Antithymocyte Globulin (Rabbit)

Name: Antithymocyte Globulin (Rabbit)

Interactions for Antithymocyte Globulin (Rabbit)

No formal drug interaction studies to date.b

Specific Drugs

Drug

Interaction

Comments

Basiliximab

No increase in adverse effectsf

Daclizumab

Limited experiencec

Immunosuppressive agents

Risk of oversuppression of the immune system and associated susceptibility to infection and malignancies, including lymphomaa b

Consider decreasing maintenance immunosuppressive therapy during concurrent usea b

Vaccines

Safety data not available on the effects of immunization with live vaccines during ATG (rabbit) therapyb

Avoid use of live vaccines in patients who have recently received ATG (rabbit)b

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
  • Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
  • Signs of high or low blood pressure like very bad headache or dizziness, passing out, change in eyesight.
  • Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
  • Signs of too much acid in the blood (acidosis) like confusion; fast breathing; fast heartbeat; a heartbeat the does not feel normal; very bad stomach pain, upset stomach, or throwing up; feeling very sleepy; shortness of breath; or feeling very tired or weak.
  • A fast heartbeat.
  • Chest pain or pressure.
  • Any unexplained bruising or bleeding.
  • Feeling very tired or weak.
  • Swelling in the arms or legs.
  • Shortness of breath.
  • Anxiety.
  • Feeling confused.
  • Feeling agitated.
  • Restlessness.
  • Very loose stools (diarrhea).
  • Very bad belly pain.

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

Onset of Action

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

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.

Warnings/Precautions

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.

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