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ATGAM

Actions and Uses

    Equine polyclonal antibodies against human thymocytes. It is produced by repeated inoculation of horses with human thymocytes. It is an effective immunosuppressant which has been in clinical use since 1981 It is used primarily in the prevention and treatment of acute renal allograft rejection.
    ATGAM is described as a lymphocyte-specific immunosuppressant. It contains antibodies specific to the antigens commonly found on the surface of T-cells (CD2, CD3, CD4, CD8, CD11a, and CD18). After binding to these surface molecules, ATGAM promotes the depletion of T-cells from the circulation.through opsonization and complement-assisted, antibody-dependent cell-mediated cytotoxicity. The damaged T-cell are subsequently cleared by the lymphreticular system (spleen, liver, and lungs)
    ATGAM is used in the
    1. Prevention and treatment of acute renal allograft rejection
    2. Prevention of graft-vs-host disease (GVHD) in bone marrow transplant (BMT) patients.
    3. Treatment of aplastic anemia in patients not suitable for BMT.

Pharmacokinetics

  • Binds to circulating lymphcytes, granulocytes, platelets, etc.
  • Plasma half-life: 36 hrs - 12 days

Contraindications and Warnings

  • Anaphylactic reactions are rare, but do occur and all precautions should be taken before ATGAM infusion is started.
  • ATGAM should not be given to patients with a history of allergy to horse serum.

Available As

    Ampule containing 250 mg of equine IgG per 5 mL.

Dose and Administration

  • A test dose (0.1 mL of a freshly prepared 0.05 mg/mL solution in NS) may be given intradermally. The patient and injection site is examined every 15 min for one hr. However, a negative test does not guarantee a reaction-free administration. Also, a positive reaction does not always mean that the drug cannont be used with extreme caution if it is absolutely essential (risk/benefit analysis is necessary).
  • Before each dose, the patient may be pretreated with diphenhydramine (Benadryl) and acetaminophen (Tylenol).
  • The ATGAM dose must be diluted in normal saline or 1/2 normal saline to a concentration not exceeding 4 mg/mL. If the drug is to be given via a peripheral line (not recommended) the concentration should be less than 1 mg/mL.
  • The ATGAM dose should be administered via iv infusion into a central line over a minimum of 4 - 8 hrs. Infusion should be stopped immediately if a systemic reaction (dyspnea, tachycardia, hypotension, or a generalized skin reaction) or anaphylaxis occurs.
  • Acute Renal Allograft Rejection: 15 mg / kg q24h for 14 days, then give q48h for 7 more doses for a total of 21 doses in 28 days. Therapy should be discontinued if severe thrombocytopenia or leukopenia occurs.
  • Aplastic Anemia: 15 mg / kg q24h for 10 days, then give q48h for 7 more doses. Another protocol which is used only in adults calls simply for 40 mg/kg q24h for 4 days.

Main Side Effects

  • Fever (most pts), chills, hypotension, hypertension, dyspnea, chest pain, tachycardia, and edema.
  • Leukopenia (>10%) and thrombocytopenia (>10%); anemia (<1%)
  • Anaphylaxis(>1)
  • Skin reactions (rash; pruritus, etc): most pts.
  • Nausea, diarrhea, stomititis, GI bleed.
  • Myalgia; back pain (>1%); seizures (<1%)
  • Infections (>10%)

Drug Interactions

  • No pharmacokinetic drug interactions have been described.
  • Excessive immunosuppression can occur when used in combination with other immunosuppressive agents.

References

  1. Brennan DC et al A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation. 1999;67(7):1011-8.
  2. Merion RM. Current use of polyclonal antilymphocyte antibody preparations. Transplant Proc. 1999;31(6):2208-9
  3. Forsythe JL. ATG--a polyclonal sledgehammer? Transpl Immunol. 1994;2(2):148-52

 

 

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