Azathioprine side effects and effects on the body. Azathioprine: indications and contraindications, features of therapy

Content

According to the accepted medical classification, Azathioprine is immunosuppressive drug, whose active substance is the substance of the same name. The medicine is designed to suppress human immunity to ensure better tissue and organ engraftment, and to treat some diseases. The drug is manufactured in Russia.

Composition and form of release

Azathioprine comes in pill format; no other form of the drug is found. The composition of the product:

Properties of the drug

Azathioprine, which is part of the tablets, blocks cell division and granulocyte proliferation, and has an immunosuppressive effect. If we compare the drug with an analogue of Mercaptopurine, then Azathioprine has a more pronounced immunosuppressive effect with a smaller cytostatic effect.

After taking the tablets, they are rapidly absorbed from the stomach, 30% bound to plasma proteins. Biotransformation of the active component occurs with the release of 6-thioinosinic acid and mercaptopurine. Both metabolites are active, penetrate into tissues and the brain. The half-life is five hours, the peak concentration is observed one and a half hours after administration, the residues are excreted in the bile and kidneys.

Indications for use

Azathioprine has many indications. The instruction highlights the following:

• prevention of a graft rejection reaction after organ transplantation (complex therapy);
• dermatomyositis;
• rheumatoid arthritis;
• ulcerative colitis;
• active chronic hepatitis;
• crohn's disease;
• myasthenia gravis;
• psoriasis;
• periarteritis nodosa;
• reiter's syndrome;
• pemphigus vulgaris;
• systemic lupus erythematosus;
• thrombocytopenic idiopathic purpura;
• autoimmune glomerulonephritis.

Method of administration and dosage

Instructions for use of Azathioprine indicate that the tablets are taken orally. The dosage is determined by the doctor individually, depending on the indications, the severity of the course of the disease, concomitant therapy. To prevent a transplanted graft, the drug is combined with Cyclosporin, a corticosteroid. The shock daily dose is 5 mg / kg of body weight for a course of 1-2 months. Then the drug is taken in a maintenance dosage of 1-4 mg / kg of body weight per day in 2-3 doses.

Supportive therapy lasts indefinitely. In the event of symptoms of rejection of the transplanted organ, the daily dose rises again to 4 mg / kg of body weight. For other diseases, the drug is taken at 1.5-2 mg / kg of body weight in 3-4 doses. It is possible to increase the daily dose to 200-250 mg, divided into 2-4 doses. When rheumatoid arthritis tablets are taken at 1-2.5 mg / kg of body weight per day in 1-2 doses for a course of at least 3 months. The maintenance dose is 0.5 mg / kg body weight once a day. With active chronic hepatitis taken 1-1.5 mg / kg of body weight per day.

special instructions

The instructions for use should read the section special instructions... Excerpts from it:

1. During the first two months of therapy, the peripheral blood count should be monitored weekly. Then analyzes are done every 14-30 days. In addition to blood, the activity of liver enzymes, the level of alkaline phosphatase, bilirubin are studied.
2. In case of impaired liver, kidney function, in combination with Allopurinol, the dose is reduced by 25% from the recommended instruction.
3. Therapy with the drug is carried out with caution in case of herpes zoster, xanthine oxidase deficiency, chickenpox, radiation or cytotoxic treatment.
4. The remedy is contraindicated in childhood, during pregnancy, lactation.

Drug interactions

The instructions should study in detail the section on drug interactions... Combinations and consequences:

1. Allopurinol enhances the toxic effects of Azathioprine, and Co-Trimoskazole increases its myelotoxic effect.
2. Concomitant use of angiotensin-converting enzyme inhibitors can lead to severe leukopenia.
3. The combination of the drug with immunosuppressants (glucocorticoids, Cyxlosporin, antibodies) often leads to the development of infection, the appearance of neoplasms.
4. Azathioprine is an antagonist of non-depolarizing muscle relaxants.
5. Vaccination during treatment with Azathioprine can increase viral replication (when using live vaccines) or suppression of antibody production (when using inactivated vaccines).

Azathioprine and alcohol

During the period of treatment, it is strictly prohibited to take alcohol and drinks or drugs based on it. Ethanol suppresses liver function, which disrupts the metabolism and work of the drug, leading to an increased incidence of side effects and increasing the risk of overdose. Ethanol is dangerous for patients suffering from diseases that the drug treats, complications and exacerbations are possible.

