Antithymocyte Globulin (Rabbit) (Monograph)

Brand name: Thymoglobulin
Drug class: Immunosuppressive Agents
- Antilymphocyte Immunoglobulins
- Immunosuppressive Agents
ATC class: L04AA04
VA class: IM600

Medically reviewed by Drugs.com on Jan 17, 2024. Written by ASHP.

Introduction

Antithymocyte globulin (rabbit) (ATG [rabbit]); rabbit-derived polyclonal antibody preparation; immunosuppressive agent.

Uses for Antithymocyte Globulin (Rabbit)

Renal Allotransplantation

Treatment of acute rejection of renal allografts in conjunction with other immunosuppressive agents.

ATG (rabbit) found to be more effective than ATG (equine) in reversing acute rejection episodes (88% compared with 76%) and preventing recurrent rejection episodes in renal transplant recipients.

Has also been used successfully as induction therapy in conjunction with maintenance immunosuppressive therapy for the prevention of renal allograft rejection^{† [off-label]}.

Hepatic Allotransplantation

Induction therapy to prevent hepatic allograft rejection and minimize maintenance immunosuppression^{† [off-label]} in pediatric patients (designated an orphan drug by FDA for this use) and in adults.

Myelodysplastic Syndrome and Aplastic Anemia

Has been used for the treatment of myelodysplastic syndrome^{† [off-label]} (designated an orphan drug by FDA for this use).

Has been used for the treatment of aplastic anemia^{† [off-label]}, usually in conjunction with cyclosporine.

Antithymocyte Globulin (Rabbit) Dosage and Administration

General

• To reduce the incidence and intensity of infusion-related adverse effects, the manufacturer and some clinicians recommend premedication with corticosteroids, acetaminophen, and/or an antihistamine (e.g., diphenhydramine) 1 hour prior to each infusion. (See Infusion-related Effects under Cautions.)

• The manufacturer recommends prophylactic antiviral therapy (e.g., acyclovir, ganciclovir, valganciclovir) during ATG (rabbit) therapy. (See Infectious Complications under Cautions.)

Administration

IV Administration

For drug compatibility information, see Compatibility under Stability.

ATG (rabbit) is administered by IV infusion. The manufacturer states that ATG (rabbit) should be infused through an inline 0.22-μm filter into a high-flow vein. Has also been administered via a peripheral vein^{† [off-label]} in some patients, but safety not fully established and may increase risk of thrombophlebitis and DVT.

Administer in conjunction with other immunosuppressive agents.

Reconstitution

Allow vial to reach room temperature before reconstituting. Reconstitute vial containing 25 mg of the drug with 5 mL of sterile water for injection to provide a solution containing 5 mg/mL. Gently rotate vial until powder is completely dissolved. Use reconstituted solution immediately. (See Storage under Stability.)

Dilution

Dilute appropriate dosage of reconstituted ATG (rabbit) in 0.9% sodium chloride or 5% dextrose injection. Each reconstituted vial should be diluted in 50 mL of infusion solution; total volume of infusion solution required generally is 50–500 mL. Recommended final concentration approximately 0.5 mg/mL. Mix diluted solution by gently inverting infusion bag only once or twice.

Rate of Administration

Administer initial dose over ≥6 hours and subsequent doses over ≥4 hours. Slowing infusion rate may help prevent or ameliorate acute infusion reactions. (See Infusion-related Effects under Cautions.)

Dosage

Appropriate dosage for Thymoglobulin differs from dosages for other antithymocyte globulin (ATG) preparations since protein composition and concentrations vary depending on source of ATG used. Exercise care to ensure prescribed dose is appropriate for the ATG preparation being administered.

Reduce ATG (rabbit) dosage by 50% if WBC is ≥2000 but ≤3000/mm³ or platelet count is ≥50,000 but ≤75,000/m³. Consider drug discontinuance if WBC <2000/mm³ or platelet count <50,000/mm³. (See Hematologic Effects and Clinical/Laboratory Monitoring under Cautions.)

