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Azathioprine information from DrugsUpdate  

See Available Brands of Azathioprine in India

P - Contraindicated in pregnancy
L - Contraindicated in lactation
FI - Food *

Azathioprine is a drug that suppresses the immune system.

Azathioprine is used in organ transplantation and autoimmune disease. Some of the autoimmune diseases are rheumatoid arthritis, pemphigus, Inflammatory Bowel Disease (such as Crohn's disease and Ulcerative Colitis), multiple sclerosis, autoimmune hepatitis and restrictive lung disease.

Azathioprine interferes with the synthesis of purines (adenine and guanine), which is required for DNA synthesis. Fast-growing cells, including T-cells and B-cells, are particularly affected by the inhibition of purine synthesis.

It is a pro-drug, converted in the body to the active metabolites 6-mercaptopurine (6-MP) and 6-thioinosinic acid.

Pharmacodynamics

Pharmacokinetics

Azathioprine is an imidazolyl derivative of mercaptopurine, which inhibits DNA, RNA and protein synthesis and antagonises purine synthesis. It also inhibits mitosis and interferes with cellular metabolism of susceptible organisms. Azathioprine inj should be converted to oral therapy as soon as the drug can be tolerated.


Absorption
Well absorbed from the GI tract (oral).

Distribution
Protein-binding: About 30%. Crosses placenta.

Metabolism
Converted hepatically to 6-mercaptopurine which is further metabolised in the liver and GI tract via 3 main pathways: Hypoxanthine guanine phosphoribosyltransferase (to 6-thioguanine-nucleotides), xanthine oxidase (to 6-thiouric acid), and thiopurine methyltransferase (TPMT), which forms 6-methylmercapotpurine (6-MMP).

Excretion
Via the urine (mainly as metabolites). Half-life elimination: Parent drug (12 minutes); mercaptopurine (0.7-3 hour); prolonged in end stage renal disease.

Azathioprine Indications / Azathioprine Uses

Information Not Available

Azathioprine Adverse Reactions / Azathioprine Side Effects

Fever, chills; bone marrow depression characterised by leucopenia, thrombocytopenia or anaemia; anorexia, nausea, diarrhoea; arthralgias; secondary infections; hepatotoxicity, rash, alopoecia.

Potentially Fatal: Myelosuppression, mutagenicity and carcinogenicity; veno-occlussive liver disease.

Precautions

Warnings
Chronic immunosuppression with this agent may increase risk of neoplasia.
Experienced physician should be very familiar with mutagenic potential and hematological profile.

Carcinogenesis
Chronic immunosuppression with azathioprine increases risk of neoplasia. Patients with rheumatoid arthritis previously treated with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan) may have prohibitive risk of neoplasia.

Mutagenesis
Chronic immunosuppression with azathioprine increases risk of neoplasia. Patients with rheumatoid arthritis previously treated with alkylating agents (eg, cyclophosphamide, chlorambucil, melphalan) may have prohibitive risk of neoplasia.

Superinfection
Serious fungal, viral, bacterial and protozoal infections may develop in patients on long-term immunosuppression.

GI toxicity
Hypersensitivity reaction with severe nausea and vomiting may occur. Frequency of gastric disturbances can be reduced by giving in divided doses or after meals.


Hematologic effects

Severe hematologic toxicities (leukopenia and/or thrombocytopenia) may occur; monitor complete blood counts weekly during the first month, twice monthly for the second and third months, then monthly. Perform more frequently if dosage alterations or other therapy changes are necessary.

Hepatoxicity
Occurs primarily in allograft recipients. Rare but life-threatening hepatic veno-occlusive disease has occurred in transplant patients; monitor LFTs.

Special Precautions

Increased risk of serious infections and neoplasia in chronic immunosuppression; leucopenia, thrombocytopenia, renal or hepatic impairment. Increased risk of haematologic toxicity in patients with thiopurine methyltransferase deficiency.


Monitor CBC (including platelet count) weekly during 1st month, twice monthly for 2nd and 3rd month, then monthly; monitor more frequently if there are dosage adjustments. Monitor LFT periodically; discontinue treatment if jaundice occurs.


