Imuran - General Information:

An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)

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Imuran (Azathioprine) is an immunosuppressive agent used to prevent rejection after a kidney transplant. It may also be used to treat rheumatoid arthritis and other conditions as determined by your doctor.

Pharmacology:

Imuran is a chemotherapy drug, now rarely used for chemotherapy but more for immunosuppression in organ transplantation and autoimmune disease such as rheumatoid arthritis or inflammatory bowel disease or Crohn's disease. It is a pro-drug, converted in the body to the active metabolite 6-mercaptopurine. Imuran acts to inhibit purine synthesis necessary for the proliferation of cells, especially leukocytes and lymphocytes. It is a safe and effective drug used alone in certain autoimmune diseases, or in combination with other immunosuppressants in organ transplantation. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication.

Imuran for patients

Patients being started on azathioprine should be informed of the necessity of periodic blood counts while they are receiving the drug and should be encouraged to report any unusual bleeding or bruising to their physician. They should be informed of the danger of infection while receiving azathioprine and encouraged to report signs and symptoms of infection to their physician. Careful dosage instructions should be given to the patient, especially when azathioprine is being administered in the presence of impaired renal function or concomitantly with allopurinol. Patients should be advised of the potential risks of the use of azathioprine during pregnancy and during the nursing period. The increased risk of neoplasia following azathioprine therapy should be explained to the patient.

Imuran Interactions

Use with Allopurinol: The principal pathway for detoxification of azathioprine is inhibited by allopurinol. Patients receiving azathioprine and allopurinol concomitantly should have a dose reduction of azathioprine, to approximately 1/3 to 1/4 the usual dose.

Use with Other Agents Affecting Myelopoesis: Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients.

Use with Angiotensln Converting Enzyme Inhibitors: The use of angiotensin converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce severe leukopenia.

Imuran Contraindications

Azathioprine should not be given to patients who have shown hypersensitivity to the drug.

Azathioprine should not be used to treat rheumatoid arthritis in pregnant women. Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a prohibitive risk of neoplasia if treated with azathioprine.

Additional information about Imuran

Imuran Indication: For use as an adjunct in the prevention of rejection in renal homotransplantation. Also for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin or other nonsteroidal anti-inflammatory drugs, or to agents in the class of which gold is an example.
Mechanism Of Action: Imuran antagonizes purine metabolism and may inhibit synthesis of DNA, RNA, and proteins. It may also interfere with cellular metabolism and inhibit mitosis. The mechanism of action of azathioprine in rheumatoid arthritis is not known but is most likely related to its immunosuppresive action.
Drug Interactions: Allopurinol Allopurinol increases the effect of thiopurine
Anisindione The thiopurine decreases the anticoagulant effect
Atracurium The agent decreases the effect of the muscle relaxant
Dicumarol The thiopurine decreases the anticoagulant effect
Doxacurium The agent decreases the effect of the muscle relaxant
Gallamine Triethiodide The agent decreases the effect of the muscle relaxant
Mesalazine The 5-ASA derivative increases the toxicity of thiopurine
Metocurine The agent decreases the effect of the muscle relaxant
Mivacurium The agent decreases the effect of the muscle relaxant
Acenocoumarol The thiopurine decreases the anticoagulant effect
Olsalazine The 5-ASA derivative increases the toxicity of thiopurine
Pancuronium The agent decreases the effect of the muscle relaxant
Sulfasalazine The 5-ASA derivative increase the toxicity of thiopurine
Tubocurarine The agent decreases the effect of the muscle relaxant
Vecuronium The agent decreases the effect of the muscle relaxant
Warfarin The thiopurine decreases the anticoagulant effect
Food Interactions: Take with food to reduce irritation.
Generic Name: Azathioprine
Synonyms: Azathioprine Sodium; Azathioprin; Azothioprine; Azatioprin
Drug Category: Antimetabolites; Antimetabolites, Antineoplastic; Antirheumatic Agents; Immunosuppressive Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Azathioprine: Azamun; Azanin; Azasan; Ccucol; Imuran; Imurek; Imurel; Muran;
Absorption: Well absorbed following oral administration.
Toxicity (Overdose): The oral LD50 for single doses of azathioprine in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death.
Protein Binding: Azathioprine and the metabolite mercaptopurine are moderately bound to serum proteins (30%).
Biotransformation: Primarily converted to the active metabolites 6-mercaptopurine and 6-thioinosinic acid.
Half Life: Approximately 5 hours for the unchanged drug and its metabolites.
Dosage Forms of Imuran: Powder, for solution Intravenous
Tablet Oral
Chemical IUPAC Name: 6-(3-methyl-5-nitroimidazol-4-yl)sulfanyl-7H-purine
Chemical Formula: C9H7N7O2S
Azathioprine on Wikipedia: http://en.wikipedia.org/wiki/Azathioprine
Organisms Affected: Humans and other mammals

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