INDICATIONS AND USAGE
ATGAM 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.
Before the first infusion of ATGAM, Pharmacia &Upjohn Company strongly recommends that patients be tested with an intradermal injection of 0.1 mL of a 1:1,000 dilution (5 µg horse IgG) of ATGAM in sodium chloride injection, USP and a contralateral sodium chloride injection control. Use only freshly diluted ATGAM for skin testing. The patient, and specifically the skin test, should be observed every 15 to 20 minutes over the first hour after intradermal injection. A local reaction of 10 mm or greater with a wheal or erythema, or both, with or without pseudopod formation and itching or a marked local swelling should be considered a positive test. Note: The predictive value of this test has not been proved clinically. Allergic reactions such as anaphylaxis have occurred in patients whose skin test is negative. In the presence of a locally positive skin test to ATGAM, serious consideration to alternative forms of therapy should be given. The risk to benefit ratio must be carefully weighed. If therapy with ATGAM is deemed appropriate following a locally positive skin test, treatment should be administered in a setting where intensive life support facilities are immediately available and with a physician familiar with the treatment of potentially life threatening allergic reactions in attendance.
A systemic reaction such as a generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis precludes any additional administration of ATGAM.
SEE WARNINGS, PRECAUTIONS, AND ADVERSE REACTIONS.