Side effects of Azathioprine

According to the instructions, Azathioprine can provoke the development of side effects while taking. The most famous reactions include:

• myelodepression;
• accession of secondary infections;
• macrocytosis;
• nausea, vomiting, anorexia;
• megaloblastic erythropoiesis;
• arthralgia;
• skin rash;
• myalgia;
• erosive and ulcerative lesions of the lips and mouth;
• drug allergy;
• cholestatic, toxic hepatitis;
• pancreatitis, erosion, ulcers, bleeding from the gastrointestinal tract, intestinal necrosis, bowel perforation (after transplantation);
• renal failure, lung diseases, meningeal reactions, hemolytic anemia (all in isolated cases);
• the drug has teratogenic, embryotoxic and carcinogenic effects, can cause the development of malignant tumors.

Overdose

If the dose of the medication specified in the instructions is exceeded, signs of dyspepsia, pancytopenia, impaired liver function, and increased other side effects may be observed. If you suspect an overdose, you should consult a doctor for an appointment. symptomatic treatmentcarrying out hemodialysis. The last procedure is of average efficiency.

Contraindications

• liver failure;
• sensitivity to the components of the composition;
• lactose intolerance, lack of lactase enzyme, impaired absorption of glucose-galactose;
• pregnancy, lactation;
• depressed hematopoiesis;
• childhood.

Terms of sale and storage

The drug is prescription, it is stored away from children at temperatures up to 25 degrees for five years.

Analogs

The drug can be replaced with agents with the same immunosuppressive properties, based on a similar or different active component. Analogs of Azathioprine include:

• Alfetin - an immunosuppressive lyophilisate for infusion containing alpha-fetoprotein, obtained from aborted blood;
• Profetal is an immunosuppressive powder for the preparation of an injection solution based on alpha-fetoprotein.

Video

Moskhimpharmaceuticals FSUE them. Semashko Moskhimpharmaceuticals named after N.A. Semashko, JSC

Country of origin

Russia

Product group

Immunomodulatory drugs and immunosuppressants

Immunosuppressive agent

Release forms

• Tablets of 50 mg - 50 pcs.

Description of the dosage form

• Tablets light yellow or light yellow with a greenish tinge, color, round, flat-cylindrical, beveled.

pharmachologic effect

Azathioprine is a thiol derivative, a competitive antagonist of hypoxanthine, in terms of chemical structure and biological action close to purine bases; has an immunosuppressive and cytostatic effect. Being involved in metabolic reactions, it disrupts the synthesis of nucleic acids, competes with hypoxanthine and guanine for hypoxanthine guanine phosphoribosyltransferase, which converts purinethol into thioinosinic acid (TIC). TEC suppresses a number of reactions involving inosinic acid (IR), including the conversion of IR to xanthine and adenylic acid. During TEC methylation, a metabolite is formed that blocks glutamine-5-phosphoribosyl pyrophosphate aminotransferase, an enzyme that initiates the pathway of purine synthesis of ribonucleotides. Due to the loss of the ability of cells to form TECs, the development of resistance of tumor cells to azathioprine is possible. The immunosuppressive effect is due to hypoplasia of lymphoid tissue, a decrease in the number of T-lymphocytes, a violation of Ig synthesis, the appearance of atypical phagocytes in the blood and suppression of cell-mediated allergic reactions. In comparison with mercaptopurine, the immunosuppressive effect is relatively stronger (with less cytostatic activity). In large doses (10 mg / kg) inhibits bone marrow function, inhibits granulocyte proliferation, and causes leukopenia.

Pharmacokinetics

Absorption: Azathioprine is well absorbed into upper divisions gastrointestinal tract. Time of onset Cmax - 1-2 hours Distribution: the connection with plasma proteins - low. Penetrates the placenta, accumulates in breast milk... Medium therapeutic doses create very low concentrations (less than 1 μg / ml), not correlating with the severity and duration of the effect. Metabolism: after the "first pass" through the liver, it is metabolized into mercaptopurine (an active metabolite), rapidly absorbed from the blood by tissues. Oxidation and methylation - in the liver, erythrocytes with the formation of a pharmacologically inactive metabolite (6-thiouric acid) under the influence of xanthine oxidase. The half-life is T1 / 2 - 5 hours. Excretion: azathioprine is predominantly excreted in the form of 6-thiouracilic acid in the urine. In urine, 1-methyl-4-nitro-5-thioimidazole is also determined in small amounts. Only a small amount of the taken dose of azathioprine is excreted unchanged in the urine. It is removed during hemodialysis, quickly disappears from the bloodstream.

