HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`Injectafer safely and effectively. See full prescribing information for
`Injectafer.
`
`INJECTAFER® (ferric carboxymaltose injection), for intravenous use
`Initial U.S. Approval: 2013
`
`------------------------------RECENT MAJOR CHANGES------------------------
`(cid:120) Warnings and Precautions, Symptomatic
`Hypophosphatemia. (5.2)
` 02/2020
`
`----------------------------INDICATIONS AND USAGE---------------------------
`Injectafer is an iron replacement product indicated for the treatment of iron
`deficiency anemia in adult patients:
`who have intolerance to oral iron or have had unsatisfactory
`(cid:120)
`response to oral iron, or
`who have non-dialysis dependent chronic kidney disease.
`
`(cid:120)
`
`----------------------DOSAGE AND ADMINISTRATION-----------------------
`For patients weighing 50 kg (110 lb) or more: Give Injectafer in two doses
`separated by at least 7 days. Give each dose as 750 mg for a total cumulative
`dose of 1500 mg of iron per course.
`
`For patients weighing less than 50 kg (110 lb): Give Injectafer in two doses
`separated by at least 7 days and give each dose as 15 mg/kg body weight.
`
`Injectafer treatment may be repeated if iron deficiency anemia reoccurs. (2)
`
`-------------------------------CONTRAINDICATIONS------------------------------
`Hypersensitivity to Injectafer or any of its inactive components. (4)
`
`-----------------------WARNINGS AND PRECAUTIONS------------------------
`Hypersensitivity reactions: Observe for signs and symptoms of
`(cid:120)
`hypersensitivity during and after Injectafer administration for at least
`3A0 minutes and until clinically stable following completion of each
`administration. (5.1)
`Symptomatic Hypophosphatemia: Monitor serum phosphate levels in
`patients at risk for low serum phosphate who require a repeat course of
`treatment. (5.2)
`Hypertension: Monitor patients closely for signs and symptoms of
`hypertension following each Injectafer administration. (5.3)
`
`(cid:120)
`
`(cid:120)
`
`------------------------------ADVERSE REACTIONS-------------------------------
`The most common adverse reactions (>2%) are nausea, hypertension,
`flushing, hypophosphatemia, and dizziness. (6.1)
`
`To report SUSPECTED ADVERSE REACTIONS, contact American
`Regent at 1-800-734-9236 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`-------------------------USE IN SPECIFIC POPULATIONS----------------------
`Lactation: Monitor breastfed infants for gastrointestinal toxicity. (8.2)
`
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`approved patient labeling.
`
`---------------------DOSAGE FORMS AND STRENGTHS----------------------
`Injection: 750 mg iron / 15 mL single-dose vial. (3)
`____________________________________________________________________________________________________________
`
`Revised:
`
`02/2020
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`INDICATIONS AND USAGE
`1
`2 DOSAGE AND ADMINISTRATION
`2.1 Recommended Dosage
`2.2 Preparation and Administration
`2.3 Repeat Treatment Monitoring Safety Assessment
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`5.1 Hypersensitivity Reactions
`5.2 Symptomatic Hypophosphatemia
`5.3 Hypertension
`5.4 Laboratory Test Alterations
`6 ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2 Post-marketing Experience
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`
`8.2 Lactation
`8.4 Pediatric Use
`8.5 Geriatric Use
`10 OVERDOSAGE
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility
`14 CLINICAL STUDIES
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to
`Oral Iron or Have Had Unsatisfactory Response to Oral Iron
`14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis
`Dependent Chronic Kidney Disease
`16 HOW SUPPLIED/STORAGE AND HANDLING
`17 PATIENT COUNSELING INFORMATION
`
`* Sections or subsections omitted from the full prescribing information are not
`listed.
`___________________________________________________________________________________________________________________________________
`
`Reference ID: 4563426
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`

`

`FULL PRESCRIBING INFORMATION
`
`INDICATIONS AND USAGE
`1
`Injectafer is indicated for the treatment of iron deficiency anemia in adult patients:
`
`(cid:120) who have intolerance to oral iron or have had unsatisfactory response to oral iron,
`or
`(cid:120) who have non-dialysis dependent chronic kidney disease.
`
`2
`
`DOSAGE AND ADMINISTRATION
`
`2.1 Recommended Dosage
`Recommended dosage for patients weighing 50 kg (110 lb) or more: Give Injectafer in
`two doses separated by at least 7 days. Give each dose as 750 mg for a total cumulative
`dose not to exceed 1500 mg of iron per course.
