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Aplastic anemia: Treatment of moderate-to-severe aplastic anemia in patients not considered suitable candidates for bone marrow transplantation
Limitations of use: The usefulness of antithymocyte globulin (equine) has not be demonstrated in patients with aplastic anemia who are suitable candidates for transplantation, or in aplastic anemia secondary to neoplastic disease, storage disease, myelofibrosis, Fanconi syndrome, or in patients with known prior treatment with myelotoxic agents or radiation therapy
Renal transplantation: Management of allograft rejection in renal transplantation (increases the frequency of resolution of acute rejection episode when administered with conventional therapy at the time of rejection)
History of severe systemic reaction (eg, anaphylactic reaction) to prior administration of antithymocyte globulin or other equine gamma globulins
Antithymocyte globulins can cause anaphylaxis when injected intravenously. Although antithymocyte globulin (equine) is processed to reduce the level of antibodies that will react to non-T cells, health care providers should be prepared for the potential risk of anaphylaxis and monitor patients for signs and symptoms during infusion.
Note: Test dose: A skin test is recommended prior to administration of the initial dose. Test initially with an epicutaneous prick of undiluted antithymocyte globulin (ATG); if no wheal in 10 minutes, then use 0.02 mL intradermally of a 1:1000 dilution of ATG in normal saline along with a separate saline control of 0.02 mL; observe in 10 minutes. A positive skin reaction consists of a wheal with the initial prick test (undiluted) or ≥3 mm in diameter larger than the saline control with the diluted intradermal test. Alternatively, a 0.1 mL test dose (5 mg/mL concentration) may be administered intradermally along with a separate saline control; erythema larger than 5 mm in diameter (compared to the control) is considered a positive test (Molldrem 2002). A positive skin test is suggestive of an increased risk for systemic allergic reactions with an infusion, although anaphylaxis may occur in patients who display negative skin tests. If ATG treatment is deemed appropriate following a positive skin test, the first infusion should be administered in a controlled environment with intensive life support immediately available. A systemic reaction precludes further administration.
Consider premedication with an antihistamine, corticosteroids, and/or an antipyretic. Concomitant immunosuppressants should also be administered.
Aplastic anemia: IV: 10 to 20 mg/kg once daily for 8 to 14 days, then if needed, may administer every other day for 7 more doses for a total of 21 doses in 28 days or
Off-label dosing: 40 mg/kg once daily for 4 days in combination with cyclosporine (Rosenfeld 1995; Scheinberg 2011)
Renal transplantation rejection (treatment): IV: 10 to 15 mg/kg once daily for 14 days, then if needed, may administer every other day for 7 more doses for a total of 21 doses in 28 days
Acute graft-versus-host disease (GVHD) treatment (off-label use): IV: 30 mg/kg every other day for 6 doses (MacMillan 2007) or 15 mg/kg twice daily for 10 doses (MacMillan 2002)
Myelodysplastic syndromes, refractory, lower-risk disease (off-label use): IV: 40 mg/kg once daily for 4 days; an intradermal test dose was administered prior to treatment (Molldrem 2002)
Refer to adult dosing. Begin at the lower end of dosing ranges.
Note: Test dose: A skin test is recommended prior to administration of the initial dose. Test initially with an epicutaneous prick of undiluted antithymocyte globulin (ATG); if no wheal in 10 minutes, then use 0.02 mL intradermally of a 1:1000 dilution of ATG in normal saline along with a separate saline control of 0.02 mL; observe in 10 minutes. A positive skin reaction consists of a wheal with the initial prick test (undiluted) or ≥3 mm in diameter larger than the saline control with the diluted intradermal test. A positive skin test is suggestive of an increased risk for systemic allergic reactions with an infusion, although anaphylaxis may occur in patients who display negative skin tests. If ATG treatment is deemed appropriate following a positive skin test, the first infusion should be administered in a controlled environment with intensive life support immediately available. A systemic reaction precludes further administration.
Consider premedication with an antihistamine, corticosteroids, and/or an antipyretic. Concomitant immunosuppressants should also be administered.
Aplastic anemia, moderate to severe when no HLA-matched sibling donor: IV: 10 to 20 mg/kg once daily for 8 to 14 days; then if needed, may administer every other day for 7 more doses for up to a total of 21 doses in 28 days or
Off-label dosing (in combination with cyclosporine): Children ≥2 years and Adolescents: IV: 40 mg/kg/day once daily for 4 days (Afable 2011; Rosenfeld 1995; Scheinberg 2009; Scheinberg 2011).
