Index of drugs

It is used as a monotherapy or more often in combination with other medicines (usually corticosteroids).In diseases with autoimmune backgroundsuch as: systemic lupus erythematosus, severe rheumatoid arthritis, dermatomyositis, polymyositis, periarteriosclerosis nodosa, pemphigus vulgaris - gangrenous hemoderma, autoimmune hemolytic anemia, chronic resistant thrombocytopenic purpura, autoimmune chronic hepatitis. Azathioprine is used when: a) these diseases are resistant to corticosteroids; b) corticosteroids are contraindicated, or c) corticosteroids should be used at doses that cause serious side effects. In patients with side effects, azathioprine is used to reduce steroid maintenance doses. Therapeutic effects may occur after several weeks or months of treatment.After organ transplantation such as: kidneys, heart and liver. The preparation is used to extend the survival time of transplanted organs and to reduce the doses of corticosteroids necessary after renal transplantation.

1 tabl contains 50 mg azathioprine. The preparation contains lactose.

Immunosuppressant - imidazole derivative of 6-mercaptopurine. The mechanism of action is the release of 6-mercaptopurine, which acts as a purine antimetabolite. Inhibition of numerous nucleic acid biosynthesis pathways occurs at many stages and, as a result, to the proliferation of cells involved in the determination and enhancement of the immune response. The deoxyribonucleic acid is damaged by the incorporation of purine thioanalogs into the DNA molecule. Due to the mechanism of action of azathioprine, the therapeutic effect of the drug may be delayed, only after weeks or months of treatment. Azathioprine is a prodrug.In vivo it is quickly converted non-enzymatically to imidazole derivatives that have some immunosuppressive effect. The major metabolite is 6-mercaptopurine, which is enzymatically converted to 6-thioguanine, the intracellular compound that is the most important for the clinical effect. Individual differences in the activity of enzymes influence the rate of change.

Hypersensitivity to azathioprine, 6-mercaptopurine or any of the excipients. Persons hypersensitive to 6-mercaptopurine may also be hypersensitive to azathioprine. Leukopenia. Low activity of thiopurine methyltransferase (TPMT). Pregnancy and breastfeeding.

During the use of the drug should be periodically carried out studies of the morphological image of the blood and liver function. During the first 8 weeks of treatment, the blood test should be carried out at least once a week, and even more frequently if high doses are used and in severe renal or hepatic impairment. In later treatment, the frequency of blood tests can be reduced by marking once monthly morphs, and then at least once every 3 months. If the number of leukocytes and / or blood platelets is below the normal level or if other undesirable symptoms occur, i.e. infection bleeding, reduce the dose of azathioprine. Azathioprine shows incomplete therapeutic efficacy in patients deficient in hypoxanthine-guanine phosphoribosyltransferase (Lesch-Nyhan syndrome). Impaired drug metabolism in these people limits its pharmacological action - the use of azathioprine in patients with this syndrome is not recommended. In patients with hepatic impairment, a full blood count and liver function tests should be used with caution and systematic. In people with congenital deficiency of the thiopurine methyltransferase (TPMT) enzyme, myelosuppression may be increased, which is enhanced by the simultaneous use of azathioprine with olsalazine, mesalazine or sulfosalazine. The product contains lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.

Due to the likely teratogenic properties of the preparation should not be used during pregnancy. The use of a drug in pregnancy is only allowed if it is absolutely necessary for the health of the mother, and the use of a safer alternative medicine is impossible or contraindicated. Breast-feeding should be discontinued during treatment.

Very often: leukopenia. Common: thrombocytopenia, hypersensitivity reactions (fever, muscle and joint pains), low blood pressure, arrhythmias, nausea, vomiting and anorexia (especially at higher doses), cholestasis and hepatic impairment (usually transient after discontinuation of the drug, these symptoms may be associated with hypersensitivity reactions), hepatic injury that is life-threatening (due to long-term use of the drug, particularly in organ transplant patients, histological changes include: dilation of vascular sinuses, hepatic purpura, hepatic obliterans and regenerative nodular hypertrophy; cases of discontinuation of azathioprine caused temporary or permanent elimination of symptoms and improvement of the histopathological picture of the liver), neoplastic diseases (during long-term use, especially in organ transplant recipients who received long-term treatment) immunosuppressive treatment). Uncommon: granulocytopenia, anemia, diarrhea (including patients with ulcerative enterocolitis, severe diarrhea, recurrent after re-administration). Rare: increased susceptibility to viral, bacterial and fungal infections (especially in the airways), hypersensitivity reactions (rash, eruptions). Very rare: agranulocytosis, pancytopenia, aplastic anemia, vasculitis, fatal cases (other serious concurrent diseases contributed to the death of the patient), alopecia (in many cases it resolved spontaneously despite continued treatment with a lower dose), in patients after transplantation of organs cases of severe complications (including colitis, diverticulitis and perforation of the intestine), pancreatitis (especially after kidney transplantation and ulcerative colitis), reversible interstitial, drug-induced pneumonia. Frequency not known: hypersensitivity reactions (malaise, dizziness, chills, pruritus). Patients with congenital deficiency of thiopurine methyltransferase (TPMT) may experience increased myelosuppression. If hypersensitivity to azathioprine occurs, discontinuation should be considered. In most cases, immediate discontinuation of azathioprine or a reduction in dose to half resulted in symptom relief. After the first administration, a few patients may experience nausea, this can be prevented by giving the medicine after meals.

Orally.Dosing in transplants in adults and children: the daily dose can be given once. The dose should be selected individually, depending on the patient's clinical condition and bone marrow function parameters (without a dangerous decrease in the number of white blood cells and platelets). One should remember about individual differences and the occurrence of hypersensitivity to the drug in approx. 0.3% of the population. On day 1 after organ transplantation, 5 mg / kg / day azathioprine is administered followed by a maintenance dose of 1-4 mg / kg / day. This dose should be adjusted to clinical response and haematological tolerability. Due to the risk of transplant rejection, treatment with azathioprine should be continued for life, even if low doses are required.Dosage in other indications in adults and children: the daily dose is 1-3 mg / kg. After achieving a clear clinical effect, the maintenance dose should be considered as low as possible. The dose can be from less than 1 mg / kg. up to 3 mg / kg If the patient's condition does not improve after 3 months of treatment, discontinuation should be considered.Special groups of patients. Elderly patients are advised to administer lower doses in the lower range of the recommended dosage. To achieve the full therapeutic effect, the drug must be administered over a period of several weeks to several months. Particular care should be taken when azathioprine is combined with immunosuppressants with a different mode of action, such as: steroids, cyclosporine or antimycotic globulin (ATG).Sometimes, especially after using the drug at higher doses, patients who are treated have nausea, vomiting or anorexia. These symptoms can be reduced by administering the medicine in divided doses and after a meal. Patients with impaired hepatic or renal function are advised to administer the lowest recommended doses (1 mg / kg / day) and control their hematopoietic function. If there is evidence of hematopoietic damage (infection, bruising of unknown cause, bleeding or other symptoms of bone marrow suppression) or liver, a dose reduction is recommended.Way of giving. Use after a meal, drink with water.