Mezavant sustained release pills, coated with enteric coating 1.2 g, 60 pcs.

Composition

1 tablet contains:Active ingredient: mesalazine 1200 mg. Auxiliary substances:Pill Core: sodium carmellose (7MF) – 11.3 mg, sodium carmellose (7HXF) – 38.7 mg, Carnauba wax-5.0 mg, stearic acid-10.0 mg, colloidal silicon dioxide -2.0 mg, sodium carboxymethyl starch (type A) – 30.0 mg, talc-11.0 mg, magnesium stearate -14.0 mg. Tablet shell:talc-17.8 mg, methacrylic acid and methyl methacrylate copolymer [1:1] – 16.0 mg, methacrylic acid and methyl methacrylate copolymer [1:2] -16.0 mg, triethyl citrate-3.2 mg, titanium dioxide-6.0 mg, iron oxide red dye-3.0 mg, macrogol 6000-1

Composition

.0 mg.

A drug with an anti-inflammatory effect used for the treatment of Crohn’s disease and UC.

Pharmaceutical action: 

Mezavant is an antimicrobial and anti-inflammatory intestinal agent.

Mesalazine is a derivative of 5-aminosalicylic acid. The mechanism of action of mesalazine is not fully understood, but it was found that the drug has a local anti-inflammatory effect on the intestinal epithelium. In patients with chronic inflammatory bowel disease, the synthesis of arachidonic acid metabolites in the mucosa is enhanced by cyclooxygenase and lipoxygenase pathways.

Mesalazine may reduce inflammation by inhibiting cyclooxygenase and inhibiting prostaglandin synthesis in the colon.

Mesalazine has the ability to inhibit the activation of the nuclear factor kappa-B-KBkB and, consequently, the production of key pro-inflammatory cytokines.

Recently, it has been suggested that the deficiency of nuclear receptors PPAR-γ (the γ-form of receptors activated by the peroxisome proliferator) may be associated with the development of ulcerative colitis. PPAR-γ receptor agonists have been shown to be effective in ulcerative colitis. Accumulated data indicate that the effect of mesalazine can be realized by acting on PPAR-γ receptors.

Pharmacokinetics: 

The Mezavant tablet has a core containing mesalazine (5-aminosalicylic acid,5-ASA) in a multicomponent matrix. The core is surrounded by a shell of methacrylic acid copolymers of types A and B; the shell is designed so that the release of mesalazine begins only when pH is reached above 7.

The mechanism of action of mesalazine is not fully understood, but it is believed that mesalazine (5-ASA) has a local effect, so the clinical effect of the drug does not correlate with the pharmacokinetic characteristics of the substance. The main route of elimination of mesalazine is metabolism to N-acetyl-5-aminosalicylic acid, which is pharmacologically inactive.

Suction

Studies with gamma scintigraphy have shown that after a single dose of 1.2 g of mesalazine taken on an empty stomach by healthy volunteers, mesalazine passes quickly and unchanged through the upper gastrointestinal tract. At the same time, traces of C-labeled mesalazine are detected throughout the large intestine, which indicates that mesalazine enters these parts of the gastrointestinal tract. Complete disintegration of the Mezavant tablet and mesalazine release were observed after approximately 17.4 hours.

After a single dose of 2.4 g or 4.8 g in healthy volunteers for 14 days, the absorption of mesalazine was 21-22% of the dose taken.

After a single dose of 1.2 g,2.4 g, and 4.8 g of mesalazine in healthy volunteers on an empty stomach, the plasma concentration of mesalazine was determined 2 hours (median) after administration and reached its maximum value in 9-12 hours (median). Pharmacokinetic parameters showed wide variability.

The level of systemic exposure to mesalazine – AUC (area under the concentration – time curve) – when taking the drug in the range from 1.2 g to 4.8 g was proportional to the dose taken. Cmax of mesalazine in plasma in the dose range from 1.2 g to 2.4 g increased approximately directly proportional, while from 2.4 g to 4.8 g increased less than proportional to the dose.

When studying single and multiple doses of the drug at a dose of 2.4 g and 4.8 g with regular food, mesalazine was detected in blood plasma after 4 hours, reaching maximum concentrations 8 hours after a single dose.

A single dose of 4.8 g of Mezavant with fatty foods was accompanied by a slowing of the absorption phase. Under these conditions, mesalazine was detected in the blood plasma approximately 6 hours after administration. However, high-fat foods increased systemic mesalazine exposure (mean Cmax by 91%, mean AUC by 16%) compared to fasting subjects.

Distribution

It is believed that the drug Mezavant has a similar distribution profile as other mesalazine-containing drugs. Mesalazine has a relatively small Vd of approximately 18 liters, which indicates a minimal systemic distribution. At plasma concentrations of mesalazine up to 2.5 mcg / ml and N-acetyl-5-aminosalicylate up to 10 mcg / ml, the substances bound to plasma proteins by 43% and 78-83%, respectively.

Metabolism

The only important metabolite of mesalazine is pharmacologically inactive N-acetyl-5-aminosalicylic acid. It is formed by the action of N-acetyltransferase-1 in liver cells and the cytosol of intestinal mucosa cells.

Deduction

Absorbed mesalazine is mainly excreted by the kidneys after acetylation to N-acetyl-5-aminosalicylic acid. However, the drug is excreted in small amounts by the kidneys and unchanged. Of the 21-22% absorbed dose, less than 8% of mesalazine is excreted unchanged in the urine within 24 hours. About 13% is excreted within 4 hours as N-acetyl-5-aminosalicylic acid. Visible T1 / 2 of mesalazine and its main metabolite after taking the drug at a dose of 2.4 and 4.8 g were on average 7-9 and 8-13 hours, respectively.

