Azathioprine

Trade Names:Azasan- Tablets 75 mg- Tablets 100 mg

Trade Names:Azathioprine- Injection 100 mg (as sodium)/vial

Trade Names:Imuran- Tablets 50 mg

Pharmacology

Suppresses cell-mediated hypersensitivities; alters antibody production and may reduce inflammation.

Pharmacokinetics

Absorption

Well absorbed after oral administration.

Distribution

Azathioprine and mercaptopurine are approximately 30% bound to serum proteins.

Metabolism

Extensively metabolized. Azathioprine is cleaved to mercaptopurine (active). Both compounds are oxidized or methylated in erythrocytes or liver. Converted to inactive 6-thiouric acid by xanthine oxidase.

Elimination

Azathioprine and mercaptopurine are rapidly eliminated from blood. No azathioprine or mercaptopurine is detectable in urine after 8 h. Partially dialyzable.

Indications and Usage

Adjunct for prevention of rejection in renal homotransplantation; treatment in adults for severe, active, erosive rheumatoid arthritis not responsive to conventional management.

Unlabeled Uses

Treatment of chronic ulcerative colitis, Crohn disease, myasthenia gravis and Behcet syndrome.

Contraindications

Pregnancy in patients with rheumatoid arthritis.

Dosage and Administration

IV / PO Initiate with 3 to 5 mg/kg/day as single daily dose. Maintenance levels are 1 to 3 mg/kg/day.

PO Initial dose is 1 mg/kg given as single dose or twice daily. Dose is increased by 0.5 mg/kg/day at 6 to 8 wk, then every 4 wk if there are no serious toxicities and if initial response is unsatisfactory. Max dose is 2.5 mg/kg/day. IV Reserved for patients unable to tolerate oral medications.

Storage/Stability

Store in a tightly closed container in a cool location.

Drug Interactions

Decreases metabolism of azathioprine. Dose of azathioprine is reduced to approximately one-third to one-fourth usual dose when used concomitantly.

Azathioprine may resist or reverse neuromuscular blockade.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Dermatologic

Rash.

GI

Nausea; vomiting.

Hematologic

Leukopenia; thrombocytopenia; macrocytic anemia; bleeding; selective erythrocyte aplasia.

Miscellaneous

Serious infections; neoplasias.

Precautions

Pregnancy

Category D .

Lactation

Excreted in breast milk.

Children

Safety and efficacy not established.

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.

Overdosage

Symptoms

Bone marrow hypoplasia, bleeding, infection, death.

Patient Information

• Instruct patient that if once-daily dose is forgotten to skip the dose, but if 2 daily doses are missed to call the health care provider. Next dose may be doubled.
• Explain importance of precautions regarding contact with individuals who have active infections and individuals who have recently received oral polio vaccine.
• Identify signs of transplant rejection (eg, localized redness, tenderness and swelling in the area of the transplant, decreased transplant organ function), and remind patient that this or similar medication will be required indefinitely to prevent transplant rejection.
• Explain that frequent follow-up appointments with a health care provider are important to adjust medication dosage.
• Instruct patient to report the following symptoms to health care provider: unusual bleeding, decreased urine output, abdominal pain.

Copyright © 2009 Wolters Kluwer Health.