Special conditions

Monitoring When azathioprine is used, there is potential danger development of toxic complications, therefore, it can be prescribed only if the patient receives adequate supervision during therapy. It is assumed that during the first 8 weeks of therapy, a complete blood count, including platelet counts, should be performed weekly or more often if a high dose of the drug is used or the patient has severe renal and / or hepatic impairment. Thereafter, blood tests can be monitored less frequently, but a complete blood count should be repeated monthly, or at least at intervals of no more than 3 months. Patients receiving azathioprine should be instructed to report promptly all cases of infection, unexpected bruising, bleeding, or other signs of bone marrow suppression. Some individuals with a congenital deficiency of the enzyme thiopurine methyltransferase (TPMT) may be hypersensitive to the myelodepressant effect of azathioprine and have a tendency to rapidly develop bone marrow depression after starting treatment with azathioprine. This problem can be exacerbated by a combination with drugs that suppress TPMT (olsalazine, mesalazine, or sulfasalazine). Renal and / or hepatic impairment Azathioprine toxicity has been suggested to increase in renal impairment, but controlled studies have not supported this assumption. However, dosages at the lower end of the dose range and close monitoring of hematological parameters are recommended. With the development of hematological toxicity, the dose should be reduced. Caution is needed when prescribing azathioprine for liver failureand regular complete blood counts and liver tests should be done. In some patients, the metabolism of azathioprine may be impaired and, therefore, its dose should be reduced if signs of hepatic and hematological toxicity develop. Scarce evidence suggests that azathioprine is unfavorable for patients with hypoxanthine-guanine-phosphoribosyltransferase deficiency (Lesch-Nichen syndrome) and should not be recommended for azathioprine. Mutagenicity Chromosomal abnormalities have been found in men and women receiving azathioprine. But the role of azathioprine in their occurrence is difficult to assess. Chromosomal abnormalities that disappear over time have been found in children of patients receiving azathioprine. Except in extremely rare cases, they did not have any obvious physical signs of these disorders. There has been a synergism between the action of azathioprine and prolonged ultraviolet irradiation in patients taking azathioprine. Influence at reproductive function The decrease in renal failure as a result of kidney transplantation followed by the appointment of azathioprine was accompanied by an increase in reproductive function in both men and women who are transplant recipients. Carcinogenicity Patients taking azathioprine are at increased risk of developing lymphomas and other malignant neoplasmsmainly skin cancer. The risk is associated with the intensity and duration of immunosuppressive therapy to a greater extent than with the use of a specific drug. It has been reported that dose reduction or withdrawal of the immunosuppressive agent can reverse the development of lymphoma. Patients receiving multiple immunosuppressive drugs are at risk of hyperimmunosuppression, so the lowest effective dose should be used. As is common practice in patients at increased risk of skin cancer, sun exposure and exposure to ultraviolet radiation should be limited by using protective clothing and using sunscreen with high degree protection. Impact on the ability to drive vehicles. Wed and fur .: No data. However, it is impossible to predict impairment of the ability to drive a car / mechanisms based on the pharmacokinetics of azathioprine.

Composition

• azathioprine 0.05 g excipients: gelatin; potato starch; milk sugar; calcium stearate

Azathioprine indications for use

• Prevention of a rejection reaction in kidney transplantation, rheumatoid arthritis, chronic active hepatitis, systemic lupus erythematosus, dermatomyositis, periarteritis nodosa, acquired hemolytic anemia, idiopathic thrombocytopenic purpura, pyoderma gangrenosum, colitis, Crohn's disease, nonspecific Reycytherapy, bladder cancer radiation dermatitis, pseudohypertrophic myopathy. Ineffectiveness and contraindications to the appointment of glucocorticosteroids or the need to reduce their dosage (in patients with side effects from their use and / or a high risk of their development). Azathioprine is used alone or in combination with corticosteroids and / or other immunosuppressants.

Azathioprine contraindications

• hypersensitivity to azathioprine and / or mercaptopurine; pregnancy.

