Approved Drug Label (PDF)
Boxed Warning
WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS
(Additions and/or revisions are underlined)
Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving Feraheme. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest.
- Only administer Feraheme as an
intravenous
infusion over at least
15 minutes and only when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions.
- …
5
Warnings and Precautions
5.1 Serious Hypersensitivity Reactions
(Additions and/or revisions are underlined)
…
Only administer Feraheme as
an intravenous infusion over at
least 15 minutes and only when
personnel and therapies are immediately available for the
treatment
of anaphylaxis
and other hypersensitivity reactions. Closely observe patients
for signs and symptoms of hypersensitivity including monitoring of blood
pressure and pulse during and after
Feraheme administration for
at least 30 minutes and until
clinically stable following completion of
each infusion.
In a clinical
study in patients with IDA,
regardless of etiology, hypersensitivity reactions were reported in 0.4%
(4/997) of subjects receiving Feraheme administered
as intravenous infusion
over at least 15 minutes. These included
one
patient with severe hypersensitivity reaction
and three patients
with moderate hypersensitivity reactions.
In clinical studies predominantly in patients with IDA and
CKD, serious hypersensitivity
reactions
were
reported in 0.2% (4/1,806) of subjects receiving Feraheme (administered as
a rapid intravenous injection – prior method
of administration no longer approved).
Other adverse reactions potentially associated
with hypersensitivity (e.g., pruritus, rash,
urticaria or wheezing) were
reported in 3.5% (63/1,806)
of these subjects.
...
5.2 Hypotension
(Additions and/or revisions are underlined)
Feraheme
may
cause clinically significant hypotension.
In a clinical
study with Feraheme
in patients with IDA, regardless of etiology, moderate hypotension was reported
in 0.2% (2/997) of subjects receiving Feraheme administered as
intravenous infusion over at least
15 minutes.
In clinical
studies
in patients with IDA and CKD, hypotension
was
reported in 1.9% (35/1,806) of subjects,
including three patients
with serious hypotensive
reactions
, who had received
Feraheme as a rapid
intravenous injection (prior method of administration no longer approved).
5.4 Magnetic Resonance (MR) Imaging Test Interference
(Subsection
title has been revised; additions and/or revisions are underlined)
Magnetic
Resonance (MR) Imaging Test Interference
6
Adverse Reactions
6.1 Clinical Trial Experience
(Additions and/or revisions are underlined)
Because clinical trials are conducted under widely varying
conditions, adverse reaction
rates
observed in the clinical
trials of a drug cannot be directly compared
to rates in the clinical trials
of another drug and may not reflect
the rates observed in practice.
In clinical
studies, 3,968 subjects were exposed to
Feraheme.
Of these subjects
31% were male and the median
age was 54 years
(range of 18 to 96 years).
The data described below reflect exposure to Feraheme in 997 patients exposed to
a 1.02 g course of ferumoxytol
administered as two 510 mg intravenous
(IV) doses: 992 subjects
(99.5%) received
at least 1 complete dose
of ferumoxytol
and 946 subjects (94.9%) received 2 complete doses. The mean cumulative IV Iron exposure was 993.80
±119.085 mg.
The safety of Feraheme was
studied in a randomized, multicenter, double-blind
clinical trial in patients with
IDA (IDA Trial 3), [see Clinical Studies (14.1)]. In
this trial, patients were randomized
to two intravenous infusions of 510 mg (1.02 g) of Feraheme (n=997), or two
intravenous infusions of 750
mg (1.500 g) of ferric carboxymaltose
(FCM) (n=1000). Both intravenous irons were infused over a period of
at least 15 minutes. Most patients received
their second infusion of Feraheme
and
FCM 7(+1) days
after Dose 1.
The mean (SD)
age
of the study population (N=1997) was 55.2 (17.16) years.
The majority of patients were
female (76.1%), white (71.4%) and non-Hispanic (81.8%).
The
mean (SD) hemoglobin
at baseline for all patients was
10.4 (1.5) g/dl.
Serious
adverse events were reported in 3.6% (71/1997)
of ferumoxytol- and
FCM- treated patients. The most common (greater than or equal to 2 subjects) serious AEs
reported in Feraheme-treated patients were syncope, gastroenteritis,
seizure, pneumonia, hemorrhagic anemia, and acute kidney injury. In FCM-treated
patients
the
most common (greater than or equal to 2 subjects) serious
AEs were syncope, cardiac
failure congestive, angina pectoris, and atrial fibrillation.
Adverse
reactions related to
Feraheme
and
reported by greater than or equal to 1% of
Feraheme-treated patients in IDA Trial 3
are
listed in Table 1.
(Table has been added; please refer to label)
Table 1: Adverse Reactions
to Feraheme Reported
in greater than or equal to 1% of IDA Patients
in IDA Trial 3
In IDA Trial 3, adverse reactions
leading to treatment
discontinuation and occurring in
greater than or equal to 2 Feraheme-treated
patients included arthralgia (0.3%), dyspnea (0.3%), flushing
(0.2%), chest
discomfort (0.2%), chest pain (0.2%),
nausea
(0.2%),
back pain (0.2%),
dizziness (0.2%) and headache (0.2%).
