Merieux Anti-Thymocyte globulin (ATG)


With the introduction of Tacrolimus and MMF, rejection resistant to steroids or these agents is uncommon.

 

Indication

May be given for treatment of rejection episodes in steroid resistant rejection (persistent biopsy proven rejection despite two courses of methylprednisolone).
 

 

Contra-indications

 


Dosage and administration

ATG is usually given over a 10 day period with an absolute T-cell count determining the administration schedule (ATG only given if absolute T-Cell count >0.05).
 

 

Test dose

 


Administration of test dose

5 mg ATG in 100 ml NaCl 0.9% can be infused through a peripheral vein over 1 hour, although administration via a central vein is preferable.
Pre-dose administration of 1g paracetamol and 10mg chlorpheniramine iv is recommended.

 


Preparation of test dose

One vial contains 25 mg ATG.
Reconstitute vial contents with accompanying diluent (5 ml water for injections), giving a solution of 5 mg ATG per ml.
Take 1 ml of solution and add to 100 ml NaCl 0.9%.

 


Observations during / after test dose

Observe patient closely
Monitor BP, pulse and temperature according to the following schedule:

 Time after dose
Frequency of observations
0 - 2 hrs 15 mins
2 - 4 hrs 30 mins
thereafter hourly


•    First full dose

 


Administration

ATG 1.5mg/kg in 0.9% NaCl given over 6 - 8 hours via a central line. Round the dose to the nearest 25 mg.

 


Preparation

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

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Observations

Observations as for test dose.

•    Further doses
Further doses given when absolute T cell count >0.05. if <0.05, ATG not given. It is unlikely that ATG will need to be given daily: more usually only 3 doses are needed over the 10 day period.

To allow calculation of T cell count, need:
DAILY FACS - convert result to decimal to plug into equation, e.g. 30% = 0.3
DAILY LYMPHOCYTE COUNT

T cell count is determined as follows:

No. lymphocytes x FACS result = T cell count
e.g. 0.2 x 0.3 = 0.06.

 

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.

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Monitoring

See observations.

Also:

 


Daily:

 

Daily differential WCC for lymphocytes } for T cell count determination
FACS                                                 } for 10 day course

FBC } during 10 day course and for 2 weeks after U & E's

 

Interrupt treatment if platelet count <50000 / mm3

Consider interrupting treatment if <2000 leukocytes / mm3

 

 


Interactions

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

DRUG

DAY

  0 1 2 3 4 5 6 7 8 9 10 11-30 31+
ATG Full * * * * * * * * * *    
Tacrolimus/
Ciclosporin
Y N N N N N N Y2 Y2 Y2 Y2 Y2  Y2
Prednisolone Y Y Y Y Y Y Y Y Y Y Y Y Y
Azathioprine/
Mycophenolate mofetil
Y N N N N N N N Y Y Y Y Y
PCP prophylaxis1 Y Y Y Y Y Y Y Y Y Y Y Y Y

 

 *Depending on T cell count

  1. For PCP prophylaxis use cotrimoxazole 480 mg daily, if patient allergic to co-trimoxale then the cotrimoxazole de-sensitisation protocol should be used (see page 39.) Continue if need to complete 3 month course.

    CMV and HSV prophylaxis using Valganciclovir for 6 months should also be used (see page33).
     
  2. Tacrolimus reinstated at dose of 0.05 mg / kg twice daily. Ciclosporin reinstated at dose 3 mg / kg twice daily.

 


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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