In patients with chronic inflammatory bowel disease in the mucosa is enhanced synthesis of metabolites of arachidonic acid by cyclooxygenase and lipoxygenase pathways. Possibly weakens mesalazine inhibiting inflammation by inhibition of cyclooxygenase and prostaglandin synthesis in the colon. Mesalazine has the ability to what is deca durabolin inhibit the activation of nuclear factor kappa-B – NFkB and hence production of key pro-inflammatory cytokines. Recently it has been suggested that the failure of the nuclear receptor PPAR-γ (γ-form of the receptors, peroxisome proliferator-activated) may be associated with the development of ulcerative colitis. The effectiveness of PPAR-γ receptor agonists for ulcerative colitis was demonstrated.Accumulating evidence suggests that the effect of mesalazine can be realized by acting on the receptors of PPAR-γ.
tablet Mezavant formulation has a core comprising mesalazine (5-aminosalicylic acid, 5-ASA) in a multi-component matrix. The core is surrounded by a sheath of methacrylic acid copolymer types A and B;the shell is designed so that the release mesalazine started only when the pH is above 7.
The mechanism of action of mesalazine is not fully understood, but it is believed that mesalazine (5-ASA) has a local effect, therefore the clinical effect of the drug is not correlated with the pharmacokinetic characteristics of the compound. The main route of excretion is mesalazine metabolism to N-acetyl-5-aminosalicylic acid, which is pharmacologically inactive. Absorption: Studies performing gamma scintigraphy showed that after a single dose of the drug to healthy volunteers fasting at a dose of 1.2 g mesalazine quickly and unaltered It passes through the upper gastrointestinal tract. Thus revealed traces of C-labeled mesalazine throughout the colon, indicating the receipt of mesalazine in the gastrointestinal tract. Complete tablet disintegration and drug release mesalazine Mezavant observed in about 17.4 hours. After a single dose of the drug to healthy volunteers at a dose of 2.4 g or 4.8 g in 14 days absorption of mesalazine was 21 – 22% of the dose. After single ingestion fasting healthy volunteers at a dose of 1.2 g, 2.4 g and 4.8 g of mesalazine concentration in plasma was determined after 2 chasa (median) after administration and reached a maximum at 9-12 hours (median). Pharmacokinetic figures showed wide variability. The level of systemic exposure of mesalazine – AUC (area under the curve “concentration – time”) -with taking the drug in the range of 1.2 g to 4.8 g was proportional to the dose. The maximum concentration (C max ) of mesalazine in the plasma at a dosage range of from 1.2 g to approximately 2.4 g was increased in direct proportion, whereas from 2.4 g to 4.8 g increased less than proportionally to dose. In the study of single and repeated administration of the drug at a dose of 2.4 g and 4.8 g with a conventional food mesalazine detected in plasma after 4 hours, reaching a maximum blacks with 8 hours after a single dose. a single dose Mezavant drug at a dose of 4.8 g with fatty foods accompanied depot phase. Under these conditions, mesalazine detected in plasma after about 6 hours after ingestion. However, foods rich in fats, increased the systemic exposure of mesalazine (mean C max – 91%, the mean AUC – 16%) as compared with the fasted state. Distribution: It is believed that Mezavant drug has a similar distribution profile that other mesalazine -containing drugs. Mesalazine has a relatively small volume of distribution of about 18 liters, indicating minimal systemic distribution.When mesalazine concentration in blood plasma and 2.5 ug / ml and the concentration of N-acetyl-5-aminosalicylate to 10 mcg / ml the substance bind to plasma proteins by 43% and 78-83%, respectively.Metabolism: One important metabolite is mesalazine pharmacologically inactive N-acetyl-5-aminosalicylic acid. It is formed by the action of N-acetyl-1 in the cytosol of liver cells and cells of the intestinal mucosa. Excretion: suck mesalazine displayed in the kidneys after acetylation to N-acetyl-5-aminosalicylic acid. However, a small amount of drug is excreted by the kidneys in unchanged form. From 21 – 22% suck dose of 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. The apparent half-life of mesalazine and its major metabolite after administration of the drug at a dose of 2.4 and 4.8 g were on average 7-9 and 8-13 hours, respectively. Specific categories of patients: the use Mezavant of these drugs in patients with impaired liver function no . After a single dose of the drug Mezavant at a dose of 4.8 g mesalazine systemic exposure in elderly patients (older than 65 years, the average creatinine clearance 68-76 ml / min) greater than that seen in younger patients (18 – 35 years, mean creatinine clearance 124 mL / min) to 2 times. Systemic exposure level is inversely proportional to renal function as assessed by creatinine clearance. This should be considered in the treatment of elderly patients drug Mezavant. In patients with impaired renal function may experience slow elimination rate and increasing mesalazine plasma concentrations that may be associated with an increased risk of unwanted side reactions on the part of the urinary system. In women, the area under the AUC curve ( ” concentration – time “) mesalazine was 2 times higher than in men. Based on the limited number of pharmacokinetic data, the pharmacokinetics of 5-ASA and N-acetyl-5-ASA at southern European people and Hispanic groups considered identical.
