Drug: Atgam

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 (lymphocyte immune globulin) 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 (lymphocyte immune globulin) 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 (lymphocyte immune globulin) contains 50 mg of horse gamma globulin stabilized in 0.3 molar glycine to a pH of approximately 6.8. Last reviewed on RxList: 10/22/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Renal Transplantation The primary clinical experience with ATGAM (lymphocyte immune globulin) Sterile Solution has been in renal allograft patients who were also receiving concurrent standard immunosuppressive therapy (azathioprine, corticosteroids). In controlled trials, investigators frequently reported the following adverse reactions: fever in 1 patient in 3; chills in 1 patient in 7; leukopenia in 1 patient in 7; thrombocytopenia in 1 patient in 9; and dermatologic reactions, such as rash, pruritus, urticaria, wheal, and flare, in 1 patient in 8. The following reactions were reported in more than 1% but less than 5% of the patients: arthralgia; chest or back pain, or both; clotted A/V fistula; diarrhea; dyspnea; headache; hypotension; nausea or vomiting, or both; night sweats; pain at the infusion site; peripheral thrombophlebitis; and stomatitis. Reactions reported in less than 1% of the patients in the controlled trials were anaphylaxis, dizziness, weakness or faintness, edema, herpes simplex reactivation, hiccoughs or epigastric pain, hyperglycemia, hypertension, iliac vein obstruction, laryngospasm, localized infection, lymphadenopathy, malaise, myalgia, paresthesia, possible serum sickness, pulmonary edema, renal artery thrombosis, seizures, systemic infection, tachycardia, toxic epidermal necrosis, and wound dehiscence. Aplastic Anemia In premarketing clinical trials with ATGAM (lymphocyte immune globulin) in the treatment of aplastic anemia, patients were also being concurrently managed with support therapy (transfusions, steroids, antibiotics, antihistamines). In these trials most patients experienced fever and skin reactions. Other frequently reported adverse reactions were chills, 1 patient in 2; arthralgia, 1 patient in 2; headache, 1 patient in 6; myalgia, 1 patient in 10; nausea, 1 patient in 15; chest pain, 1 patient in 15 and phlebitis, 1 patient in 20. The following reactions were reported by at least one patient and less than 5% of the total patients: diaphoresis, joint stiffness, periorbital edema, aches, edema, muscle ache, vomiting, agitation/lethargy, listlessness, light-headedness, seizures, diarrhea, bradycardia, myocarditis, cardiac irregularity, hepatosplenomegaly, possible encephalitis or post viral encephalopathy, hypotension, congestive heart failure, hypertension, burning soles/palms, foot sole pain, lymphadenopathy, post-cervical lymphadenopathy, tender lymph nodes, bilateral pleural effusion, respiratory distress, anaphylactic reaction, and proteinuria. In other support studies in patients with aplastic anemia and other hematologic abnormalities who have received ATGAM (lymphocyte immune globulin) , abnormal tests of liver function (SGOT, SGPT, alkaline phosphatase) and renal function (serum creatinine) have been observed. In some trials, clinical and laboratory findings of serum sickness were seen in a majority of patients. Postmarketing Experience During approximately 5 years of post approval marketing experience, the frequency of adverse reactions in voluntarily reported cases is as follows: fever 51%; chills 16%; thrombocytopenia 30%; leukopenia 14%; rashes 27%; systemic infection 13%. Events reported in 5% to 10% of reported cases include abnormal renal function tests; serum sickness-like symptoms; dyspnea/apnea; arthralgia; chest, back, or flank pain; diarrhea and nausea and/or vomiting. Events reported with a frequency of less than 5% include: hypertension, Herpes Simplex infection, pain, swelling or redness at infusion site, eosinophilia, headache, myalgias, or leg pains, hypotension, anaphylaxis, tachycardia, edema, localized infection, malaise, seizures, GI bleeding or perforation, deep vein thrombosis, sore mouth/throat, hyperglycemia, acute renal failure, abnormal liver function tests, confusion or disorientation, cough, neutropenia or granulocytopenia, anemia, thrombophlebitis, dizziness, epigastric or stomach pain, lymphadenopathy, pulmonary edema or congestive heart failure, abdominal pain, nosebleed, vasculitis, aplasia or pancytopenia, abnormal involuntary movement or tremor, rigidity, sweating, laryngospasm/edema, hemolysis or hemolytic anemia, viral hepatitis, faintness, enlarged or ruptured kidney, paresthesias, and renal artery thrombosis. The recommended management for some of the adverse reactions that could occur with treatment with ATGAM (lymphocyte immune globulin) follows:
  1. Anaphylaxis is uncommon but serious and may occur at any time during therapy with ATGAM (lymphocyte immune globulin) . Stop infusion of ATGAM (lymphocyte immune globulin) immediately; administer 0.3 mL aqueous epinephrine (1:1,000 solution) intramuscularly. Administer steroids; assist respiration; and provide other resuscitative measures. DO NOT resume therapy with ATGAM (lymphocyte immune globulin) .
  2. Hemolysis can usually be detected only in the laboratory. Clinically significant hemolysis has been reported rarely. Appropriate treatment of hemolysis may include transfusion of erythrocytes; if necessary, administer intravenous mannitol, furosemide, sodium bicarbonate, and fluids. Severe and unremitting hemolysis may require discontinuation of therapy with ATGAM (lymphocyte immune globulin) .
  3. Thrombocytopenia is usually transient in renal transplant patients; platelet counts generally return to adequate levels without discontinuing therapy with ATGAM (lymphocyte immune globulin) . Platelet transfusions may be necessary in patients with aplastic anemia. (See PRECAUTIONS, WARNINGS, and DOSAGE AND ADMINISTRATION.)
  4. Respiratory distress may indicate an anaphylactoid reaction. Discontinue infusion of ATGAM (lymphocyte immune globulin) . If distress persists, administer an antihistamine, epinephrine, corticosteroids, or some combination of the three.
  5. Pain in chest, flank, or back may indicate anaphylaxis or hemolysis. Treatment is that indicated above for those conditions.
  6. Hypotension may indicate anaphylaxis. Stop infusion of ATGAM (lymphocyte immune globulin) and stabilize blood pressure with pressors if necessary.
  7. Chills and fever occur frequently in patients receiving ATGAM (lymphocyte immune globulin) . ATGAM (lymphocyte immune globulin) may release endogenous leukocyte pyrogens. Prophylactic and/or therapeutic administration of antihistamines, antipyretics, or corticosteroids generally controls this reaction.
  8. Chemical phlebitis can be caused by infusion of ATGAM (lymphocyte immune globulin) through peripheral veins. This can often be avoided by administering the infusion solution into a high-flow vein. A subcutaneous arterialized vein produced by a Brescia fistula is also a useful administration site.
  9. Itching and erythema probably result from the effect of ATGAM (lymphocyte immune globulin) on blood elements. Antihistamines generally control the symptoms.
  10. Serum sickness-like symptoms in aplastic anemia patients have been treated with oral or IV corticosteroids. Resolution of symptoms has generally been prompt and long-term sequelae have not been observed. Prophylactic administration of corticosteroids may decrease the frequency of this reaction.
Read the Atgam (lymphocyte immune globulin) Side Effects Center for a complete guide to possible side effectsLearn More »

