Antithymocyte Globulin (Equine)

Lymphocyte immune globulin, antithymocyte globulin (equine) (ATG [equine]); equine-derived polyclonal antibody preparation; immunosuppressive agent.7 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

General

Usually administered in conjunction with other immunosuppressive agents (e.g., azathioprine and corticosteroids).a b

Intradermal Sensitivity Testing

• Because of risk of severe systemic reaction (e.g., anaphylaxis), intradermal sensitivity testing is recommended in all individuals prior to administration of initial ATG (equine) dose.a b

• Skin test procedure: Inject intradermally 0.1 mL of a 1:1000 dilution of ATG (equine) concentrate for injection in 0.9% sodium chloride (5 mcg of equine IgG); only use fresh diluted ATG (equine).a b Administer control test of 0.9% sodium chloride injection contralaterally to facilitate interpretation of results.a b

• Observe patient and skin test site every 15–20 minutes during the first hour after intradermal injection of drug for positive reaction (wheal and/or area of erythema ≥10 mm in diameter, with or without pseudopod formation, and itching or marked local swelling) and question patient about occurrence of systemic manifestations.85 86 a b

• If intradermal skin test is positive, seriously consider alternative forms of therapy and weigh risk of administration against risk of withholding ATG (equine).a b If therapy considered appropriate following a positive skin test reaction, administer drug only in a setting in which facilities for intensive life support are immediately available and where a clinician familiar with management of potentially life-threatening allergic reactions is in attendance.a b

  A systemic reaction to the skin test (e.g., generalized rash, tachycardia, dyspnea, hypotension, anaphylaxis) usually precludes further ATG (equine) administration.85 a b (See Contraindications under Cautions.)

• Predictive value of skin test procedure not proven clinically; allergic reactions, including anaphylaxis, have occurred in patients whose skin test was negative.a b Always take precautions to treat severe systemic reactions.a b

Premedication

• To minimize or prevent infusion-related adverse effects (including fever and chills), the manufacturer and some clinicians recommend premedication with an antipyretic (e.g., acetaminophen), antihistamine (e.g., diphenhydramine), or corticosteroids or some combination of these agents prior to ATG (equine) infusion.23 30 33 34 35 37 43 a b

Prophylactic Antiviral Therapy

• Although not specifically recommended by manufacturer, some clinicians administer prophylactic antiviral therapy (e.g., acyclovir, ganciclovir, valganciclovir) during ATG (equine) therapy.n hh ii jj kk ll (See Immunosuppressive-related Infectious Complications and Hematologic Effects under Cautions.)

Administration

IV Administration

For solution compatibility information, see Stability.

Administer ATG (equine) by slow IV infusion.a b Allow to reach room temperature prior to administration.b

Because slight granular or flaky deposits may develop in ATG (equine) concentrate for injection during storage, the manufacturer states that ATG (equine) solutions should be infused through an inline 0.2- to 1-mcm filter.a b

Administer into a high-flow central vein, vascular shunt, or arteriovenous fistula (e.g., Brescia-Cimino fistula) to minimize risk of phlebitis and thrombosis.23 a b

ATG (equine) concentrate for injection must be diluted prior to IV infusion.a b

Dilute appropriate dose of ATG (equine) concentrate for injection in 0.9% sodium chloride injection, 5% dextrose and 0.225% sodium chloride injection, or 5% dextrose and 0.45% sodium chloride injectiona b (usually 250–1000 mL);7 23 27 30 34 35 37 45 46 47 50 b final concentration preferably should not provide >4 mg of equine IgG per mL.1 2 a b

Invert IV infusion solution container into which ATG (equine) is added to prevent contact of undiluted ATG (equine) with air inside container.2 a b Mix diluted solution by gently rotating or swirling container; do not shake.a b

Infuse the appropriate dose over at least 4 hoursa b (usually 4–8 hours).23 27 30 34 45 46 47 50 a

Dosage

Dosage of ATG (equine) is expressed in terms of equine IgG.a b

Some clinicians have monitored peripheral blood levels of rosette-forming cells (RFCs) during ATG (equine) therapy in allograft recipients to determine the degree of immunosuppression attained and guide dosage adjustment, with ATG (equine) dosage adjusted to maintain RFC level at about 10% of the pretreatment level,22 23 32 77 a while other clinicians have questioned the reliability and value of this method.71 78 a The availability of monoclonal antibodies has allowed monitoring of specific T-cell subsets,79 80 a and some clinicians previously have monitored peripheral blood levels of OKT3-reactive cells as a method for guiding dosage adjustment, with ATG (equine) dosage adjusted to maintain the level of OKT3-reactive cells at about 10% of the pretreatment value.80 a Monitoring of CD3 T cells currently is used by some clinicians to guide ATG (equine) dosage adjustment and reduce risk of immunosuppression and treatment costs.k ff gg

Pediatric Patients

15 mg/kg daily for 14 days followed by 15 mg/kg every other day for an additional 14 days (total of 21 doses in 28 days).a b Usually continue other immunosuppressive therapies used for prevention and/or treatment of renal transplant rejection (e.g., azathioprine, corticosteroids, graft irradiation).2 17 18 19 20 21 22 23 24 25 26 27 30 31 32 33 34 35 a b (See Interactions.)

