Azathioprinum

General characteristics. Structure:

Active ingredient: 50 mg of Azathioprinum in 1 tablet.

Drug with the expressed immunodepressive action.

Pharmacological properties:

Pharmacodynamics. Is a structural analog (antimetabolite) of adenine, hypoxanthine and guanine, being a part of nucleic acids (DNA and RNA), breaks biosynthesis of nucleotides and suppresses proliferation of fabrics.

The immunodepressive effect is caused by a hypoplasia of an adenoid tissue, decrease in quantity of T lymphocytes, disturbance of synthesis of immunoglobulins, emergence in blood of atypical phagocytes and, finally, suppression of cell-mediated reactions of hypersensitivity.

Pharmacokinetics. After intake it is quickly and completely soaked up. Cmax is reached in 1–2 h. Linkng with proteins of a blood plasma — 30%. After "the first passing" through a liver it biotransformirutsya in an active metabolite — Mercaptopurinum. T1/2 makes 5 h. Gets through a placental barrier and cosecretes in breast milk. Is oxidized it (is inactivated) in a liver with the participation of a xanthineoxidase with formation of 6-thiouric acid. Oxidation and methylation of Azathioprinum happens also in erythrocytes. Concentration in blood does not correlate with expressiveness of effect since Azathioprinum and its active metabolite — Mercaptopurinum, are quickly utilized from blood by fabrics. It is removed almost completely with bile, through kidneys — no more than 1-2%.

Indications to use:

Prevention of reaction of graft rejection (as a part of a combination therapy), a pseudorheumatism, chronic active hepatitis, a system lupus erythematosus, nonspecific ulcer colitis, a dermatomyositis, a myasthenia, a nodular periarteritis, a vulgar pemphigus, an autoimmune glomerulonephritis, an idiopathic Werlhof's disease, psoriasis.

Route of administration and doses:

Inside. The dose is established individually taking into account indications, by weights of a course of a disease, a dosage of at the same time appointed drugs. At transplantation: a shock dose to 5 mg/kg in 2–3 receptions within 1–2 months, then in a dose of 1-4 mg/kg during the long term (several years). At drug withdrawal the dose needs to be reduced gradually. In case of signs of graft rejection the dose is raised to 4 mg/kg/days again.

At other diseases: 1–2,5 mg/kg/days in stages, duration of therapy are established individually.

Features of use:

It is not necessary to apply it is long (induction of neoplastic processes is possible). During the first 8 weeks of treatment weekly control of a picture of peripheral blood (in the subsequent — 1–2 times a month), and also periodic control of activity of serumal hepatic transaminases, ShchF and level of bilirubin is shown. At renal failures and/or a liver, and also at a concomitant use of Allopyrinolum Azathioprinum should be applied in lower doses (1/4 from an average dose).

During treatment of the woman of childbearing age have to use reliable methods of contraception.

Side effects:

From cardiovascular system and blood (a hemopoiesis, a hemostasis): miyelodepressiya (leukopenia, thrombocytopenia, anemia), megaloblastny erythrogenesis and macrocytosis.

From bodies of a GIT: nausea, loss of appetite, vomiting, diarrhea, abdominal pain, abnormal liver function (hyperbilirubinemia, increase in activity of hepatic transaminases and ShchF), cholestatic hepatitis, erosive cankers of an oral cavity and lips; recipients of transplants have a pancreatitis, an ulceration of a stomach and duodenum, intestinal bleeding, a necrosis and perforation of intestines; at prolonged use — toxic hepatitis.

Allergic reactions: skin rash, medicinal fever.

Others: mialgiya, arthralgia, pan-uveitis, development of consecutive infection (bacterial, virus, fungal, protozoan), alopecia; in isolated cases — an acute renal failure, hemolitic anemia, acute pulmonary diseases, meningeal reactions; at prolonged use — a mutagenicity (is potentially mutagen and causes chromosomal changes in the person), teratogenecity, carcinogenicity (developing of malignant tumors is possible: limforetikulyarny, epithelial, skin tumors on the sites subjected to influence of sunshine).

Interaction with other medicines:

Exponentiates effects of immunodepressants, tsitostatik. Azathioprinum inhibits anticoagulating effect of warfarin.

Allopyrinolum slows down metabolism of Azathioprinum, promotes its cumulation and strengthening of toxic action, at simultaneous use Azathioprinum dose decline is necessary (to 1/4 from an average dose).

At combined use of Azathioprinum with co-trimoxazole strengthening of myelotoxic action of Azathioprinum, with APF inhibitors — increase in risk of development of anemia and a heavy leukopenia, with other immunodepressants is possible (corticosteroids, cyclosporine, anti-CD3 - antibodies) — the risk of development of an infection and developing of tumors increases.

At vaccination by live virus vaccines along with reception of Azathioprinum strengthening of replication of a virus, the inactivated vaccines — oppression of products of antibodies is possible.

With care to apply Azathioprinum along with Sulfasalazinum or mesalaziny.

Contraindications:

Hypersensitivity, including to Mercaptopurinum, oppression of a hemogenesis (hypoplastic and aplastic anemia, a leukopenia, a lymphopenia, thrombocytopenia), a liver failure, pregnancy, breastfeeding, children's age.

Restrictions to use. With care (taking into account a ratio advantage/risk) apply at chicken pox, the surrounding herpes, insufficiency of a xanthineoxidase, radiation and cytotoxic therapy.

Overdose:

Symptoms: the dispeptic phenomena, a pancytopenia, increase in concentration of bilirubin and transaminases in blood serum.

Treatment: symptomatic, a hemodialysis (at a hemodialysis Azathioprinum is removed not completely).

Storage conditions:

To store at a temperature of 15-25 °C, in dry, protected from light and the place, unavailable to children. Period of validity 3 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 50 mg, 20 tablets in each blister, on one, two or three blisters together with the application instruction in cardboard packaging.