Source: http://www.rxlist.com

Renal Allograft Recipients Adult renal allograft patients have received ATGAM (lymphocyte immune globulin) Sterile Solution at the dosage of 10 to 30 mg/kg of body weight daily. The few children studied received 5 to 25 mg/kg daily. ATGAM (lymphocyte immune globulin) has been used to delay the onset of the first rejection episode(2–5) and at the time of the first rejection episode.(6–10) Most patients who received ATGAM (lymphocyte immune globulin) for the treatment of acute rejection had not received it starting at the time of transplantation. Usually, ATGAM (lymphocyte immune globulin) is used concomitantly with azathioprine and corticosteroids, which are commonly used to suppress the immune response. Exercise caution during repeat courses of ATGAM (lymphocyte immune globulin) ; carefully observe patients for signs of allergic reactions. Delaying the Onset of Allograft Rejection: Give a fixed dose of 15 mg/kg daily for 14 days, then every other day for 14 days for a total of 21 doses in 28 days. Administer the first dose within 24 hours before or after the transplant. Treatment of Rejection: The first dose of ATGAM (lymphocyte immune globulin) can be delayed until the diagnosis of the first rejection episode. The recommended dose is 10 to 15 mg/kg daily for 14 days. Additional alternate-day therapy up to a total of 21 doses can be given. Aplastic Anemia The recommended dosage regimen is 10 to 20 mg/kg daily for 8 to 14 days. Additional alternate-day therapy up to a total of 21 doses can be administered.(11–13) Because thrombocytopenia can be associated with the administration of ATGAM (lymphocyte immune globulin) , patients receiving it for the treatment of aplastic anemia may need prophylactic platelet transfusions to maintain platelets at clinically acceptable levels. Preparation of Solution Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. However, because ATGAM (lymphocyte immune globulin) is a gamma globulin product, it can be transparent to slightly opalescent, colorless to faintly pink or brown, and may develop a slight granular or flaky deposit during storage. ATGAM (lymphocyte immune globulin) (diluted or undiluted) should not be shaken because excessive foaming and/or denaturation of the protein may occur. Dilute ATGAM (lymphocyte immune globulin) for intravenous infusion in an inverted bottle of sterile vehicle so the undiluted ATGAM (lymphocyte immune globulin) does not contact the air inside. Add the total daily dose of ATGAM (lymphocyte immune globulin) to the sterile vehicle (see Compatibility and Stability). The concentration should not exceed 4 mg of ATGAM (lymphocyte immune globulin) per mL. The diluted solution should be gently rotated or swirled to effect thorough mixing. Administration The diluted ATGAM (lymphocyte immune globulin) should be allowed to reach room temperature before infusion. ATGAM (lymphocyte immune globulin) is appropriately administered into a vascular shunt, arterial venous fistula, or a high-flow central vein through an in-line filter with a pore size of 0.2 to 1.0 micron. The in-line filter should be used with all infusions of ATGAM (lymphocyte immune globulin) to prevent the administration of any insoluble material that may develop in the product during storage. The use of high-flow veins will minimize the occurrence of phlebitis and thrombosis. Do not infuse a dose of ATGAM (lymphocyte immune globulin) in less than 4 hours. Always keep appropriate resuscitation equipment at the patient's bedside while ATGAM (lymphocyte immune globulin) is being administered. Observe the patient continuously for possible allergic reactions throughout the infusions (See ADVERSE REACTIONS). Compatibility and Stability ATGAM (lymphocyte immune globulin) , once diluted, has been shown to be physically and chemically stable for up to 24 hours at concentrations of up to 4 mg per mL in the following diluents: 0.9% sodium chloride injection, 5% dextrose and 0.225% sodium chloride injection, and 5% dextrose and 0.45% sodium chloride injection. Adding ATGAM (lymphocyte immune globulin) to dextrose injection is not recommended, as low salt concentrations can cause precipitation. Highly acidic infusion solutions can also contribute to physical instability over time. It is recommended that diluted ATGAM (lymphocyte immune globulin) be stored in a refrigerator if it is prepared prior to the time of infusion. Even if it is stored in a refrigerator, the total time in dilution should not exceed 24 hours (including infusion time).

