LYMPHOCYTE IMMUNE GLOBULIN

LYMPHOCYTE IMMUNE GLOBULIN (lymph'o-site) Antithymocyte Globulin, ATG, Atgam Classifications: biologic response modifier; immunoglobulin; Therapeutic: immunoglobulin; immunosuppressant Prototype: Immune globulin Pregnancy Category: C

Availability

50 mg/mL injection

Action

An immunoglobulin (IgG) and lymphocyte-selective immunosuppressant derived from serum of healthy horses that have been immunized with human thymus lymphocytes. During rejection of allografts, human leukocyte antigens (HLAs) bind to peptides and form complexes. Helper T-lymphocytes activate these complexes and produce interleukins, cytotoxic T-cells, and natural killer cells, resulting in destruction of transplanted tissue. Antithymocyte globulin (ATG) reduces the number of circulating T-lymphocytes, altering T-cell activation and cytotoxic function.

Therapeutic Effect

Alters the formation of T lymphocytes (killer cells) and reduces their number, thus reversing acute allograft rejection.

Uses

Primarily to prevent or delay onset or to reverse acute renal allograft rejection.

Unlabeled Uses

Moderate and severe aplastic anemia in patients unsuitable for bone marrow transplantation, T-cell malignancy, acute and chronic graft-vs-host disease, and to prevent rejection of skin allografts.

Contraindications

Hypersensitivity to thimerosal (preservative) or to other equine gamma globulin preparations; history of previous systemic reaction to ATG, hemorrhagic diatheses; leporine protein hypersensitivity; use in kidney transplant patient not receiving a concomitant immunosuppressant; fungal or viral infections; pregnancy (category C), lactation.

Cautious Use

Children (experience limited); hypotension, infection, leukopenia, lymphoma, neoplastic disease, thrombocytopenia, vaccination, varicella.

Route & Dosage

Renal Allotransplantation Adult: IV 10–30 mg/kg/d by slow IV infusion Child: IV 5–25 mg/kg/d by slow IV infusion Prevention of Allograft Rejection Adult: IV 15 mg/kg/d for 14 d followed by 15 mg/kg every other day for 14 d Treatment of Allograft Rejection Adult: IV 10–15 mg/kg/d for 14 d followed by 15 mg/kg every other day for 14 d if needed Aplastic Anemia Adult/Child: IV 10–20 mg/kg/d x 8–14 d followed by 10–20 mg/kg every other day for 7 doses

Administration

Intravenous Administer lymphocyte immune globulin (ATG) ONLY if experienced with immunosuppressant therapy and management of kidney transplant patients. Do an intradermal skin test to rule out allergy to the drug before first dose. Inject 0.1 mL of a 1:1000 dilution (5 mcg equine IgG in normal saline) and a saline control. If local reaction occurs (wheal or erythema more than 10 mm) or if there is pseudopod formation, itching, or local swelling, use caution during infusion. Discontinue infusion if systemic reaction develops (generalized rash, tachycardia, dyspnea, hypotension, anaphylaxis). PREPARE: IV Infusion: • Withdraw required dose of ATG concentrate and inject into IV solution container of 0.45% NaCl or NS. Invert IV container during injection of ATG to prevent its contact with air inside container. Use enough IV solution to create a concentration ≤4 mg/mL.• Inspect concentrate and diluted solution for particulate matter (may develop during storage) and discoloration; discard if present.  ADMINISTER: IV Infusion: Give through an in-line 0.2–1.0 mcg filter into a high-flow vein to decrease potential for phlebitis and thrombosis. Give over ≥4 h (usually 4–8 h). Must finish infusion within 12 h of preparation.

• Total storage time for diluted solutions: NO MORE than 12 h (including storage time and actual infusion time). Refrigerate ampules and diluted solutions (if prepared before time of infusion) at 2°–8° C (35°–46° F). Do not freeze.

Adverse Effects (≥1%)

CNS: Headache, paresthesia, seizures. CV: Peripheral thrombophlebitis, hypotension, hypertension. GI: Nausea, vomiting, diarrhea, stomatitis, hiccups, epigastric pain, abdominal distension. Hematologic: Leukopenia, thrombocytopenia. Musculoskeletal: Arthralgia, myalgias, chest or back pain. Respiratory: Dyspnea, laryngospasm, pulmonary edema. Skin: Rash, pruritus, urticaria, wheal and flare. Body as a Whole: Chills, fever, night sweats, pain at infusion site, hyperglycemia, systemic infection, wound dehiscence; anaphylaxis, serum sickness, herpes simplex virus reactivation.

Interactions

Drug: Azathioprine, corticosteroids, other immunosuppressants increase degree of immunosuppression.

Pharmacokinetics

Distribution: Poorly distributed into lymphoid tissues (spleen, lymph nodes); probably crosses placenta and into breast milk. Elimination: About 1% of dose is excreted in urine. Half-Life: Approximately 6 d.

Nursing Implications

Assessment & Drug Effects

• Discontinue infusion and initiate appropriate therapy promptly with onset of anaphylactic response (respiratory distress; pain in chest, flank, back; hypotension, anxiety).
• Monitor BP, vital signs, and patient's complaints during entire administration period carefully. Prompt treatment is indicated for observed and reported symptoms of anaphylaxis (incidence: 1%), serum sickness, or allergic response. Always have equipment for assisted respiration, epinephrine, antihistamines, corticosteroid, and vasopressor available at bedside.
• Predictive value of skin test is not proven. Observe patient carefully; allergic reaction can occur even when test is negative.
• Watch closely for S&S of serum sickness: fever, malaise, arthralgia, nausea, vomiting, lymphadenopathy and morbilliform eruptions on trunk and extremities. Rash begins as asymptomatic pale pink macules in periumbilical region, axilla, and groin, then rapidly becomes generalized, erythematous, and confluent. Bands of progressive erythema along the sides of hands, fingers, feet, toes, and at margins of palm or plantar skin are characteristic. In ATG-induced serum sickness, when platelet count is low, petechiae and purpura rapidly replace rash distribution over the body. Petechial areas are especially noticeable on legs but also on palms and soles. Serum sickness usually occurs 6–18 d after initiation of therapy; may occur during drug administration or when treatment is stopped.
• Monitor carefully for S&S of thrombocytopenia, concurrent infection, and leukopenia; patient usually receives concomitant corticosteroids and antimetabolites.
• Monitor patient's temperature and attend to complaints of sore throat or rhinorrhea. Report to physician; ATG treatment may be stopped.

Patient & Family Education

• Notify physician immediately of pain in chest, flank, or back; chills; pruritus; night sweats; sore throat.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug