Ulkolfri - instructions for use, dose, side effects, contraindications

Excipients: hypromellose 46.00 mg, carmellose sodium 41.00 mg, microcrystalline cellulose 26.00 mg, crospovidone 22.00 mg, silicon dioxide colloid 20.00 mg, magnesium stearate 10.00 mg; enteric membrane: methacrylic acid and methyl methacrylate copolymer [1: 1] 49.72 mg, methacrylic acid and methyl methacrylate copolymer [1: 2] 16.58 mg, talc 11.88 mg, diacetylated monoglycerides 9.00 mg, titanium dioxide (E 171) 3 , 53 mg, macrogol-6000 2.09 mg, ferric oxide red oxide (E 172) 2.20 mg; materials for creating a polished surface: Macrogol-6000 3.00 mg.

Description:

Biconvex, capsular tablets covered with a coat from brown to reddish-brown in color, on the cross section - the core is from white to almost white.

Pharmacotherapeutic group:Antimicrobial and anti-inflammatory intestinal

ATX: & nbsp

A.07.E.C.02 Mesalazine

A.07.E.C Aminosalicylic acid and its analogues

Pharmacodynamics:

Mesalazine during oral administration exerts a predominantly local anti-inflammatory effect in the mucosa and the submucosal base of the intestinal wall, acting from the side of its lumen. It inhibits the synthesis of arachidonic acid metabolites (prostaglandins), the activity of neutrophilic lipoxygenase, inhibits the migration, degranulation and phagocytosis of neutrophils, the secretion of immunoglobulins by lymphocytes, binds and breaks free oxygen radicals. Mesalazine has the ability to inhibit the activation of the transcription factor kappa-bi (NFkB) and, consequently, the production of key pro-inflammatory cytokines.

Pharmacokinetics:

Scintigraphic studies revealed traces of the indicator throughout the colon, indicating that mesalazine is entering these parts of the gastrointestinal tract. The complete disintegration of the tablet and the release of mesalazine were observed after approximately 17.4 hours.

Suction

In the small intestine absorbed 21-22% of the dose. After a single dose of the preparation by healthy volunteers on an empty stomach at doses of 1.2-4.8 g, the concentration of mesalazine in plasma was determined, on average, after 2 hours and reached a maximum value after 9-12 hours. Absorption of the drug, defined as the area under the pharmacokinetic curve "concentration-time" (AUC) when taking the drug in a dose range from 1.2 g to 4.8 g, was proportional to the dose taken.

Simultaneous reception with fatty food slows down absorption, but generally increases the system exposure of the drug.

Distribution

The volume of distribution is approximately 18 liters. Mesalazine binds to plasma proteins in unchanged form by 43%, and in acetylated form - by 73-83%. It penetrates through the placental barrier and is excreted in breast milk.

Metabolism

The only important metabolite (N-acetyl-5-aminosalicylic acid) is pharmacologically inactive. It is formed in the cells of the liver and in the cytosol of the cells of the intestinal mucosa.

Excretion

Excretion of metabolized and unaltered mesalazine is carried out through the kidneys and intestines. The absorbed dose of the drug is mainly excreted by the kidneys both as the main metabolite (about 13%) for 4 hours, and unchanged (less than 8%) for 24 hours.

After taking the drug at doses of 2.4 g and 4.8 g, the elimination half-life averaged 7-9 and 8-13 hours, respectively.

Special categories of patients

Impaired liver function

The pharmacokinetics of mesalazine does not depend on liver function. Data on the use of Ulcolfri® in patients with impaired liver function are absent.

Elderly patients

The dependence of pharmacokinetic parameters on renal function was determined, regardless of the age of the patient.

Impaired renal function

The level of systemic exposure is inversely proportional to the function of the kidneys, estimated by the creatinine clearance. In patients with impaired renal function, a decrease in the rate of excretion may be observed.

Female

Value AUC twice this figure in men.

Racial differences

Based on a limited amount of pharmacokinetic data, the pharmacokinetics of 5-ASA and N-acetyl-5-ASA in persons of the South European and Hispanic group is considered the same.

Indications:

Exacerbation of ulcerative colitis of moderate and mild severity; maintenance of remission and / or long-term therapy of ulcerative colitis.

Contraindications:

Hypersensitivity to the components of the drug, a derivative of salicylic acid.

Severe kidney failure.

