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Antithymocyte Globulin (Rabbit)


(an te THY moe site GLOB yu lin RAB bit)

Index Terms

  • Antithymocyte Immunoglobulin
  • rATG

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Thymoglobulin: 25 mg (1 ea) [contains glycine, mannitol, sodium chloride]

Brand Names: U.S.

  • Thymoglobulin

Pharmacologic Category

  • Immune Globulin
  • Immunosuppressant Agent
  • Polyclonal Antibody


Antithymocyte globulin (rabbit) is a polyclonal antibody which appears to cause immunosuppression by acting on T-cell surface antigens and depleting CD4 lymphocytes

Onset of Action

T-cell depletion: Within 24 hours (Hardinger 2006)

Duration of Action

Lymphopenia may persist for up to 1 year (Hardinger 2006)

Half-Life Elimination

2 to 3 days

Use: Labeled Indications

Renal transplant rejection: Prophylaxis and treatment of acute rejection in renal transplantation (in conjunction with concomitant immunosuppression)

Note: In a multicenter, double-blind, randomized trial, antithymocyte globulin (rabbit) was shown to be superior to antithymocyte globulin (equine) in reversing acute rejection and preventing subsequent episodes (Gaber 1998). Based on data from studies (including 10 years follow up) comparing ATG (rabbit) to ATG (equine) for induction, ATG (rabbit) has emerged as the T-cell lymphocyte depleting induction therapy of choice over ATG (equine) in adult kidney transplantation due to its improved efficacy and lower incidence of acute rejection (Brennan 1999; Hardinger 2008).


Hypersensitivity (allergy or anaphylaxis) to rabbit proteins or any component of the formulation; active acute or chronic infection which contraindicate additional immunosuppression

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Note: Premedicate with corticosteroids, acetaminophen, and/or an antihistamine 1 hour prior to infusion to reduce the incidence and severity of infusion-related reactions. Administer antifungal and antibacterial prophylaxis therapy if clinically indicated. Antiviral prophylaxis is recommended in patients who are CMV-seropositive at the time of transplant and for CMV-seronegative patients scheduled to receive a kidney from a CMV-seropositive donor.

Renal transplant (acute rejection treatment): IV: 1.5 mg/kg/day for 7 to 14 days

Renal transplant (induction therapy): IV: 1.5 mg/kg/day for 4 to 7 days; the first dose should be administered prior to reperfusion of the donor kidney

Off-label induction dosing: IV: 1.5 mg/kg once daily for 5 to 7 days (Brennan 1999; Brennan 2006; Hardinger 2008) or 1 mg/kg once daily for 3 to 6 days (Goggins 2003); alternative dosing strategies with higher doses for shorter durations such as 2 mg/kg once daily for 3 days have also been recommended (Hardinger 2010); dosing based on peripheral blood CD3+ lymphocyte counts has also been described with an initial dose of 1.5 mg/kg followed by repeat doses when CD3+ count is >20 cells/mm3 (Peddi 2002)

Chronic graft-versus-host disease (prevention) (off-label use): IV: 0.5 mg/kg administered 2 days prior to transplant and 2 mg/kg administered 1 day before and 1 day after transplant (Walker 2016) or 2.5 mg/kg once daily for 3 days beginning 3 days prior to transplant (Ruutu 2013).

Heart transplant (induction therapy in high risk patients) (off-label use): IV: 1 to 1.5 mg/kg once daily for up to 7 days (Zuckermann 2015)

Heart transplant (acute cellular rejection, treatment) (off-label use): IV: 0.75 to 1.5 mg/kg/day for 5 to 14 days (ISHLT [Costanzo 2010])

Intestinal and multivisceral transplantation (induction therapy) (off-label use): IV: 2 mg/kg/day on postoperative days 0, 2, 4, 6, and 8 (in combination with rituximab) (Vianna 2008). Additional trials data may be necessary to further define the role of antithymocyte globulin (rabbit) in this condition.

Lung transplant (induction therapy) (off-label use): IV: 1.5 mg/kg/day for 3 days; the first dose was administered within 24 hours of transplantation (Palmer 1999; Hartwig 2008). Additional trails may be necessary to further define the role of antithymocyte globulin (rabbit) for prevention of rejection after lung transplant.

