Important Safety Information for Azasan® Azathioprine Tablets, USP
WARNING - MALIGNANCY Chronic immunosuppression with this purine antimetabolite
increases risk of malignancy in humans. Reports of malignancy include post-transplant
lymphoma and hepatosplenic T-cell lymphoma (HSTCL) in patients with inflammatory bowel
disease. Physicians using this drug should be very familiar with this risk as well as with the
mutagenic potential to both men and women and with possible hematologic toxicities.
Physicians should inform patients of the risk of malignancy with AZASAN®.
AZASAN® (azathioprine tablets) is contraindicated in 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 malignancy if treated with AZASAN.
Patients receiving immunosuppressants, including AZASAN, are at increased risk of developing
lymphoma and other malignancies, particularly of the skin. Physicians should inform patients of the risk
of malignancy with AZASAN. As usual for patients with increased risk for skin cancer, exposure to
sunlight and ultraviolet light should be limited by wearing protective clothing and using a sunscreen with
a high protection factor.
Severe leukopenia, thrombocytopenia, anemias including macrocytic and/or pancytopenia may occur in
patients being treated with AZASAN. Severe bone marrow suppression may also occur. Patients with
intermediate thiopurine S-methyl transferase (TPMT) activity may be at an increased risk of
myelotoxicity if receiving conventional doses of AZASAN. Patients with low or absent TPMT activity are
at an increased risk of developing severe, life-threatening myelotoxicity if receiving conventional doses
of AZASAN. Hematologic toxicities are dose related and may be more severe in renal transplant patients
whose homograft is undergoing rejection. It is suggested that patients on AZASAN have complete blood
counts, including platelet counts, weekly during the first month, twice monthly for the second and third
months of treatment, then monthly or more frequently if dosage alterations or other therapy changes
are necessary. Delayed hematologic suppression may occur. Leukopenia does not correlate with
therapeutic effect; therefore, the dose should not be increased intentionally to lower the white blood
Serious infections are a constant hazard for patients receiving chronic immunosuppression, especially
for homograft recipients. Fungal, viral, bacterial, and protozoal infections may be fatal and should be
treated vigorously. Reduction of azathioprine dosage and/or use of other drugs should be considered.
Azathioprine has been reported to cause temporary depression in spermatogenesis and reduction in
sperm viability and sperm count in mice at doses 10 times the human therapeutic dose; a reduced
percentage of fertile matings occurred when animals received 5 mg/kg.
AZASAN can cause fetal harm when administered to a pregnant woman. AZASAN should not be given
during pregnancy without careful weighing of risk versus benefit. Whenever possible, use of AZASAN in
pregnant patients should be avoided. The use of AZASAN in nursing mothers is not recommended.
AZASAN should be used in caution with allopurinol, aminosalicylates, agents affecting myelopoesis,
Angiotensin-Converting Enzyme Inhibitors, warfarin, and ribavirin.
A gastrointestinal hypersensitivity reaction characterized by severe nausea and vomiting has been
reported with AZASAN. The principal and potentially serious toxic effects of AZASAN are hematologic
and gastrointestinal. The frequency and severity of adverse reactions depend on the dose and duration
of AZASAN as well as on the patient's underlying disease or concomitant therapies. The incidence of
hematologic toxicities and neoplasia encountered in groups of renal homograft recipients is significantly
higher than that in studies employing AZASAN for rheumatoid arthritis. Common adverse events in renal
homograft patients were leukopenia, <2500 cells/mm3, infections, and neoplasia. Common adverse
events in rheumatoid arthritis patients were leukopenia, <2500 cells/mm3, nausea, and vomiting.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch/ or call 1-800-FDA-1088.
For product information, adverse event reports, and product complaint reports, please contact:
Salix Product Information Call Center
Please see complete Prescribing Information for AZASAN, including BOXED WARNING.
The information contained on this page is intended for US residents, healthcare providers, and pharmacists only.