IMPORTANT SAFETY INFORMATION
INDICATIONS
Injectafer®
(ferric carboxymaltose
injection) is indicated for
the treatment of iron
deficiency anemia (IDA) in
adult and pediatric patients
1 year of age and older who
have either intolerance or
an unsatisfactory response
to oral iron, and in adult
patients who have
non-dialysis dependent
chronic kidney disease.
Injectafer is also indicated
for iron deficiency in adult
patients with heart failure
and New York Heart
Association class II/III to
improve exercise capacity.
CONTRAINDICATIONS
Injectafer is contraindicated in
patients with hypersensitivity
to Injectafer or any of its
inactive components.
WARNINGS AND PRECAUTIONS
Symptomatic
Hypophosphatemia
Symptomatic hypophosphatemia
with serious outcomes including
osteomalacia and fractures
requiring clinical intervention
has been reported in patients
treated with Injectafer in the
post-marketing setting. These
cases have occurred mostly after
repeated exposure to Injectafer
in patients with no reported
history of renal impairment.
However, symptomatic
hypophosphatemia has been
reported after one dose.
Possible risk factors for
hypophosphatemia include a
history of gastrointestinal
disorders associated with
malabsorption of fat-soluble
vitamins or phosphate,
inflammatory bowel disease,
concurrent or prior use of
medications that affect proximal
renal tubular function,
hyperparathyroidism, vitamin D
deficiency, malnutrition, and
hereditary hemorrhagic
telangiectasia (HHT or
Osler-Weber-Rendu syndrome). In
most cases, hypophosphatemia
resolved within three months.
Correct pre-existing
hypophosphatemia prior to
initiating therapy with
Injectafer. Monitor serum
phosphate levels in patients at
risk for chronic low serum
phosphate. Check serum phosphate
levels prior to a repeat course
of treatment in patients at risk
for low serum phosphate and in
any patient who receives a
second course of therapy within
three months. Treat
hypophosphatemia as medically
indicated.
Hypersensitivity Reactions
Serious hypersensitivity
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. 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 were not limited to,
pruritus, rash, urticaria,
wheezing, or hypotension were
reported in 1.5% (26/1775) of
these subjects.
Hypertension
In clinical studies, hypertension
was reported in 4% (67/1775) 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% (106/1775)
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.
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.
ADVERSE REACTIONS
Adults
In two randomized clinical
studies [Studies 1 and 2], a
total of 1775 patients were
exposed to Injectafer, 15 mg/kg
of body weight, up to a maximum
single dose of up to 750 mg of iron on
two occasions, separated by at
least 7 days, up to a cumulative
dose of 1500 mg of iron. Adverse
reactions reported by >2% of
Injectafer-treated patients were
nausea (7.2%); hypertension
(4%); flushing (4%); injection
site reactions (3%); erythema
(3%); hypophosphatemia (2.1%);
and dizziness (2.1%).
Pediatric
The safety of Injectafer in
pediatric patients was evaluated
in Study 3. Study 3 was a
randomized, active-controlled
study in which 40 patients (1 to
12 years of age: 10 patients, 12
to 17 years of age: 30 patients)
received Injectafer 15 mg/kg to
a maximum single dose of up to 750 mg
(whichever was smaller) on Days
0 and 7 for a maximum total dose
of 1500 mg; 38 patients
evaluable for safety in the
control arm received an
age-dependent formulation of
oral ferrous sulfate for 28
days. The median age of patients
who received Injectafer was 14.5
years (range, 1-17); 83% were
female; 88% White and 13% Black.
The most common adverse
reactions (≥4%) were
hypophosphatemia (13%),
injection site reactions (8%),
rash (8%), headache (5%), and
vomiting (5%).
Patients with Iron Deficiency
and Heart Failure
The safety of Injectafer was
evaluated in adult patients with
iron deficiency and heart
failure in randomized controlled
trials FAIR-HF (NCT00520780),
CONFIRM-HF (NCT01453608) and
AFFIRM-AHF (NCT02937454) in
which 1016 patients received
Injectafer versus 857 received
placebo. The overall safety
profile of Injectafer was
consistent across the studied
indications.
Post-Marketing Experience
The following adverse reactions
have been identified during post
approval use of Injectafer.
Because these reactions are
reported voluntarily from a
population of uncertain size, it
is not always possible to
reliably estimate their
frequency or establish a causal
relationship to drug exposure.
The following adverse reactions
have been reported from the
post-marketing spontaneous
reports with Injectafer:
cardiac disorders:
tachycardia; general
disorders and administration
site conditions: chest
discomfort, chills, pyrexia;
metabolism and nutrition
disorders:
hypophosphatemia;
musculoskeletal and
connective tissue
disorders: arthralgia,
back pain, hypophosphatemic
osteomalacia; nervous system
disorders: syncope;
respiratory, thoracic and
mediastinal disorders:
dyspnea; skin and
subcutaneous tissue
disorders: angioedema,
erythema, pruritus, urticaria;
pregnancy: fetal
bradycardia.
USE IN SPECIFIC POPULATIONS
Pregnancy – Fetal/Neonatal Adverse Reactions
Severe adverse reactions including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.
You are
encouraged to report Adverse
Drug Events to American Regent,
Inc. at 1-800-734-9236
or to the FDA by visiting www.fda.gov/medwatch or
calling 1-800-FDA-1088.