Reduce dose promptly or withdraw drug temporary if there is rapid decrease/persistently low WBC or signs of bone marrow depression. Dose reduction may be necessary in patients with reduced TPMT (thiopurine methyltransferase) activity.

Other Drug Interactions

Increased risk of haematotoxicity with aminosalicylates, drugs that affect myelopoesis e.g. co-trimoxazole or trimethoprim. Increased risk of infections with intra-uterine devices and live vaccines. Increased risk of leucopenia with ACE inhibitors. Concurrent use may reduce the anticoagulant effect of vitamin K antagonists e.g. warfarin. Increased risk of myelosuppressive effects when used with drugs that inhibit TPMT (thiopurine methyltransferase) or xanthine oxidase e.g. olsalazine, allopurinol.

Potentially Fatal: Increased risk of serious haematotoxicity or hepatotoxicity with leflunomide. Increased risk of bone marrow suppression with mycophenolate mofetil. Increased risk of infections and malignancies with efalizumab.

Other Interactions

Food interactions
Avoid cat's claw and echinacea.

Dosage

Oral
Prevention of rejection in organ and tissue transplant.
Adult: 1-5 mg/kg/day. Adjust dose according to clinical response and haematological tolerance. Dose may also be given via IV admin.


 


Renal impairment: Dose adjustments may be needed.
Hepatic impairment: Dose adjustments may be needed.

Oral
Auto-immune diseases
Adult: 1-3 mg/kg/day. Discontinue treatment if there is no improvement after 12 weeks.
Renal impairment: Dose adjustments may be needed.
Hepatic impairment: Dose adjustments may be needed.

Oral
Rheumatoid arthritis
Adult: Initially, 1 mg/kg/day given in 1-2 divided doses for 6-8 weeks, may increase by 0.5 mg/kg every 4 weeks until response or up to 2.5 mg/kg/day. Maintenance: Reduce dose gradually to achievse the lowest effective dose.
Renal impairment: Dose adjustments may be needed.
Hepatic impairment: Dose adjustments may be needed.


 


Intravenous
Renal homotransplantation
Adult: Usual initial doses: 3-5 mg/kg daily beginning at the time of transplantation. Usually given as a single dose on the day of transplantation, may be given 1-3 days before transplantation in some cases. May reduce dose to maintenance levels at 1-3 mg/kg daily. May convert to use of oral tablets subsequently at the same dose level. Treatment discontinuation may be needed in cases of severe haematologic or other toxicity.

Renal impairment: Dose adjustments may be needed.
Hepatic impairment: Dose adjustments may be needed.

Reconstitution
10 ml of sterile water for Inj to be added to the vial containing 100 mg of the drug, giving a resultant concentration of 10 mg/ml. This may be given by slow IV inj or further diluted in saline or dextrose to be used as IV infusion usually over 30-60 minutes. Infusion periods of 5 minutes to 8 hours have been used.

Food(before/after)

May be taken with or without food. (Preferably taken w/ or after meals to reduce GI discomfort.)

List of Contraindications

Azathioprine and Pregnancy

Contraindicated in pregnancy.


Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Azathioprine and Lactation

Contraindicated in lactation

Azathioprine and Children

Safety and efficacy of Azathioprine in pediatric patients have not been established.

Azathioprine and Geriatic

Information Not Available

Azathioprine and Other Contraindications

Hypersensitivity; previous treatment with alkylating agents; pregnancy, lactation.

Storage

Intravenous
Powder for inj: Store intact vials between 15-25°C. Protect from light.

Reconstituted solution:Stable for up to 2 weeks at room temperature or up to 4 days refrigerated, however, manufacturer recommends use within 24 hours of reconstitution.

Oral
Store between 15-25°C.

Lab interference

Intravenous
Powder for inj: Store intact vials between 15-25°C. Protect from light.

Reconstituted solution:Stable for up to 2 weeks at room temperature or up to 4 days refrigerated, however, manufacturer recommends use within 24 hours of reconstitution.

Oral
Store between 15-25°C.

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