Across
two clinical trials in patients
with IDA (IDA
Trial 1 and 2), [see Clinical Studies (14.1)],
patients were randomized to: two injections (rapid
intravenous injection - prior method
of administration no longer approved) of
510 mg of Feraheme (n=1,014), placebo (n=200), or
five
injections/infusions of 200 mg of
iron sucrose (n=199). Most patients received
their second Feraheme
injection
3 to 8 days after
the
first injection. Adverse reactions
related to Feraheme and
reported by greater than or equal to 1% of Feraheme-treated
patients in these trials were similar to those
seen in Trial 3.
In Trials 1 and
2, adverse reactions leading to treatment
discontinuation and occurring in greater than or equal to 2 Feraheme-treated
patients included hypersensitivity
(0.6%), hypotension
(0.3%),
and rash (0.2%).
In addition, a total of 634 subjects enrolled in and
completed participation in
a Phase 3 open label
extension study. Of these,
337 subjects met IDA treatment
criteria and
received
Feraheme.
Adverse reactions following this repeat
Feraheme dosing were generally similar in type and
frequency to
those observed after the first
two intravenous injections.
Across three randomized clinical
trials in patients with IDA
and CKD (CKD Trials 1, 2, and 3), a
total of 605 patients were
exposed to two injections of 510 mg of
Feraheme and a total of 280
patients were exposed to 200
mg/day of oral iron
for 21 days. Most patients received their
second
Feraheme injection 3
to 8 days after
the first injection.
Adverse
reactions related to
Feraheme
and
reported by greater than or equal to 1% of Feraheme-treated
patients in the CKD randomized
clinical trials are listed in Table 2.
Diarrhea (4%),
constipation (2.1%) and hypertension (1%) have also
been reported in Feraheme-treated
patients.
(Table has been revised; please refer to label)
Table 2: Adverse Reactions to Feraheme Reported
in greater than or equal to 1% of Patients with IDA
and CKD Trials
1, 2 and 3
In these clinical trials in patients with
IDA and CKD,
adverse reactions leading to treatment discontinuation and occurring in
greater than or equal to 2 Feraheme-treated patients included
hypotension (0.4%), chest pain (0.3%), and dizziness (0.3%).
ADVERSE REACTIONS
(Additions and/or revisions are underlined)
The following serious
adverse reactions
are described elsewhere in the
labeling:
- Serious
Hypersensitivity Reactions
- Hypotension
- Iron Overload
- Magnetic Resonance (MR) Imaging Test
Interference
8
Use in Specific Populations
8.1 Pregnancy
(Additions and/or revisions are underlined)
Risk Summary
Limited available data with ferumoxytol
use in pregnant women
are insufficient to inform a drug
associated risk of adverse developmental
outcomes. There are risks
to the mother and fetus associated with
untreated iron deficiency anemia (IDA) in
pregnancy (see Clinical Considerations). In
animal studies, administration of ferumoxytol to
pregnant rabbits during
organogenesis caused adverse developmental outcomes
including fetal malformations
and decreased fetal weights
at maternally toxic doses of 6
times the estimated human daily dose.
The estimated background
risk of major birth defects
and miscarriage for
the indicated populations is unknown.
All pregnancies
have a background risk of birth defect,
loss, or other adverse outcomes. In
the U.S. general population, the estimated background risk of
major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Untreated iron
deficiency anemia (IDA) in pregnancy is
associated with adverse maternal
outcomes such as post-partum anemia. Adverse pregnancy outcomes
associated with IDA include increased risk for preterm
delivery and low
birth weight.
Data
Animal Data
Administration of
ferumoxytol during organogenesis, at
doses of 31.6 mg Fe/kg/day in
rats
and 16.5 mg Fe/kg/day in
rabbits,
did not result in maternal or fetal effects….
8.2 Lactation
(Newly
added subsection)
Risk Summary
There are no
data on the
presence of ferumoxytol in human
milk, the effects on the breastfed
child, or the effects on milk
production. Ferumoxytol has been
detected in the
milk of lactating rats. However, due
to species-specific differences in
lactation physiology,
the
clinical relevance of these data are not clear.
The developmental
and
health benefits
of breastfeeding should
be considered along
with the mother’s clinical
need
for
Feraheme
and any potential
adverse effects on the breastfed
child from Feraheme or from the underlying maternal condition.
8.5 Geriatric Use
(Additions
and/or revisions are underlined)
In controlled clinical trials, 833
patients ? 65 years of
age
were treated with Feraheme….
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
Advise the
patient to read
the FDA-approved
patient labeling (Patient Information) Prior History of Allergies to Parenteral Iron Products
Question patients regarding any prior history of allergies to parenteral iron products.
Hypersensitivity Reactions
Advise patients
to immediately report
any symptoms
of hypersensitivity that may develop
during and following Feraheme administration,
such as rash, itching, dizziness, light-headedness, swelling, and breathing problems.
Medication Guide
(Medication Guide Table has been added; please refer to label)
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