1 serious adverse events following falsely elevated glucose measurements resulting from...
TRANSCRIPT
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Serious Adverse Events Following Falsely Elevated Glucose
Measurements Resulting from Administration of an
IGIV Product Containing Maltose
BPAC Meeting, Gaithersburg, MD, November 4, 2005
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Adverse Event Case Report Summary
Ann Gaines, PhD, MT(ASCP)Division of EpidemiologyOffice of Biostatistics and EpidemiologyCenter for Biologics Evaluation and Research
BPAC Meeting, Gaithersburg, MD, November 4, 2005
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Artifactual Hyperglycemia
Falsely increased glucose results may occur in patients:
Who receive parenteral maltose-, parenteral
galactose-, or oral d-xylose-containing biologic and
drug products.
When blood glucose levels are measured by
methodologies that are non-specific for glucose in
presence of maltose-, galactose-, or d-xylose-
containing products.
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Clinical Consequence
Falsely elevated glucose results due to maltose,
galactose, or d-xylose may result in life-threatening or
fatal hypoglycemia when:
Insulin is inappropriately administered for artifactual
hyperglycemia, e.g.,
glucose-non-specific methodology = 231 mg/dL, yet
glucose-specific methodology = 84 mg/dL.
Treatment is not provided for actual hypoglycemia, e.g.,
glucose-non-specific methodology = 167 mg/dL, yet
glucose-specific methodology = 41 mg/dL.
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Case Reports
CBER is aware of 6 case reports involving maltose-containing intravenous immune globulin products andfalsely elevated blood glucose measurements.
Case Location Year Outcome 1 U.S. 2005 Fatal
2 U.K. 2002 Fatal
3 France 2003 Resolved 4 France 2003 Resolved 5 Australia 2004 Resolved 6 Australia 2004 Resolved
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Case Report 1
86-year-old male patient with complicated medical history, including diabetes.
Admitted with 4-day history of cellulitis of foot.
Received OCTAGAM* for treatment of septic shock.
Experienced complicated hospital course.
Monitored blood glucose levels [and adjusted insulin doses] primarily with glucose non-specific methodology.
Became hypoglycemic then comatose.
Expired.
* IGIV manufactured by Octapharma; contains 10% maltose.
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Case Report 1 (continued)Blood glucose levels in conjunction with OCTAGAM administration
0
100
200
300
400
500
600
Sequential blood glucose measurements
Blo
od g
luco
se (m
g/dL
)
Glucose-specific
Glucose non-specific
Octagam
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Case Report 1 (continued)Blood glucose levels in conjunction with insulin administration
0
100
200
300
400
500
600
Sequential blood glucose measurements
Blo
od g
luco
se (m
g/dL
)
Glucose-specific
Glucose-nonspecific
SC insulin
IV insulin
Octagam
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Case Report 2
Reported to the Medicines and Healthcare Products
Regulatory Agency (U.K.) in 2002:
50-year-old diabetic male with failing pancreas-renal
transplant received OCTAGAM as anti-rejection
agent.
Based on artifactual hyperglycemia, inappropriate
insulin administered.
Developed severe hypoglycemia, became comatose,
expired.
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Case Reports 3 and 4
Reported to the French Health Products Safety Agency
in 2003; both cases involved 3-week-old non-diabetic
males:
Received OCTAGAM for unknown indications.
Developed artifactual hyperglycemia.
Recognized or resolved without intervention.
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Case Reports 5 and 6Reported in Medical Journal of Australia in 2004:
64-year-old diabetic female on dialysis received Intragam P* for ITP: developed artifactual hyperglycemia. increased insulin administered. developed actual hypoglycemia. resolved without apparent sequelae.
35-year-old non-diabetic female on parenteral nutrition received Intragam P* for ITP: developed artifactual hyperglycemia. recognized and resolved without intervention.
* IGIV manufactured by CSL Limited; contains 10% maltose
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Unknown Frequency of Adverse Event
FDA’s adverse event surveillance for licensed
products uses primarily passive surveillance.
Limitations of passive surveillance systems, such as FDA’s MedWatch (e.g., voluntary reporting).
Actual incidence rate of artifactual hyperglycemia adverse event (e.g., occurrences per 100,000 patients) unknown.
Estimated reporting rate of artifactual hyperglycemia adverse event (e.g., reports per 1,000,000 prescriptions) unknown.
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Adverse Event ReportingPhysicians, other health care professionals, andpatients encouraged to submit serious adverse eventreports for any FDA-approved product:
Directly to FDA:
by Internet at http://www.fda.gov/medwatch.
by telephone at 1-800-FDA-1088.
by fax at 1-800-FDA-0178.
by mail at MedWatch, HF-2, 5600 Fishers Lane,
Rockville, MD 20852-9787.
To FDA through manufacturers or distributors: contact information generally available in professional package inserts or on web sites.