Pediatric Patients

Renal Allotransplantation

Prevention of Renal Allograft Rejection (Induction Therapy)†

IV Infusion

Optimum dosage not established; 1.5–2.5 mg/kg once daily for 5–10 days has been given.

Adults

Renal Allotransplantation

Treatment of Allograft Rejection

IV Infusion

1.5 mg/kg once daily for 7–14 days. Usually continue other immunosuppressive agents used for treatment of acute renal transplant rejection (e.g., azathioprine, corticosteroids, cyclosporine) during therapy. (See Interactions.)

Prevention of Renal Allograft Rejection (Induction Therapy)†

IV Infusion

Optimum dosage not established; 1.5 mg/kg once daily for 5–14 days or 3 mg/kg once daily on day 1 then 1.5 mg/kg once daily on days 2 and 3 has been given. Intermittent dosage regimens based on CD3⁺ lymphocyte counts and regimens in which the first dose is administered intraoperatively also have been given.

Myelodysplastic Syndrome† and Aplastic Anemia†

Myelodysplastic Syndrome†

IV Infusion

Optimum dosage not established; 3.75 mg/kg once daily for 5 days has been given.

Aplastic Anemia†

IV Infusion

Optimum dosage not established; 3.5 mg/kg once daily for 5 days has been given.

Special Populations

No special population dosage recommendations at this time.

Cautions for Antithymocyte Globulin (Rabbit)

Contraindications

• Known hypersensitivity to rabbit proteins or any ingredient in the formulation; history of anaphylaxis following ATG (rabbit) administration.

• Active or acute infections that contraindicate any additional immunosuppression.

Warnings/Precautions

Warnings

See Boxed Warning.

Close medical supervision required during and after IV infusion of ATG (rabbit).

Cytokine Release Syndrome

Severe cytokine release syndrome (CRS), an immune-mediated reaction, reported. Severe, acute CRS may cause serious cardiorespiratory effects and/or death.

Infectious Complications

Possible increased risk of infections (bacterial, fungal, viral, and protozoal), reactivation of infections (particularly cytomegalovirus [CMV]), and sepsis when ATG (rabbit) is used in combination with multiple immunosuppressive agents. Severe, acute infections may be fatal. The manufacturer recommends careful patient monitoring and appropriate anti-infective prophylaxis.

Sensitivity Reactions

Anaphylaxis

Serious and fatal anaphylactic reactions reported.

If anaphylaxis or other severe hypersensitivity reaction occurs, discontinue ATG (rabbit) infusion immediately and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen, IV fluids, antihistamines, maintenance of BP).

Patients with a history of anaphylaxis to ATG (rabbit) should not receive the drug again.

General Precautions

Malignancies

Possible increased risk of malignancies with immunosuppressive therapy, including rabbit ATG (e.g., lymphoma, posttransplant lymphoproliferative disease [PTLD]).

Hematologic Effects and Clinical/Laboratory Monitoring

T cells decrease during ATG (rabbit) therapy. Monitor lymphocyte counts (i.e., total lymphocytes and/or T-cell subsets) to assess level of T-cell depletion in patients receiving the drug.

Thrombocytopenia and/or leukopenia (including lymphopenia and neutropenia) commonly reported. Monitor WBC and platelet count; reduce dosage and/or consider drug discontinuance in patients who develop leukopenia and/or thrombocytopenia. (See Dosage under Dosage and Administration.)

Antibody Formation

Anti-rabbit antibodies developed in 68% of renal transplant patients who received ATG (rabbit) for 7–14 days for treatment of acute rejection; these antibodies were still present in 24% of patients at 90 days. Presence of anti-rabbit antibodies not correlated with treatment success or failure in these patients; possible effects of these antibodies on drug’s efficacy during subsequent use not evaluated.

Infusion-related Effects

Risk of infusion-related effects (e.g., fever, chills and/or rigors, dyspnea, nausea and/or vomiting, diarrhea, hypotension or hypertension, malaise, rash, and/or headache); may occur as soon as first or second infusion during a single course of treatment.

