Azathioprine
Azathioprine: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Azathioprine
ATX code: L04AX01
Active ingredient: azathioprine (azathioprine)
Manufacturer: JSC "Moskhimfarmpreparaty" them. N. A. Semashko "(Russia)
Description and photo update: 2019-16-09
Azathioprine is a drug with a powerful immunosuppressive and cytostatic effect.
Release form and composition
Azathioprine is available in 0.05 g film-coated tablets.
Pharmacological properties
Pharmacodynamics
The immunosuppressive effect of the drug leads to a more significant inhibition of delayed-type hypersensitivity, as well as cellular cytotoxicity (in comparison with the production of antibodies). The active substance inhibits the metabolism of purines, can suppress the synthesis of protein, RNA and DNA, as well as affect cellular metabolism, suppress mitosis. In rheumatoid arthritis or other autoimmune processes, the mechanism of action of azathioprine is unknown, however, presumably, it is due to immunosuppression. As a result of using the drug, the need for taking glucocorticoids during combination therapy decreases.
Azathioprine has the following pharmacological effects:
- immunosuppressive (after discontinuation of the drug, clinical effects can persist for a long time);
- antirheumatic (a drug that transforms the disease): begins to act in 6-8 weeks;
- anti-inflammatory (for systemic lupus erythematosus and bowel disease): begins to act in 4-8 weeks.
Pharmacokinetics
Azathioprine is characterized by high absorption from the gastrointestinal tract and a low binding to blood plasma proteins (30%). Mainly biotransformed to active metabolites: 6-thioinosinic acid and 6-mercaptopurine. Further metabolism takes place in the liver (mainly with the participation of xanthine oxidase) and in erythrocytes, the ratio of which differs in different patients. Elimination is carried out by the liver (with bile) and kidneys (with urine) - from 1 to 2% in the form of an unchanged substance. Partially removed during hemodialysis.
Indications for use
The drug suppresses reactions of tissue incompatibility and delayed hypersensitivity.
According to the instructions, Azathioprine is used for the following diseases:
- Idiopathic thrombocytopenic purpura;
- Myasthenia gravis;
- Rheumatoid arthritis;
- Dermatomyositis;
- Crohn's disease;
- Psoriasis;
- Autoimmune glomerulonephritis;
- Pemphigus vulgaris;
- Nonspecific ulcerative colitis;
- Periarteritis nodosa;
- Active chronic hepatitis;
- Systemic lupus erythematosus;
- Gangrenous pyoderma.
Azathioprine is also prescribed to prevent organ transplant rejection.
Contraindications
The use of Azathioprine has the following contraindications:
- Hypersensitivity to drug components;
- Liver failure;
- Suppression of hematopoiesis (aplastic and hypoplastic anemia, lymphopenia, leukopenia, thrombocytopenia);
- Pregnancy;
- Breast-feeding;
- Childhood.
Instructions for the use of Azathioprine: method and dosage
The dosage regimen and the duration of the course of treatment with the drug is determined by the attending physician individually and depends on the general condition of the patient and the clinical picture of the course of the disease.
In transplantation, for the prevention of rejection reaction, Azathioprine is prescribed in combination with cyclosporine and corticosteroids according to the following scheme: 4 mg / kg in 2-3 doses a week before surgery and for 1-2 months after it, then the dosage is reduced to 2-3 mg / kg per day. If there are signs of transplant rejection, the daily dose of the drug is increased to 4 mg / kg.
For other diseases, the drug is prescribed at 1.5-2.0 mg / kg in 3-4 doses.
Azathioprine is rapidly absorbed from the stomach and intestines, the highest concentration in blood plasma is observed 1-2 hours after ingestion.
Side effects
According to the instructions, Azathioprine can cause the following side effects:
- Allergic reactions: arthralgia, myalgia, skin rash, drug fever;
- From the digestive tract: decreased appetite, nausea, vomiting, abdominal pain, diarrhea, liver dysfunction;
- In patients after organ transplantation: ulcerative lesions of the stomach and duodenum, pancreatitis, intestinal bleeding, perforation and intestinal necrosis;
Other side effects: panuveitis, development of secondary infections, acute renal failure, meningeal reactions, alopecia, interstitial pneumonitis.
Overdose
No data available.
special instructions
The first 2 months of using Azathioprine, it is necessary to monitor peripheral blood parameters (every week), as well as monitor liver function, regularly conducting liver tests.
The drug should be withdrawn gradually.
Application during pregnancy and lactation
It is forbidden to use Azathioprine for treatment during pregnancy and lactation.
With impaired renal function
In case of impaired renal function, the drug should be used with caution.
For violations of liver function
In case of impaired liver function, the drug should be used with caution.
Drug interactions
The inhibition of xanthine oxidase, which is observed with the simultaneous use of allopurinol and azathioprine, can significantly increase the toxicity and effectiveness of the latter. It is recommended to avoid the combination of these drugs, especially in kidney pathologies, because of the high probability of accumulation of 6-mercaptopurine (a metabolite of azathioprine) and an increase in its toxicity in case of transplant rejection. If it is necessary to jointly use allopurinol and azathioprine, it is recommended to reduce the dose of the latter by 25–33%, as well as to carefully monitor the patient's condition, adjusting the dose depending on the presence of signs of toxicity and response to therapy.
When azathioprine is used, its immunosuppressive effect can lead to a weakened immune response to the use of killed vaccines. An interval must be observed between the completion of therapy and immunization (from 3 to 12 months, depending on the severity of immunosuppression, the type of vaccine and other factors).
