Azasan (Azathioprine) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS:

Use with Allopurinol:    The principal pathway for detoxification of AZASAN® is inhibited by allopurinol. Patients receiving AZASAN® and allopurinol concomitantly should have a dose reduction of AZASAN®, to approximately 1/3 to 1/4 the usual dose.

Use with Other Agents Affecting Myelopoiesis:    Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal transplant recipients.

Use with Angiotensin-Converting Enzyme Inhibitors:    The use of angiotensin-converting enzyme inhibitors to control hypertension in patients on azathioprine has been reported to induce severe leukopenia.

Carcinogenesis, Mutagenesis, Impairment of Fertility:    See WARNINGS section.

Pregnancy:    Teratogenic Effects: Pregnancy Category D. See WARNINGS section.

Nursing Mothers:    The use of AZASAN® in nursing mothers is not recommended. Azathioprine or its metabolites are transferred at low levels both transplacentally and in breast milk. Because of the potential for tumorgenicity shown for azathioprine, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:    Safety and efficacy of azathioprine in pediatric patients have not been established.

OVERDOSAGE

The oral LD₅₀ s for single doses of AZASAN® in mice and rats are 2500 mg/kg and 400 mg/kg, respectively. Very large doses of this antimetabolite may lead to marrow hypoplasia, bleeding, infection, and death. About 30% of AZASAN® is bound to serum proteins, but approximately 45% is removed during an 8-hour hemodialysis. A single case has been reported of a renal transplant patient who ingested a single dose of 7500 mg azathioprine. The immediate toxic reactions were nausea, vomiting, and diarrhea, followed by mild leukopenia and mild abnormalities in liver function. The white blood cell count, SGOT, and bilirubin returned to normal 6 days after the overdose.

CONTRAINDICATIONS

AZASAN® should not be given to patients who have shown hypersensitivity to the drug.

AZASAN® should not be used for treating rheumatoid arthritis in pregnant women.

Patients with rheumatoid arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan, or others) may have a prohibitive risk of neoplasia if treated with AZASAN®.