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Iron dextran carries greatest anaphylaxis risk of marketed IV iron products
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Iron dextran appeared to carry the greatest risk for anaphylaxis at first exposure of all marketed IV iron products among patients with anemia in the U.S. Medicare nondialysis population, according to findings from a retrospective study conducted by the FDA.
The lowest risk for anaphylaxis at first exposure occurred with iron sucrose, results showed.
Although most clinicians offer oral iron replacement as the treatment strategy for patients with iron deficiency anemia, IV iron may be used due to the side effects associated with oral iron.
As of June 2013, there were five iron products marketed in the U.S.; however, a comparative safety profile of each of these therapies had not yet been established.
“An anaphylaxis reaction can happen with any IV iron product at first or subsequent exposure,” Cunlin Wang, MD, PhD, director of the division of epidemiology at the center for drug evaluation and research at the FDA, said in a statement provided to HemOnc Today. “This study provides information on the relative safety of currently approved IV iron products on the U.S. market up to 2013, not including [ferric carboxymaltose (Injectafer, Luitpold)].”
Wang and colleagues sought to compare the risk for anaphylaxis among all U.S. marketed IV iron products. These included high–molecular-weight iron dextran, low–molecular-weight iron dextran, iron gluconate, iron sucrose (Venofer, Luitpold) and ferumoxytol (Feraheme, AMAG Pharmaceuticals).
Because it was not possible to differentiate between the two iron dextrans within claims data as they shared the same HCPCS code during much of the study period, researchers evaluated them together.
“From January 2006 through March 2008, during which the use of two dextran products could be distinguished, there was very low use of high–molecular-weight dextran,” Wang said in the statement. “This suggested that the study results likely represent the risk of the low–molecular-weight dextran.”
The analysis included data from 688,183 patients who enrolled in the U.S. fee-for-service Medicare program between 2003 and 2013. Analysis of ferumoxytol did not begin until 2010 because it was not approved by the FDA until June 2009.
Overall, there were 274 cases of anaphylaxis at the time of first exposure to the IV administration of an iron product and an additional 170 incidences of anaphylaxis at subsequent administrations.
The risk for anaphylaxis at first exposure to IV iron was 68 per 100,000 individuals (95% CI, 57.8-78.7) for iron dextran vs. 24 per 100,000 individuals (95% CI, 20-29.5) for all other nondextran products combined (adjusted OR = 2.6; 95% CI, 2-3.3).
Compared with iron sucrose, the adjusted OR for anaphylaxis at first exposure was 3.6 (95% CI, 2.4-5.4) for iron dextran, 2 (95% CI, 1.2-3.5) for iron gluconate and 2.2 (95% CI, 1.1-4.3) for ferumoxytol.
Because each product carries a specific dose recommendation and administration schedule, researchers calculated the cumulative anaphylaxis risk following total iron repletion of 1,000 mg within a 12-week period. Results showed the risk appeared highest with iron dextran (82 per 100,000 individuals; 95% CI, 70.5-93.1) and lowest with iron sucrose (21 per 100,000 individuals; 95% CI, 15.3-26.4).
The researchers noted these data may not extend to patients on dialysis or younger patients. Further, researchers acknowledged their inability to differentiate between the two dextrans as a study limitation.
“In contrast to prior efforts to assess safety, our study was not based on postmarket passive case reporting, such as the FDA’s spontaneous adverse events reporting system, which is limited in its ability to support comparative safety analyses due to different approval dates and indication of IV iron products, variations in reporting over time, choice of denominator used, and variations in the diagnostic criteria of anaphylaxis,” Wang and colleagues wrote. “Our study provides a more reliable estimate of the relative risk between individual IV iron products based on a prespecified algorithm for anaphylaxis, a well-defined and characterized population at risk, and adjustment for imbalances in baseline risk factors for anaphylaxis.” – by Anthony SanFilippo
For more information:
Cunlin Wang, MD, PhD, can be reached at cunlin.wang@fda.hhs.gov.
Disclosure: All of the researchers are employees or contractors of the Centers for Medicare and Medicaid Services or the FDA.
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