It enhances the ulcerogenicity of glucocorticoids, the toxicity of methotrexate, the hypoglycemic effect of sulfonylurea derivatives, the hypoprothrombinemic effect of anticoagulants. Slows down the absorption of cyanocobalamin. Weakens the activity of furosemide, spironolactone, rifampicin.

Precautions while using mesalazine

Before starting, during (1-2 times a month), and also after treatment (every 3 months), the composition of peripheral blood, the level of urea, creatinine, and urinalysis should be monitored. If acute intolerance syndrome is suspected, mesalazine should be discontinued. However, it should be borne in mind that the syndrome of acute intolerance in some cases can be difficult to differentiate from a severe exacerbation of inflammatory bowel disease.

Mesalazine storage conditions

List B.: In a dry, dark place, at a temperature not exceeding 25 ° C.

Mesalazine shelf life

Belonging of the drug Mesalazine to the ATX-classification:

A Digestive tract and metabolism

A07 Antidiarrheals, intestinal anti-inflammatory and antimicrobials

A07E Intestinal anti-inflammatory drugs

A07EC Aminosalicylic acid and its analogues

Anti-inflammatory drugs - derivatives of salicylic acid.

Composition

The active substance is mesalazine.

Manufacturers

Canonpharma production (Russia)

pharmachologic effect

Pharmacological action - anti-inflammatory.

It inhibits the synthesis of PG, inhibits chemotaxis, degranulation and phagocytosis of neutrophils, the secretion of immunoglobulins by lymphocytes, and has antioxidant properties.

Plasma concentration is low.

In the intestinal mucosa and liver forms N-acetyl-5-aminosalicylic acid.

Effective in the treatment of colitis, ileitis in Crohn's disease, for the prevention of exacerbations of ulcerative colitis in patients with hypersensitivity to sulfasalazine, is well tolerated.

Reduces the risk of recurrence in Crohn's disease, especially in patients with ileitis and a long duration of the disease.

Side effect

Feeling of discomfort, pain in the abdomen, nausea, flatulence, frequent urge to defecate, exacerbation of hemorrhoids, hyperthermia, flu-like syndrome and acute intolerance syndrome (colic, bloody diarrhea, fever, headache, rash), asthenia, drug-induced lupus-like syndrome, arthralgia, alopecia, methemoglobinemia, increased levels of transaminases, alkaline phosphatase, creatinine, urea nitrogen, allergic skin rashes.

Indications for use

Inflammatory bowel disease (ulcerative colitis, Crohn's disease), in the acute stage and prevention of their recurrence.

Contraindications

Hypersensitivity (including to other derivatives of salicylic acid), severe violations of the liver and kidneys, blood diseases, hemorrhagic diathesis, peptic ulcer of the stomach and duodenum, pregnancy, breastfeeding (stop for the duration of treatment), children's age (up to 2 years).

Overdose

No information.

Interaction

It enhances the ulcerogenicity of glucocorticoids, the toxicity of methotrexate, the hypoglycemic effect of sulfonylurea derivatives, the hypoprothrombinemic effect of anticoagulants.

Slows down the absorption of cyanocobalamin.

Weakens the activity of furosemide, spironolactone, rifampicin.

special instructions

The choice of dosage form depends on the localization of the intestinal lesion and its prevalence.

With common forms of ulcerative colitis (total and subtotal), as well as Crohn's disease with damage to the small intestine, tablets are used.

In distal forms (proctitis, proctosigmoiditis), rectal administration of the drug in the form of suppositories or enemas is preferable.

With a left-sided lesion of the colon, both therapy using only suppositories or enemas is possible, as well as their combination with tablets.

Before, during, and after treatment, the composition of peripheral blood, the level of urea, creatinine, and urinalysis should be monitored.

If acute intolerance syndrome is suspected, mesalazine should be discontinued.

Anti-inflammatory drugs - derivatives of salicylic acid.

Composition Mesalazine

The active substance is mesalazine.

Manufacturers

Canonpharma production (Russia)

pharmachologic effect

Pharmacological action - anti-inflammatory.

It inhibits the synthesis of PG, inhibits chemotaxis, degranulation and phagocytosis of neutrophils, the secretion of immunoglobulins by lymphocytes, and has antioxidant properties.

Plasma concentration is low.

In the intestinal mucosa and liver forms N-acetyl-5-aminosalicylic acid.

Effective in the treatment of colitis, ileitis in Crohn's disease, for the prevention of exacerbations of ulcerative colitis in patients with hypersensitivity to sulfasalazine, is well tolerated.

Reduces the risk of recurrence in Crohn's disease, especially in patients with ileitis and a long duration of the disease.

Side effects of mesalazine

Indications for use

Inflammatory bowel disease (ulcerative colitis, Crohn's disease), in the acute stage and prevention of their recurrence.

Contraindications Mesalazine

Overdose

No information.

Interaction

It enhances the ulcerogenicity of glucocorticoids, the toxicity of methotrexate, the hypoglycemic effect of sulfonylurea derivatives, the hypoprothrombinemic effect of anticoagulants.

Slows down the absorption of cyanocobalamin.

Weakens the activity of furosemide, spironolactone, rifampicin.