ANTITHYMOCYTE GLOBULIN (RABBIT) 
Pronounciation
Trade Name(s)
Baseline studies indicated; see Monitor.
To reduce the incidence and intensity of side effects during the infusion of anti-thymocyte globulin; premedication 1 hour before the infusion with corticosteroids (e.g., dexamethasone), acetaminophen, and/or an antihistamine (e.g., diphenhydramine) is recommended.
1.5 mg/kg of body weight daily for 7 to 14 days. Given as an infusion into a high-flow vein. Used in conjunction with maintenance immunosuppression (e.g., tacrolimus [Prograf], mycophenolate [Cell-Cept]); see Drug/Lab Interactions.
Reduce dose by one-half if WBC count is between 2,000 and 3,000 cells/mm3 or if platelet count is between 50,000 and 75,000 cells/mm3.
■ Consider withholding dose or stopping anti-thymocyte therapy if WBC count falls below 2,000 cells/mm3 or platelets fall below 50,000 cells/mm3.
Calculate the number of vials required (25 mg/vial); 5 mL of SWFI as diluent per vial is supplied. Drug and diluent must be warmed to room temperature before dilution. Absolute sterile technique required throughout dilution process. For each vial required use a new syringe and needle. Withdraw 5 mL of diluent and inject into lyophilized powder. Rotate vial gently until powder is completely dissolved. Do not shake. Each reconstituted vial contains 25 mg (5 mg/mL). Must be further diluted by transferring into 50 mL of infusion solution (saline or dextrose) for each 25 mg of anti-thymocyte globulin. Total volume is usually between 50 to 500 mL. Invert the infusion bag gently once or twice to mix the solution.
Use of a 0.22-micron in-line filter recommended.
Refrigerate and protect from light until removed to prepare for reconstitution. Do not freeze. Do not use after expiration date on vial. Use reconstituted vials within 4 hours. Use infusion solutions immediately. Discard unused drug.
Administration through a separate line without mixing with other IV fluids or medications is suggested because of specific use and potential for anaphylaxis.
Other sources suggest a few specific compatibilities dependent on concentration and manufacturer; consult a pharmacist.
Use of a high-flow vein and a 0.22-micron filter recommended. Well-tolerated and less likely to produce side effects (e.g., chills and fever) when administered at the recommended rate and the patient is premedicated.
A total daily dose equally distributed over a minimum of 6 hours.
A total daily dose equally distributed over a minimum of 4 hours.
A purified, pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. Mechanism of action not fully understood. May induce immunosuppression by T-cell depletion and immune modulation. Made up of a variety of antibodies that recognize key receptors on T-cells (those cells responsible for attacking and rejecting a foreign substance within the body). Anti-thymocyte globulin antibodies can inactivate and kill these T-cells, thus reversing the rejection process. May prevent organ loss and reduce the need for retransplantation. T-cell depletion is usually observed within a day of initiating thymoglobulin therapy. Half-life averages 2 to 3 days but the drug remains active, targeting the offending immune cells for days to weeks after treatment.
Treatment of kidney transplant acute rejection in conjunction with concomitant immunosuppression.
Compassionate use in the treatment of acute rejection in bone marrow, heart, and liver transplants. Treatment of myelodysplastic syndrome (MDS).
Patients with a known allergy to rabbit proteins, an acute viral illness, or a history of anaphylaxis during rabbit immunoglobulin administration.
Administered only under the direction of a physician experienced in immunosuppressive therapy and management of renal transplant patients in a facility with adequate laboratory and supportive medical resources.
■ Not considered effective for treating antibody-mediated (humoral) rejections.
■ Prolonged use or overdose in combination with other immunosuppressive agents may cause over-immunosuppression resulting in severe infections and may increase the incidence of lymphoma or posttransplant lymphoproliferative disease (PTLD) or other malignancies. Use of appropriate antiviral, antibacterial, antiprotozoal, and/or antifungal prophylaxis is recommended. In clinical trials, viral prophylaxis with ganciclovir infusion was used.
■ In clinical trials, anti-rabbit antibodies developed in 68% of patients. Controlled studies on repeat use of anti-thymocyte globulin in patients with anti-rabbit antibodies have not been conducted. Use caution if repeat courses are indicated; monitoring of lymphocyte count is recommended to ensure that T-cell depletion is achieved.
■ If anaphylaxis occurs during or after therapy, further administration of anti-thymocyte globulin is contraindicated.
Obtain baseline and monitor WBC and platelet counts during therapy. Thrombocytopenia or neutropenia may occur and are reversible following dose adjustment; see Dose Adjustments.
■ Close clinical observation is imperative. Monitor for side effects during and after infusion. Anaphylaxis has occurred; emergency equipment, medications, and supplies must be available.
■ Monitoring of the lymphocyte count (i.e., total lymphocyte count and T-cell counts [absolute and/or subset]) may help assess the degree of T-cell depletion.
■ Monitor carefully for signs of infection.
■ Prophylactic antibiotics may be indicated pending results of C/S in a febrile neutropenic patient.
■ See Precautions and Drug/Lab Interactions.
Imperative that all medications (especially immunosuppressants) be reviewed with physician.
■ Report any previous hypersensitivity/anaphylactic reaction.
■ Report acute viral infections immediately.
■ Promptly report chest pain, irregular or rapid heartbeat, shortness of breath, swelling of the face or throat, or wheezing during infusion of medication.
■ See Appendix D, .
■ May be associated with an increased risk of malignancy.
Category C: safety for use during pregnancy and breast-feeding not established. Safety and effectiveness for use in pediatric patients not established. Use only if clearly needed.
■ Has been used in pediatric patients in limited European studies and in the United States for compassionate use. Response similar to adults.
Specific information not available.
Concurrent use with immunosuppressants (e.g., azathioprine, cyclosporine, mycophenolate, tacrolimus) may potentiate the immunosuppressive action of these agents; many transplant centers decrease maintenance immunosuppression therapy during the period of antibody therapy.
■ May stimulate the production of antibodies, which cross-react with rabbit immune globulins.
■ May interfere with rabbit antibody-base immunoassays and with cross-match or panel-reactive antibody cytotoxicity assays.
Are dose-limiting. Abdominal pain, asthenia, diarrhea, dizziness, dyspnea, fever, headache, hyperkalemia, hypertension, infection, infusion reaction (e.g., chills and fever), leukopenia, malaise, nausea, pain, peripheral edema, tachycardia, and thrombocytopenia were reported frequently. Anaphylaxis has been reported.
Leukopenia or thrombocytopenia.
Notify physician of all side effects. Most can be managed symptomatically. Manage leukopenia or thrombocytopenia during therapy or in overdose with dose reduction. Infusion reactions are managed with premedication and reduction in the rate of infusion. Treat infections aggressively; see Precautions. May require discontinuation of therapy. Discontinue infusion and/or therapy immediately if anaphylaxis occurs. Treat anaphylaxis immediately with epinephrine, diphenhydramine, oxygen, vasopressors (e.g., dopamine), corticosteroids, IV fluids, and ventilation equipment as indicated. Resuscitate as necessary.