Azathioprine dosage

• 50 mg

Azathioprine side effects

• The incidence of side effects when using azathioprine varies depending on the underlying pathology. Classification of unwanted adverse reactions by frequency: Very common: more than or equal to 1/10 of the appointments Frequent: more than or equal to 1/100 -

Drug interactions

Allopurinol / oxypurinol / thiopurinol The activity of xanthine oxidase is inhibited by allopurinol, oxypurinol to thiopurinol, which is accompanied by a decrease in the conversion of biologically active 6-thioinosinic acid to biologically inactive 6-thiouracilic acid. When allopurinol, oxypurinol, and / or thiopurinol are given concomitantly with 6-MP or azathioprine, the dose of the latter should be reduced by one quarter of the original dose. Neuromuscular blockers Azathioprine can increase the neuromuscular blockade caused by depolarizing drugs (succinylcholine) and may reduce the blockade caused by non-depolarizing drugs (tubocurarine). The strength of these interactions varies considerably. Warfarin Suppression of the anticoagulant effect of warfarin when administered with azathioprine has been reported. Cytostatic / myelodepressant drugs Concomitant use with azathioprine should be avoided if possible cytotoxic drugs or drugs with myelodepressant effects, such as penicillamine. There are clinical data on the interaction of azathioprine and cotrimoxazole with the development of hematological disorders. A description of a case is given that suggests a connection between hematological disorders and the simultaneous administration of azathioprine and captopril. There is a suggestion that cimetidine and indomethacin may enhance the myelodepressant effect of azathioprine when administered simultaneously. Aminosalicylates Aminosalicylic derivatives (olsalazine, mesalazine or sulfasalazine) inhibit the TPMT enzyme in vitro and should therefore be administered with caution in patients receiving azathioprine therapy. Other interactions Furosemide in vitro interferes with the metabolism of azathioprine by liver tissue. The clinical significance of this interaction is unknown. Vaccines The immunosuppressive activity of azathioprine can cause an atypical or potentially adverse response to live vaccines, so live vaccines are theoretically contraindicated in patients taking azathioprine. A decrease in the response to killed vaccines is likely and was observed to the hepatitis B vaccine in patients receiving combination therapy with azathioprine and corticosteroids. It has been shown that the standard therapeutic doses of azathioprine do not induce an adverse response to the multivalent pneumococcal vaccine, which was assessed based on the mean concentration of the anticapsular specific antibody.

Overdose

Symptoms: dyspeptic symptoms, pancytopenia, increased activity of "hepatic" transaminases, hyperbilirubinemia. Ulceration of the mucous membrane of the pharynx, bruising and bleeding are the main symptoms of bone marrow depression resulting from an overdose of azathioprine, which reach a maximum after 9-14 days of use. Their appearance is more likely with chronic than with acute single overdose. A patient was reported who took a single overdose of 7.5 g of azathioprine. The immediate toxic manifestations of this overdose were nausea, vomiting and diarrhea, followed by mild leukopenia and mild liver dysfunction. The recovery was incomplete. Treatment: gastric lavage. There is no specific antidote. Follow-up with hematologic monitoring is necessary to provide quick help with the development of adverse reactions. The effectiveness of dialysis is unknown, although azathioprine is partially cleared by hemodialysis.

Storage conditions

• store in a dry place
• keep away from children
• store in a dark place

Information provided
Manufacturer: MOSKHIMFARMPREPARATY them. N.A. Semashko JSC (Russia)
Release forms:

• Tablets, 50 mg, No. 50

Price for Azathioprine in pharmacies: from 263 rubles. up to 263 rubles. (1 offers)


Azathioprine - russian drug from the group of immunosuppressants, it is produced in tablets of 50 mg (No. 50). The drug promotes hypoplasia of lymphoid tissue, reduces the number of T-lymphocytes, disrupts the synthesis of immunoglobulins. In large doses, it inhibits the function of the bone marrow, inhibits the formation of granulocytes, and causes leukopenia. Used for diseases of an autoimmune nature: rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, chronic autoimmune hepatitis, Werlhof's disease. It is used in multiple sclerosis and other demyelinating diseases, myasthenia gravis, psoriasis, to suppress the reaction of tissue incompatibility in organ transplantation. Apply the medicine for a long time. The dose and duration of therapy depends on the patient's condition, the effectiveness and tolerability of the drug. May cause allergies, dyspepsia, toxic hepatitis, myelodepression, teratogenic and carcinogenic effects. Cannot be used with strong suppression of hematopoiesis, severe liver and kidney pathology, women during gestation and breastfeeding.

