This document guides how to prescribe, order, administer and manage patients receiving intravenous immunoglobulin (IVIg) at the RCH.

Description

• IVIg is manufactured from human plasma. It contains IgG antibodies and is used in the treatment of a growing number of immunologic, haematologic and neurologic illnesses. 
• All IVIg products undergo a number of steps to minimise the possibility of pathogen transmission.  

Authorisation to administer IVIg

• The use of IVIg in Australia is governed by the National Blood Authority (NBA) and is issued by the Australian Red Cross Blood Service (the Blood Service). 
• Conditions where evidence of clinical efficacy exists are outlined in  The Criteria for the clinical use of intravenous immunoglobulin in Australia (The Criteria), 2018. Access to IVIg is based on the patient meeting conditions or circumstances listed in The Criteria. 
• IVIg authorisations are processed via an online system called BloodSTAR.  This system facilitates authorisations, dispensing and reviews. 
• Medical staff must register with BloodSTAR to request authorisation and complete all required steps including:
  • Patient demographics 
  • Diagnosis 
  • Patient weight 
  • Consent - BloodSTAR specific ‘Record of privacy consent’. This indicates the patient understands their personal information will be recorded in BloodSTAR. 
    
• Medical staff need to register at each hospital they prescribe IVIg. To be eligible to register at RCH an APHRA number and RCH email address are required. For assistance registering call 13 000 BLOOD (13 000 25663).
• If the patient's condition does not meet The Criteria for NBA funded IVIg, application to Drug Usage Committee (DUC) for hospital funded IVIg (Issued via Pharmacy) can be made.  
• Nursing staff can register in the same process as above and can view patient information related to IVIg authorisations, previous and planned treatments, planning sheets and the record of privacy consent.

IVIg products available in Australia

• Australian produced:  
  
  • Intragam^®10
• Imported: 
  • Privigen^® 
  • Fleboamma^® 5%
  • Flebogamma^® 10%
• The NBA determines which patient conditions qualify for funded Australian or imported product. Historically, Australian IVIg has been issued for RCH paediatric patients when local supplies are available to support this. 
• Where a chronic shortage of Australian produced IVIg is experienced, patients will be issued imported IVIg.  Alternatively, clinicians may request imported IVIg via BloodSTAR. For further assistance contact 13 000 BLOOD (13 000 25663)

Storage

• Stored in blood bank between 2 to 6 degrees Celsius. Once removed from blood bank store at room temperature. 
• Do not place in fridges in clinical areas. 
• If IVIg treatment is delayed for any reason return the product to blood bank.

Consent and patient information

Record the consent for the administration of IVIg on the Patient Consent to Blood Products MR634/A. 

Inform the patient of:

• The reason why they need IVIg
• The risks and benefits of the treatment
• The risks of not receiving IVIg

Consent is valid for the duration of the admission. However, consent for patients receiving regular IVIg is valid for 12 months. This should be indicated on the MR634/A.  

Print and provide the patient/family information explaining IVIg:

• RCH Kids Health Info fact sheet – Intravenous Immunoglobulin (IVIg)
• National Blood Authority (NBA): Patient Information: Immunoglobulin Treatment

Consumer information produced by manufactures:

• Intragam^® 10 
• Privigen^®
• Flebogamma^®5% DIF
• Flebogamma^®10% DIF

Contraindications

• True anaphylactic reactions to human immunoglobulins (especially in patients with antibodies against IgA)
• Privigen and Flebogamma are contraindicated in IgA deficient patients with anti-IgA antibodies
• Flebogamma is contraindicated in patients with hereditary problem of fructose intolerance and should not be administered to children under two years of age as this may be undiagnosed. 
  

Precautions

• Reactions to IVIg tend to be related to the infusion rate and are most likely to occur during the first hour of the infusion. Commence the infusion slowly as per recommendations below.
• Intragam 10 has been approved as a modified IVIg product. The stabilising agent is glycine and contains a high concentration of immunoglobulin (10%)
• In IgA deficient patients, product with the lowest level of IgA should be selected. 
• IVIg should not be infused rapidly to patients at increased risk of thromboembolic and renal adverse events, particularly when using the higher concentration IVIg products. Administer at the minimum rate of infusion and dose practicable.
• Renal impairment: patients receiving IVIg have an increased risk of renal failure or dysfunction. Assess renal function prior to product commencement. Administer at the minimum rate of infusion and dose practicable
• Assess renal function prior to product commencement. Administer at the minimum rate of infusion and dose practicable

Medical order

• Order IVIg in EMR. The order must contain:
  • Type of IVIg product and percentage concentration (i.e. Intragam^® 10%, Privigen^® 10%, Flebogamma^® 5%, Flebogamma^® 10%)
  • Patient weight 
  • Total dose in grams
  • Rate of infusion. This should include the target rate along with any rate changes. 
  • Planned date of infusion 
  • Any premedication or requirement for intravenous fluids.  