Pharmacokinetics in special clinical cases

There are no data on the use of Mezavant in patients with impaired liver function. After a single dose of 4.8 g of Mesavant, the systemic exposure of mesalazine in elderly patients (older than 65 years, mean creatinine clearance 68-76 ml/min) was higher than in younger patients (18-35 years, mean creatinine clearance 124 ml / min). up to 2 times.

The level of systemic exposure is inversely proportional to renal function as assessed by creatinine clearance. This should be taken into account when treating elderly patients with Mezavant.

Patients with impaired renal function may experience a decrease in the rate of elimination and an increase in the concentration of mesalazine in blood plasma, which may be accompanied by an increased risk of undesirable side effects from the urinary system.

In women, the AUC of mesalazine was 2 times higher than in men. Based on the limited amount of pharmacokinetic data, the pharmacokinetics of 5-ASA and N-acetyl-5-ASA in the Southern European and Spanish-speaking groups are considered to be the same.

Indications

Use during pregnancy and lactation

Pregnancy Limited data on the use of mesalazine during pregnancy do not indicate an increased risk of congenital malformations. Mesalazine penetrates the placental barrier, but the concentration of the substance in fetal tissues is significantly lower than when used in therapeutic doses in adults. Animal studies have not shown any adverse effects of mesalazine on pregnancy, embryo/fetal development, delivery, and postnatal development of offspring. Mesalazine should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. Caution should be exercised when prescribing high doses of the drug. Lactation periodimEsalazine is excreted in breast milk in small amounts, and the metabolite N-acetyl-5-aminosalicylic acid-in a higher concentration. During lactation, mesalazine should be used with caution and only if the possible benefit to the mother exceeds the potential risk to the child. Cases of sporadic diarrhea have been reported in infants. Ability to conceive The available data do not indicate a long-term effect of mesalazine on the ability of men to conceive.

Contraindications

With caution

Side effects

From the digestive system: nausea, vomiting, heartburn, diarrhea, decreased appetite, abdominal pain, increased activity of “liver” transaminases, hepatitis, pancreatitis.

From the cardiovascular system: palpitations, tachycardia, increased or decreased blood pressure, pain behind the sternum, shortness of breath.

Nervous system disorders: headache, tinnitus, dizziness, polyneuropathy, tremor, depression.

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

Allergic reactions: skin rash, pruritus, dermatosis, bronchospasm.

Hematopoietic disorders: anemia (hemolytic, megaloblastic, aplastic), leukopenia, agranulocytosis, thrombocytopenia, hypoprothrombinemia.

Others: weakness, mumps, photosensitivity, lupus-like syndrome, oligospermia, alopecia, decreased production of tear fluid.

Interaction

Clinical studies in healthy adult patients did not reveal clinically significant interactions of Mezavant with the 4 most commonly used antibiotics (amoxicillin, ciprofloxacin, metronidazole, and sulfamethoxazole). Nevertheless, there are data on the interaction of other mesalazine-containing drugs with drugs:It is recommended to use mesalazine with caution simultaneously with drugs that have a nephrotoxic effect, including nonsteroidal anti-inflammatory drugs (NSAIDs) and azathioprine, as this may increase the risk of developing adverse events from the kidneys. Mesalazine inhibits thiopurine methyltransferase activity. It is recommended to take mesalazine with caution at the same time as azathioprine or mercaptopurine, as this may increase the risk of disruption of blood cell composition. The use of mesalazine together with coumarin anticoagulants, for example, warfarin, may be accompanied by a decrease in the activity of the latter. If this combination is necessary, prothrombin time should be carefully monitored.

How to take, course of administration and dosage

The drug Mezavant is intended for oral administration 1 time a day with meals. Tablets should not be crushed or chewed and should be swallowed whole. Adults, including the elderly (over 65 years of age)Induction of remission: 2.4-4.8 g (2-4 tablets) 1 time per day. For patients who are not sensitive to the minimum dose, the recommended maximum daily dose is 4.8 g. When taking the maximum dose (4.8 g / day), the effect of treatment should be evaluated after 8 weeks. Maintenance of remission: 2.4 g (2 tablets) 1 time per day. Children and teenagers under 18 years of age:Due to the lack of data on safety and efficacy, Mezavant is not recommended for use in children under 18 years of age. Special studies of the use of Mezavant in patients with impaired liver or kidney function have not been conducted.

Overdose

The drug Mezavant is an aminosalicylate; signs of salicylate intoxication include tinnitus, vertigo, headache, confusion, drowsiness, pulmonary edema, dehydration with increased sweating, diarrhea and vomiting, hypoglycemia, hyperventilation, electrolyte imbalance and blood pH, hyperthermia. In case of acute overdose, standard methods of treating acute salicylate intoxication should be used. Hypoglycemia and impaired water-electrolyte balance should be corrected by appropriate therapy. Adequate renal function should be maintained.

Special instructions

It is advisable to regularly conduct a general blood test (before, during, and after treatment) and urine, and monitor the excretory function of the kidneys.

Patients who are “slow acetylators” have an increased risk of developing side effects. There may be staining of urine and tears in yellow-orange color, staining of soft contact lenses.

If you miss taking the drug, the missed dose should be taken at any time or together with the next dose. If you miss several doses, then, without stopping treatment, consult a doctor.

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

Form of production

Long-acting enteric coated tablets

Storage conditions

In a place protected from moisture, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Mesalazine

Conditions of release from pharmacies

By prescription

Dosage form

of long-acting tablets

Purpose

For pregnant women as prescribed by a doctor, For Nursing mothers as prescribed by a doctor, For Children as prescribed by a doctor, For adults as prescribed by a doctor

Indications

Colitis, Crohn

‘s Disease Weight

Weight: 128 g.