|Drug Name:||Azathioprine Sodium|
Manufactured for: AZP02Bedford Laboratories™ Rev.02/99Bedford, Ohio 44146Manufactured by:Ben Venue Laboratories, Inc.Bedford, Ohio 44146
Azathioprine Sodium for Injection is indicated as an adjunct for the prevention of rejection in renal homotransplantation.It is also indicated for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin or other nonsteriodal anti-inflammatory drugs, or to agents in the class of which gold is an example.
Azathioprine Sodium for Injection should not be given to patients who have shown hypersensitivity to the drug.Azathioprine should not be used for treating rheumatoid arthritis in pregnant women.Patients with rheumatiod arthritis previously treated with alkylating agents (cyclophosphamide, chlorambucil, melphalan or others) may have a prohibitive risk of neoplasia if treated with azathioprine.9
Severe leukopenia and/or thrombocytopenia may occur in patients on azathioprine.
Macrocytic anemia and severe bone marrow depression may also occur.
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 azathioprine 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.
Prompt reduction in dosage or temporary withdrawal of the drug may be necessary if there is a rapid fall in, or persistently low leukocyte count or other evidence of bone marrow depression.
Leukopenia does not correlate with therapeutic effect; therefore the dose should not be increased intentionally to lower the white blood cell count.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 is mutagenic in animals and humans, carcinogenic in animals, and may increase the patient’s risk of neoplasia.
Renal transplant patients are known to have an increased risk of malignancy, predominantly skin cancer and reticulum cell or lymphomatous tumors.10 The risk of post-transplant lymphomas may be increased in patients who receive aggressive treatment with immunosuppresive drugs.11 The degree of immunosuppression is determined not only by the immunosuppressive regimen but also by a number of other patient factors.
The number of immunosuppressive agents may not necessarily increase the risk of post-transplant lymphomas.
However, transplant patients who receive multiple immunosuppressive agents may be at risk for over-immunosuppression; therefore, immunosuppressive drug therapy should be maintained at the lowest effective levels.
Information is available on the spontaneous neoplasia risk in rheumatoid arthritis,12,13 and on neoplasia following immunosuppressive therapy of other autoimmune diseases.14,15 It has not been possible to define the precise risk of neoplasia due to azathioprine.16 The data suggest the risk may be elevated in patients with rheumatoid arthritis, though lower than for renal transplant patients.11,13 However, acute myelogenous leukemia as well as solid tumors have been reported in patients with rheumatoid arthritis who have received azathioprine.Data on neoplasia in patients receiving azathioprine can be found under ADVERSE REACTIONS.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 dose17; a reduced percentage of fertile matings occurred when animals received 5 mg/kg.18