azathioprine
Imuran

azathioprine sodium
Imuran

Available forms
Available by prescription only
Injection: 100 mg/vial
Tablets: 50 mg

Indications and dosages
 Prevention of the rejection of kidney transplants. Adults and children: Initially, 3 to 5 mg/kg P.O. as a single daily dose on day of transplantation or (rarely) 1 to 3 days before. After transplantation, dosage may be administered I.V., until patient is able to tolerate oral dosage. Usual maintenance dosage is 1 to 3 mg/kg daily. Dosage varies with patient response.
 Severe, refractory rheumatoid arthritis. Adults: Initially, 1 mg/kg (about 50 to 100 mg) P.O. taken as a single dose or in divided doses. If patient response is unsatisfactory after 6 to 8 weeks, dose may be increased by 0.5 mg/kg daily (up to a maximum of 2.5 mg/kg daily) at 4-week intervals. If no response after 12 weeks, discontinue.

Pharmacodynamics
Immunosuppressant action: The mechanism of immunosuppressive activity is unknown; however, drug may inhibit RNA and DNA synthesis, mitosis, or (in patients undergoing renal transplantation) coenzyme formation and functioning. Azathioprine suppresses cell-mediated hypersensitivity and alters antibody production.

Pharmacokinetics
Absorption: Well absorbed orally.
Distribution: Drug and its major metabolite, mercaptopurine, are distributed throughout the body; both are 30% protein-bound. Azathioprine and its metabolites cross the placental barrier.
Metabolism: Metabolized primarily to mercaptopurine.
Excretion: Small amounts of azathioprine and mercaptopurine are excreted in urine intact; most of a given dose is excreted in urine as secondary metabolites.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and during pregnancy. Use cautiously in patients with impaired renal or hepatic function.

Interactions
Drug-drug. ACE inhibitors: Increase risk of anemia and severe leukopenia. Use together cautiously.
Allopurinol: Major metabolic pathway of azathioprine is inhibited by allopurinol, which competes for the oxidative enzyme xanthine oxidase. Avoid use together. If use together is unavoidable, reduce azathioprine dose by one-third to one-fourth the usual amount.
Cyclosporine: Decreases cyclosporine levels. Monitor patient for this effect.
Methotrexate: Increases plasma levels of 6-MP, a metabolite. Monitor patient for toxicity.
Pancuronium, tubocurarine: May reverse neuromuscular blockade caused by nondepolarizing muscle relaxants. Monitor patient for this effect.

Adverse reactions
CNS: fever.
GI: nausea, vomiting, pancreatitis, steatorrhea, diarrhea, abdominal pain.
Hematologic: LEUKOPENIA, bone marrow suppression, anemia, pancytopenia, thrombocytopenia, immunosuppression (possibly profound).
Hepatic: hepatotoxicity, jaundice.
Metabolic: hyperuricemia.
Musculoskeletal: arthralgia, myalgia.
Skin: rash, alopecia.
Other: infections, increased risk of neoplasia.

Effects on lab test results
• May increase AST, ALT, alkaline phosphatase, and bilirubin levels. May decrease uric acid levels.
• May decrease hemoglobin and WBC, RBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include nausea, vomiting, diarrhea, and extension of hematologic effects.
 Supportive treatment may include administering blood products, if needed.

Special considerations
• If NSAIDs are used to treat rheumatoid arthritis, continue them when azathioprine therapy starts.
• Chronic immunosuppression with azathioprine is linked to an increased risk of neoplasia.
• Reconstitute 100 mg vial with 10 ml of sterile water for injection. The resulting concentration is 10 mg/ml. Visually inspect for particles before use. Drug may be administered by direct I.V. injection or further diluted in normal saline solution for injection or D₅W and infused over 30 to 60 minutes. Use only in patients who are unable to tolerate oral medications.
• Monitor patient for signs of hepatic damage: clay-colored stools, dark urine, jaundice, pruritus, and elevated liver enzyme levels.
• Watch for unusual bleeding or bruising, fever, or sore throat.
• Monitor hematologic status while patient is receiving azathioprine. CBCs, including platelet counts, should be monitored at least weekly during the first month, twice monthly for the second and third months, then monthly.
• If infection occurs, reduce drug dosage.
• If nausea and vomiting occur, dose may be divided or given with or after meals.
• Drug may cause temporary depression of spermatogenesis.
Pregnant patients
• Drug may cause fetal harm.

Patient education
• Explain possible adverse effects of medication and importance of reporting them, especially unusual bleeding or bruising, fever, sore throat, mouth sores, abdominal pain, pale stools, or dark urine.
• Encourage compliance with therapy and follow-up visits.
• Advise patient to avoid pregnancy during therapy and for 4 months after stopping therapy.
• Tell patient with rheumatoid arthritis that clinical response may not be apparent for up to 12 weeks.
• Suggest taking drug with or after meals or in divided doses to prevent nausea.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use