Canterbury DHB

ATG/ALG Guidelines

Horse antilymphocyte globulin has been shown to be superior to rabbit ALG. Prescribe it by the name of ATGAM to avoid confusion:

• Prednisone is given with ATG for the sole purpose of preventing side effects.
• ATGAM must be given as an in-patient.
• The dose of ATGAM is 40 mg/kg/d for 4 days given as a 12 to 18 hour infusion.
• A test dose must be given.
• A PICC or Hickman line must be used.

Test Dose

Test dose - Add approximately 0.5 mL (25 mg) Atgam® to 100 mL normal saline and infuse intravenously over one hour.

For monitoring details, see Administration and Monitoring below.

The purpose of the test dose is to see if the patient develops anaphylaxis. The signs of anaphylaxis are tingling in the extremities and around the mouth, swelling of the lips and larynx, bronchospasm, urgency of defecation, hypotension. It is rare in patients not previously exposed medically to animal protein but is obviously potentially fatal. During the test dose a doctor must be present throughout. Have adrenaline, chlorphenamine and hydrocortisone drawn up beforehand. The reaction will normally stop immediately with hydrocortisone 100 mg IV plus chlorphenamine IV but adrenaline may be necessary.

A severe systemic reaction or anaphylaxis to the test dose needs to be discussed with the consultant before proceeding with treatment. It may be necessary to discontinue treatment with this product.

Administration following test dose

Therapeutic dose – Add prescribed dose (40 mg/kg) of Atgam® to 500 to 1000 mL normal saline and infuse intravenously over 12 to 18 hours. See notes above.

Atgam® is ideally diluted down to a concentration of 1 mg/mL, but should not ever exceed a concentration of 4 mg/mL. Give it within 12 hours of being made up. Precede each daily dose of ALG/ATG with:

• Platelets (if the platelet count is < 30 X 10⁹/L):
  • 1-ATD for an adult and proportionally less for a child.
  • If platelet count is ≥ 30 x 10⁹/L, platelets do not need to be given before ATG.
  • Do not give the platelets during ALG/ATG infusion (because of its anti-platelet activity).
• Methylprednisolone 1 mg/kg IV and promethazine 25 mg IV.

Side Effects

Immediate (During administration)

• Fevers and rigors (tend to be worse on the first day and diminish with subsequent doses of ALG/ATG).
• Rash, anaphylaxis rarely, and fluid retention (usually multi-factorial: normal saline diluent, blood and platelets, corticosteroids, chronic anaemia etc).
• Hypotension or hypertension.
• Neutropenia and thrombocytopenia

Late (after administration = serum sickness)

Onset is 7 to 13 days after starting ALG/ATG.

• Fever, rash (maculopapular or urticarial starting on trunk and spreading to extremities. Serpiginous palmar-plantar distribution is classical. Rash may become purpuric).
• Arthralgia, myalgia, nausea, vomiting, proteinuria (usually mild), splenomegaly, lymphadenopathy, increased platelet requirement.
• Glycosuria and/or hyperglycaemia due to corticosteroids.

Very rarely

• Positive DAGT +/- haemolysis, massive pulmonary haemorrhage and capillary leak.

Administration and Monitoring

• Always give through a central line (i.e. a Hickman or PICC line) because severe thrombophlebitis may occur if ALG/ATG is administered via a peripheral vein.
• Remove required number of vials from the refrigerator an allow to reach room termperature before reconstitution (approx. 30 minutes).
• Reconstitute each vial slowly by injecting 5 mL of sterile water for injection to the inside wall of each vial.
• Avoid forceful impact of the water for injection on the powder and avoid foaming. Do this by by slow dropwise addition of water for injection down the inside of the vial and not directly onto the lyophilsed cake. Tilt and roll each vial gently. Do not invert or shake. See Medsafe data sheet for more detail.
• Use an inline filter with a pore size of 0.2 to 1.0 micron.
• Carefully monitor for evidence of bleeding.
• Monitor blood pressure.
• Full fluid balance including daily weigh.
• Daily CBC + diff.

Observations

• Before starting infusion, perform baseline observations of temperature, blood pressure, respiratory rate and heart rate.
• After starting infusion, perform observations:
  • at 15-minute intervals up to one hour, and then
  • at hourly intervals until completion.
• Perform a final set of observations once the infusion is complete.
• For both initial and following infusions, closely monitor the patient for adverse events during and for 3 to 4 hours after completion of the infusion.
• If there is clinical indication, monitor observations more frequently.
• For further information, see Antithymocyte globulin for graft versus host disease (GVHD) prophylaxis in blood and marrow transplant (BMT) on eviQ.

Contraindications of ALG/ATG Treatment

• Systemic reaction to test dose.
• ALG/ATG may exacerbate viral and parasitic infections, so do not give in the presence of active infection.
• There is a theoretical risk of acute haemolysis in patients with Paroxysmal Nocturnal Haemoglobinuria (PNH) who are already haemolysing. However, ALG/ATG can be given cautiously to patients with a quiescent PNH clone.

Topic Code: 27305