Clinical Information
Gen. Code and Des.
28256 anti-thymocyte globulin,rabbit INTRAVEN VIAL 25 MG
Strength
25 mg
Dose Form
VIAL (EA)
Product Category
RX Pharmaceuticals
Fine Line Class
850085008510 All Rx Products
DEA Class
NC
OMP Family
AHFS Class
92440000 IMMUNOSUPPRESSIVE AGENTS
Active Ingredients
6244 anti-thymocyte globulin, rabbit 308067609
Inactive Ingredients
2272 mannitol 69658
THYMOGLOBULIN- lapine t-lymphocyte immune globulin injection, powder, lyophilized, for solution
Genzyme Corporation
Sterile Lyophilized Powder
For Intravenous Use Only
WARNING
Thymoglobulin� should only be used by physicians experienced in immunosuppressive therapy for the management of renal transplant patients.
DESCRIPTION
Thymoglobulin� [Anti-thymocyte Globulin (Rabbit)] is a purified, pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. This immunosuppressive product contains cytotoxic antibodies directed against antigens expressed on human T-lymphocytes.
Thymoglobulin is a sterile, freeze-dried product for intravenous administration after reconstitution with Sterile Water for Injection, USP (SWFI).
Each 10 mL vial contains 25 mg anti-thymocyte globulin (rabbit) as well as 50 mg glycine, 50 mg mannitol, and 10 mg sodium chloride.
After reconstitution with 5 mL SWFI, each vial of reconstituted product contains approximately 5 mg/mL of Thymoglobulin, of which >90% is rabbit gamma immune globulin (IgG). The reconstituted solution has a pH of 6.5 � 7.2. Human red blood cells are used in the manufacturing process to deplete cross-reactive antibodies to non-T-cell antigens. The manufacturing process is validated to remove or inactivate potential exogenous viruses. All human red blood cells are from US registered or FDA licensed blood banks. A virus removal step (nanofiltration, using a 20 nm filter) and a viral inactivation step (pasteurization, i.e., heat treatment of active ingredient at 60�C/10 hr) are performed for each lot. Each Thymoglobulin lot is released following potency testing (lymphocytotoxicity and E-rosette inhibition assays), and cross-reactive antibody testing (hemagglutination, platelet agglutination, antiglomerular basement membrane antibody, and fibroblast toxicity assays on every lot).
PHARMACOLOGY
Mechanism of Action
The mechanism of action by which polyclonal antilymphocyte preparations suppress immune responses is not fully understood. Possible mechanisms by which Thymoglobulin may induce immunosuppression in vivo include: T-cell clearance from the circulation and modulation of T-cell activation, homing, and cytotoxic activities. Thymoglobulin includes antibodies against T-cell markers such as CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, HLA-DR, HLA Class I heavy chains, and �2 micro-globulin. In vitro, Thymoglobulin (concentrations >0.1 mg/mL) mediates T-cell suppressive effects via inhibition of proliferative responses to several mitogens. In patients, T-cell depletion is usually observed within a day from initiating Thymoglobulin therapy.
Thymoglobulin has not been shown to be effective for treating antibody (humoral) mediated rejections.
Pharmacokinetics and Immunogenicity
After an intravenous dose of 1.25 to 1.5 mg/kg/day (over 4 hours for 7�11 days) 4�8 hours post-infusion, Thymoglobulin levels were on average 21.5 mcg/mL (10�40 mcg/mL) with a half-life of 2�3 days after the first dose, and 87 mcg/mL (23�170 mcg/mL) after the last dose. During the Thymoglobulin 1 Phase 3 randomized trial, of the 108 of 163 patients evaluated, anti-rabbit antibodies developed in 68% of the Thymoglobulin-treated patients, and anti-horse antibodies developed in 78% of the Atgam 2-treated patients (p=n.s.). No controlled studies have been conducted to study the effect of anti-rabbit antibodies on repeat use of Thymoglobulin. However, monitoring the lymphocyte count to ensure that T-cell depletion is achieved upon retreatment with Thymoglobulin is recommended. Based on data collected from a limited number of patients (Clinical study Phase 3, n=12), T-cell counts are presented in the chart below. These data were collected using flow cytometry (FACSCAN, Becton-Dickinson).