Severe hepatic insufficiency.

Stomach ulcer or duodenal ulcer.

Hemorrhagic diathesis.

Children under 18 years of age (data on the safety and efficacy of the drug in this category of patients are absent).

Carefully:

Renal / hepatic failure of mild to moderate severity.

Diseases of the lungs (especially bronchial asthma).

Diseases predisposing to the development of myo- or pericarditis.

If there is an allergy to sulfasalazine (cross-reactivity of hypersensitivity to mesalazine is possible).

Pregnancy and lactation:

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 the fetal tissues is much lower than when applied in therapeutic doses in adults.

It is allowed to apply mesalazine during pregnancy, only if the expected benefit for the mother exceeds the potential risk to the fetus. Care should be taken when administering high doses of the drug.

In the last 2-4 weeks of pregnancy, the drug should be withdrawn.

Mesalazine excreted in breast milk. At the time of taking the drug, breastfeeding should be discontinued.

Ability to conceive

The available data do not indicate a prolonged effect of mesalazine on the ability of men to conceive.

Dosing and Administration:

Inside. Take 1 time a day with meals.

Tablets can not be crushed or chewed, they should be swallowed whole. The duration of therapy is determined by the attending physician.

Adults, including patients older than 65 years

Treatment of exacerbation of ulcerative colitis: 2.4 g-4.8 g (2-4 tablets) 1 time per day.The maximum daily dose of 4.8 g is recommended for patients not sensitive to smaller doses of mesalazine. When taking the maximum dose (4.8 g / day), the effect of treatment should be evaluated after 8 weeks.

Maintenance of remission and / or long-term therapy for ulcerative colitis: 2.4 g (2 tablets) once a day. The duration of the prevention of relapse can be several years.

Children and teenagers under 18 years of age

Ulcalfrey® is not recommended for use in children younger than 18 years of age.

Special studies of the use of the drug in patients with impaired liver or kidney function were not performed.

Side effects:

The frequency of side effects is classified according to the frequency of occurrence: often (1/10 - 1/100 appointments), infrequently (1/100 - 1/1000 appointments), rarely (1/1000 - 1/10 000 appointments), very rarely less than 1/10 000 appointments, including single cases).

On the part of the organs of hematopoiesis

Very rarely - eosinophilia, anemia (including aplastic), leukopenia, granulocytopenia, agranulocytosis, thrombocytopenia, pancytopenia.

From the immune system

Very rarely - hypersensitivity reactions, drug fever, Quincke's edema.

From the nervous system

Rarely - dizziness; very rarely - peripheral neuropathy, benign intracranial hypertension (in patients at pubertal age).

From the cardiovascular system *

Rarely - myocarditis, pericarditis.

From the respiratory system*

Very rarely - dyspnea, cough, allergic alveolitis, pulmonary eosinophilia, pulmonary infiltration, pneumonia, bronchospasm, interstitial lung disease.

From the digestive system

Often - diarrhea, abdominal pain, nausea, vomiting, flatulence; rarely - increased levels of amylase, pancreatitis *; very rarely - exacerbation of symptoms of colitis.

From the hepatobiliary system

Very rarely - increased activity of "liver" enzymes and bilirubin, hepatotoxicity * (hepatitis, cirrhosis, hepatic insufficiency).

From the skin

Often - hives, erythema; very rarely - photosensitivity, reversible alopecia.

From the side of the musculoskeletal system

Very rarely - myalgia, arthralgia.

From the urinary system

Very rarely - interstitial nephritis *, nephrotic syndrome, changes in urine color, transient renal failure.

Other

Often - a headache, a fever.

* - the mechanism of development of adverse reactions is presumably allergic.

Overdose:

Ulcolfree® is an aminosalicylate; signs of intoxication of salicylates include tinnitus, vertigo, headache, confusion, drowsiness, pulmonary edema, dehydration amid sweating, diarrhea and vomiting, hypoglycemia, hyperventilation, electrolyte imbalance and blood pH, hyperthermia.

Cases of overdose are rare. Specific antidotes are absent. It is recommended to wash the stomach and take measures to enhance diuresis. In the case of the development of acidosis, alkalosis, dehydration, hyperventilation or pulmonary edema, it is necessary to restore the acid-base and water-electrolyte balance by appropriate therapy. Adequate renal function should be maintained.

