ATG (Anti-thymocyte Globulin)

Merieux Anti-Thymocyte Immunogloblins (ATG)

Indication:

  • Induction therapy for high immunological risk recipients
  • Treatment of vascular rejection or steroid resistant rejection (persistent biopsy proven rejection despite a course of methylprednisolone)

Contra-indications:

  • known allergy to rabbit proteins
  • acute viral illness
  • Previous anaphylaxis to ATG

Dosage and administration:

Thymoglobulin is usually administered through a central line but may be given peripherally if necessary. In such circumstances, 1000 units heparin should be added directly to 0.9% NaCl infusion bag to prevent superficial thrombophelebitis. The combination of thymoglobulin, heparin and hydrocortisone in 5% dextrose should be avoided as precipitation has been reported. Thymoglobulin should be administered through an in-line 0.22um filter.

Induction therapy

(NB: Basiliximab is not given if using ATG for induction)

Dose: 1.5mg/kg in 250mls 0.9% NaCl to run over a minimum of 6 hours for 4 days (Day 0,1,2,3) for a cumulative of 6mg/kg.
No test dose required

  • Day 0: First dose should be administered intra-operatively, prior to allograft reperfusion but after 500mg methyl prednisolone has been given via CVP line. Premedication with 1g paracetamol PO and 10mg chlorpheniramine IV should also be given before thymoglobulin infusion. Significant first dose reactions are not common and do not tend to involve hypotension or bronchospasm. If a reaction occurs intra-operatively, the infusion should be stopped and consideration given for re-starting post-operatively.
  • Day 1: As for Day 0 (following second dose of 500mg methylprednisolone, with 1g paracetamol PO and 10mg chlorpheniramine IV)
  • Day 2,3: Premedication of Hydrocortisone 200mg IV, paracetamol 1g PO and chlorpheniramine 10mg IV before administering thymoglobulin.

Reduce the dose by half if total WCC <3 x109/l &/or Platelets <75 x109/l.

Withhold dose if total WCC < 2 x109/l or platelet count < 50 x109/l.

NB: Tacrolimus, MMF prescribed as for standard immunosuppression. Omit oral prednisolone 20mgDay 2,3,4 and start day 5.

Treatment for acute rejection:

  • The recommended dosage of Thymoglobulin for treatment of acute renal graft rejection is 1.5 mg/kg of body weight administered daily for 5 to 7 days (cumulative dose 7.5 – 10.5mg/kg). Although licensed for 7 – 14 days for AR treatment, this duration is usually not necessary.
  • After the initial 5-7 days dosing, an assessment should be made, and further treatment may be given if the rejection process is ongoing.
  • Reduce the dose by half if total WCC <3 x109/l and/or Platelets <75 x109/l. Dose should be withheld when total WCC < 2×109/l or platelet count < 50×109/l.
  • Premedication of Hydrocortisone 200mg IV (omit oral prednisolone), paracetamol 1g PO and chlorpheniramine 10mg IV before administering thymoglobulin.
  • A test dose is NOT needed for ATG treatment in most cases. However, if the patient has had a previous reaction to ATG or has a history of close exposure to rabbits, it may be considered [5 mg ATG in 100 ml NaCl 0.9% infused through a peripheral vein over 1 hour]. Preparation of test dose:
    • Reconstitute 1 vial (25mg) with 5 ml water for injections, giving a solution of 5 mg ATG per ml.
    • Take 1 ml (5mg) of solution and add to 100 ml NaCl 0.9%

First dose of ATG

Administration:

ATG 1.5 mg/kg in 0.9% NaCl given over 6 – 8 hours ideally via a central line, but  a wide bore peripheral line may be used. Round the dose to the nearest 25 mg.

Preparation:

  • Reconstitute required number of vials with 5 ml dilutent per vial.
  • Add contents of reconstituted vials to 0.9% NaCl, allowing 50 ml per vial (250 ml bag usually appropriate).

Observations:

Time after dose Frequency of Observations
0 – 2 hours 15 minutes
2 – 4 hours 30 minutes
4 – 6 hours Hourly

Side effects:

  • Anaphylaxis, with a drop in arterial pressure, respiratory distress, fever and urticaria may appear during or just after the infusion.
  • Other hypersensitivity reactions include rigors (1%), fever (4%), arthralgia (1%), erythema (1%) and pruritic skin eruptions (0.5%).
  • Symptoms are most commonly seen after the first injection and decrease during the course of treatment.
  • Other side effects include thrombocytopenia (approx. 5%), neutropenia, serum sickness (3%) and lymphoma.

Monitoring:

See observations:

Daily:  FBC and U&Es during course.

Interactions:

Risk of over-immunosuppression, hence the following schedule should be followed:

  • Hold tacrolimus and anti-metabolite while ATG is being given. These can be reinstated the day after the final ATG dose (note that the anti-metabolite may need to be deferred depending on cell counts).
  • For PCP prophylaxis use co-trimoxazole 480 mg daily, if patient allergic to co-trimoxale then the co-trimoxazole desensitization protocol should be used (see page 34). Continue if need to complete 3 month course.
  • CMV and HSV prophylaxis using valganciclovir for 6 months should also be used (see page 35).

Ordering:

Mon-Fri 8.30 – 1700: contact unit pharmacist.
Out of hours: contact resident pharmacist, bleep 2268
Small stock held in pharmacy.

Storage:

Both the dry powder and reconstituted solution to be stored in fridge; protect from light.

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