List of available analogues of the drug Azathioprine

An analogue is cheaper from 97 rubles.

Manufacturer: North Star (Russia)
Release forms:

• Tab. 2.5 mg, 50 pcs.

The price for Methotrexate in pharmacies: from 60 rubles. up to 4995 rubles. (2334 offers)

Methotrexate is an analogue of Azathioprine, produced in Russia and countries far abroad in the form of tablets of 2.5, 5 and 10 mg (No. 50), as well as a solution for injection and for oral administration. The drug inhibits cellular mitosis, the growth of actively proliferating tissues, and inhibits the growth of malignant neoplasms. It is used for acute lymphocytic leukemia, cancer of the body and cervix, tumors of the head and neck, cancer of the esophagus, sarcoma of bones and soft tissues, lung cancer, breast cancer, bladder, testicles. It is used for systemic rheumatological diseases, multiple sclerosis, severe psoriasis, Crohn's disease and ulcerative colitis, for transplantation of various organs and tissues to prevent graft rejection. May cause allergies, dyspepsia, anemia, thrombocytopenia, anorexia, respiratory failure, hypotension, development of renal and hepatic failure, disorders menstrual cycle, miscarriages, fetal malformations. Cannot be used for idiosyncrasy, pregnant and lactating women, with infectious diseases, gout, diseases accompanied by vomiting and diarrheal syndrome.

An analogue is cheaper from 60 rubles.

Manufacturer: Orion Corporation (Finland)
Release forms:

• Tablets 4 mg, 30 pcs.

Price for Metipred in pharmacies: from 156 rubles. up to 434 rubles. (1696 offers)

Metipred (analogue) - produced in Russia, Finland and Portugal in 4 mg tablets (No. 30) and in the form of a lipophysate for preparing a solution for intravenous and intramuscular injection in vials of 250 g. It is a glucocorticosteroid with immunosuppressive activity. In addition, it has anti-inflammatory and anti-allergic effects. It is used in systemic rheumatological diseases such as rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis and others. Used for multiple sclerosis and other demyelinating diseases nervous system, for acute and chronic diseases joints, bronchial asthma, severe allergic reactions, autoimmune thyroiditis and nephritis, to prevent and relieve cerebral edema, with melo- and lymphocytic leukemia, myeloma and other blood diseases. It is used in transplantation to prevent the rejection of the transplanted organ. Cannot be used in case of intolerance, pregnancy and breastfeeding, severe liver and kidney disease, infectious diseases, after vaccinations, with severe immunodeficiencies.

Solu-Medrol (lyophilisate) → substitute Rating: 8 votes

An analogue is more expensive from 58 rubles.

Manufacturer: PFIZER MFG. BELGIUM N.V. (Belgium)
Release forms:

• Lyophilisate for intravenous and intramuscular administration, 250 mg, No. 1

The price of Solu-Medrol in pharmacies: from 321 rubles. up to 1030 rubles. (368 offers)
Solu-Medrol (analogue) - produced in Belgium in the form of a lipophysate for the preparation of a solution for parenteral (intramuscular or intravenous) use in bottles of 250, 500 or 1000 mg. it hormonal drugbelonging to the group of corticosteroids. It has a pronounced anti-inflammatory and anti-allergic effect, is a powerful immunosuppressive agent. Used to treat exacerbations multiple sclerosis and other demyelinating diseases of the brain and spinal cord, with systemic diseases connective tissue, autoimmune thyroiditis, kidney damage of an autoimmune nature, with severe allergic reactions, with rheumatoid arthritis, acute and chronic adrenal insufficiency, severe forms of psoriasis, Stevens-Johnson syndrome, exfoliative dermatitis and other skin lesions, with leukemia and many other diseases. May cause allergies, dyspepsia, hypertension, cardiac arrhythmias, arthralgia, myalgia, a tendency to infections, renal and hepatic failure, immune and endocrine disorders. Contraindications are similar to metipred.

An analogue is more expensive from 568 rubles.