First dose given within 24 hours before or after transplantation.a b

10–15 mg/kg daily for 14 days; if necessary, may be followed by 10–15 mg/kg every other day for an additional 14 days (total of 21 doses in 28 days).a b Usually continue other immunosuppressive therapies used for prevention and/or treatment of renal transplant rejection (e.g., azathioprine, corticosteroids, graft irradiation).2 17 18 19 20 21 22 23 24 25 26 27 30 31 32 33 34 35 a b (See Interactions.)

First dose given when initial episode of acute rejection is diagnosed.a b

10–20 mg/kg daily for 8–14 consecutive days,36 37 41 91 103 104 107 a b followed by 10–20 mg/kg every other day for up to an additional 14 days if necessary (up to a total of 21 doses in 28 days). 41 91 a b

Prophylactic platelet transfusions may be necessary to maintain platelet counts at clinically acceptable levels because thrombocytopenia may occur in aplastic anemia patients receiving ATG (equine) therapy.a b

Optimum dosage not established; various dosage regimens including 5–15 mg/kg daily, 15–30 mg/kg every other day, and 15 mg/kg twice daily have been given for at least 1–10 doses in adult and pediatric patients.d e f g h i r v

Adults

15 mg/kg daily for 14 days followed by 15 mg/kg every other day for an additional 14 days (total of 21 doses in 28 days).a b Usually continue other immunosuppressive therapies used for prevention and/or treatment of renal transplant rejection (e.g., azathioprine, corticosteroids, graft irradiation).2 17 18 19 20 21 22 23 24 25 26 27 30 31 32 33 34 35 a b (See Interactions.)

First dose given within 24 hours before or after transplantation.a b

10–15 mg/kg daily for 14 days; may be followed by 10–15 mg/kg every other day for another 14 days (total of 21 doses in 28 days).a b Usually continue other immunosuppressive therapies used for prevention and/or treatment of renal transplant rejection (e.g., azathioprine, corticosteroids, graft irradiation).2 17 18 19 20 21 22 23 24 25 26 27 30 31 32 33 34 35 a b (See Interactions.)

First dose given when initial acute rejection episode diagnosed.a b

10–20 mg/kg daily for 8–14 consecutive days,36 37 41 91 103 104 107 a b followed by 10–20 mg/kg every other day for up to an additional 14 days if necessary (up to a total of 21 doses in 28 days). 41 91 a b

Prophylactic platelet transfusions may be necessary to maintain platelet counts at clinically acceptable levels because thrombocytopenia may occur in aplastic anemia patients receiving ATG (equine) therapy.a b

Optimum dosage not established; various dosage regimens including 5–15 mg/kg daily, 15–30 mg/kg every other day, and 15 mg/kg twice daily have been given for at least 1–10 doses in adult and pediatric patients.45 50 d e f g h i v

Optimum dosage not established; 7 or 10 mg/kg every other day for 6 doses has been given.45 46 47 a

Prescribing Limits

Adults

Not determined; manufacturer states that some patients have received up to 50 doses of ATG (equine) (10–20 mg/kg per dose) in 4 months and others have received 28-day courses of 21 doses followed by up to 3 additional courses.a b

Special Populations

No special population dosage recommendations at this time.a b

Absorption

Onset

Immediate reduction in rosette-forming cell (RFC) levels in peripheral blood occurs following IV administration of ATG (equine); time for RFCs to recover to normal levels after drug discontinuance depends on the patient’s catabolic rate and, in some patients, duration of therapy.2 a

Plasma Concentrations

Peak plasma levels of equine IgG vary following IV administration of ATG (equine) depending on the patient’s ability to catabolize foreign IgG.2 a Mean peak plasma concentrations of equine IgG averaged 727 ± 310 mcg/mL after IV infusion of ATG (equine) 10 mg/kg daily for 5 days.2 a

Distribution

Extent

Not fully characterized.2 87 a b

ATG (equine) is likely to be poorly distributed into lymphoid tissues (e.g., spleen, lymph nodes), since antilymphocyte serum poorly distributes into these tissues.3 6 9 a

In vitro, ATG (equine) binds to essentially all circulating lymphocytes, granulocytes, and platelets; bone marrow cells; visceral tissues, including thymus and testis cell membranes, and to nuclear and cytoplasmic components of tonsil, kidney, breast, liver, lung, intestine, and testes (including Leydig cells).87 a

Not known whether ATG (equine) crosses placenta, but placental distribution likely since other immunoglobulins cross placenta;15 a virtually all transplacental passage of immunoglobulins occurs during the last 4 weeks of pregnancy.15 a

Not known whether ATG (equine) distributes into human milk; however, may be distributed into milk since other immunoglobulins (e.g., IgA, IgM, IgG) are present in colostrum.16 a b

Elimination

Elimination Route

Approximately 1% excreted in urine, principally as unchanged equine IgG.2 a

Half-life

Plasma half-life averages about 6 days (1.5–12 days).2 a b

• Tell all of your health care providers that you take antithymocyte globulin. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
• You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• Talk with your doctor before getting any vaccines while you take antithymocyte globulin and after you stop taking it. Vaccine use with this medicine may either raise the chance of an infection or make the vaccine not work as well. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using antithymocyte globulin while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein over a period of time.
• You will be given a test dose before your first dose.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

(an te THY moe site GLOB yu lin, E kwine)

• Anti-Thymocyte Globulin (Equine)
• Antithymocyte Immunoglobulin
• ATG
• Horse Antihuman Thymocyte Gamma Globulin
• Lymphocyte Immune Globulin

• Atgam

There are no dosage adjustments provided in the manufacturer's labeling.

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.