Equine thymocyte immune globulin

ATGAM is an immunoglobulin G indicated for: • Renal allograft rejection. • Aplastic anemia (moderate to severe) in patients unsuitable for bone marrow transplantation. • Limitations of Use: 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.

ATGAM is composed of antibodies that bind a wide variety of proteins on the surface of lymphocytes. In addition, ATGAM binds to granulocytes, platelets, bone marrow cells, and other cell types. The mechanism of ATGAM-induced immunosuppression has not been determined. Published data indicate that the primary mechanism is the depletion of circulating lymphocytes, with greatest effect on T lymphocytes. Lymphocyte depletion may be caused by complement dependent lysis and/or activation-induced apoptosis. In addition, immunosuppression may be mediated by the binding of antibodies to lymphocytes which results in partial activation and induction of T lymphocyte anergy. The mechanism of ATGAM therapy for aplastic anemia is attributed to its immunosuppressive actions.

For intravenous use only. Administer ATGAM intravenously and use with concomitant immunosuppressants. Indication Dosage Renal allograft rejection 10 to 15 mg/kg daily intravenously for 14 days, additional alternate-day therapy up to a total of 21 doses may be given. Aplastic anemia 10 to 20 mg/kg daily intravenously for 8 to 14 days, additional alternate-day therapy up to a total of 21 doses may be given.

Do not administer ATGAM to a patient who has had an anaphylactic reaction during prior administration of ATGAM or any other equine gamma globulin preparation. Anaphylactic reaction during prior administration of ATGAM or any other equine gamma globulin preparation.

Boxed warning (anaphylaxis): Anaphylaxis has been reported with the use of ATGAM. ATGAM can cause potentially life‑threatening anaphylaxis when injected intravenously. Monitor patients for signs and symptoms of anaphylaxis during infusion and for at least 24 hours after infusion. WARNING: ANAPHYLAXIS. • Anaphylaxis, which can be life-threatening, has been reported. To identify those at greatest risk, skin testing before treatment is strongly recommended. Discontinue ATGAM if anaphylaxis occurs. • Monitor patients for signs and symptoms of cytokine release syndrome. • Monitor patients for signs and symptoms of infusion-associated reactions. • Monitor patients for signs and symptoms of serum sickness. • Monitor and report any infection suspected to have been transmitted.

The most clinically significant adverse reactions are anaphylaxis, infection, thrombocytopenia, leukopenia, arthralgia, edema, bradycardia, and abnormal renal and liver function tests. The most common (incidence >10%) adverse reactions are pyrexia, chills, rash, thrombocytopenia, leukopenia, and arthralgia.

A potential pharmacodynamic interaction concerns the concomitant administration of ATGAM with corticosteroids and other immunosuppressants, which are associated with an increased susceptibility to bacterial, viral and fungal infections, as they inhibit the immune system. The severity of the infections such as septicemia may be masked and their clinical presentations may be atypical. Monitor patients receiving ATGAM and immunosuppressive agents such as corticosteroids when the dose of corticosteroids and other immunosuppressants is being reduced, since this adjustment of dose may result in reduced immunosuppression and lead to development of previously masked reactions to ATGAM. Previously masked reactions to ATGAM may appear following reduced doses of immunosuppressants.

Store in a refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE. Store in the original carton to protect from light. For storage conditions of diluted solution, see Dosage and Administration.