Manufacturer: Teva (Israel)
Release forms:

• Soft capsules, 25 mg, No. 50

Price for Ecoral in pharmacies: from 829 rubles. up to RUB 3465 (103 offers)

Ekoral (analog) - produced in Germany, Switzerland, Czech Republic and Israel in soft capsules of 25, 50 or 100 mg (No. 50). The drug reversibly inhibits the mitotic phases G0 and G1, inhibits the formation of interleukin-2 and the proliferation of immunocompetent T-lymphocytes. Does not affect the function of hematopoiesis. It is used in transplantology to prevent the development of a rejection reaction, in rheumatoid arthritis, systemic lupus erythematosus, systemic scleroderma, dermatomyositis, polymyositis, glomerulonephritis, nephrotic syndrome, demyelinating diseases, severe psoriasis and atopic dermatitis... May cause skin rash and itching, angioedema, bronchospasm, cough, sneezing, anaphylactic shock, nausea, vomiting, abdominal pain, headache, convulsive syndrome, sensitivity disorders, renal and hepatic failure, myopathy, hypertension, electrolyte disturbance of the blood, can provoke the development of infections. Cannot be used with intolerance, severe uncontrolled increase blood pressure, infections, cancer, severe liver and kidney pathology, pregnancy and breastfeeding.

The instruction "Azathioprine" warns that this drug has an immunosuppressive effect. This drug is controversial. It depresses immune system human, blocks the division and proliferation of cells, tissues, affects the production of antibodies. Azathioprine has many analogs that have a more pronounced therapeutic effect.

Description

Analogs of "Azathioprine" are similar to this drug, but differ in composition and characteristics of administration. The tool is available in the form of round flat-cylindrical tablets. The package contains blisters with 50 tablets. The action of "Azathioprine" is immunosuppressive. It eliminates hypersensitivity, slows down the processes of cell division in case of pathological phenomena, suppresses tissue incompatibility. The tablets are light yellow with a greenish tinge. The drug is produced in Russia. You can buy only with a prescription.

How to apply

Analogues of "Azathioprine", like the drug itself, are taken orally. The dosage is set individually, taking into account the course of the disease and the patient's state of health. If Azathioprine is prescribed as a prophylaxis for organ transplant rejection, the dosage is 5 mg / kg two to three times a day for one or two months. In this case, other drugs are prescribed together with "Azathioprine". Maintenance therapy lasts several years, and the dose is gradually reduced.

If the patient has symptoms of organ rejection, the dose of the drug is increased. In the case of prescribing a drug for the treatment of other diseases, the tablets are taken three to four times a day at 1.5-2 mg / kg. The duration of admission is discussed with the attending physician, but is usually at least twelve weeks. If you use "Azathioprine" with "Allopurinol" at the same time, you can increase side effects first, and also provoke a toxic reaction. The combination of "Azathioprine" with "Co-Trimoxazole" enhances the myelotoxic effect.

It is not recommended to use the drug with ACE inhibitors, as this leads to the development of severe leukopenia. The combination with other immunosuppressants, for example, with "Cyclosporin" provokes the appearance of malignant neoplasms and the development of infections. During the period of taking "Azathioprine" it is not recommended to get vaccinated. If the patient has kidney or liver pathologies, the dose of the drug is reduced. With caution, therapy is prescribed for patients with chickenpox, herpes zoster.

Indications for use

The instruction "Azathioprine" reminds that you need to use the drug only as directed by your doctor. Absolute indications for use are the following diseases and states:

• Psoriasis.
• Chronic hepatitis.
• Lupus erythematosus.
• Ulcerative colitis.
• Myasthenia gravis.
• Crohn's disease.
• Dermatomyositis.
• Advanced arthritis.
• Pemphigus.
• Reiter's Syndrome.

The drug "Azathioprine" (indicated in the instructions) is prescribed as a prophylaxis for the rejection of transplanted organs together with other immunosuppressants.

Contraindications

In what cases should you not take Azathioprine? User reviews confirm that this drug is contraindicated for people with individual intolerance to the active substances in the composition. Manufacturers warn: "Azathioprine" is prohibited for use during pregnancy, during her planning or lactation, as it can cause intoxication of the embryo or fetus. You can not be treated with the drug and men who are trying to conceive a child. The remedy causes severe adverse reactions, including dyspeptic disorders, intoxication, in the event of which the patient is prescribed hemodialysis.

If the following reactions occur, you must inform your doctor about them:

• joint and muscle pain;
• secondary infections;
• allergic reactions;
• lack of appetite;
• nausea and vomiting;
• anemia;
• difficulty breathing;
• renal failure;
• the appearance of ulcers in the corners of the mouth.