Source: http://www.rxlist.com

When the dose of corticosteroids and other immunosuppressants is being reduced, some previously masked reactions to ATGAM (lymphocyte immune globulin) may appear. Under these circumstances, observe patients especially carefully during therapy with ATGAM (lymphocyte immune globulin) . Last reviewed on RxList: 10/22/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Renal Transplantation ATGAM (lymphocyte immune globulin) 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. Aplastic Anemia ATGAM (lymphocyte immune globulin) 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 (lymphocyte immune globulin) may induce partial or complete hematologic remission. In a controlled trial, patients receiving ATGAM (lymphocyte immune globulin) 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 (lymphocyte immune globulin) and supportive care, 2) ATGAM (lymphocyte immune globulin) administered following 3 months of supportive care alone, 3) ATGAM (lymphocyte immune globulin) , mismatched marrow infusion, androgens, and supportive care, or 4) ATGAM (lymphocyte immune globulin) , 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 (lymphocyte immune globulin) 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. Skin Testing Before the first infusion of ATGAM (lymphocyte immune globulin) , 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 (lymphocyte immune globulin) in sodium chloride injection, USP and a contralateral sodium chloride injection control. Use only freshly diluted ATGAM (lymphocyte immune globulin) 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 (lymphocyte immune globulin) , serious consideration to alternative forms of therapy should be given. The risk to benefit ratio must be carefully weighed. If therapy with ATGAM (lymphocyte immune globulin) 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.

Source: http://www.rxlist.com

Do not administer ATGAM (lymphocyte immune globulin) Sterile Solution to a patient who has had a severe systemic reaction during prior administration of ATGAM (lymphocyte immune globulin) or any other equine gamma globulin preparation. Last reviewed on RxList: 10/22/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

Because of its mode of action and because it is a biologic substance, the maximal tolerated dose of ATGAM (lymphocyte immune globulin) Sterile Solution would be expected to vary from patient to patient. To date, the largest single daily dose administered to a patient, a renal transplant recipient, was 7,000 mg administered at a concentration of approximately 10 mg/mL Sodium Chloride Injection, USP, approximately seven times the recommended total dose and infusion concentration. In this patient, administration of ATGAM (lymphocyte immune globulin) was not associated with any signs of acute intoxication. The greatest number of doses (10 to 20 mg/kg/dose) that can be administered to a single patient has not yet been determined. Some renal transplant patients have received up to 50 doses in 4 months, and others have received 28-day courses of 21 doses followed by as many as three more courses for the treatment of acute rejection. The incidence of toxicologic manifestations did not increase with any of these regimens.

