ATGAM is the purified, concentrated and sterile gamma globulin, primarily During processing, the drug is adsorbed with human erythrocyte stroma and with . Globulin [Equine] Sterile Solution. Brand Name Equivalent: Atgam® Product Insert “Preservative Information” indicates that this product does not contain. Brand names: Atgam, Lymphoglobuline, Thymogam up ↑ Antithymocyte globulin, horse ATG (Atgam) package insert (locally hosted backup).
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Antithymocyte globulins can cause anaphylaxis when injected intravenously.
Although ATGAM is processed to reduce the level of antibodies that will react to non-T cells, physicians should be prepared for the potential risk of anaphylaxis packxge monitor patients for signs and symptoms during infusion. ATGAM is indicated for the management of allograft rejection in renal transplant patients; when administered with conventional therapy atga, the time of rejection ATGAM increases the frequency of resolution of the acute rejection episode [see Clinical Studies ATGAM is indicated for the treatment of moderate to severe aplastic anemia in patients unsuitable for bone marrow transplantation [see Clinical Studies Argam 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 used with concomitant immunosuppressants. Additional alternate-day therapy up to a total of 21 doses may be given.
Because thrombocytopenia can be associated with the administration of ATGAM, patients receiving it for the treatment of aplastic anemia may need ;ackage platelet transfusions to maintain platelets at clinically acceptable levels. Select the dose for an elderly patient with caution, starting at the low end of the dosage range [see Use in Specific Populations 8.
Clinical signs associated with anaphylaxis, other infusion associated reactions, and serum sickness have been reported. A systemic reaction such insret a generalized rash, tachycardia, dyspnea, hypotension, or anaphylaxis precludes any additional administration of ATGAM. To identify those at greatest risk of systemic anaphylaxis, skin testing potential recipients is strongly recommended before commencing treatment. A conservative, conventional approach would first employ epicutaneous prick testing with undiluted ATGAM.
If the subject does not show a wheal ten minutes after pricking, proceed to intradermal testing with 0. Read the result at 10 minutes: The predictive value of this test has not been proven clinically.
Allergic reactions such as anaphylaxis have occurred in patients whose skin test is negative. Also, skin testing done as described above will not predict for later development of serum sickness. In the presence of a locally positive skin test to ATGAM, serious consideration to alternative forms of therapy should be given.
Antithymocyte globulin, horse ATG (Atgam) | – A Hematology Oncology Wiki
The risk to benefit ratio must be 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 a physician familiar with the treatment of potentially life threatening allergic reactions is in attendance. Because ATGAM is made from equine and human blood components, it may carry a risk of transmitting infectious agents, e.
All infections suspected by oackage physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Pfizer, Inc. Monitor patients for concurrent infection. Some studies have suggested an increase in the incidence of cytomegalovirus infection in patients receiving ATGAM. Do not administer live vaccines to patients about to receive, receiving, or after treatment with ATGAM.
Concomitant administration of ATGAM with live virus vaccines carries a potential of uncontrolled viral replication in the immunosuppressed patient. There is insufficient information to fully define the extent of the risk, or the period of time during which the risk exists. The most clinically significant adverse reactions are anaphylaxis, infection, thrombocytopenia, leukopenia, arthralgia, edema, bradycardia, and abnormal renal and liver function tests. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of ATGAM has been evaluated in patients with renal transplant and patients with aplastic anemia. The renal transplantation and atam anemia patients received a similar dosing regimen, and these data were pooled to obtain the frequencies listed in Tables 1 and 2 below. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hepatitis viral, Localized infection, Systemic infection.
Blood and lymphatic system disorders: Respiratory, thoracic and mediastinal disorders: Apnea, Cough, Epistaxis, Oropharyngeal pain. Abdominal pain, Gastrointestinal hemorrhage, Gastrointestinal perforation, Oral pain.
Musculoskeletal and connective tissue disorders: Flank pain, Muscle rigidity, Myalgia, Pain in extremity. Renal and urinary disorders: Kidney enlargement, Kidney rupture, Renal failure acute. General disorders and imsert site conditions: Infusion site erythema, Infusion site swelling, Pain. Previously masked reactions to ATGAM may appear when the dose of atga, and other immunosuppressants is being reduced. There are no adequate and well-controlled studies in pregnant women.
It is also not known whether ATGAM can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. ATGAM should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing neonates and infants from ATGAM, a decision should be made whether to discontinue nursing or to discontinue the drug taking into account the importance of the drug to the mother.
Experience with children has been limited. ATGAM has been administered safely to a small number of pediatric renal allograft recipients and pediatric aplastic anemia patients at dosage levels comparable to those in adults. The dose for an elderly patient should be selected with caution, starting at the low end of the dosage range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in this age group.
