Parenteral Manual

Anti-thymocyte globulin Equine (eATG) and Anti-thymocyte globulin Rabbit (rATG)

Disclaimer: Official controlled document is the CHEO online copy. It is the responsibility of user to ensure that any paper copy version is the same as the online version before use.

Alternate Name(s): 
ATGAM (equine), Thymoglobulin (rabbit)
Classification: 
Immunosuppressant
Original Date: 
December 2006
Revised Date: 
September 2012
Indications: 

    Prevention and/or treatment of acute allograft rejection (kidney, heart, skin, bone marrow, heart/lung, liver)

·          Treatment of severe aplastic anemia

·          Treatment of graft-versus-host disease (GVHD)

·          Prevention of bone-marrow graft failure

Reconstitution and Stability: 

Equine ATG:

  • Available as a 50 mg/mL solution in 5 mL ampoules (250 mg/amp). Refrigerate ampoules; DO NOT FREEZE.
  • Stable for only 24 hours refrigerated after dilution with IV solution (including infusion time)
  • DO NOT use if precipitate present

Rabbit ATG:

·          Available as a 25 mg powder for reconstitution. Refrigerate vial. Protect from light.

·          Allow diluent and contents of vial to reach room temperature prior to reconstitution.

·          Reconstitute 25 mg vial with 5 mL of sterile water for injection = 5 mg/mL solution 

·          Reconstituted vials are to be used within 4 hours if kept at room temperature.

·          Reconstituted solutions should be clear and should not be used if discoloured or opaque or if particles are present.

Diluted solutions stable 24 hours at room temperature (including infusion time)

Compatibility: 

- Solutions compatible:

Equine ATG: 0.45% NaCl, NS and dextrose/saline combinations

Rabbit ATG: D5W and normal saline

 

- Incompatible:

Equine ATG: D5W alone

No information on compatibility with potassium chloride, morphine or TPN; run in dedicated line.

Administration: 

(For approved routes of administration by nursing personnel, refer to Policy for the Administration of Intravenous Medications.)

SC NO, test dose is intradermal
IM NO
IV Direct NO
IV Intermittent Infusion

Equine ATG: YES, preferably in a central line to minimize phlebitis, thrombosis and pain

Usual dilution: 1 mg/mL
Fluid restricted: 4 mg/mL
Infusion time: 4-8 hours

Rabbit ATG:YES, preferably in a central line to minimize phlebitis, thrombosis and pain

 

Usual dilution: 0.5-2 mg/mL

Infusion time: 6-8 hours; Slow infusion rate over 8 hours if peripheral IV in order to avoid phlebitis.  Increase infusion rate over 4 hours if previous doses have been tolerated without reaction.

NOTE: Use 0.22 micron in-line filter to infuse anti-thymocyte globulin rabbit
 and  0.2 - 1 micron in-line filter for anti-thymocyte globulin equine. Will clog the filter.  Change the filter frequently throughout the infusion
IV Continuous Infusion NO

 

Dosage: 

(For neonatal dosages, refer to Neonatal IV Drug Manual.)

NOTE: Doses of these agents are not equivalent. Rabbit ATG is 10 times the potency of equine ATG

 

Equine ATG:

PEDIATRIC:

  • Renal allograft recipients:
    - Prevention of rejection: 15 mg/kg/24 hr x 14 days, then alternate days x 7
    more doses (1st dose within 24 hrs of transplant)
    - Treatment of rejection: 10-15 mg/kg/24 hr x 14 days, then alternate
    days x 7 more doses
  • Prevention of bone marrow graft failure:
    - Dose according to specific protocol
  •  Treatment of aplastic anemia:
    - 10-20 mg/kg/24 hr for 21 days OR 40 mg/kg/day once daily for 4 days,
    then 10-30 mg/kg/dose every other day for 7 more doses
  • TEST DOSE:
    - 5 mcg intradermally (see below for preparation).  A control test using NS
    should be given contralaterally.  Observe patient and skin test site every 15
    minutes during the first hour following the test dose injection.  A local reaction
    >10 mm in diameter with a wheal (>3 mm) or erythema or both should be
    considered a positive skin test.

Rabbit ATG:

Pediatric:

 

·          Aplastic anemia

3.5 mg/kg/day once daily for 5 days

 

·          Bone marrow transplantation

1.5-3 mg/kg/day once daily for 4 consecutive days before transplantation

 

·          Graft-versus-host disease

            1.5 mg/kg/dose once daily or every other day

 

·          Renal transplantation

Induction:            1-2 mg/kg/day once daily for 4-5 days initiated at time of transplant

Acute rejection:   1.5 mg/kg/day once daily for 7-14 days

 

Potential hazards of parenteral administration: 

  • Potential hazards of parenteral administration:

    ·          Anaphylaxis is uncommon but serious.  If anaphylaxis occurs, stop ATG; give epinephrine and steroids.  Assist ventilation.  Do not re-administer ATG

    ·          Patients should be monitored continuously throughout an IV infusion of ATG for respiratory distress, hypotension and skin rash as these may be signs of anaphylaxis

    ·          Keep anaphylaxis kit at bedside during administration of test dose and infusions

    ·          Chills and fever are frequent during infusion; premedication with diphenhydramine, methylprednisilone and acetaminophen 1 hour prior to ATG may help

    ·          Thrombocytopenia, leukopenia, hemolysis (may be severe)

    ·          Itching, erythema (may be controlled with antihistamines)

    ·          Serum sickness-like symptoms (fever, arthralgia, nausea, vomiting, lymphadenopathy, rash) have been noted in aplastic anemia patients

    ·          Hypertension, tachycardia, peripheral edema

     

Notes: 

  • Notes:

     

    ·          Different anti-thymocyte globulins (rabbit and equine) are not interchangeable.

    ·          Monitor WBC count (including lymphocytes), platelets and creatinine daily

    ·          May cause direct antiglobulin test to become positive

Equine ATG:

  • Preparation of 5 mcg test dose (to be prepared by Pharmacy)
  • 0.1 mL of undiluted solution (50 mg/mL = 5 mg) + 9.9 mL normal saline (solution A = 500 mcg/mL)
  • 0.1 mL solution A (50 mcg) + 0.9 mL normal saline (solution B = 50 mcg/mL)
  • Test dose - 0.1 mL solution B (= 5 mcg/0.1 mL)
References: 

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