Source: http://www.rxlist.com

ATGAM (lymphocyte immune globulin) Sterile Solution, containing 50 mg of horse gamma globulin/mL, is supplied as follows: 5 – 5 mL ampoules.....................NDC 0009-7224-02 Storage Store in a refrigerator at 2° to 8°C (36° to 46°F). DO NOT FREEZE. REFERENCES 2. Cosimi AB, Wortis HH, Delmonico FL, Russell PS: Randomized clinical trial of antithymocyte globulin in cadaver renal allograft recipients: importance of T cell monitoring. Surgery. 1976; 80:155–163. 3. Wechter WJ, Brodie JA, Morrell RM, Rafi M, Schultz JR: Antithymocyte globulin (ATGAM (lymphocyte immune globulin) ) in renal allograft recipients. Transplantation. 1979; 28(4):294–302. 4. Kountz SL, Butt KHM, Rao TKS, Zielinski CM, Rafi M, Schultz JR: Antithymocyte globulin (ATG) dosage and graft survival in renal transplantation. Transplant. Proc. 1977; 9:1023–1025. 5. Butt KMH, Zielinski CM, Parsa I, Elberg AJ, Wechter WJ, Kountz SL: Trends in immunosuppression for kidney transplantation. Kidney Int. 1978; 13(Suppl 8): S95–S98. 6. Filo RS, Smith EJ, Leapman SB: Reversal of acute renal allograft rejection with adjunctive ATG therapy. Transplant. Proc. 1981; 13(1): 482–490. 7. Nowygrod R, Appel G, Hardy M: Use of ATG for reversal of acute allograft rejection. Transplant. Proc. 1981; 13(1): 469–472. 8. Hardy MA, Nowygrod R, Elberg A, Appel G: Use of ATG in treatment of steroid-resistant rejection. Transplantation. 1980; 29:162–164. 9. Shield CH, Cosimi AB, Tolkoff-Rubin N, Rubin R, Herrin J, Russell PS: Use of antithymocyte globulin for reversal of acute allograft rejection. Transplantation. 1979; 28(6): 461–464. 10. Cosimi AB: The clinical value of antilymphocyte antibodies. Transplant. Proc. 1981; 13(1): 462–468. 11. Cosimi AB, Peters C, Harmon D, Ellman L: Treatment of severe aplastic anemia with a prolonged course of antithymocyte globulin. Transplant. Proc. 1982; 14:761–764. 12. Champlin R, Ho W, Gale R: Antithymocyte globulin treatment in patients with aplastic anemia. N Engl J Med. 1983; 308(3):113–118. 13. Doney K, Dahlberg S, Monroe D et al: Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: The effect of HLA-haploidentical marrow infusion. Blood. 1984; 63(2):342–348. Distributed by Pharmacia and Upjohn Company, Division of Pfizer Inc, NY, NY 10017. Revised November 2005. FDA Rev date: n/a Last reviewed on RxList: 10/22/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

General Because ATGAM (lymphocyte immune globulin) Sterile Solution is an immunosuppressive agent ordinarily given with corticosteroids and antimetabolites, watch patients carefully for signs of leukopenia, thrombocytopenia, or concurrent infection. Several studies have suggested an increase in the incidence of cytomegalovirus infection in patients receiving ATGAM (lymphocyte immune globulin) (1). In one study it has been found that it may be possible to reduce this risk by decreasing the dosage of other immunosuppressive agents administered concomitantly with ATGAM (lymphocyte immune globulin) . If infection occurs, institute appropriate adjunctive therapy promptly. On the basis of the clinical circumstances, a physician should decide whether or not therapy with ATGAM (lymphocyte immune globulin) will continue. The safety and effectiveness of ATGAM (lymphocyte immune globulin) have been demonstrated only in renal transplant patients who received concomitant immunosuppressive therapy and in patients with aplastic anemia. Dilution of ATGAM (lymphocyte immune globulin) in dextrose injection, USP, is not recommended, as low salt concentrations may result in precipitation. The use of highly acidic infusion solutions is also not recommended because of possible physical instability over time. Pregnancy Pregnancy category C— ATGAM (lymphocyte immune globulin) has not been evaluated in either pregnant or lactating women. Animal reproduction studies have not been conducted with ATGAM (lymphocyte immune globulin) . It is also not known whether ATGAM (lymphocyte immune globulin) can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Administration of ATGAM (lymphocyte immune globulin) to pregnant women is not recommended and should be considered only under exceptional circumstances. Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ATGAM (lymphocyte immune globulin) Sterile Solution, caution should be exercised when ATGAM (lymphocyte immune globulin) is administered to a nursing woman. Pediatric Use Experience with children has been limited. ATGAM (lymphocyte immune globulin) 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. REFERENCES 1. Rubin RH, Cosimi AB, Hirsch MS, Herrin JT: Effects of antithymocyte globulin on cytomegalovirus infection in renal transplant recipients. Transplantation. 1981; 31(2):143–145. Last reviewed on RxList: 10/22/2008
This monograph has been modified to include the generic and brand name in many instances.

Source: http://www.rxlist.com

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