Renal transplantation rejection (treatment): Children and Adolescents: IV: 10 to 15 mg/kg once daily for 14 days, then if needed, may administer every other day for 7 more doses for up to a total of 21 doses in 28 days
Acute graft-versus-host disease (GVHD) treatment (off-label use): Children and Adolescents: IV: 30 mg/kg every other day for 6 doses (MacMillan 2007) or 15 mg/kg twice daily for 10 doses (MacMillan 2002)
There are no dosage adjustments provided in the manufacturers labeling.
There are no dosage adjustments provided in the manufacturers labeling.
Dilute into inverted container of sterile infusion solution to ensure that undiluted lymphocyte immune globulin does not contact air. Gently rotate or swirl to mix; do not shake (to avoid excessive foaming and/or denaturation of the protein). Final concentration should not exceed 4 mg/mL. May be diluted in NS, D51/4NS, or D51/2NS (do not use D5W; low salt concentrations may result in precipitation). Inspect for particulate matter or discoloration prior to administration (solution may be transparent to slightly opalescent, colorless to faintly pink or brown, and may develop a slight granular or flaky deposit during storage).
For IV use only. Infuse over at least 4 hours through a 0.2 to 1 micron inline filter. Allow solution to reach room temperature prior to infusion. Infusion must be completed with 24 hours of preparation. May cause vein irritation (chemical phlebitis) if administered peripherally; high flow veins are preferred to reduce phlebitis (infuse into vascular shunt, arterial venous fistula, or high-flow central vein).
Monitor closely throughout the infusion for allergic reactions. Appropriate resuscitative equipment should be nearby during administration. May require premedication with an antipyretic, antihistamine, and/or a corticosteroid to prevent reactions. Discontinue infusion for anaphylaxis or respiratory distress. Administer epinephrine, corticosteroids, antihistamines, and/or antipyretics as indicated to manage reactions.
Due to possible infusion-related reactions, it may be preferable to avoid initiating treatment late in the day or on weekends; consider withholding beta-blockers prior to administration to avoid suppressing compensatory responses to anaphylaxis (Scheinberg, 2012).
Store ampules at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). Do not freeze. Do not shake. Solutions diluted for infusion NS, D51/4NS, or D51/2NS to a concentration of up to 4 mg/mL are stable for 24 hours (including infusion time) under refrigeration. Allow infusion solution to reach room temperature prior to administration.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injectable, Intravenous:
Atgam: 50 mg/mL (5 mL) [thimerosal free]
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
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
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
Complete blood count with differential and platelet count, monitor vital signs during administration; monitor for infusion reactions; monitor for signs/symptoms of infection
>10%:
Central nervous system: Chills, headache
Dermatologic: Dermatological reaction (wheal/flare), pruritus, skin rash, urticaria
Hematologic & oncologic: Leukopenia, thrombocytopenia
Neuromuscular & skeletal: Arthralgia
Miscellaneous: Fever
1% to 10%:
Cardiovascular: Bradycardia, cardiac disease, cardiac failure, chest pain, edema, hypertension, hypotension, myocarditis, phlebitis, thrombophlebitis
Central nervous system: Agitation, brain disease (viral), burning sensation (burning of soles and burning of palms), dizziness, encephalitis, generalized ache, lethargy, seizure
Dermatologic: Diaphoresis, night sweats
Gastrointestinal: Diarrhea, nausea, stomatitis, vomiting
Genitourinary: Proteinuria
Hematologic & oncologic: Lymphadenopathy
Hepatic: Abnormal hepatic function tests, hepatosplenomegaly
Hypersensitivity: Anaphylaxis, serum sickness
Infection: Viral infection
Local: Injection site reaction (pain, redness, swelling)
Neuromuscular & skeletal: Back pain, joint stiffness, myalgia
Ophthalmic: Periorbital edema
Renal: Renal function test abnormality
Respiratory: Dyspnea, pleural effusion, respiratory distress
<1% (Limited to important or life-threatening: Abdominal pain, acute renal failure, anaphylactoid reaction, anemia, aplasia, apnea, confusion, cough, deep vein thrombosis, disorientation, dizziness, enlarged kidney (and ruptured kidney), eosinophilia, epigastric pain, epistaxis, erythema, flank pain, gastrointestinal hemorrhage, gastrointestinal perforation, granulocytopenia, hemolysis, hemolytic anemia, herpes simplex infection (reactivation), hiccups, hyperglycemia, iliac vein obstruction, infection, involuntary body movements, laryngospasm, malaise, muscle rigidity, neutropenia, pancytopenia, paresthesia, pulmonary edema, renal artery thrombosis, sore mouth, sore throat, tachycardia, toxic epidermal necrolysis, tremor, vasculitis, viral hepatitis, weakness, wound dehiscence
