Generic Name

Azathioprine

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Classification

FDA Approved Indications

• Prevention of organ rejection in transplant patients
• Treatment of rheumatoid arthritis
• Treatment of inflammatory bowel disease (Crohn's disease and ulcerative colitis)

Mechanism of Action

Azathioprine is converted into 6-mercaptopurine in the body, which inhibits purine synthesis. This results in suppression of the immune response by decreasing lymphocyte proliferation.

Dosage and Administration

Adult: Variable based on indication; typical dose ranges from 50 to 3,000 mg/day divided doses. Dose should be individualized based on patient's clinical response and tolerability.

Pediatric: Dose varies with weight and indication; usually starting at 1-3 mg/kg/day, adjusted as needed.

Geriatric: Use with caution; start at lower doses due to increased risk of toxicity.

Renal Impairment: Adjust dosage based on renal function; consult specific guidelines.

Hepatic Impairment: Use cautiously; no specific dosing guidelines, monitor closely.

Pharmacokinetics

Absorption: Well absorbed orally.

Distribution: Widely distributed in body tissues; crosses the placenta.

Metabolism: Primarily hepatic via thiopurine methyltransferase (TPMT) and xanthine oxidase pathways.

Excretion: Renal excretion of metabolites.

Half Life: Approximately 5 hours, but active metabolites may persist longer.

Contraindications

• Known hypersensitivity to azathioprine or 6-mercaptopurine
• Pregnant women due to teratogenicity

Precautions

• Monitor for myelosuppression, hepatotoxicity, and gastrointestinal toxicity; use cautiously in elderly and those with pre-existing liver disease or immune suppression.

Adverse Reactions - Common

• Nausea (Common)
• Leukopenia (Common)
• Hepatotoxicity (Common)
• Increased risk of infections (Common)

Adverse Reactions - Serious

• Myelosuppression leading to anemia, leukopenia, thrombocytopenia (Serious)
• Liver failure (Serious)
• Malignancies (lymphoma, skin tumors) (Serious)

Drug-Drug Interactions

• Allopurinol (increases azathioprine toxicity)
• ACE inhibitors (monitor renal function)
• Other immunosuppressants

Drug-Food Interactions

• Alcohol (increase hepatotoxicity)

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report signs of infection or unusual bleeding immediately
• Avoid live vaccines and to practice good hygiene
• Inform about potential side effects and the importance of regular blood tests

Special Considerations

Black Box Warnings:

• Increased risk of malignancy, especially lymphoma and skin tumors

Genetic Factors: TPMT enzyme activity influences drug toxicity; testing recommended before initiation.

Lab Test Interference: May cause false-positive tests for urinary catecholamines.

Overdose Management

Signs/Symptoms: Severe myelosuppression, hepatotoxicity, bone marrow suppression, infections.

Treatment: Supportive care, stop medication, administer leucovorin as an antidote if appropriate, monitor blood counts and organ function.

Storage and Handling

Storage: Store at room temperature, away from moisture and light.

Stability: Stable until expiration date on container.