`
`Recommended dosage for patients weighing less than 50 kg (110 lb): Give Injectafer in
`two doses separated by at least 7 days. Give each dose as 15 mg/kg body weight for a
`total cumulative dose not to exceed 1500 mg of iron per course.
`
`Each mL of Injectafer contains 50 mg of elemental iron.
`
`2.2 Preparation and Administration
`Administer Injectafer intravenously, either as an undiluted slow intravenous push or by
`infusion. When administered via infusion, dilute up to 750 mg of iron in no more than
`250 mL of sterile 0.9% sodium chloride injection, USP, such that the concentration of the
`infusion is not less than 2 mg of iron per mL and administer over at least 15 minutes.
`
`When added to an infusion bag containing 0.9% sodium chloride injection, USP, at
`concentrations ranging from 2 mg to 4 mg of iron per mL, Injectafer solution is
`physically and chemically stable for 72 hours when stored at room temperature. To
`maintain stability, do not dilute to concentrations less than 2 mg iron/mL.
`
`Inspect parenteral drug products visually for the absence of particulate matter and
`discoloration prior to administration. The product contains no preservatives. Each vial of
`Injectafer is intended for single-dose only.
`
`When administering as a slow intravenous push, give at the rate of approximately 100 mg
`(2 mL) per minute. Avoid extravasation of Injectafer since brown discoloration of the
`extravasation site may be long lasting. Monitor for extravasation. If extravasation
`occurs, discontinue the Injectafer administration at that site.
`
`Discard unused portion.
`
`2.3 Repeat Treatment Monitoring Safety Assessment
`Injectafer treatment may be repeated if iron deficiency anemia reoccurs. Monitor serum
`phosphate levels in patients at risk for low serum phosphate who require a repeat course of
`treatment [see Warnings and Precautions (5.2)].
`
`Reference ID: 4563426
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`3
`
`DOSAGE FORMS AND STRENGTHS
`
`Injection: 750 mg iron / 15 mL single-dose vial.
`
`CONTRAINDICATIONS
`4
`Injectafer is contraindicated in patients with a history of hypersensitivity to Injectafer or
`any of its components [see Warnings and Precautions (5.1)].
`
`5
`
`WARNINGS AND PRECAUTIONS
`
`5.1 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. [see Adverse Reactions (6.1, 6.2)]. 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.
`
`5.2 Symptomatic Hypophosphatemia
`Symptomatic hypophosphatemia requiring clinical intervention has been reported in
`patients at risk of low serum phosphate in the postmarketing setting. These cases have
`occurred mostly after repeated exposure to Injectafer in patients with no reported history
`of renal impairment. Possible risk factors for hypophosphatemia include a history of
`gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or
`phosphate, concurrent or prior use of medications that affect proximal renal tubular
`function, hyperparathyroidism, vitamin D deficiency and malnutrition. In most cases,
`hypophosphatemia resolved within three months.
`
`Monitor serum phosphate levels in patients at risk for low serum phosphate who require a
`repeat course of treatment. [see Dosage and Administration (2.3)].
`
`5.3 Hypertension
`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 (2)].
`
`Reference ID: 4563426
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`5.4 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.
`
`6
`
`ADVERSE REACTIONS
`
`The following clinically significant adverse reactions are discussed in greater detail in
`other sections of the labeling:
`Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
`(cid:120)
`Hypophosphatemia [see Warnings and Precautions (5.2)]
`(cid:120)
`Hypertension [see Warnings and Precautions (5.3)]
`(cid:120)
`Laboratory Test Alterations [see Warnings and Precautions (5.4)]
`(cid:120)
`
`6.1 Clinical Trials Experience
`
`Because clinical trials are conducted under widely varying conditions, the adverse
`reaction rates observed cannot be directly compared to rates in other clinical trials and
`may not reflect the rates observed in clinical practice.
`
`In two randomized clinical studies [Studies 1 and 2, see Clinical Studies (14)], a total of
`1,775 patients were exposed to Injectafer 15 mg/kg body weight up to a maximum single
`dose of 750 mg of iron on two occasions separated by at least 7 days up to a cumulative
`dose of 1500 mg of iron.
