self belief [1%:<0.01). Atgam-treated patients achieved a rejection resolution rate of 80% (36/45) compared with 54% (25/46) in the control group. There was a statistically significant improvement in functional graft survival favoring the Atgam group (p> <0.01), and a statistically significant steroid sparing effect during the first rejection episode among patients in the Atgam group. 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. In this study, the addition of Atgam to standard rejection therapy (bolus doses of Solu-Medrol ) for treatment of acute rejection in recipients of living related renal transplants resulted in an increased frequency of rejection resolution and improvement in functional graft survival. 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. Marginal statistical significance was demonstrated in rejection reversal rate and intravenous steroid sparing among Atgam patients (p=0.10 and p=0.07). 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. One study investigated two different regimens of Atgam; immediate and delayed therapy. Patients were enrolled at the time of first rejection episode and randomized among three treatment groups: control (no Atgam), immediate Atgam, and delayed Atgam. Patients in all three treatment groups received standard rejection therapy in the form of bolus doses of Solu-Medrol 15 mg/kg/day IV, while patients in the two Atgam groups received Atgam therapy in addition to Solu-Medrol . In the immediate Atgam group, Atgam administration started at the time of diagnosis of rejection (concurrent with standard therapy). In the delayed Atgam group, Atgam administration started on rejection day 4 (following the first three doses of Solu-Medrol ). Patients in both of the treated groups received from 10 to 21 doses of Atgam. Results favored the two Atgam groups (and particularly the immediate Atgam group) in both outcome of first rejection and functional graft survival. The improvement in functional graft survival was statistically significant (p=0.05). There was also a statistically significant difference in patient survival rate favoring the Atgam-treated groups (p=0.02). The effectiveness of Atgam for reversal of acute renal allograft rejection was also demonstrated in other controlled studies performed in various medical centers. In these studies, Atgam was administered at time of diagnosis of the first rejection episode at a range of 10 to 15 mg/kg per day for 14 to 15 days, followed by alternate day therapy for a total of 21 doses in 28 days. Aplastic Anemia 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). 10 to 20 mg/kg daily for 8 to 14 days Study 1 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. Twenty-one (n=21) patients in the Atgam treatment group received 20 mg/kg/day for 8 days, while control patients (n=20) were observed for 3 months. All patients were given oral prednisone (40 mg/m 2 /day) starting on day 8 then tapered over 1 to 2 weeks. 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. A statistically significant (p> <0.01) difference was observed between the two treatment groups in hematological improvement based on the investigator's evaluation; 11 of 21 (52%) patients in the Atgam group responded, compared with no patients (0 of 20) in the control group. Six of the 11 crossover patients from the control group showed improvement after 3 months of therapy. Overall, of 32 patients in both the Atgam group and the control group who crossed over to receive Atgam, 17 patients (53%) had a hematological improvement. Estimated 1-year survival rate was 62% for all 32 patients treated with Atgam. The 2-year survival rate was 100% among the Atgam responders [17 of the 32 patients (53%) compared to 14% for the nonresponders]. Fever, chills, and erythematous or urticarial rash were seen in all Atgam treated patients. Platelet counts decreased during Atgam infusion and daily platelet transfusions were necessary. Serum sickness occurred in all patients within 6 to 18 days of Atgam initiation and was well-controlled with standard therapy. Three patients experienced transient hypotension. Study 2 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 anemia 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. Eighteen patients received Atgam at a dose of 16 mg/kg/day for 10 doses with concomitant androgens (OXY) at a dose of 3 mg/kg/day for a minimum of 3 months, and 24 patients received an infusion of bone marrow from an HLA-mismatched donor 48 hours after the completion of Atgam treatment. At 3 months after entry into the study, 51% of patients with disease of idiopathic etiology (21 of the 41 evaluable patients from both groups) showed improvement based on investigator's evaluation of transfusion requirements and peripheral blood counts. Hematological