Lung transplant (persistent acute cellular rejection, treatment) (off-label use): IV: Pulse treatments have been used to manage persistent acute cellular rejection (Martinu 2000). Additional data may be necessary to further define the role of antithymocyte globulin (rabbit) in treatment of acute cellular rejection after lung transplantation.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Renal transplant (induction therapy and acute rejection treatment): Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adjustment for Toxicity

Renal transplantation:

WBC count 2,000 to 3,000 cells/mm3 or platelet count 50,000 to 75,000 cells/mm3: Reduce dose by 50%.

WBC count <2,000 cells/mm3 or platelet count <50,000 cells/mm3: Consider discontinuing treatment.

Dosing: Obesity

American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) to calculate mg/kg dosing for hematopoietic stem cell transplant conditioning regimens (Bubalo 2014).


Allow vials to reach room temperature, then reconstitute each vial with SWFI 5 mL to a concentration of 5 mg/mL. Rotate vial gently until completely dissolved. Prior to administration, further dilute for infusion, each 25 mg vial should be diluted in 50 mL NS or D5W (total volume is usually 50 to 500 mL depending on total number of vials needed per dose). Mix by gently inverting infusion bag only once or twice. For peripheral administration, dilution in 500 mL NS (only) with the addition of 1,000 units heparin and 20 mg hydrocortisone has been reported (Trofe-Clark 2012).


Infuse the first dose over at least 6 hours; subsequent doses may be infused over at least 4 hours. Infuse through a high-flow vein (central line). Administer through an in-line 0.22 micron filter. Premedication with corticosteroids, acetaminophen, and/or an antihistamine 1 hour prior to infusion may reduce the incidence and severity of infusion-related reactions. Reducing the infusion rate may minimize infusion reactions. Infusion rate may vary for off-label uses; refer to specific protocol.

In renal transplantation, administration through a peripheral vein has been reported with the addition of 1,000 units heparin and 20 mg hydrocortisone (in 500 mL NS only) to decrease the risk of thrombosis and phlebitis (Marvin 2003; Trofe-Clark 2012). The first 2 doses were infused over 6 hours and subsequent doses were infused over 4 hours (Trofe-Clark 2012).


See Trissel’s IV Compatibility Database


Store intact vial at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Reconstituted product is stable for up to 24 hours at room temperature; however, the product contains no preservative and room temperature storage is not recommended; the manufacturer recommends use immediately after reconstitution and preparation for infusion in D5W or NS.

Drug Interactions

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Test Interactions

Potential interference with rabbit antibody-based immunoassays and with cross-match or panel-reactive antibody cytotoxicity assays. Has not been shown to interfere with routine clinical laboratory tests which do not use immunoglobulins.

Adverse Reactions


Cardiovascular: Hypertension (27% to 37%), tachycardia (23%), peripheral edema (20%), hypotension (10% to 16%)

Central nervous system: Chills (55% to 57%), headache (27% to 40%), pain (26%), insomnia (12% to 20%), malaise (9% to 13%), acne vulgaris (12%)

Dermatologic: Skin rash (7% to 13%), diaphoresis (6% to 13%), acne vulgaris (12%)

Endocrine & metabolic: Hyperkalemia (17% to 27%), hypokalemia (12%)

Gastrointestinal: Abdominal pain (17% to 38%), nausea (29% to 37%), diarrhea (20%), vomiting (20%), constipation (15%)

Hematologic & oncologic: Leukopenia (49% to 57%; including lymphopenia and neutropenia), thrombocytopenia (29% to 37%), leukocytosis (13%), anemia (12%)

Infection: Infection (31%), cytomegalovirus disease (13%), sepsis (12%)

Neuromuscular & skeletal: Myalgia (11% to 20%), arthralgia (15%), weakness (13%), back pain (12%)

Respiratory: Dyspnea (15% to 28%), pulmonary disease (12%)

Miscellaneous: Fever (46%)

1% to 10%:

Cardiovascular: Chest pain (9%), edema (6%)

Central nervous system: Anxiety (7%)

Dermatologic: Pruritus (6%)

Endocrine & metabolic: Acidosis (9%), hypophosphatemia (6%)

Gastrointestinal: Dyspepsia (10%), anorexia (6%), intestinal candidiasis (5%), gastritis (1%)

Hematologic & oncologic: Malignant neoplasm (2%)

Hypersensitivity: Serum sickness (2%)

Infection: Herpes simplex infection (5%)

Respiratory: Increased cough (7%)

Miscellaneous: Drug overdose (6%)

<1% (Limited to important or life-threatening): Anaphylaxis, blood coagulation disorder, cytokine release syndrome, decreased oxygen saturation, increased liver enzymes, infusion related reaction, lymphadenopathy, lymphoproliferative disorder (post-transplant), malignant lymphoma, proteinuria, solid tumor

ALERT: U.S. Boxed Warning

Experienced physician:

Anti-thymocyte globulin should only be used by physicians experienced in immunosuppressive therapy in transplantation.