`
`(cid:36)(cid:71)(cid:89)(cid:72)(cid:85)(cid:86)(cid:72)(cid:3)(cid:85)(cid:72)(cid:68)(cid:70)(cid:87)(cid:76)(cid:82)(cid:81)(cid:86)(cid:3)(cid:85)(cid:72)(cid:83)(cid:82)(cid:85)(cid:87)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:149)(cid:20)(cid:8)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:85)(cid:72)(cid:68)(cid:87)(cid:72)(cid:71)(cid:3)(cid:83)(cid:68)(cid:87)(cid:76)(cid:72)(cid:81)(cid:87)(cid:86)(cid:3)(cid:68)(cid:85)(cid:72)(cid:3)(cid:86)(cid:75)(cid:82)(cid:90)(cid:81)(cid:3)in the following table.
`
`Table 1. Adverse reactions reported (cid:76)(cid:81)(cid:3)(cid:149)(cid:20)(cid:8)(cid:3)(cid:82)(cid:73)(cid:3)(cid:54)(cid:87)(cid:88)(cid:71)(cid:92)(cid:3)(cid:51)atients in Clinical Trials 1 and 2
`Injectafer
`Pooled
`Oral
`Comparatorsa
`iron
`
`Term
`
`(N=1783)
`(N=1775)
`%
`%
`1.8
`7.2
`Nausea
`1.9
`3.8
`Hypertension
`0.2
`3.6
`Flushing/Hot Flush
`0.1
`2.1
`Blood Phosphorus Decrease
`1.2
`2.0
`Dizziness
`0.5
`1.7
`Vomiting
`0.3
`1.4
`Injection Site Discoloration
`0.9
`1.2
`Headache
`0.2
`1.1
`Alanine Aminotransferase Increase
`2.1
`1.1
`Dysgeusia
`1.9
`1.0
`Hypotension
`0.9
`0.5
`Constipation
`a Includes oral iron and all formulations of IV iron other than Injectafer
`
`(N=253)
`%
`1.2
`0.4
`0.0
`0.0
`0.0
`0.4
`0.0
`0.0
`0.0
`0.0
`0.0
`3.2
`
`(cid:50)(cid:87)(cid:75)(cid:72)(cid:85)(cid:3)(cid:68)(cid:71)(cid:89)(cid:72)(cid:85)(cid:86)(cid:72)(cid:3)(cid:85)(cid:72)(cid:68)(cid:70)(cid:87)(cid:76)(cid:82)(cid:81)(cid:86)(cid:3)(cid:85)(cid:72)(cid:83)(cid:82)(cid:85)(cid:87)(cid:72)(cid:71)(cid:3)(cid:69)(cid:92)(cid:3)(cid:149)(cid:19)(cid:17)(cid:24)(cid:8)(cid:3)(cid:82)(cid:73)(cid:3)(cid:87)(cid:85)(cid:72)(cid:68)(cid:87)(cid:72)(cid:71)(cid:3)(cid:83)(cid:68)(cid:87)(cid:76)(cid:72)(cid:81)(cid:87)(cid:86)(cid:3)(cid:76)(cid:81)(cid:70)(cid:79)(cid:88)(cid:71)(cid:72)(cid:3)(cid:68)(cid:69)(cid:71)(cid:82)(cid:80)(cid:76)(cid:81)(cid:68)(cid:79)(cid:3)(cid:83)(cid:68)(cid:76)(cid:81)(cid:15)(cid:3)
`diarrhea, gamma glutamyl transferase increased, injection site pain/irritation, rash,
`
`Reference ID: 4563426
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`paraesthesia, sneezing. Transient decreases in laboratory blood phosphorus levels (<2
`mg/dL) have been observed in 27% (440/1638) of patients in clinical trials.
`
`6.2 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:
`
`(cid:120) Cardiac disorders: Tachycardia
`(cid:120) General disorders and administration site conditions: Chest discomfort, chills,
`pyrexia
`(cid:120) Metabolism and nutrition disorders: Hypophosphatemia
`(cid:120) Musculoskeletal and connective tissue disorders: Arthralgia, back pain,
`hypophosphatemic osteomalacia (rarely reported event)
`(cid:120) Nervous system disorders: Syncope
`(cid:120) Respiratory, thoracic and mediastinal disorders: Dyspnea
`(cid:120) Skin and subcutaneous tissue disorders: Angioedema, erythema, pruritus,
`urticaria
`
`8
`
`USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`
`Risk Summary
`Published studies on the use of ferric carboxymaltose in pregnant women have not
`reported an association with ferric carboxymaltose and adverse developmental outcomes.
