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)
Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia [Completed]
RATIONALE: Immunosuppressive therapies, such as anti-thymocyte globulin and cyclosporine,
may improve bone marrow function and increase blood cell counts. PURPOSE: This phase II
trial is studying how well giving anti-thymocyte globulin together with cyclosporine as
first-line therapy works in treating patients with severe aplastic anemia.
Study of Antithymocyte Globulin for Treatment of New-onset T1DM [Terminated]
Antithymocyte globulin (e. g., Thymoglobulin®) is an antibody preparation that is commonly
used to treat and prevent organ transplant rejection. The START trial aims to determine
whether antithymocyte globulin (ATG) treatment can halt the progression of newly diagnosed
type 1 diabetes when given within 12 weeks of disease diagnosis.
Antithymocyte Globulin and Cyclosporine to Treat Myelodysplasia [Completed]
This study will determine the safety and effectiveness of a combination of the
immune-suppressing drugs antithymocyte globulin (ATG) and cyclosporine for treating
myelodysplasia, a disorder of low blood cell counts. It will: evaluate whether this drug
combination can increase blood counts in patients and reduce their need for transfusions;
compare survival of patients who respond to ATG and cyclosporine treatment with those who do
not respond; and determine the side effects of the treatment.
Myelodysplasia is thought to result from an immune system abnormality in which cells called
lymphocytes attack the marrow's blood-forming cells. The resulting deficiencies of
platelets and red and white blood cells cause anemia, susceptibility to infections, and easy
bruising and bleeding. Various therapies, such as blood transfusions for anemia and
bleeding, antibiotics for infection, chemotherapy and bone marrow transplantation are used
to treat myelodysplasia, but all have disadvantages and some carry serious risks.
Patients 18 years of age and older with myelodysplasia may be eligible for this study.
Candidates will be screened with a physical examination and medical history, blood tests,
chest X-ray, electrocardiogram and bone marrow biopsy (removal of a marrow sample from the
hipbone for microscopic examination).
Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant [Completed]
This clinical trial is studying how well giving cyclophosphamide together with
anti-thymocyte globulin followed by methotrexate and cyclosporine works in preventing
chronic graft-vs-host disease (GVHD) in patients with severe aplastic anemia undergoing
donor bone marrow transplant. Giving low doses of chemotherapy, such as cyclophosphamide,
before a donor bone marrow transplant helps stop the growth of abnormal 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 system and help destroy any remaining abnormal cells.
Sometimes the transplanted cells from a donor can also make an immune response against the
body's normal cells. Giving anti-thymocyte globulin before and methotrexate and cyclosporine
after transplant may stop this from happening
Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia [Recruiting]
RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor
stem cell transplant helps to remove the patient's cells to allow for the transplant cells
to take and grow. It also helps stop the patient's immune system from rejecting the donor's
stem cells. When the healthy stem cells from a donor are infused into the patient, they may
help the patient's bone marrow make stem cells, red blood cells, white blood cells, and
platelets. Sometimes the transplanted cells can make an immune response against the body's
normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells
before transplant and giving cyclosporine before and after transplant may stop this from
PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide,
fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see
how well it works in treating patients with Fanconi anemia.
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