The maximum tolerated dose of ATGAM Sterile Solution would be expected to vary from patient to patient due to the biological nature of the product. In this patient, the administration of ATGAM was not associated with any signs of acute intoxication or late sequelae. A maximum therapeutic dose has not been established therefore the definition of overdose for ATGAM has not been clearly defined.
Some renal transplant patients have received up to 50 doses in 4 months, and others have received day courses of 21 doses followed by as many as 3 more courses for the treatment of acute rejection. The incidence of toxicologic manifestations did not increase with any of these regimens; however, close monitoring of the patient is recommended. 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 [see Dosage and Administration 2.
Precise methods of determining the potency of ATGAM have not been established, thus activity may potentially vary from lot to lot. 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 meet the acceptance criteria for pyrogens and test negative for antihuman serum protein antibody and antiglomerular basement membrane antibody are released. ATGAM is composed of antibodies that bind a wide variety of proteins on the surface of lymphocytes.
Published data indicate that the primary mechanism is the depletion of circulating lymphocytes, with greatest effect on T lymphocytes.
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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 range for half-life was 1. ATGAM treatment was not associated with male or female hormonal or copulation behavior changes. While the etiology of this toxicity is uncertain, it may be attributed to hemolytic anemia due to cross-reactivity of ATGAM to a monkey red blood agtam. In embryo-fetal toxicity studies, ATGAM was administered to rats and cynomolgus monkeys for 11 and 16 days, packags during organogenesis.
The maternal and fetal deaths were attributed to maternal anemia packagr to red blood cell antigen that humans do not share. Therefore, this toxicity is not considered relevant to human fetal development. The effectiveness of ATGAM for treatment of acute allograft rejection was evaluated in three different treatment applications: A randomized controlled trial of the use of ATGAM as a substitute for standard therapy for treatment of the first acute rejection episode insrrt conducted at one transplant center in recipients of living related renal allografts.
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In this study, ATGAM was at least effective as standard therapy for treatment of acute allograft rejection. The effect of ATGAM when administered in conjunction with standard therapy at the time of diagnosis of the first rejection episode was studied under two different protocols with cadaveric and living related renal transplant patients. The results from these studies demonstrate the efficacy associated with the addition of ATGAM to standard therapy for treatment of the first rejection episode in renal allograft recipients.
There was no difference in the patient survival rate between the two treatment groups. Study 2 was a randomized controlled trial conducted at five different transplant centers.
Due to the small sample size, the difference between the ATGAM group and the control group in functional graft survival rate did not achieve statistical significance. Patient survival rates were similar in the two treatment groups. Results from randomized controlled trials in patients with first acute renal allograft rejection episodes refractory to conventional steroid therapy have demonstrated that ATGAM, when administered in conjunction with standard therapy, yields efficacy results superior to those of standard therapy alone.
Patients were enrolled at the time of first rejection episode and randomized among three treatment groups: The effectiveness of ATGAM for reversal of acute renal allograft rejection was also demonstrated in other controlled studies performed in various medical centers.
The use of ATGAM for the treatment of moderate to severe aplastic anemia in patients who are unsuitable for bone marrow transplantation is based on data from three controlled studies. The effectiveness of the ATGAM therapy in the studies described below was evaluated by the hematological response and survival rates Table 3. A total of 41 patients with moderate or severe aplastic anemia ages 6 to 69 years, who were not candidates for bone marrow transplantation were enrolled in a randomized controlled study.
The objective of this study was to determine the efficacy of ATGAM as a single agent, in restoring hematopoiesis in patients with moderate to severe aplastic anemia.
At 3 months post-study enrollment, 11 patients in the supportive care group who showed no improvement became eligible and were crossed over to receive ATGAM therapy.
Efficacy was evaluated as sustained improvement in peripheral blood counts within 3 months of entry into the study.
Six of the 11 crossover patients from the control group showed improvement after 3 months of therapy.
Serum sickness occurred in all patients within 6 to paackage days of ATGAM initiation and was well-controlled with standard therapy. Three patients experienced transient hypotension. A randomized double-blind, placebo prospective, controlled study was conducted to compare the safety and efficacy of ATGAM and androgen oxymetholone; OXY immunosuppressive therapy with the combination of ATGAM, androgen OXY and an infusion of HLA mismatched bone marrow in patients with severe aplastic xtgam who were not candidates for bone marrow transplantation.
Allocation to treatment group was based on the availability of mismatched bone marrow donors. A total of 42 patients, ages 1 to 69 years were treated. The most commonly reported adverse events were rash, fever, arthralgias, chills, headache, myalgia and pruritus.