Interaction:

There were no clinically significant interactions of mesalazine with the most commonly used antimicrobial agents (amoxicillin, ciprofloxacin, metronidazole and sulfamethoxazole).

With the simultaneous use of mesalazine with 6-mercaptopurine or azathioprine, the risk of suppression of bone marrow function (leukopenia, thrombocytopenia, erythrocytopenia / anemia or pancytopenia) is increased.

Simultaneous administration of mesalazine and other drugs with nephrotoxicity, for example, non-steroidal anti-inflammatory drugs and azathioprine, increases the risk of developing adverse reactions from the kidneys.

The use of mesalazine together with anticoagulants of the coumarin group, 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.

Slows the absorption of cyanocobalamin (vitamin B₁₂), enhances the hypoglycemic action of sulfonylurea derivatives, ulcerogenicity of glucocorticosteroids, toxicity of methotrexate, weakens the activity of furosemide, spironolactone, sulfonamides, rifampicin, probenecid and sulfinpyrazone, enhances the effect of anticoagulants, and increases the effectiveness of uricosuric drugs (tubular secretion blockers).

With the simultaneous use of medications of mesalazine and digoxin, digoxin absorption is reduced.

Special instructions:

When using drugs containing mesalazine or its precursors, cases of renal dysfunction are described, including minimal nephropathy and acute / chronic interstitial nephritis. Ulcalfrey® should be used with caution in patients with confirmed mild or moderate renal impairment. All patients are recommended to conduct a study of kidney function before treatment and at least 2 times a year during treatment. During the entire course of treatment, the concentration of creatinine in the blood should be monitored regularly.

When appointing mesalazine, patients with lung diseases, in particular bronchial asthma, need careful monitoring of the patients' condition during treatment.

In rare cases, after the administration of mesalazine, severe disruption of the cellular composition of the blood developed. If a patient experiences unexplained bleeding, bruising, purple, anemia, fever, or sore throat, a blood test should be performed. If there is a suspicion of a disorder in the cellular composition of the blood, treatment should be discontinued.

When using drugs containing mesalazine, rare cases of reactions of hypersensitivity from the heart (myo- and pericarditis) are described. Caution is necessary to prescribe this drug to patients with diseases predisposing to the development of myo- or pericarditis.

If hypersensitivity reaction is suspected, re-use of drugs containing mesalazine, is unacceptable.

The use of mesalazine is associated with the development of an acute intolerance syndrome, which, in some cases, is difficult to distinguish from an exacerbation of inflammatory bowel disease. Although the frequency of this phenomenon is not accurately established, it was 3% in controlled clinical trials of mesalazine or sulfasalazine. Symptoms include intestinal cramps, acute pain in the abdomen, diarrhea with an admixture of blood, sometimes a fever, a headache and a rash. If suspected of developing an acute intolerance syndrome, the mesalazine drug should be immediately discontinued and its repeated use is unacceptable.

There have been reports of increased hepatic transaminase activity in patients taking drugs containing mesalazine. It is recommended to be cautious when prescribing Ulcolri® to patients with impaired functionliver.

Care should be taken when treating patients who are allergic to sulfasalazine, because of possible cross-sensitivity to mesalazine.

Organic or functional obstruction of the upper gastrointestinal tract can slow the development of the drug effect.

If renal function is impaired during the treatment period, the nephrotoxicity caused by mesalazine should be taken into account.

Impact on laboratory tests

The use of mesalazine may lead to falsely elevated test results in the measurement of urinary normetanephrine by liquid chromatography with electrochemical detection due to the similarity of the chromatograms of normetanephrine and the main metabolite of mesalazine- N-acetylaminosalicylic acid (N-Ac-5-ACA). Therefore, to determine the content of normetanephrine in urine, an alternative selective method should be used.

Effect on the ability to drive transp. cf. and fur:

Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions,since the drug may cause dizziness and other side effects that may affect these abilities.

Form release / dosage:

Tablets of prolonged action, covered with enteric coating, 1200 mg.

Packaging:

For 10 tablets in an aluminum blister.

For 6 or 12 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004001

Date of registration:06.12.2016

Expiration Date:06.12.2021

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDr. Reddy`c Laboratoris Ltd.Dr. Reddy`c Laboratoris Ltd.

Information update date: & nbsp16.01.2017

Illustrated instructions

Instructions

Ulcolfree® (Ulcofree)