response rate (complete/moderate based on sponsor's evaluation) at 3 months for the Atgam and androgen group was 44% compared with 43% for the group receiving Atgam, androgen and bone marrow infusion. The group of patients who received mismatched bone marrow infusion had better estimated 1-year survival rate, although the difference between these estimates was not statistically significant (p=0.14); 83% at 12 months for the group receiving bone marrow infusion versus 59% for the Atgam and androgen alone group. Estimated 1-year survival rate for both groups combined was 73%. The most commonly reported adverse events were rash, fever, arthralgias, chills, headache, myalgia and pruritus. A pooled analysis of data from Studies 1 and 2 revealed an overall estimated 1-year survival rate of 69% in Atgam-treated patients. Study 3 A total of 53 patients (3 to 76 years of age) participated in this randomized, placebo-controlled, double-blind study to determine if androgens add to the efficacy of Atgam in providing favorable hematologic response rates in patients with moderate to severe aplastic anemia. All patients were treated with Atgam 20 mg/kg/day IV for 8 days, and were randomized to receive the oral androgen (oxymetholone 4 mg/kg/day or fluoxymesterone 25 mg/m 2 /day) (n=26), or a matched placebo (n=27). Both groups received oral prednisone (40 mg/m 2 /day) beginning on Day 8 which was tapered and discontinued in 1 to 2 weeks. A group of historical controls from previous studies (n=68; 1 to 72 years of age) who received Atgam (20 mg/kg/day IV for 8 days) without androgens were included for treatment results comparison. The proportions of subjects who presented complete or partial response at 6 months were 42% in the Atgam plus androgen group, 44% in the Atgam plus placebo group, and 51% in the historical controls. The difference in response rates was not significant (p> 0.9). Survival at 2 years was also comparable in the two groups for patients with severe aplastic anemia; 55% in the Atgam plus androgen group compared with 50% in the Atgam plus placebo group (p=0.65), and 56% for the historical controls. In patients with moderate aplastic anemia, two-year survival for the Atgam plus androgen group was 63% compared with 100% in those receiving Atgam plus placebo and 72% in the historical controls who received Atgam alone. Adverse reactions in both groups were comparable and included rash, chills, gastrointestinal disturbances, and joint pain during Atgam infusion, as well as symptoms of serum sickness in all patients. Five patients had asymptomatic sinus bradycardia; six patients required antihypertensive therapy. Alanine transaminase or alkaline phosphatase levels increased to >2 times the upper limits of normal in 7 patients receiving Atgam plus androgen, and in nine patients receiving Atgam plus placebo. Table 3. Key Studies with Atgam for the Treatment of Aplastic Anemia Study Atgam + comparator or other therapy No. of Subjects Response rate % (endpoint) * P Value Survival rate % (time point) P Value (or 95% CI) * Hematologic response was defined differently in different studies. Sponsor's evaluation of response Investigator's evaluation of response This survival estimate includes the 21 subjects who were randomized to receive Atgam, plus another 11 subjects who were crossed over from the control group. Patients with severe aplastic anemia only. 10 to 20 mg/kg/day for 8 to 14 days Study 1 Atgam 21 47 / 52 (3 mo) <0.01 /> <0.01 62 (12 mo) NA Control 20 6 / 0 (3 mo) Study 2 Atgam + Bone marrow infusion 24 43 (3 mo) Not reported 83 (12 mo) =0.14 Atgam 18 44 (3 mo) 59 (12 mo) Study 3 Atgam + Androgen 26 42 (6 mo)> 0.9 55 (24 mo) =0.65 Atgam + Placebo 27 44 (6 mo) 50 (24 mo) Atgam historical controls 68 51 (6 mo) NA 56 (24 mo) REFERENCES Hardy MA, Nowygrod R, Elberg A, Appel G. Use of ATG in treatment of steroid-resistant rejection. Transplantation 1980; 29(2):162 4. Nowygrod R, Appel G, Hardy MA. Use of ATG for reversal of acute allograft rejection. Transplant Proc 1981; 13(1):469 72. Filo RS, Smith EJ, Leapman SB. Reversal of acute renal allograft rejection with adjunctive ATG therapy. Transplant Proc 1981; 13(1):482 90. Shield CF III, Cosimi AB, Tolkoff Rubin N, et al. Use of antithymocyte globulin for reversal of acute allograft rejection. Transplantation 1979; 28(6):461 4. Rubin RH, Cosimi AB, Hirsch MS, Herrin JT. Effects of antithymocyte globulin on cytomegalovirus infection in renal transplant recipients. Transplantation 1981; 31(2):143 5. 