Patients who have undergone organ transplants and are prescribed Azathioprine may inflame the pancreas and develop ulcers in the intestines, causing bleeding.

The disadvantages of the drug include provoking renal and hepatic failure, chromosome mutations, negative effects on the reproductive function of men and women, and carcinogenicity. In addition, patients who take "Azathioprine" for a long time have a high probability of malignant neoplasms.

What does it consist of

The composition of "Azathioprine" includes the active substance of the same name - 0.05 g. The auxiliary ingredients in the preparation are potato starch, lactose, gelatin, calcium stearate. The shelf life of the medicine is five years. Store it in a dark place. The tablets are rapidly absorbed in the gastrointestinal tract. The active substance penetrates into the tissues in small quantities. The highest concentration is formed in plasma two hours after ingestion. It is excreted from the body by the liver with bile and kidneys.

Features:

In patients who have been prescribed the drug, the question arises: why is there no Azathioprine in pharmacies? Indeed, sometimes a medicine cannot be found in a pharmacy network, especially in small towns and other settlements. In this case, analogs are prescribed.

The effect of taking an immunosuppressive drug may not appear for several days or weeks after starting. If the patient's condition does not improve after treatment with Azathioprine, it should be canceled and another therapy regimen prescribed.

The peculiarity is that if a patient with transplanted organs has been using the drug for many years, then after its cancellation, the probability of their rejection is high. For the first eight weeks, a blood test should be done as often as possible to determine the level of platelets. While taking the medicine, you can not stay in the sun for a long time, spontaneously cancel the drug or change the dosage. "Azathioprine" artificially suppresses human immunity, inhibits the formation of new cells, their division. This leads to the suspension of the development of malignant neoplasms, the emergence of severe conditions. Effective in autoimmune diseases.

At "Azathioprine" analogs have the same pharmachologic effectare aimed at treating identical diseases. This drug is structurally similar to guanine, adenine, hypoxanthine. All of them are included in the structure of the nucleic acid. If we compare "Azathioprine" with "Mercaptopurine", the former has a more pronounced medicinal action... According to its purpose, the drug has a similarity with Alfetin, Revlimid, Stemokin, Profetal.

The peculiarity of all analogues and the drug itself is that with prolonged use, the likelihood of intoxication is high. It makes sense to use the medicine if the patient is under medical supervision. Many are interested in: what analogues to buy? Which is better - "Imuran" or "Azathioprine"? The medicine "Imuran" has a less aggressive and toxic effect. However, it is more difficult to find in pharmacies.

In addition, you cannot buy such medicines on your own without a doctor's recommendation. "Imuran" in high doses is capable of inhibiting bone marrow functions and causing leukopenia. Has the same indications for use, contraindications and side effects as in "Azathioprine". With prolonged use and high dosages, it causes the occurrence of secondary infections, tissue proliferation, drug fever, severe allergic reaction, anorexia, hepatitis, bleeding in the gastrointestinal tract, necrosis, myalgia, in rare cases - renal failure.

Price

Analogues of "Azathioprine", like the drug itself, are inexpensive. average price in Russian pharmacies of this medicine is 200 rubles. In different pharmacy chains, the price varies and may exceed the indicated one by 50 rubles.

Azathioprine is a strong immunosuppressive drug of cytostatic and cytotoxic action.

Composition of Azathioprine

The active ingredient is azathioprine (0.05 g).

Excipients:

• Gelatin;
• Milk sugar;
• Potato starch;
• Calcium stearate.

Release form

Azathioprine is available in the form of film-coated tablets in a blister strip of 10 pieces. The cardboard box contains 5 packages.

Azathioprine's analogs

TO medicines with a similar active substance include:

• Azasan;
• Azanin;
• Azamun;
• Azapress;
• Imuran;
• Imurel.

Pharmacological action of Azathioprine

Azathioprine has an immunosuppressive effect, mainly aimed at delayed hypersensitivity and cellular cytotoxicity. Blocks proliferation (proliferation) of tissues and cell division. Suppresses reactions of tissue incompatibility. Has less effect on antibody synthesis. Azathioprine has a more pronounced immunosuppressive effect with less cytostatic activity compared to mercaptopurine.

It is a structural analogue of guanine, hypoxanthine and adenine, which are part of nucleic acids.

When taken orally, the drug is well absorbed from the gastrointestinal tract. About 30% binds to proteins. During biotransformation, active metabolites (6-mercaptopurine and 6-thioinosinic acid) are formed.

