Antithymocyte Globulin (Equine)

Name: Antithymocyte Globulin (Equine)

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  • Equine-derived polyclonal antibody immunosuppressive agent. 7 10 17 18 19 20 21 22 23 24 25 26 27 28 30 31 32 33 34 35 51 52 53 54 55 83 a b c

  • Exact mechanism of immunosuppressive action not fully elucidated; appears to involve clearance of peripheral antigen-reactive T lymphocytes (T cells) and/or alteration of T-cell function.2 3 4 5 6 8 9 14 a b

    Exact mechanism of hematologic effects variable, complex, and not fully elucidated.48 49 89 90 a In vitro studies indicate ATG (equine) essentially binds to all circulating lymphocytes (both T and B cells),58 87 a granulocytes,87 a and platelets.87 a May produce leukopenia,2 7 19 32 35 a b thrombocytopenia,2 7 17 19 23 33 35 a b and/or hemolysis.2 a b Also produces a hematopoietic response in some patients with aplastic anemia.36 37 38 39 40 41 42 91 107 108 a

    Appears to have some antineoplastic activity against malignant lymphomas.57 58 59 60 a

Pharmacologic Category

  • Immune Globulin
  • Immunosuppressant Agent
  • Polyclonal Antibody

Use Labeled Indications

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 been 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

Warnings/Precautions

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.

For Healthcare Professionals

Applies to lymphocyte immune globulin, anti-thy (equine): intravenous solution

General

General side effects have included fever, chills, herpes simplex reactivation, localized infection, systemic infection, possible serum sickness, lymphadenopathy, post-cervical lymphadenopathy, tender lymph nodes and night sweats.[Ref]

Hypersensitivity

Hypersensitivity side effects have included anaphylaxis.[Ref]

Dermatologic

Dermatologic side effects have included rash, pruritus, urticaria, wheal, flare, toxic epidermal necrosis and wound dehiscence.[Ref]

Musculoskeletal

Musculoskeletal side effects have included arthralgia, chest, flank or back pain, leg pains, myalgia, joint stiffness, muscle ache, burning soles, burning palms, and foot sole pain.[Ref]

Gastrointestinal

Gastrointestinal side effects have included GI bleeding or perforation, hiccoughs, epigastric pain, stomach pain, diarrhea, abdominal pain, stomatitis, laryngospasm, nausea and vomiting.[Ref]

Cardiovascular

Cardiovascular side effects have included hypertension, hypotension, tachycardia, congestive heart failure, edema, vasculitis and deep vein thrombosis, thrombophlebitis, clotted A-V fistula, myocarditis, cardiac irregularity, bradycardia, renal artery thrombosis, and iliac vein obstruction.[Ref]

Hematologic

Hematologic side effects have included thrombocytopenia, leukopenia, hepatosplenomegaly, neutropenia or granulocytopenia, anemia and thrombophlebitis.[Ref]

Respiratory

Respiratory side effects have included respiratory distress, dyspnea, apnea, pulmonary edema, bilateral pleural effusion, laryngospasm/edema, cough and sore mouth/throat.[Ref]

Nervous system

Nervous system side effects have included headache, dizziness, paresthesia, weakness or faintness, agitation/lethargy, listlessness, lightheadedness, seizures, malaise, confusion or disorientation, abnormal involuntary movement or tremor, possible encephalitis or post viral encephalopathy and rigidity.[Ref]

Local

Local side effects have included pain at the infusion site.[Ref]

Renal

Renal side effects have included proteinuria.[Ref]

Ocular

Ocular side effects have included periorbital edema.[Ref]

Metabolic

Metabolic side effects have included hyperglycemia.[Ref]

Hepatic

Hepatic side effects have included hepatosplenomegaly.[Ref]

Some side effects of lymphocyte immune globulin, anti-thy (equine) may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Pediatric Dose for Aplastic Anemia

Experience with children has been limited. Lymphocyte immune globulin has been administered safely to a small number of pediatric renal allograft recipients and pediatric aplastic anemia patients at dosage levels comparable to those in adults.

10 to 20 mg/kg/day for 8 to 14 days. Additional alternating day therapy can be administered for up to 21 doses in 28 days.

Dialysis

Data not available

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