Oral iron also may be an inadequate treatment for pregnant
women with iron deficiency, as shown in recent studies sug-
gesting that, if a mother’s ferritin level is <15 µg/mL, the iron
status of the neonate is compromised. 2
In a prospective trial of 2,400 pregnant women with iron
deficiency who received oral iron, maternal hemoglobin (Hb)
and iron parameters improved, but 45 percent of the neonates
were iron-deficient at birth. This wouldn’t be a big deal, except
that neonatal iron deficiency has been associated with statisti-
cally significant increase in cognitive and behavioral abnormal-
ities that persist through early adulthood. 3
IV iron – in any of its preparations – is underused in this
setting.
Ralph V. Boccia, MD: I agree, and I would add that oral iron
probably is overused in the general population – not just in
pregnant women. Still, oral iron in the pregnant population
presents many problems, as these women already have fatigue,
have a lower exercise tolerance, and tend to become more anemic
during pregnancy. Because of these factors, pregnant women are
also less likely to remain adherent or compliant with oral iron.
Parenteral iron is a good option for patients with iron defi-
ciency, and particularly for pregnant women who have impaired
iron absorption. Given the data about neonatal concerns, why
wouldn't we want to be treating these patients with IV iron?
Dr. Auerbach: We agree completely on that point. The issue,
then, is which iron should we use? Six formulations are available
in the U.S. and Europe: ferric gluconate (FG), iron sucrose
(IS), low-molecular-weight iron dextran (LMWID), ferric
carboxymaltose (FCM), iron isomaltoside, and ferumoxytol.
Based on the preponderance of data from prospective trials, they
are all equally safe and efficacious.
For the sake of this discussion, I believe we can discard two
options right away: FG and IS. These agents are administered
over five visits, while other iron products require only one visit
to achieve the same effect. So, while FG and IS are safe and effec-
tive, we can’t reasonably expect a pregnant woman to come into
the clinic for five or more visits for IV iron.
The remaining options (LMWID, FCM, iron isomaltoside,
and ferumoxytol) are all excellent formulations, but each re-
quires different dosing and administration.
Although it is an off-label usage, LMWID is routinely ad-
ministered at 1,000 mg for one hour in pregnant women with
iron deficiency. We have little evidence about ferumoxytol in the
pregnant population, but, anecdotally, we have treated several
hundred patients with ferumoxytol 1,020 mg administered in a
15-minute infusion. However, this is not routinely approved and
then we routinely give ferumoxytol 510 mg on two different days
in three to five minutes because we know it to be safe. The drug
was originally approved at a rapid infusion rate (510 mg over 17
seconds), but the 15-minute infusion time was adopted after a
high rate of infusion reactions was observed. 4 Personally, I think
that the 15-minute approval was an overreaction to the earlier
imprudent use of that drug. This formulation cost 400 percent of
the price of LMWID.
FCM is another excellent iron product. It can be given as
a single 1,000-mg infusion in 15 minutes. There is a litany of
evidence to support this dosing, but, in the U.S., FCM is only
available as a 750-mg vial. Because published evidence suggests
giving more than 1,000 mg at once is not clinically beneficial,
we are forced to use 1,500 mg of this drug to give a 1,000-mg
dose. Therefore, as the per-mg price of FCM is the highest of
the four formulations, administering FCM costs 600 percent
more than administering LMWID and 150 percent of the cost
of ferumoxytol.
Dr. Boccia: We have used all three of these iron products and
our experience with them in the pregnant population has been
equally good. With FCM, the question will always be, “How
much should we give – 1,000 mg or 1,500 mg?”
I don’t know what the correct “standard-of-care” dose of
FCM should be, and the answer to this question varies by pa-
tient. Certain patients – especially women with iron deficiency
who are in their menstrual years and may have heavy uterine
bleeding – will need more IV iron than another patient. But,
while some patients may require more than 1,000 mg, I always
tell my patients, “One size does not fit all, but one size is what
you’re going to get – at least until we have enough time to
measure its effect.”
”Given the data about
neonatal concerns [with
oral iron], why wouldn't
we want to be treating
these patients with IV iron?”
—RALPH V. BOCCIA, MD
In the “old days,” we would calculate the dose deficit, based
on the amount of iron the patient needed (accounting for body
size and Hb levels). For example, a woman presenting with a
Hb 7 g/dL and iron deficiency is clearly going to need more
iron than a woman who has a Hb 11.5 g/dL and is iron defi-
cient but only mildly anemic. In all likelihood, the first patient
would do better with a 1,500-mg dose, while the second patient
would benefit from a 1,000-mg dose.
Dr. Auerbach: You’re right – a 1,500-mg dose probably is more
prudent in someone with lower Hb levels. The question is,
“Should you give her 1,500 mg in one treatment, or should you
divide it, wait four weeks, and then give the second part of the
treatment?” That statement is supported by prospective data,
October 2018
7