Dose

• The dose (grams) of IVIg prescribed will vary according to the indication, please refer to The Criteria for further information.  Example: typical dose for Kawasaki Disease is 2g/kg, typical dose for immunodeficiency is 0.4 - 0.5 g/kg
• Doses are rounded up or down so that all of the opened vial is administered. In the instance of weights between the lowest Ig vial size and the second vial size e.g. 3g and 12g, suggest clinical consideration for dose size.

IVIg administration rates and comparisons

Administration rates vary between products and presentations.

IVIg products and presentations are not interchangeable.

• The rate of administration will vary according to the product prescribed. Each product has different formulations, with varying vial size and different administration instructions. 
• Infusion rates should be individualised to the patient’s risk factors, comorbidities and tolerability. 
• Patient at risk for Aseptic Meningitis Syndrome (AMS), renal failure or thromboembolic adverse reactions should have IVIg administered at the minimum rate of infusion and dose practicable.
• Patients receiving IVIg for the first time or are switching brands of IVIg, should commence at the slowest rate and grade up according to the table provided below
• All patients receiving Intragam^® 10 for the first time must commence the infusion rate at the slowest rate to ensure safety and tolerability.
• For subsequent doses of Intragam 10, if previously tolerated it is recommended that the rate is commenced at:
  • 1 ml/kg/hr for 30 minutes
  • If tolerated, increase to 2 ml/kg/hr  for 30 minutes
  • If tolerated, increase to maximum of 4 ml/kg/hr
• Subsequent doses: limited experience at the RCH with infusing Privigen^®, Flebogamma^® 5% or Flebogamma^® 10%. Suggest following the table below as a guide. 

Foot Notes:

1. Intragam® 10 - The use of Intragam® 10 in the paediatric population has not been established in clinical studies.
2. Flebogamma^® 5% and 10% is contraindicated in patients with hereditary problem of fructose intolerance. Babies and young children may not yet be diagnosed with this condition may be fatal) and should not receive this product. 

Administering and completing IVIg 

• Allow IVIg to reach room temperature
• Administer directly via the bottle provided by blood bank. Do not remove IVIg from the bottle and attempt to administer via a syringe driver.
  
• IVIg does not contain any antimicrobial preservative, therefore each bottle of IVIg must be administered within 6 hours from spiking the bottle.
• Use a vented system
• Commence with the smallest vials first. 
• During EMR downtime IVIg will be issued with a compatibility report. Complete all details and send to HIS for scanning. 
  

Observing the patient receiving IVIg

• Observations will include:
  • Temperature
  • Pulse
  • Respiratory Rate
  • Blood Pressure
  • Oxygen Saturations
  • Site Observations (IV site or CVAD)
• Observations will be conducted:
  • At baseline
  • 15 minutes after commencement and 15 minutes after each rate change
  • Hourly during the infusion
  • At conclusion
• Ask the patient or parent to report:
  • Any unusual symptoms
  • If they feel unwell
  • Pain at IV site
  • Unusual symptoms in the 24 hours after infusion

Reactions, adverse events and near misses

Reactions:

• Manage and report reactions as per the Fresh Blood Product Transfusion Procedure including reporting to blood bank and in the electronic medical record.
• Most reactions are mild in nature and can include: 
  • Flushing, headache, chills, fever, vomiting, nausea, mild allergic reactions, mild changes in HR or blood pressure. 
• These types of reactions may be rate dependant and may respond to a reduction in the rate of infusion.  
• Continue to closely observe the patient

Other possible reactions:

• Anaphylaxis is a rare but documented adverse effect of IVIg.  Please refer to the  Anaphylaxis guideline for management
• Haemolysis:  IVIg contains blood group antibodies that can cause haemolysis. Most commonly anti-A in patients of blood group A and AB.  The antibody can coat the patient’s red cells resulting in a positive direct antiglobulin test and occasionally haemolytic anaemia
• Thromboembolic events: Infusion of IVIg may lead to a relative increase in blood viscosity.  Patients should be adequately hydrated prior to commencement of the infusion.  Assess renal function prior to product commencement. Administer at the minimum rate of infusion and dose practicable
• Aseptic meningitis syndrome: Has been reported to occur after IVIg treatment For patients at risk consider:
  

Intragam^® 10 – as this is a new product, with an unknown side effect profile in children, the clinical haematology team suggest the following investigations in the event of a severe headache:

• Venous gas
• Electrolytes including calcium, magnesium and phosphate
• Ammonia 
• Report as a transfusion reaction and liaise with the on-call haematologist 

Adverse events or near miss:

• Report any adverse events or near miss via VHIMS. These will be reported to the Transfusion Committee who will report to CSL and the TGA as needed.

Overdose:

• Overdose of IVIg may lead to fluid overload and hyperviscosity, particularly in patients with renal impairment.

Interactions with other medicines

• Immunoglobulin infusion may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella for a period of at least six weeks and up to three months.
• Interaction with other medicines has not been established.