INDICATIONS AND USAGE
Thymoglobulin is indicated for the treatment of renal transplant acute rejection in conjunction with concomitant immunosuppression.
CONTRAINDICATIONS
Thymoglobulin is contraindicated in patients with history of allergy or anaphylaxis to rabbit proteins or to any product excipients, or who have active acute or chronic infections which contraindicate any additional immunosuppression.
WARNINGS
Thymoglobulin should only be used by physicians experienced in immunosuppressive therapy for the treatment of renal transplant patients. Medical surveillance is required during Thymoglobulin infusion.
Immune-mediated reactions
Serious immune-mediated reactions have been reported with the use of Thymoglobulin and consist of anaphylaxis or severe cytokine release syndrome (CRS).
Infection
Thymoglobulin is routinely used in combination with other immunosuppressive agents. Infections (bacterial, fungal, viral and protozoal), reactivation of infection (particularly cytomegalovirus [CMV]) and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. These infections can be fatal.
Hematologic Effects
Thrombocytopenia and/or leukopenia (including lymphopenia and neutropenia) have been identified and are reversible following dose adjustments (See DOSAGE AND ADMINISTRATION).
Infection
Infections, reactivation of infection, and sepsis have been reported after Thymoglobulin administration in combination with multiple immunosuppressive agents. Careful patient monitoring and appropriate anti-infective prophylaxis are recommended.
Malignancy
Use of immunosuppressive agents, including Thymoglobulin, may increase the incidence of malignancies, including lymphoma or lymphoproliferative disorders (which may be virally mediated). These events have been associated with fatal outcome
OVERDOSAGE
Thymoglobulin overdosage may result in leukopenia (including lymphopenia and neutropenia) or thrombocytopenia, which can be managed with dose reduction (See DOSAGE AND ADMINISTRATION).
DOSAGE AND ADMINISTRATION
The recommended dosage of Thymoglobulin for treatment of acute renal graft rejection is 1.5 mg/kg of body weight administered daily for 7 to 14 days. The recommended route of administration is intravenous infusion using a high-flow vein. Thymoglobulin should be infused over a minimum of 6 hours for the first infusion and over at least 4 hours on subsequent days of therapy.
Thymoglobulin should be administered through an in-line 0.22 micrometer filter.
Thymoglobulin is supplied as a 10 mL vial containing lyophilized (solid) Thymoglobulin (25 mg).
Please see Preparation for Administration for vial reconstitution and dilution in infusion solution recommendations. Investigations indicate that Thymoglobulin is less likely to produce side effects when administered at the recommended flow rate. Administration of antiviral prophylactic therapy is recommended. Premedication with corticosteroids, acetaminophen, and/or an antihistamine 1 hour prior to the infusion is recommended and may reduce the incidence and intensity of side effects during the infusion (See PRECAUTIONS: General and ADVERSE REACTIONS: Post-Marketing Experience). Medical personnel should monitor patients for adverse events during and after infusion. Monitoring T-cell counts (absolute and/or subsets) to assess the level of T-cell depletion is recommended. Total white blood cell and platelet counts should be monitored.
Overdosage of Thymoglobulin may result in leukopenia (including lymphopenia and neutropenia) and/or thrombocytopenia. The Thymoglobulin dose should be reduced by one-half if the WBC count is between 2,000 and 3,000 cells/mm3 or if the platelet count is between 50,000 and 75,000 cells/mm3. Stopping Thymoglobulin treatment should be considered if the WBC count falls below 2,000 cells/mm3 or platelets below 50,000 cells/mm3.
HOW SUPPLIED
Thymoglobulin is available as sterile, lyophilized powder to be reconstituted with sterile Water for Injection, USP (SWFI). Each package contains a 10 mL vial of freeze-dried Thymoglobulin (25 mg) NDC# 58468-0080-1.
Storage
Store in refrigerator at 2�C to 8�C (36�F to 46�F).
Protect from light.
Do not freeze.
Do not use after the expiration date indicated on the label.
Reconstituted Thymoglobulin is physically and chemically stable for up to 24 hours at room temperature; however, room temperature storage is not recommended. As Thymoglobulin contains no preservatives, reconstituted product should be used immediately.
Infusion solutions of Thymoglobulin must be used immediately.
Any unused drug remaining after infusion must be discarded.
