Description of hypersensitivity adverse events following administration of heparin that was potentially contaminated with oversulfated chondroitin sulfate in early 2008.
OBJECTIVE
To characterize the nature of a heparin contaminant's clinical effects in cases reported to the Adverse Event Reporting System (AERS). The FDA received reports of heparin-associated adverse events (AEs) starting in late 2007-early 2008 during a national investigation of allergic-type events. The investigation identified Baxter Healthcare-brand heparin product due to its strongest association with the events. Later, oversulfated chondroitin sulfate (OSCS), a heparin-like contaminant, was discovered.


METHODS
This study was a case series of heparin reports in AERS received 1 January 2008 to 31 March 2008. Variables considered were frequency of treatment settings, AEs, mortality; as well as heparin dose and OSCS contamination.


RESULTS
Five hundred seventy-four AERS cases (unduplicated reports) were identified and included. Of 94 cases with a fatal outcome, 68 reported at least one AE term from the list used to identify an allergic-type event. Nearly 75% of AEs in cases of IV administration (n = 170/233) reportedly occurred within 10 minutes, whereas over half of subcutaneous administration cases (n = 13/23) resulted in times-to-event of greater than 24 hours. Although cases with a time-to-event of less than 10 minutes appeared to correlate with higher levels of OSCS contamination, no clear differences were noted between high- and low-to-absent OSCS concentration lots with respect to AEs observed.


CONCLUSIONS
Intravenous administration and a higher OSCS concentration appeared to correlate with a more rapid onset of event. The FDA continues to monitor AEs associated with heparin use and has taken appropriate regulatory action to ensure a safe heparin drug supply.
McMahon
Ann W
AW
Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993, USA. ann.mcmahon@fda.hhs.gov
Pratt
Robert G
RG
Hammad
Tarek A
TA
Kozlowski
Steven
S
Zhou
Esther
E
Lu
Susan
S
Kulick
Corrinne G
CG
Mallick
Tarun
T
Dal Pan
Gerald
G
D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects* / Q000737:chemistry / Q000592:standards; D002648:Child; D002675:Child, Preschool; D002809:Chondroitin Sulfates / Q000009:adverse effects* / Q000737:chemistry / Q000592:standards; D004340:Drug Contamination; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors; D014481:United States; D014486:United States Food and Drug Administration; D055815:Young Adult
D000925:Anticoagulants; D006493:Heparin; D002809:Chondroitin Sulfates