azathioprine

azathioprine /aza·thio·prine/ (az″ah-thi´o-prēn) a 6-mercaptopurine derivative used as the base or the sodium salt as an immunosuppressant for prevention of transplant rejection and for treatment of rheumatoid arthritis and various autoimmune diseases.

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az·a·thi·o·prine (z-th-prn)

n.

An immunosuppressive agent used especially to prevent organ rejection in kidney transplant recipients.

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azathioprine

[az′əthī′ōprēn]

an immunosuppressive.

indications It is prescribed to prevent organ rejection after transplantation and to treat lupus erythematosus and other systemic inflammatory diseases, such as rheumatoid arthritis unresponsive to other agents.

contraindications Known hypersensitivity to this drug prohibits its use. It is contraindicated in rheumatoid arthritis and in pregnant women.

adverse effects Among the most serious adverse reactions are bone marrow depression and hepatotoxicity. Nausea and fever are common.

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azathioprine (az´thīōprēn),

n brand name: Imuran;
drug class: immunosuppressant;
action: inhibits purine synthesis in cells, thereby preventing RNA and DNA synthesis;
uses: renal transplants to prevent graft rejection, refractory rheumatoid arthritis, bone marrow transplants, glomerulonephritis.

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azathioprine

a mercaptopurine derivative used as a cytotoxic and immunosuppressive agent in the treatment of leukemia and autoimmune diseases and in transplantation therapy.

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immunosuppressants

Drugs that prevent or reduce the immune response. They are used in the treatment of a variety of severe inflammations such as uveitis, scleritis, keratoconjunctivitis sicca, Behçet's syndrome, sympathetic ophthalmia, and to prevent corneal graft rejection. They include the corticosteroids (e.g. prednisolone), ciclosporin (cyclosporine), tacrolimus, and cytotoxic agents (e.g. azathioprine, chlorambucil, cyclophosphamide, methotrexate). It must be noted that immunosuppressants render the patient more susceptible to infection because immunity is reduced.

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azathioprine

Azasan, Immunoprin (UK), Imuran

Pharmacologic class: Purine antagonist

Therapeutic class: Immunosuppressant

Pregnancy risk category D

FDA Boxed Warning

• Drug may cause chronic immunosuppression, increasing neoplasia risk. Physicians using it should be familiar with this risk and with possible hematologic toxicities and mutagenic potential in both sexes.

Action

Prevents proliferation and differentiation of activated B and T cells by interfering with synthesis of purine, DNA, and RNA

Availability

Tablets (azathioprine): 25 mg, 50 mg, 75 mg, 100 mg

⊘Indications and dosages

➣ To prevent rejection of kidney transplant

Adults and children: Initially, 3 to 5 mg/kg/day P.O. as a single dose. Give on day of transplantation or 1 to 3 days before day of transplantation. Maintenance dosage is 1 to 3 mg/kg/day P.O.

➣ Rheumatoid arthritis

Adults and children: Initially, 1 mg/kg P.O. in one or two daily doses. Increase dosage in steps at 6 to 8 weeks and thereafter at 4-week intervals; use dosage increments of 0.5 mg/kg/day, to a maximum dosage of 2.5 mg/kg/day. Once patient stabilizes, decrease in decrements of 0.5 mg/kg/day to lowest effective dosage.

Dosage adjustment

• Renal disease
• Concurrent allopurinol therapy
• Elderly patients

Off-label uses

• Crohn's disease
• Myasthenia gravis
• Chronic ulcerative colitis

Contraindications

• Hypersensitivity to drug
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• chickenpox, herpes zoster, impaired hepatic or renal function, decreased bone marrow reserve
• previous therapy with alkylating agents (cyclophosphamide, chlorambucil, melphalan) for rheumatoid arthritis
• elderly patients
• women of childbearing age.

Administration

• Give after meals.

Route	Onset	Peak	Duration
P.O.	6-8 wks	12 wks	Unknown

Adverse reactions

CNS: malaise

EENT: retinopathy

GI: nausea, vomiting, diarrhea, stomatitis, esophagitis, anorexia, mucositis, pancreatitis

Hematologic: anemia, thrombocytopenia, leukopenia, pancytopenia

Hepatic: jaundice, hepatotoxicity

Musculoskeletal: muscle wasting, joint and muscle pain

Skin: rash, alopecia

Other: chills, fever, serum sickness, neoplasms, serious infection

Interactions

Drug-drug. Allopurinol: increased therapeutic and adverse effects of azathioprine

Anticoagulants, cyclosporine: decreased actions of these drugs

Atracurium, pancuronium, tubocurarine, vecuronium: reversal of these drugs' actions

Drugs affecting bone marrow and bone marrow cells (such as angiotensin-converting enzyme inhibitors, co-trimoxazole): severe leukopenia

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin: increased levels

Albumin, hemoglobin, uric acid: decreased levels

Urine uric acid: decreased level

Drug-herbs. Astragalus, echinacea, melatonin: interference with immunosuppressant action

Patient monitoring

☞ Monitor CBC, platelet level, and liver function test results.
• Assess for signs and symptoms of hepatotoxicity (clay-colored stools, pruritus, jaundice, and dark urine).
• Watch for signs and symptoms of infection.
• Monitor for bleeding tendency and hemorrhage.

Patient teaching

☞ Tell patient that drug lowers resistance to infection. Instruct him to immediately report fever, cough, breathing problems, chills, and other symptoms.
☞ Instruct patient to immediately report unusual bleeding or bruising.
• Tell patient that drug effects may not be obvious for up to 8 weeks in immunosuppression and up to 12 weeks for rheumatoid arthritis relief.
☞ Emphasize importance of avoiding pregnancy during therapy and for 4 months afterward.
• Caution patient to avoid activities that may cause injury. Tell him to use soft toothbrush and electric razor to avoid gum and skin injury.
• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
• Tell patient he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and herbs mentioned above.

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azathioprine

Imuran^® Immunology An immunosuppressant used to prevent rejection of heart, kidney, lung and other allografts, acting primarily on T-cells; it is used in rheumatoid arthritis, myasthenia gravis Adverse effects BM suppression–leukopenia, thrombocytopenia, macrocytic anemia, GI tract–N&V, diarrhea, fever, malaise, myalgia, LFT abnormalities, hepatotoxicity, pancreatitis; should not be given with allopurinol. See Heart transplant, Kidney transplant, Lung transplant, Transplantation.