Ferumoxytol effective, safe for iron deficiency, iron deficiency anemia of pregnancy
Click Here to Manage Email Alerts
Iron replacement with IV ferumoxytol appears effective and safe for iron-deficient pregnant women with anemia in their second or third trimester, according to study results published in Therapeutic Advances in Hematology.
Researchers observed no difference in outcomes among women who received a single infusion of 1020 mg and those who received the same dose over two infusions on different days — the current FDA approved schedule.
The findings corroborate “a litany of quality publications using other formulations which allow total dose infusion of iron in a single visit,” researcher Michael Auerbach, MD, FACP, clinical professor of medicine at Georgetown University School of Medicine, told Healio. These formulations include low molecular weight iron dextran, ferric carboxymaltose and ferric derisomaltose.
The results also suggest this approach is a more convenient and less expensive alternative to formulations that require multiple visits, such as iron sucrose and ferric gluconate.
“This important paper supports the growing body of evidence that a single infusion of IV iron should represent a new paradigm for iron depletion,” Auerbach told Healio.
An ‘enormous’ burden
The burden of iron deficiency in pregnancy is “enormous,” Auerbach said.
He estimated 40% to 60% of pregnant women are iron deficient; however, most are not anemic at presentation, meaning they would be missed by what Auerbach called “draconian guidelines.”
“In the absence anemia, iron deficiency is almost never looked for,” Auerbach told Healio. “It is not on the typical internist’s or obstetrician’s radar. We should be screening all pregnant women for iron deficiency.”
Iron deficiency is associated with peripartum hemorrhage and preterm labor, as well as a small increment in maternal mortality.
Intra-natal iron deficiency anemia also is associated with considerable morbidity, including autism, schizophrenia and abnormal brain structure.
“High-quality neonatology evidence suggests iron deficiency during any week of gestation is associated with a statistically significant increment of autism spectrum disorder,” Auerbach said. “It also has been shown that iron-deficient babies have cognitive, behavioral and motor decrements measurable up to 19 years of age. This is an unmet clinical need in American medicine.”
Potential role for ferumoxytol
Oral iron replacement — which is widely available and inexpensive — is the frontline standard for iron deficiency of pregnancy. However, if a pregnant woman is iron deficient, oral iron will not reach the developing fetus.
“This is especially concerning as the rapidly developing fetal brain is in particular need of iron sufficiency,” Auerbach and colleagues wrote.
In addition, oral iron has been linked to high incidence of gastrointestinal adverse events, which results in poor adherence.
These findings have prompted recommendations that IV iron be frontline therapy for pregnant women in the second and third trimester with hemoglobin concentrations less than 10.5 g/dL, and for all women in the third trimester.
Iron sucrose has become the “time-honored standard” in the United States for IV iron repletion during pregnancy. Although this approach is effective and safe, iron sucrose administration requires four to seven visits instead of one.
Ferumoxytol (Feraheme, AMAG Pharmaceuticals) is one of several newer formulations of IV iron. It is approved in the United States as treatment for all causes of iron-deficiency anemia after oral iron intolerance, or in settings when oral iron is harmful or ineffective.
Ferumoxytol — a superparamagnetic iron oxide linked to polyglucose sorbitol carboxymethylether-binding elemental iron — allows complete replacement doses to be administered in 15 to 30 minutes.
Auerbach and colleagues assessed IV ferumoxytol for 131 consecutive, nonselected, iron-deficient pregnant women (mean age, 29.6 years; range, 19-42; mean gestational age, 29.4 weeks; range, 14-38) referred to their practice for treatment of iron deficiency anemia of pregnancy.
The women — all of whom were in their second (n = 18) or third (n = 107) trimester — received either one 1,020-mg infusion administered over 30 minutes (n = 52), or two 510-mg infusions administered over 15 minutes 3 to 8 days apart (n = 79). The groups were well-balanced with regard to age, number of pregnancies, parity and gestational age at first treatment.
Four women with a history of asthma or multiple drug allergies received methylprednisolone and ranitidine via IV prior to infusion; otherwise, no premedication was administered.
Efficacy, safety results
Mean follow-up from initial infusion was 13.7 weeks (range, 4-29).
In the entire cohort, researchers reported statistically significant improvement from baseline to follow-up in hemoglobin (mean change, 1.9 g/dL; P < .0001), transferrin saturation (mean change, 17.1%; P < .0001) and serum ferritin (mean change, 113.3 ng/mL; P < .0001). The increase in hemoglobin appeared consistent with prior reports of the FDA-approved regimen of two 510-mg doses.
Investigators observed no statistically significant differences from baseline to follow-up between the 510-mg or 1,020-mg infusion groups with regard to hemoglobin (mean change, 1.8 g/dL vs. 2.3 g/dL), transferrin saturation (mean change, 19.1% vs. 14.3%) or mean corpuscular volume (mean change, 1.8 fL vs. 5.2 fL). However, the difference in ferritin change between the 510-mg and 1,020-mg groups did reach statistical significance (mean change, 134.9 ng/mL vs. 79.2 ng/mL; P = .03).
Nineteen women — 11 of whom received two 510-mg infusions and eight of whom received the single 1,020-mg infusion — experienced minor infusion reactions. These included nasal congestion, facial flushing, or pressure in the chest or back.
All resolved within minutes, and all but one woman who refused to be rechallenged received the planned dose.
Before resumption of planned therapy, 16 women received methylprednisolone and either famotidine or ranitidine without reaction recurrence.
Researchers reported no serious adverse events, no hospitalizations and no cases of hypotension.
None of the 72 women for whom post-partum data were available reported adverse events at delivery.
“This experience with the tolerability of ferumoxytol mirrors what we have noted with the use of several thousand doses of ferumoxytol in the authors’ practice, as well as with the several other IV iron formulations (low molecular weight iron dextran, ferric carboxymaltose and ferric derisomaltose) we have employed,” Auerbach and colleagues wrote.
“The preponderance of published evidence supports an increased use of IV iron for iron deficiency of pregnancy,” the researchers added. “The ability to administer a full replacement dose of IV iron in [15 to 30 minutes] increases convenience to both practitioners and patients, decreases cost and improves adherence.”
Collapse
Read more about
Click Here to Manage Email Alerts