azathioprine

Action

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

Availability

Injection: 100-mg vial

Tablets: 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. or I.V. as a single dose. Give on day of transplantation or 1 to 3 days before day of transplantation; then 3 to 5 mg/kg/day I.V. after surgery until patient can tolerate P.O. route. Maintenance dosage is 1 to 3 mg/kg/day P.O.

➣ Rheumatoid arthritis

Adults and children: Initially, 1 mg/kg P.O. or I.V. 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.

• Be aware that I.V. administration is intended for use only when patients can't tolerate oral medications.

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

Angiotensin-converting enzyme (ACE) inhibitors, co-trimoxazole: severe leukopenia

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 ACE 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.