Serious adverse events following falsely high glucose measurements resulting from administration of an IGIV product containing maltose

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Serious adverse events following falsely high
glucose measurements resulting from
administration of an IGIV product containing
maltose

• L. Ross Pierce, M.D.
• Medical Officer, Clinical Review Branch, Div. of
  Hematology, FDA

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Popularity and Pitfalls of Glucose Meter Testing
Adverse Drug/Device Interaction

• Point-of-care capillary blood glucose meters
  widely used in hospitals/clinics and at home.
• Test strips using Glucose Dehydrogenase
  Pyrrolo-Quinoline Quinone (GDH-PQQ) not specific
  for glucose only some bear PRECAUTION in PI.
• Non-specific glucose test methods still
  inappropriately used in patients who are
  receiving parenteral maltose-containing products
  (some IGIVs)

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Two Different Glucose Dehydrogenase Enzymes

• GDH-PQQ does not contain NAD
• Uses EITHER glucose or maltose as substrates
• Used in many test strip systems.
• NAD-dependent Glucose Dehydrogenase
• Uses glucose but NOT maltose as substrate
• Used in gt 1 glucose meter test strip system.

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BIOCHEMICAL, CHEMICAL, ELECTROCHEMICAL
REACTIONSTHAT OCCUR DURING GDH-PQQ ASSAYS
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BIOCHEMICAL, CHEMICAL, ELECTROCHEMICAL OR
COLORIMETRIC REACTIONSTHAT OCCUR DURING GDH-PQQ
ASSAYS
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Relevant Redox Forms of PQQ
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Enzyme Specificity (Maltose Interference)
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Parenteral Maltose Causes False Hyperglycemia
Results with which Test Systems?

• Maltose Interference
• GDH-PQQ
• NAD-independent
• Point of Care Glucose Meters (Electrode)
• Point of Care Colorimetric systems
  (e.g.,glucose-dye-oxidoreductase)
• No PaO2 effect

• No Maltose Interference
• NAD-dependent GDH (no PaO2 effect)
• Hexokinase (low PaO2 interferes)
• Glucose Oxidase (low PaO2 mannitol gt 5 mg/mL
  interfere)

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Which IgG products contain maltose?

• Octagam 5 (Octapharma)
• Gamimune N 5 (Bayer/Talecris)
• WinRho SDF Liquid (Cangene)
• No interference expected at labeled doses
• Vaccinia Immune Globulin (Cangene)
• Only available through CDC
• Interference expected at labeled doses

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What recent actions has CBER taken in response to
these adverse events?

• Formed CBER/CDRH working group
• Strengthen Labeling of maltose-containing IGIVs
• Asked sponsors to issue IMPORTANT DRUG WARNING
  letters to physicians, customers, and hospitals.
• Coordination with CDRH and CDER on Health Alerts
  for FDA websites and MEDWATCH Listservs.
• Drafting an article to be submitted
  widely-circulated medical journal(s).

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Work with Sponsors

• Revise package inserts Re potential for falsely
  elevated blood glucose results
• add a WARNING
• strengthen PRECAUTIONS

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New Class Labeling for Maltose-Containing IGIVs

• Labeling will indicate
• Some types of blood glucose testing systems (e.g.
  GDH-PQQ or glucose-dye-oxidoreductase methods)
  falsely interpret maltose as glucose.
• This has resulted in inappropriate administration
  of insulin, resulting in life-threatening
  hypoglycemia.

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Class Labeling for Maltose-Containing IGIVs
(cont.)

• When administering maltose-containing IGIVs, use
  a glucose-specific method for measuring glucose.
• Carefully review the product information of the
  glucose testing system, including that of the
  test strips, to determine if the system is
  appropriate for use in patients receiving
  maltose-containing parenteral products. Contact
  the manufacturer of the test system if there is
  any uncertainty.

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References (partial list)

• Medical Device Alert. Medicines and Healthcare
  Products Regulatory Agency. April 16, 2003.
• Kannan S et al. Intragam can interfere with blood
  glucose monitoring.
  MJA 2004180251-252
• ISMP Medication Safety Alert!
  Sept 8 22, 2005.
• WWW.Octapharma.com/USA