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(2):155 63. Wechter WJ, Brodie JA, Morrell RM, et al. Antithymocyte globulin (Atgam) in renal allograft recipients: multicenter trials using a 14-dose regimen. Transplantation 1979; 28(4):294 302. Butt KMH, Zielinski CM, Parsa I, et al. Trends in immunosuppression for kidney transplantation. Kidney Int 1978; 13(Suppl 8): S95 S8. Ettenger RB, Rosenthal JT, Marik JL, et al. Improved cadaveric renal transplant outcome in children. Pediatric Nephrol 1991; 5:137 42. How Supplied/Storage and Handling Atgam Sterile Solution, containing 50 mg/mL lymphocyte immune globulin, anti-thymocyte globulin [equine], is supplied as follows: 5 5 mL ampoules NDC 0009-7224-02 Store in a refrigerator at 2 to 8 C (36 to 46 F). DO NOT FREEZE. For storage conditions of diluted solution, see Dosage and Administration (2.2) . Patient Counseling Information Advise patients receiving Atgam that they will be monitored in a facility equipped and staffed with adequate laboratory and supportive medical resources. Inform patients that Atgam may cause serious allergic reactions, infection or abnormal liver or renal function. Serious Allergic Reactions Advise the patient to discontinue Atgam and seek immediate medical attention if any signs/symptoms of an allergic or immune reaction occur [see Warnings and Precautions (5.1) ] . Skin Testing Despite screening and testing, products manufactured using components of human blood such as Atgam may carry a risk of transmitting infectious agents (e.g., viruses). Discuss the risks and benefits of therapy with patients before initiating treatment [see Warnings and Precautions (5.2) ] . Infections Advise the patient to discontinue Atgam and report any sign/symptoms of leukopenia, thrombocytopenia, or infection (e.g., fever, sweating, chills, muscle aches, cough, shortness of breath, diarrhea or stomach pain) [see Warnings and Precautions (5.1) , (5.2) , (6) ] . Healthcare providers should refer to labels.fda.gov or DailyMed for the most updated version of the labeling. This product's label may have been updated. For full prescribing information, please visit www.pfizer.com. U.S. Govt. License No. 1216 LAB-0019-7.0 PRINCIPAL DISPLAY PANEL - 5 mL Ampule Label 5 mL NDC 0009-7224-01 Atgam lymphocyte immune globulin, anti-thymocyte globulin (equine) 250 mg protein 50 mg/mL For I.V. use only DOSAGE AND USE: See accompanying prescribing information. U.S. License No. 1216. ATTENTION May contain particles; this is normal. Use 0.2µ to 1.0µ in-line filter. See insert. Distributed by Pharmacia & Upjohn Co Division of Pfizer Inc, NY, NY 10017 Rx only PAA042882 LOT / EXP PRINCIPAL DISPLAY PANEL - 5 5 mL Ampule Carton NDC 0009-7224-02 Contains 5 of NDC 0009-7224-01 5 5 mL Ampoules (single use containers) Atgam lymphocyte immune globulin, anti-thymocyte globulin (equine) 250 mg protein 50 mg/mL ATTENTION This product may contain a granular or flaky deposit; this is normal. See infusion instructions described in the enclosed product insert. For I.V. use only Pfizer Injectables Rx only Atgam equine thymocyte immune globulin injection, solution Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0009-7224 Route of Administration INTRAVENOUS DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength EQUINE THYMOCYTE IMMUNE GLOBULIN (EQUINE THYMOCYTE IMMUNE GLOBULIN) EQUINE THYMOCYTE IMMUNE GLOBULIN 50 mg in 1 mL Packaging # Item Code Package Description 1 NDC:0009-7224-02 5 AMPULE in 1 CARTON 1 NDC:0009-7224-01 5 mL in 1 AMPULE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103676 11/17/1981 Labeler - Pharmacia and Upjohn Company (829076566) Establishment Name Address ID/FEI Operations Pharmacia and Upjohn Company 829076566 ANALYSIS(0009-7224), API MANUFACTURE(0009-7224), LABEL(0009-7224), MANUFACTURE(0009-7224), PACK(0009-7224) Revised: 04/2015 Pharmacia and Upjohn Company Next Interactions Print this page Add to My Med List More about Atgam (lymphocyte immune globulin, anti-thy (equine)) Side Effects During Pregnancy Dosage Information Drug Interactions Support Group En Español 0 Reviews Add your own review/rating Drug class: selective immunosuppressants Consumer resources Atgam equine Atgam Professional resources Atgam (AHFS Monograph) Related treatment guides Aplastic Anemia Renal Transplant ]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only C Pregnancy Category Risk cannot be ruled out N/A CSA Schedule Not a controlled drug Manufacturer Pfizer Inc. Drug Class Selective immunosuppressants Related Drugs selective immunosuppressants leflunomide , CellCept , mycophenolate mofetil , Arava , Tecfidera , Orencia Aplastic Anemia Promacta , eltrombopag , Leukine , sargramostim , lymphocyte immune globulin, anti-thy (equine) , More... Renal Transplant furosemide , Lasix , azathioprine , Imuran , Thymoglobulin , Azasan , lymphocyte immune globulin, anti-thy (equine) , More... Atgam Rating No Reviews - Be the first! No Reviews - Be the first! Not Rated - Be the first!} } which is not
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