ATGAM Sterile Solution contains lymphocyte immune globulin, anti-thymocyte globulin [equine]. It is the purified, concentrated, and sterile gamma globulin, primarily monomeric IgG, from hyperimmune serum of horses immunized with human thymus lymphocytes. ATGAM is a transparent to slightly opalescent aqueous protein solution. It may appear colorless to faintly pink or brown and is nearly odorless. It may develop a slight granular or flaky deposit during storage. (For information about in-line filters, see Infusion Instructions in the DOSAGE AND ADMINISTRATION SECTION.)
Before release for clinical use, each lot of ATGAM is tested to assure its ability to inhibit rosette formation between human peripheral lymphocytes and sheep red blood cells in vitro. In each lot, antibody activity against human red blood cells and platelets is also measured and determined to be within acceptable limits. Only lots that test negative for antihuman serum protein antibody, antiglomerular basement membrane antibody and pyrogens are released.
Each milliliter of ATGAM contains 50 mg of horse gamma globulin stabilized in 0.3
molar glycine to a pH of approximately 6.8.
INDICATIONS AND USAGE
Renal TransplantationATGAM Sterile Solution is indicated for the management of allograft rejection in renal transplant patients. When administered with conventional therapy at the time of rejection, it increases the frequency of resolution of the acute rejection episode. The drug has also been administered as an adjunct to other immunosuppressive therapy to delay the onset of the first rejection episode. Data accumulated to date have not consistently demonstrated improvement in functional graft survival associated with therapy to delay the onset of the first rejection episode.
ATGAM is indicated for the treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation.
When administered with a regimen of supportive care, ATGAM may induce partial or complete hematologic remission. In a controlled trial, patients receiving ATGAM showed a statistically significantly higher improvement rate compared with standard supportive care at 3 months. Improvement was defined in terms of sustained increase in peripheral blood counts and reduced transfusion needs.
Clinical trials conducted at two centers evaluated the 1-year survival rate for patients with severe and moderate to severe aplastic anemia. Seventy-four of the 83 patients enrolled were evaluable based on response to treatment. The treatment groups studied consisted of 1) ATGAM and supportive care, 2) ATGAM administered following 3 months of supportive care alone, 3) ATGAM, mismatched marrow infusion, androgens, and supportive care, or 4) ATGAM, androgens, and supportive care. There were no statistically significant differences between the treatment groups. The 1-year survival rate for the pooled treatment groups was 69#. These survival results can be compared with a historical survival rate of about 25# for patients receiving standard supportive care alone.
The usefulness of ATGAM has not been demonstrated in patients with aplastic anemia who are suitable candidates for bone marrow transplantation or in patients with aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi’s syndrome, or in patients known to have been exposed to myelotoxic agents or radiation.
To date, safety and efficacy have not been established in circumstances other than renal transplantation and aplastic anemia.
Do not administer ATGAM Sterile Solution to a patient who has had a severe systemic reaction during prior administration of ATGAM or any other equine gamma globulin preparation.
Because ATGAM Sterile Solution is an immunosuppressive agent ordinarily given with corticosteroids and antimetabolites, watch patients carefully for signs of leukopenia, thrombocytopenia, or concurrent infection. Several studies have suggested an increase in the incidence of cytomegalovirus infection in patients receiving ATGAM(1). In one study it has been found that it may be possible to reduce this risk by decreasing the dosage of other immunosuppressive agents administered concomitantly with ATGAM. If infection occurs, institute appropriate adjunctive therapy promptly. On the basis of the clinical circumstances, a physician should decide whether or not therapy with ATGAM will continue.
The safety and effectiveness of ATGAM have been demonstrated only in renal transplant patients who received concomitant immunosuppressive therapy and in patients with aplastic anemia.
Dilution of ATGAM in dextrose injection, USP, is not recommended, as low salt concentrations may result in precipitation. The use of highly acidic infusion solutions is also not recommended because of possible physical instability over time.
When the dose of corticosteroids and other immunosuppressants is being reduced, some previously masked reactions to ATGAM may appear. Under these circumstances, observe patients especially carefully during therapy with ATGAM. ATGAM