- The induction of remission of clinical and endoscopic parameters in patients with mild to moderate ulcerative colitis.
- Maintaining remission in patients with ulcerative colitis.
- Hypersensitivity to salicylates (including mesalazine) or any subsidiary component of the drug.
- Severe renal impairment (GFR <30 ml / min / 1.73 m 2 ).
- Severe hepatic dysfunction.
- Children under the age of 18 years (due to lack of data on safety and efficacy in these patients).Carefully
- Mild to moderate renal impairment.
- Chronic lung function (asthma).
- Diseases that predispose to the development of myo- or pericarditis.
- The drug is prescribed with caution to patients who have an allergy to sulfasalazine, because of possible cross-hypersensitivity to mesalazine.
Pregnancy and lactation
Limited data on the use of mesalazine what is deca durabolin during pregnancy do not indicate an increased risk of congenital malformations. Mesalazine crosses the placental barrier, but the concentration of the substance in the fetal tissues is significantly lower than when used in therapeutic doses in adults. Animal studies revealed no adverse effect of mesalazine on pregnancy, embryo / fetus, childbirth and the postnatal development of the 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 in the appointment of high doses of the drug. Lactation Mesalazine is excreted in breast milk in small quantities, and the metabolite N-acetyl-5-amino salicylic acid – a higher concentration. The mesalazine during lactation should be used with caution and only if the potential benefit to the mother outweighs the potential risk to the child. In infants, sporadic cases of diarrhea have been described. The ability to conceive Available data do not indicate a long-term effect of mesalazine on the ability of men to conceive.
Dosing and Administration
Mezavant The drug is intended for oral administration of 1 times a day with meals. Tablets can not crush or chew and should be swallowed whole. The adults, including the elderly (over 65 years) induction of remission: 2.4 – 4.8 g (2 – 4 tablets) 1 times a day. For patients who are not responsive to the minimum dose, the recommended maximum daily dose is 4.8 g When you receive a maximum dose (4.8 grams / day), the effect of treatment should be evaluated after 8 weeks. Maintenance of remission: 2.4g (2 tablets) 1 times a day. children and adolescents under 18 years: due to lack of data on safety and efficacy Mezavant drug is not recommended for use in children under 18 years of age. Special Mezavant trials of the drug in patients with impaired liver or renal function has not been carried out.
The most frequently occurring adverse events in clinical trials were headache, abdominal pain and nausea. For any of unwanted side reaction frequency does not exceed 10%. In applying the drug Mezavant other adverse reactions were observed less frequently.
Adverse reactions Mezavant drug and adverse reactions encountered when taking other medicines containing mesalazine-systematized with respect to each of the organ systems using the following classification of frequency of occurrence:
Very commonly (≥1 / 10)
Often (≥1 / 100, <1/10)
Uncommon (≥1 / 1000, <1/100)
rare (≥1 / 10,000, <1/1000)
Very rare (<1/10000), including isolated cases From the blood and lymphatic system Uncommon: thrombocytopenia rare: agranulocytosis frequency not known: aplastic anemia, leukopenia, neutropenia, pancytopenia. On the part of the central nervous system: Common: headache. Uncommon:. dizziness, drowsiness, tremor frequency is unknown: neuropathy cardio-vascular system Common: increased blood pressure. Uncommon:. tachycardia, hypotension frequency unknown: myocarditis, pericarditis. respiratory system: Uncommon:. pain in the throat / larynx unknown frequency: bronchospasm On the part of the gastrointestinal tract Common: abdominal distension, abdominal pain , diarrhea, dyspepsia, vomiting, flatulence, nausea, deviation indicators of liver function tests (aspartate aminotransferase, alanine aminotransferase, bilirubin). Uncommon:. colitis, pancreatitis, polyp rectum frequency not known: hepatitis, cholelithiasis. skin and subcutaneous tissue disorders Common: itching , rash. Uncommon: acne rash, alopecia. immune system: Uncommon:. urticaria not known frequency: pneumonitis, as a manifestation of a hypersensitivity (including interstitial pneumonitis, allergic alveolitis, eosinophilic pneumonitis), angioedema, a syndrome similar to systemic lupus erythematosus, anaphylaxis, Stevens-Johnson syndrome, drug skin reaction, accompanied by eosinophilia and systemic symptoms (DRESS). On the part of the musculoskeletal system, connective and bone tissue: Common:. arthralgia, related muscle pain, back pain is not common: myalgia . From the urogenital system: rare: renal failure frequency is unknown: interstitial nephritis. General state Common: asthenia, fever. Uncommon: swelling of the face, weakness.
