Abstract
Spontaneously-reported rates of adverse events (AEs) of intravenous (i. v.) iron products
have not been compared since 2007. AEs in Europe (Eur) and North America (NA) have
never been compared. New products have been marketed and many changes in prescribing
habits have occurred since then, and the effect on AEs reporting is unclear. It was
hypothesized that changing practices for i. v. iron products has caused changes in
the rates of serious AEs and large differences exist between Eur and NA. Rates of
AEs for three i. v. iron preparations (iron sucrose [IS], ferric gluconate [FG] and
high and low MW iron dextran [HMWID, LMWID]) were compared by product and continent
from January 1, 2003 to June 30, 2009 for selected countries in Eur and NA, using
the Uppsala Monitoring Center’s database. Rates of total, anaphylaxis and other serious
allergic AEs were calculated as number of AEs divided by i. v. iron sales standardized
to 100 mg dose equivalents (DEq) of iron. Quarterly sales (millions of 100 mg DEq
of iron) increased from the first quarter 2003 to the end of the second quarter of
2009 by 1% for FG, 16% for IS and 2% for ID. Total AEs for NA plus Eur were similar
for FG and IS, but total AEs were 6- to 7-fold higher for ID. Rates of anaphylaxis
were 6- to 11-fold higher in Eur plus NA combined for ID than for IS or FG. In NA,
there were substantially higher reports for total, anaphylaxis and other serious allergic
AEs with FG compared to IS, whereas the reverse was the case in Eur. Odds ratios (OR)
showed higher risks of anaphylaxis with FG in NA vs. Eur (OR = 4.40, P < 0.0001) and lower risks with IS (OR = 0.24, P < 0.0001). Odds
of anaphylaxis with LMWID in Eur vs. FG and IS were 42.08 and 16.92 (both P < 0.0001), respectively. In NA, odds of anaphylaxis
with ID vs. FG and IS were 2.36 and 17.73 (both P < 0.0001), respectively.
Differences between NA and Eur may be related to varied treatment practices. ID had
the highest rates of all types of AEs, and IS and FG had a continued trend for lowest
rates of AEs.
Key words Adverse events - Allergy - Anaphylaxis - Hypersensitivity - Intravenous iron