Concerns related to adverse effects:
- Anaphylaxis: [US Boxed Warning]: Antithymocyte globulins may cause anaphylaxis when injected intravenously. Although antithymocyte globulin (equine) is processed to reduce the level of antibodies that will react to non-T cells, health care providers should be prepared for the potential risk of anaphylaxis and monitor for signs/symptoms during infusion. Hypersensitivity and anaphylactic reactions may occur; discontinue for symptoms of anaphylaxis; immediate treatment (including epinephrine 1 mg/mL) should be available. Systemic reaction (rash, dyspnea, hypotension, tachycardia, or anaphylaxis) precludes further administration of antithymocyte globulin (equine; ATG). Respiratory distress, hypotension, or pain (chest, flank, or back) may indicate an anaphylactoid/anaphylactic reaction. Serious immune-mediated reactions have been reported (rare), including anaphylaxis, infusion reactions, and serum sickness. Skin testing is recommended prior to administration of the initial ATG dose. A positive skin test is suggestive of an increased risk for systemic allergic reactions with an infusion, although anaphylaxis may occur in patients who display negative skin tests. If ATG treatment is deemed appropriate following a positive skin test, the first infusion should be administered in a controlled environment with intensive life support immediately available. Also observe for signs/symptoms of allergic reactions during repeat courses of administration. Skin testing is not predictive for later development of serum sickness.
- Hematologic toxicity: Thrombocytopenia may occur; may require platelets transfusion support. Discontinue if severe and unremitting leukopenia or thrombocytopenia occur in solid organ transplant patients.
- Hemolysis: Clinically significant hemolysis has been reported (rarely). Severe and unremitting hemolysis may require treatment discontinuation. Chest, flank or back pain may indicate hemolysis.
- Hepatic function: Abnormal hepatic function tests have been observed in patients with aplastic anemia and other hematologic disorders receiving ATG.
- Infection: ATG is an immunosuppressant; monitor closely for signs of infection. An increased incidence of cytomegalovirus (CMV) infection has been reported in studies.
- Renal function: Abnormal renal function tests have been observed in patients with aplastic anemia and other hematologic disorders receiving ATG.
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: Live viral vaccines may not replicate and antibody response may be reduced if administered during ATG treatment. Patients should not be immunized with attenuated live viral vaccines prior to planned ATG treatment, during, and after treatment.
Other warnings/precautions:
- Administration: Administer via central line due to chemical phlebitis that may occur with a peripheral vein. Dose must be administered over at least 4 hours; patient may need to be pretreated with an antipyretic, antihistamine, and/or corticosteroid. Should be administered with concomitant immunosuppressants.
- Disease transmission: Product of equine and human plasma; may have a risk of transmitting disease, including a theoretical risk of Creutzfeldt-Jakob disease (CJD).
- Potency: Product potency and activity may vary from lot to lot.
Adverse events were observed in some animal reproduction studies. Women exposed to antithymocyte globulin (equine) during pregnancy may be enrolled in the National Transplantation Pregnancy Registry (877-955-6877).
Immunosuppressant involved in the elimination of antigen-reactive T lymphocytes (killer cells) in peripheral blood or alteration in the function of T-lymphocytes, which are involved in humoral immunity and partly in cell-mediated immunity; induces complete or partial hematologic response in aplastic anemia
Poor into lymphoid tissues; binds to circulating lymphocytes, granulocytes, platelets, bone marrow cells
Urine (~1%)
5.7 ‚ ± 3 days
- 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 headache. muscle pain, or joint pain. Have patient report immediately to prescriber signs of infection, angina, tachycardia, signs of breathing problems (shortness of breath, wheezing, coughing, or breathing gets worse), severe dizziness, passing out, bruising, bleeding, severe back pain, loss of strength and energy, illogical thinking, severe skin irritation, seizures, or injection site irritation (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.