May minimize or prevent infusion-related effects by administering initial ATG (rabbit) infusions over ≥6 hours, administering a pretreatment regimen (corticosteroid, acetaminophen, and/or an antihistamine) 1 hour prior to each ATG (rabbit) infusion, and/or slowing the infusion rate. (See General and see Administration under Dosage and Administration.)

Immunization

Safety of attenuated live vaccine administration following ATG (rabbit) therapy not established. Manufacturer states that immunization with attenuated live vaccines not recommended in patients who recently received the drug.

Laboratory Test Interference

Potential interference with rabbit antibody-based immunoassays and with cross-match or panel-reactive antibody cytotoxicity assays.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether ATG (rabbit) is distributed into milk; however, other immunoglobulins are distributed into human milk. Discontinue nursing or the drug.

Pediatric Use

The manufacturer states that safety and efficacy not established in children <18 years of age in controlled trials. However, ATG (rabbit) has been used as induction therapy in conjunction with maintenance immunosuppressive therapy to prevent renal or hepatic allograft rejection^† in pediatric patients 5 months–18 years of age. (See Hepatic Allotransplantation under Uses.)

Dosage, efficacy, and adverse effect profile in pediatric patients generally appear to be the same as in adults.

Common Adverse Effects

Infectious complications (including sepsis, urinary tract infections, and CMV infections), fever, chills, leukopenia, lymphopenia, thrombocytopenia, cytokine release syndrome, abdominal pain, nausea, diarrhea, asthenia, dyspnea, headache, pain, hyperkalemia, hypertension, peripheral edema, tachycardia, dizziness, infusion site pain/swelling/erythema.

Drug Interactions

No formal drug interaction studies to date.

Specific Drugs

Antithymocyte Globulin (Rabbit) Pharmacokinetics

Absorption

Onset

T-cell depletion usually observed within 1 day after initiating therapy.

Plasma Concentrations

Average 21.5 and 87 mcg/mL 4–8 hours post-infusion after first and last IV doses, respectively, when given for 7–11 days.

Duration

Lymphopenia may persist ≥1–2 years after ATG (rabbit) administration.

Distribution

Extent

Not known whether ATG (rabbit) distributes into human milk; however, other immunoglobulins are distributed into human milk.

Elimination

Half-life

2–3 days after first dose; may increase after multiple-dose administration.

Stability

Storage

Parenteral

Powder for Injection

2–8°C; do not freeze. Protect from light.

Although reconstituted solutions are stable at room temperature for up to 24 hours, room temperature storage is not recommended by the manufacturer since the preparation contains no preservatives; use immediately.

Use diluted solutions immediately.

Discard any unused drug after infusion.

Compatibility

Parenteral

Drug CompatibilityHID

Incompatibility not observed with polyvinyl chloride bags or infusion sets.

Actions

• Rabbit-derived polyclonal antibody; immunosuppressive agent.

• Exact mechanism of immunosuppressive action not fully elucidated; appears to involve clearance of peripheral antigen-reactive T lymphocytes (T cells) and modulation of T-cell activation, homing, and cytotoxicity.

• ATG (rabbit) contains antibodies that bind T-cell surface receptors, including CD2, CD3, CD4, CD8, CD11a, CD18, CD25, CD44, CD45, HLA-DR, HLA class I heavy chains, and β₂-microglobulin.

• Induces profound depletion of CD2, CD3, CD4, CD8, CD16, CD25, and CD45 lymphocytes within 24 hours of first dose administration.

• Not effective for treating antibody-mediated (humoral) transplant rejections.

Advice to Patients

• Importance of informing patients about the potential benefits of ATG (rabbit) and attendant risks of immunosuppressive therapy.

• Risk of decreased number of platelets and/or WBCs, including lymphocytes. Necessity of administration under supervision of a clinician with regular monitoring of platelet and WBC counts.

• Potential for reduction of lymphocyte counts, which could increase risk of infection or malignancy. Importance of informing clinicians promptly if any signs or symptoms of infection or malignancy occur.

• Advise patient of risk of possible fever, chills, itching, and/or rash during ATG (rabbit) infusion and that medication will be given to help control these reactions.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal or nutritional supplements, as well as any concomitant illnesses.

• Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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