During the period of treatment with azathioprine, it is necessary to avoid the introduction of live vaccines due to the likelihood of a violation of the immune response and an increased risk of side effects. Vaccination should be carried out no earlier than 3-12 months after the end of treatment with azathioprine (depending on the severity of immunosuppression, the type of vaccine and other factors). If leukemia is in remission for 3 months after completing chemotherapy, patients should not receive live viral vaccines. For those who come into direct contact with the patient, use of the live oral polio vaccine should be delayed.
Azathioprine can decrease the activity of warfarin, which requires an increase in the dose of the latter.
In the case of the simultaneous administration of other immunosuppressants (mercaptopurine, cyclosporine, cyclophosphamide, chlorambucil), the risk of developing tumors and the appearance of infections may increase.
With the combined use of angiotensin-converting enzyme (ACE) inhibitors, the risk of leukopenia and anemia may increase.
There is a possibility of increased myelotoxicity when azathioprine is combined with radiation therapy or when taking the following myelodepressants that exhibit predictable dose-dependent myelotoxicity: azathioprine, abacavir, alemtuzumab, aldesleukin, amphotericin B (in cases of systemic use), amphotericin B, liposomal, anastrozolretamine, systemic use in high doses), valganciclovir, vincristine, vinblastine, ganciclovir, vinorelbine, hydroxyurea, gemcitabine, dactinomycin, dacarbazine, didanosine, daunorubicin, docetaxel, doxorubicin, zoledronic acid, zoledronic acid, zoledronic acid, zidovinibudine andfacial, carboplatin, capecitabine, carmustine (in cases of systemic use), colchicine, clozapine, lomustine, lamivudine, mercaptopurine, melphalan, mitoxantrone, methotrexate, mitomycin,sodium phosphate, sodium iodide, oxaliplatin, plikamycin, paclitaxel, pegaspargase, procarbazine, streptozocin, strontium chloride, teniposide, temozolomide, thiotepa, thioguanine, topotecan, flucytosine, fludarabine, fluoroburacil, cicloramidin, cytarabine, etoposide, epirubicin. With the sequential or parallel use of two or more myelodepressants (including with a history of their use), it may be necessary to reduce the dose of azathioprine based on the results of a blood picture. The same applies to combination with radiation therapy.fluorouracil (in cases of systemic use), chloramphenicol, chlorambucil, cisplatin, cyclophosphamide, cytarabine, etoposide, epirubicin. With the sequential or parallel use of two or more myelodepressants (including with a history of their use), it may be necessary to reduce the dose of azathioprine based on the results of a blood picture. The same applies to combination with radiation therapy.fluorouracil (in cases of systemic use), chloramphenicol, chlorambucil, cisplatin, cyclophosphamide, cytarabine, etoposide, epirubicin. With the sequential or parallel use of two or more myelodepressants (including with a history of their use), it may be necessary to reduce the dose of azathioprine based on the results of a blood picture. The same applies to combination with radiation therapy.
The myelotoxic effect of azathioprine can be enhanced with the parallel use of co-trimoxazole.
When combined with rifampicin, graft rejection is possible.
Azathioprine enhances the neuromuscular blockade caused by suxamethonium and reduces the severity of muscle relaxation caused by non-depolarizing muscle relaxants.
In some cases, it is possible to increase thrombocytopenia and / or leukopenia with the sequential or parallel use of azathioprine and the following drugs with unpredictable dose-independent myelotoxicity: amidopyrine, alemtuzumab, antithyroid drugs, tricyclic antidepressants, valproic acid, anticonvulsants (hydroconvulsants), anticonvulsants enzyme, gold compounds, clozapine, carbamazepine, loxapine, levamisole, mirtazapine, maprotiline, non-steroidal anti-inflammatory drugs (especially phenylbutazone), pentamidine, penicillamine, primidone, pimozide, procainamide, primaferine, pyrimethafene (high dose) 2b, pseudoephedrine, rituximab, sulfonamides (for systemic use), sulfamethoxazole, sulfasalazine,antidiabetic agents (sulfonylurea derivatives), ticlopidine, temozolomide, trastuzumab, thioxanthenes, trimethoprim, phenothiazines, felbamate, sodium foscarnet, flecainide, chloramphenicol, epirubicin, cetirizine. Based on the analysis of the blood picture, it may be necessary to reduce the dose of azathioprine.
When mixed with alkaline solutions (especially when heated), azathioprine can decompose with the subsequent formation of 6-mercaptopurine. Similar processes are possible in the presence of compounds that contain sulfhydryl groups (glutathione, cysteine, hydrogen sulfide).
Analogs
Analogues of Azathioprine include the following drugs: Alpha-fetoprotein, Alfetin, Profetal Lyophilisate, Revlimid, Stemokin. These drugs contain other active substances, but they have a similar effect on the body.
Storage conditions and periods
Store in a dry, dark place. The shelf life of Azathioprine is 5 years from the date of production.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Azathioprine
Reviews of Azathioprine are quite controversial. Some users with autoimmune diseases note that the drug is quite effective and has almost no side effects (compared to hormone therapy). Authors of other reviews note the complete absence of changes when taking the drug.
Users pay special attention to the fact that the indications for the use of Azathioprine are very serious, so only a doctor should prescribe it.
Price for Azathioprine in pharmacies
The approximate price for Azathioprine is 200 rubles (50 tablets per pack).
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
