Included as part of the PRECAUTIONS section.
reactions, including anaphylactic-type reactions, some of which have been
life-threatening and fatal, have been reported in patients receiving Injectafer.
Patients may present with shock, clinically significant hypotension, loss of
consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity
during and after Injectafer administration for at least 30 minutes and until
clinically stable following completion of the infusion. Only administer Injectafer
when personnel and therapies are immediately available for the treatment of
serious hypersensitivity reactions. [see ADVERSE
REACTIONS]. In clinical trials, serious anaphylactic/anaphylactoid
reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer.
Other serious or severe adverse reactions potentially associated with
hypersensitivity which included, but not limited to, pruritus, rash, urticaria,
wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.
In clinical studies,
hypertension was reported in 3.8% (67/1,775) of subjects in clinical trials 1
and 2. Transient elevations in systolic blood pressure, sometimes occurring
with facial flushing, dizziness, or nausea were observed in 6% (106/1,775) of
subjects in these two clinical trials. These elevations generally occurred
immediately after dosing and resolved within 30 minutes. Monitor patients for
signs and symptoms of hypertension following each Injectafer administration [see
DOSAGE AND ADMINISTRATION].
Laboratory Test Alterations
In the 24 hours following administration
of Injectafer, laboratory assays may overestimate serum iron and transferrin
bound iron by also measuring the iron in Injectafer.
Patient Counseling Information
- Question patients regarding any prior history of
reactions to parenteral iron products.
- Advise patients of the risks associated with Injectafer.
- Advise patients to report any signs and symptoms of
hypersensitivity that may develop during and following Injectafer
administration, such as rash, itching, dizziness, lightheadedness, swelling and
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with
Ferric carboxymaltose was not genotoxic in the following
genetic toxicology studies: in vitro microbial mutagenesis (Ames) assay, in
vitro chromosome aberration test in human lymphocytes, in vitro mammalian cell
mutation assay in mouse lymphoma L5178Y/TK+/- cells, in vivo mouse micronucleus
test at single intravenous doses up to 500 mg/kg.
In a combined male and female fertility study, ferric
carboxymaltose was administered intravenously over one hour to male and female
rats at iron doses of up to 30 mg/kg. Animals were dosed 3 times per week (on
Days 0, 3, and 7). There was no effect on mating function, fertility or early
embryonic development. The dose of 30 mg/kg in animals is approximately 40% of
the human dose of 750 mg based on body surface area.
Use In Specific Populations
Pregnancy - Pregnancy Category C
Adequate and well controlled studies in pregnant women
have not been conducted. However, animal reproduction studies have been
conducted with ferric carboxymaltose. In these studies, administration of
ferric carboxymaltose to rabbits during the period of organogenesis caused
fetal malformations and increased implantation loss at maternally toxic doses
of approximately 12% to 23% of the human weekly dose of 750 mg (based on body
surface area). The incidence of major malformations in human pregnancies has
not been established for Injectafer. However, all pregnancies, regardless of
exposure to any drug, has a background rate of 2 to 4% for major malformations,
and 15 to 20% for pregnancy loss. Injectafer should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus.
Administration of ferric carboxymaltose to rats as a
one-hour intravenous infusion up to 30 mg/kg/day iron on gestation days 6 to 17
did not result in adverse embryofetal findings. This daily dose in rats is
approximately 40% of the human weekly dose of 750 mg based on body surface
area. In rabbits, ferric carboxymaltose was administered as a one-hour infusion
on gestation days 6 to 19 at iron doses of 4.5, 9, 13.5, and 18 mg/kg/day.
Malformations were seen starting at the daily dose of 9 mg/kg (23% of the human
weekly dose of 750 mg). Spontaneous abortions occurred starting at the daily iron
dose of 4.5 mg/kg (12% of the human weekly dose based on body surface area). Pre-implantation
loss was at the highest dose. Adverse embryofetal effects were observed in the
presence of maternal toxicity.
A pre- and post-natal development study was conducted in
rats at intravenous doses up to 18 mg/kg/day of iron (approximately 23% of the
weekly human dose of 750 mg on a body surface area basis). There were no
adverse effects on survival of offspring, their behavior, sexual maturation or
A study to determine iron concentrations in breast milk
after administration of Injectafer (n=11) or oral ferrous sulfate (n=14) was
conducted in 25 lactating women with postpartum iron-deficiency anemia. Mean
breast milk iron levels were higher in lactating women receiving Injectafer
than in lactating women receiving oral ferrous sulfate.
Safety and effectiveness have not been established in
Of the 1775 subjects in clinical studies of Injectafer,
50% were 65 years and over, while 25% were 75 years and over. No overall
differences in safety or effectiveness were observed between these subjects and
younger subjects, and other reported clinical experience has not identified
differences in responses between the elderly and younger patients, but greater
sensitivity of some older individuals cannot be ruled out.