Concerns related to adverse effects:

• Hematologic effects: Reversible leukopenia, neutropenia, thrombocytopenia, and lymphopenia may occur. Monitor blood counts. Leukopenia and/or thrombocytopenia may require dosage adjustment.

• Hypersensitivity: Hypersensitivity and fatal anaphylactic reactions have been reported. Stop infusion immediately if anaphylactic reaction occurs. Immediate treatment (including subcutaneous epinephrine and corticosteroids) should be available during infusion for management of hypersensitivity.

• Infection: Severe infections (bacterial, fungal, viral and/or protozoal) may develop following concomitant use of immunosuppressants with antithymocyte globulin. Reactivation of infections (particularly CMV) and sepsis have been reported. Appropriate antiviral, antibacterial, antiprotozoal, and/or antifungal prophylaxis is recommended. Monitor closely for infection.

• Infusion reactions: Release of cytokines by activated monocytes and lymphocytes may lead to cytokine release syndrome (CRS) during infusion; may cause serious cardiopulmonary events (sometimes fatal). Rapid infusion rates have been associated with CRS (case reports). Other infusion reaction symptoms, including flu-like symptoms (fever, chills, nausea, muscle/joint pain) may also occur. Local infusion site reactions (pain, swelling, skin redness) have been reported.

• Malignancy: Immunosuppressants, including antithymocyte globulins may increase the incidence of malignancies, including lymphoma, post-transplant lymphoproliferative disease (PTLD) or other malignancies; may be fatal.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Immunizations: Patients should not be immunized with attenuated live viral vaccines during or shortly after treatment; safety of immunization following therapy has not been studied.

Disease-related concerns:

• Liver transplantation induction: Antithymocyte globulin (rabbit) has been associated with increased adverse effects when used for induction in liver transplantation and should be used cautiously in this population (Boillot 2009)

Other warnings/precautions:

• Administration: Initial dose must be administered over at least 6 hours into a high flow vein. Reducing the infusion rate (and prolonging the administration time) may minimize infusion reactions. May pretreat with an antipyretic, antihistamine, and/or corticosteroid.

• Experienced physician: [US Boxed Warning]: Should only be used by physicians experienced in immunosuppressive therapy in transplantation. Maintenance immunosuppression may require dosage reduction. Medical surveillance is required during the infusion. Should be administered in combination with other immunosuppressants.

• Product selection: Antithymocyte globulin (ATG) (rabbit) is available (based on region) in different product formulations, ATG-Thymoglobulin and ATG-Fresenius; the dosing differs among the formulations. Dosing of antithymocyte globulin (rabbit) also differs from dosing of other antithymocyte globulin products (eg, ATG [equine]); protein compositions and concentrations are different. Use caution to ensure dose prescribed is intended for product being administered.

Monitoring Parameters

Lymphocyte count (total lymphocyte and/or T-cell subset), CBC with differential and platelet count; vital signs during administration; signs and symptoms of infection

Solid organ transplant: Absolute CD3 count (cells/µL) monitoring and CD3 based dosing has been considered in renal and heart transplant recipients. It may be beneficial in certain patient populations but is not routinely recommended or utilized. Dose adjustments have been recommended based on the CD3 count (Krasinska 2002).

Pregnancy Considerations

Animal reproduction studies have not been conducted. Females of reproductive potential should use effective contraception during and for at least 3 months following treatment.

The National Transplantation Pregnancy Registry (NTPR) is a registry which follows pregnancies which occur in maternal transplant recipients or those fathered by male transplant recipients. The NTPR encourages reporting of pregnancies following solid organ transplant by contacting them at 877-955-6877 or

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience nausea, vomiting, abdominal pain, acne, muscle pain, joint pain, insomnia, sweating a lot, constipation, back pain, injection site pain or irritation, or diarrhea. Have patient report immediately to prescriber signs of infection, signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), angina, tachycardia, bruising, bleeding, severe headache, severe dizziness, passing out, vision changes, severe loss of strength and energy, swelling of arm or leg, shortness of breath, or signs of cytokine release syndrome (chills, dizziness, loss of strength and energy, fever, headache, passing out, rash, angioedema, difficulty breathing, nausea, vomiting, or wheezing) HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.