The drug Mezavant – it aminosalicylate; signs of salicylate toxicity include tinnitus, vertigo, headache, confusion, drowsiness, pulmonary edema, dehydration, against the backdrop of increased sweating, diarrhea and vomiting, hypoglycaemia, hyperventilation, electrolyte imbalance and blood pH, hyperthermia.
In acute overdose is necessary to apply the standard treatment of acute intoxication salicylates.Hypoglycemia and disruption of water and electrolyte balance should be corrected by appropriate treatment.It is necessary to maintain adequate kidney function.
Interaction with other drugs Clinical studies on healthy adult patients showed no clinically significant drug interactions Mezavant 4 most commonly used antibiotics (amoxicillin, ciprofloxacin, metronidazole and sulfamethoxazole). Nevertheless, there are data on the interaction of other mesalazine-containing drugs with the drugs:
- It is recommended to be used with caution in conjunction with mesalazine drugs that provide nephrotoxicity, including nonsteroidal anti-inflammatory drugs (NSAIDs) and azathioprine, as this may increase the risk of adverse events by the kidneys.
- Mesalazine inhibits tiopurinmetiltransferazy. It is recommended to take care mesalazine simultaneously with azathioprine or mercaptopurine, since it may increase the risk of the blood cell disorders.
Use of mesalazine with anticoagulant coumarin group, such as warfarin, may be accompanied by lower activity of the latter.If necessary, use this combination should be closely monitored prothrombin time.
Special instructions and precautions
In the application of preparations containing mesalazine or its predecessors, cases of impaired renal function are described, including minimum nephropathy, and acute / chronic interstitial nephritis. Mezavant drug should be used with caution in patients with confirmed mild to moderate renal impairment. All patients are encouraged to go through the study of renal function prior to initiation of treatment and at least 2 times a year during treatment.
Patients with chronic lung function (asthma) are at increased risk of hypersensitivity reactions, and should be under constant medical supervision.
After receiving mesalazine in rare cases develop severe violation of the cellular composition of the blood. When the patient’s unexplained bleeding, bruising, purpura, anemia, fever or sore throat should conduct a blood test. If you what is deca durabolin suspect a violation of the blood cell composition, treatment should be discontinued.
In applying the drug Mezavant or other preparations containing mesalazine are described rare cases of hypersensitivity reactions on the part of the heart (myocardial and pericardial effusion). It should be used with caution in this drug to patients with diseases predisposing to the development of myo- or pericarditis. For suspected hypersensitivity reaction, re-use of products containing mesalazine is unacceptable.
The use of mesalazine linked to the development of acute intolerance syndrome, which in some cases it is difficult to distinguish from an exacerbation of inflammatory bowel disease. Although the frequency of this phenomenon is not certain, in controlled clinical trials of mesalazine or sulfasalazine it was 3%. Symptoms include intestinal cramps, acute abdominal pain, diarrhea mixed with blood, sometimes fever, headache and rash. If you suspect that the development of an acute intolerance syndrome should be lifted immediately preparations containing mesalazine and their re-use is not allowed.
There are reports of increased activity of “liver” transaminases in patients taking preparations containing mesalazine. Caution is advised when administering the drug Mezavant patients with impaired hepatic function.
Caution should be exercised when treating patients allergic to sulfasalazine, because of possible cross-hypersensitivity to mesalazine.
Organic or functional obstruction of the upper gastrointestinal tract may delay the development of drug effect.
if the kidney function during treatment of patients with drug Mezavant should be considered caused by mesalazine nephrotoxicity.
The use of mesalazine may result in falsely elevated test results when measuring the content of normetanephrine in urine by liquid chromatography with electrochemical detection because of the similarity of chromatograms normetanephrine and the main metabolite of mesalazine – N -atsetilaminosalitsilovoy acid (N-Ac-5-ACA). Therefore, to determine the content in the urine Normetanephrine selective alternative method should be used.
Effects on ability to drive and other mechanical means of
drug influence Mezavant Research on ability to drive and has not been moving mechanisms. It is believed that Mezavant drug has no effect on this ability.