Only physicians experienced in immunosuppressive therapy in the treatment of renal transplant or aplastic anemia patients should use ATGAM.
Patients receiving ATGAM should be treated in facilities equipped and staffed with adequate laboratory and supportive medical resources.
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.
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.
Published Studies Related to Atgam (Equine Thymocyte Immune Globulin)
A prospective, randomized, double-blinded comparison of thymoglobulin versus Atgam for induction immunosuppressive therapy: 10-year results. [2008.10.15]
BACKGROUND: Use of induction for renal transplantation is controversial because of the concerns about long-term safety and efficacy... CONCLUSIONS: This long-term follow-up showed that thymoglobulin was associated with higher event-free survival and improved QALYs, without increased posttransplant lymphoproliferative disorder or cytomegalovirus disease, compared with Atgam at 10 years.
Clinical Trials Related to Atgam (Equine Thymocyte Immune Globulin)
Sirolimus, Tacrolimus, Anti-Thymocyte Globulin, and Rituximab in Preventing Graft-versus-Host Disease in Patients Undergoing Donor Stem Cell Transplant [Recruiting]
This pilot phase II trial studies how well giving sirolimus, tacrolimus, anti-thymocyte
globulin, and rituximab work in preventing graft-versus-host disease (GHVD) in patients
undergoing donor stem cell transplant. Giving sirolimus, tacrolimus, anti-thymocyte
globulin, and rituximab may be an effective treatment for GVHD caused by a stem cell
Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia [Recruiting]
This phase II clinical trial is studying how well giving busulfan, fludarabine phosphate,
and antithymocyte globulin followed by donor stem cell transplant and azacitidine works in
treating patients with high-risk myelodysplastic syndrome and older patients with acute
myeloid leukemia. Giving low doses of chemotherapy, such as busulfan and fludarabine
phosphate, before a donor stem cell transplant helps stop the growth of cancer cells. It
also stops the patient's immune system from rejecting the donor's stem cells. The donated
stem cells may replace the patient's immune cells and help destroy any remaining cancer
cells (graft-vs-tumor effect). Sometimes the transplanted cells from a donor can also make
an immune response against the body's normal cells. Giving antithymocyte globulin before
transplant and giving azacitidine, tacrolimus, and methotrexate after the transplant may
stop this from happening
Tacrolimus and ATG as GVHD Prophylaxis in Patients Undergoing Related Donor HSCT [Recruiting]
This phase II trial studies how well giving tacrolimus and anti-thymocyte globulin together
works in preventing graft-vs-host disease (GVHD) in patients with hematologic malignancies
undergoing donor peripheral blood stem cell transplant (PBSCT). Sometimes the transplanted
cells from a donor can make an immune response against the body's normal cells. Giving
tacrolimus together with anti-thymocyte globulin may stop this from happening
Antithymocyte Globulin and Sirolimus in Treating Patients With Relapsed Multiple Myeloma [Recruiting]
RATIONALE: Biological therapies, such as antithymocyte globulin may stimulate the immune
system in different ways and stop cancer cells from growing. Sirolimus may stop the growth
of cancer cells by blocking some of the enzymes needed for cell growth. It may also prevent
or reduce the side effects of antithymocyte globulin. Giving antithymocyte globulin together
with sirolimus may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of antithymocyte
globulin when given together with sirolimus in treating patients with relapsed multiple
Reduced Intensity Conditioning With Clofarabine, Antithymocyte Globulin (ATG), Total Lymphoid Irradiation (TLI) Followed by Allogeneic Stem Cell Transplant [Recruiting]
This study will examine the safety of clofarabine, TLI and ATG as a reduced conditioning
regimen prior to allogeneic transplantation. The impact of the conditioning regimen on the
presence of the circulating regulatory as compared to activated T cell populations will be
assessed. The recovery of DC populations post-transplant will be examined, along with the
effect of the regimen on disease free and overall survival.
Reports of Suspected Atgam (Equine Thymocyte Immune Globulin) Side Effects
Renal Failure Acute (6),
Generalised Oedema (5),
Bone Marrow Failure (5),
Bronchopulmonary Aspergillosis (5),
Cytolytic Hepatitis (5),
Drug Interaction (4),
Hepatic Failure (4),
Pyrexia (4), more >>
Page last updated: 2009-02-08