The concentration of azathioprine in the tissues is negligible; its smallest amount is determined in the brain. The maximum concentration in blood plasma is reached within 1-2 hours. Half-life active substance and its metabolites is about 5 hours. The drug is almost completely excreted in the bile through the liver, and through the kidneys - no more than 1-2%.

Indications for use

Azathioprine, according to the instructions, is indicated for the following diseases:

• Rheumatoid arthritis;
• Ulcerative colitis;
• Chronic active hepatitis;
• Systemic lupus erythematosus;
• Periarteritis nodosa;
• Dermatomyositis;
• Myasthenia gravis;
• Pemphigus vulgaris;
• Idiopathic thrombocytopenic purpura;
• Autoimmune glomerulonephritis;
• Psoriasis.

Azathioprine, according to reviews, can be used as part of combination therapy as a prophylaxis for transplant rejection reactions.

Contraindications

The medicine is contraindicated in hypersensitivity to azathioprine or mercaptopurine.

Application during pregnancy and lactation

The drug is strictly contraindicated in pregnancy. Contraception is essential for women of childbearing age. During lactation, breastfeeding should be stopped.

Dosing and administration of Azathioprine

The tablets are taken orally. The dose is set individually. This takes into account not only the indications and severity of the course of the disease, but also the dosage of simultaneously prescribed drugs, as well as hematological tolerance. Treatment is usually long-term.

Average daily doses are:

• Rheumatoid arthritis - 1-2.5 mg / kg for 1-2 times. Maintenance therapy - 0.5 mg / kg. The course of treatment is 12 weeks;
• Chronic active hepatitis - 1-1.5 mg / kg;
• Prevention of transplant rejection reactions - 5 mg / kg for 2-3 doses for 1-2 months. Azathioprine, according to doctors, is most effective in combination with corticosteroids and cyclosporine. The maintenance dose is 1-4 mg / kg for several years. In case of drug withdrawal, the dosage is reduced gradually. If symptoms of transplant rejection occur, then the daily dose is again increased to 4 mg / kg;
• Other diseases - 1.5-2 mg / kg 3-4 times. If necessary, the dose is increased to 200-250 mg in 2-4 doses.

Overdose of Azathioprine

Signs of an overdose include:

• Dyspeptic symptoms;
• Pancytopenia;
• Dysfunction of the liver;
• Strengthening other side effects.

Treatment is symptomatic. Hemodialysis may be prescribed.

Side effects of Azathioprine

The instruction for Azathioprine indicates the following side effects:

• Hematopoietic system - myelosuppression (anemia, thrombocytopenia, leukopenia), development of secondary infections, macrocytosis and megaloblastic erythropoiesis, hemolytic anemia;
• Digestive system - vomiting, nausea, cholestatic and toxic hepatitis, anorexia, erosive and ulcerative lesions of the oral mucosa, bleeding from the gastrointestinal tract, pancreatitis, intestinal perforation and necrosis;
• Allergic reactions - skin rash, myalgia, arthralgia, drug fever.

Sometimes inflammation is possible meninges, acute renal failure, pulmonary diseases.

Experimental data indicate teratogenic, embryotoxic and carcinogenic effects of Azathioprine (there is a risk of malignant neoplasms).

special instructions

During the first 8 weeks of therapy, it is necessary to monitor the peripheral blood picture on a weekly basis (subsequently - 1-2 times a month). The activity of serum hepatic transaminases is monitored periodically, alkaline phosphatases and bilirubin levels.

The dose is reduced to 1/4 if allopurinol azathioprine is simultaneously prescribed, as well as in case of impaired liver or kidney function.

With chickenpox, herpes zoster or xanthine oxidase deficiency, as well as with cytotoxic and radiation therapy, Azathioprine is prescribed with caution.

Drug interactions

The simultaneous intake of azathioprine with various substances causes a number of consequences:

• Allopurinol - toxic effects increase;
• Co-trimoxazole - myelotoxic effect increases;
• ACE inhibitors - severe leukopenia develops;
• Other immunosuppressants - increases the risk of infections and tumors;
• Live viral vaccines - viral replication is enhanced;
• Inactivated vaccines - antibody production is inhibited.

Azathioprine is incompatible with non-depolarizing muscle relaxants.

Storage conditions for Azathioprine

Store in a dark place out of reach of children. The shelf life is 5 years.