Expiration date: 09/2026

The composition and form of issue:

Capsules. 1 capsule contains:

azathioprine 0.05 g

excipients: gelatin potato starch sugar dairy calcium stearate 

in a contour acheikova packing 10 PCs. in cardboard pack of 5 packs.

Feature:

The immunosuppressant from the group of antimetabolites.

Pharmacokinetics:

After oral azathioprine is well absorbed from the gastrointestinal tract. Protein binding is low (~ 30%). In the body biotransformiroetsa with the formation of 6-mercaptopurine and 6-thioinosinic acid (active metabolites). Active substance penetrates the tissues at low concentrations the least amount of azathioprine is determined in the brain. T1/2 for azathioprine and its active metabolites approximately 5 h. Cmax in plasma achieved through 1-2 h after ingestion. Excreted almost entirely through the liver in the bile, through the kidneys — no more than 1-2%.

Description pharmacological action:

Being a structural analogue of adenine, hypoxanthine and guanine, forming part of nucleic acids, azathioprine inhibits cell division and tissue proliferation.

Immunosuppressive effect of azathioprine is focused on the reaction of delayed hypersensitivity and cellular cytotoxicity. Suppress the reaction of tissue incompatibility. To a lesser extent, acts on the synthesis of antibodies. Compared with mercaptopurine has a more pronounced immunosuppressive effect when lesser cytostatic activity.

Indications:

• prevention of graft rejection (in a combination therapy)
  
• rheumatoid arthritis
  
• chronic active hepatitis
  
• systemic lupus erythematosus
  
• ulcerative colitis
  
• dermatomyositis
  
• myasthenia gravis
  
• periarteritis nodosa
  
• pemphigus vulgaris
  
• autoimmune glomerulonephritis
  
• idiopathic thrombocytopenic purpura
  
• psoriasis.
  

Contraindications:

• hypersensitivity to the effects of azathioprine and/or mercaptopurine
  
• pregnancy.
  

Application of pregnancy and breast-feeding:

Contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding.

Side effects:

Mielodepressiya (leukopenia, thrombocytopenia, anemia), development of secondary infections, megaloblastic erythropoiesis and macrocytosis, nausea, vomiting, anorexia, rash, arthralgia, myalgia, erosive-ulcerative lesions of the oral cavity and lips, drug Allergy, cholestatic hepatitis, toxic hepatitis. In recipients of transplants possible pancreatitis, erosive and ulcerative lesions and bleeding from the gastrointestinal tract, necrosis and intestinal perforation. There are few reports on the development of acute renal failure, hemolytic anemia, acute lung diseases, meningeal reactions. In experimental studies found no teratogenic, embryotoxic and carcinogenic effects. Patients may experience malignant tumors.

Drug interactions:

With simultaneous use with allopurinol increases toxicity of azathioprine with co-trimoxazole — may increase myelotoxic action of azathioprine with ACE inhibitors — may develop severe leukopenia with other immunosuppressants (corticosteroids, cyclosporine, anti-?D3 antibodies, etc.) increases the risk of infections and of tumours.

Azathioprine is an antagonist of non-depolarizing muscle relaxants.

By vaccination with live viral vaccines along with azathioprine may increase the replication of the virus, inactivated vaccines — suppression of production of antibodies.

Method of application and dose:

Inside. Dose set individually depending on the evidence, the severity of the disease, at the same time dosage of prescribed drugs. For the prevention of rejection reactions of the graft used in the treatment (usually in conjunction with cyclosporine and corticosteroids) loading dose to 5 mg/kg orally in 2-3 doses for 1-2 months. Then prescribe maintenance therapy from 1 to 4 mg/kg orally for a long period (several years). If you cancel the drug dose should be reduced gradually. In case of any signs of graft rejection, the daily dose was increased again to 4 mg/kg.

In other diseases — usually 1.5–2 mg/kg per day in 3-4 reception. If necessary, the daily dose may be increased to 200-250 mg 2-4 doses. The duration of treatment is determined individually.

Rheumatoid arthritis — 1-2. 5 mg/kg/day in 1-2 reception. The course of treatment — not less than 12 weeks. Maintenance dose — 0.5 mg/kg 1 time per day.

In chronic active hepatitis daily dose 1-1,5 mg/kg.

Overdose:

Symptoms: dyspepsia, pancytopenia, abnormal liver function (increased concentration cium and transaminaz in plasma), increased other side effects (see "Side effects").

Treatment: symptomatic, hemodialysis.

During hemodialysis azathioprine is displayed not completely.

Precautions:

During treatment, women of childbearing age should use reliable methods of contraception.

Special instructions:

During the first 8 weeks of treatment are shown weekly monitoring of peripheral blood (in the subsequent 1-2 times per month), as well as periodic monitoring of serum hepatic transaminases, alkaline phosphatase, and bilirubin.

When renal dysfunction and/or liver, as well as the simultaneous administration allopurinol azathioprine should be used at lower doses (1/4 of the average dose). With caution (taking into account the ratio benefit/risk) are used in varicella, herpes zoster, deficiency of xanthine oxidase, radiation and cytotoxic therapy.