`However, these studies cannot establish or exclude the absence of any drug-related risk
`during pregnancy because the studies were not designed to assess for the risk of major
`birth defects (see Data). There are risks to the mother and fetus associated with untreated
`iron deficiency anemia in pregnancy (see Clinical Considerations).
`
`In animal reproduction studies, administration of ferric carboxymaltose to rabbits during
`the period of organogenesis caused adverse developmental outcomes including 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 estimated background risk of major birth defects and miscarriage for the indicated
`populations is unknown. Adverse outcomes in pregnancy occur regardless of the health
`of the mother or the use of medications. In the U.S. general population, the estimated
`background risk of major birth defects and miscarriage in clinically-recognized
`pregnancies is 2-4% and 15-20%, respectively.
`
`Reference ID: 4563426
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`

`Clinical Considerations
`Disease-Associated Maternal and/or Embryo/Fetal Risk
`Untreated iron deficiency anemia in pregnancy is associated with adverse maternal
`outcomes such as post-partum anemia. Adverse pregnancy outcomes associated with
`iron deficiency anemia include increased risk for preterm delivery and low birth weight.
`
`Data
`Human Data
`Published data from randomized controlled studies, prospective observational studies and
`retrospective studies on the use of ferric carboxymaltose in pregnant women have not
`reported an association with ferric carboxymaltose and adverse developmental outcomes.
`However, these studies cannot establish or exclude the absence of any drug-related risk
`during pregnancy because of methodological limitations, including that the studies were
`not primarily designed to capture safety data nor designed to assess the risk of major birth
`defects. Maternal adverse events reported in these studies are similar to those reported
`during clinical trials in adult males and non-pregnant females [see Adverse Reactions
`(6.1)].
`
`Animal Data
`Administration of ferric carboxymaltose to rats as an one-hour intravenous infusion up to
`30 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryonic or fetal
`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 embryonic or fetal 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 reproductive parameters.
`
`8.2 Lactation
`
`Risk Summary
`The available published data on the use of ferric carboxymaltose in lactating women
`demonstrate that iron is present in breast milk. However, the data do not inform the full
`potential exposure of iron for the breastfed infant. Among the breastfed infants, there
`were no adverse events reported that were considered related to ferric carboxymaltose
`exposure through breastmilk. There is no information on the effects of ferric
`carboxymaltose on milk production. The developmental and health benefits of
`breastfeeding should be considered along with the mother’s clinical need for Injectafer in
`addition to any potential adverse effects on the breastfed child from the drug or from the
`underlying maternal condition.
`
`Reference ID: 4563426
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`Clinical Considerations
`Monitor breastfed infants for gastrointestinal toxicity (constipation, diarrhea).
`
`8.4 Pediatric Use
`Safety and effectiveness have not been established in pediatric patients.
`
`8.5 Geriatric Use
`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.
`
`10 OVERDOSAGE
`Excessive dosages of Injectafer may lead to accumulation of iron in storage sites
`potentially leading to hemosiderosis. A patient who received Injectafer 18,000 mg over 6
`months developed hemosiderosis with multiple joint disorder, walking disability, and
`asthenia. Hypophosphatemic osteomalacia was reported in a patient who received
`Injectafer 4000 mg over 4 months. Partial recovery followed discontinuation of Injectafer.
`
`DESCRIPTION
`11
`Ferric carboxymaltose, an iron replacement product, is an iron carbohydrate complex
`with the chemical name of polynuclear iron (III) hydroxide 4(R)-(poly-(1(cid:111)4)-O-(cid:68)-D-
`glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate. It has a relative
`molecular weight of approximately 150,000 Da corresponding to the following empirical
`formula:
`
`[FeOx(OH)y(H2O)z]n [(cid:94)(C6H10O5)m (C6H12O7)(cid:96)l]k,
`
`where n (cid:124) 103, m (cid:124) 8, l(cid:124) 11, and k (cid:124) 4
`(l represents the mean branching degree of the ligand).
`
`The chemical structure is presented below:
`
`Reference ID: 4563426
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`Injectafer (ferric carboxymaltose injection) is a dark brown, sterile, aqueous, isotonic
`colloidal solution for intravenous injection. Each mL contains 50 mg iron as ferric
`carboxymaltose in water for injection. Injectafer is available in 15 mL single-dose vials.
`Sodium hydroxide and/or hydrochloric acid may have been added to adjust the pH to 5.0-
`7.0.
`
`Vial closure is not made with natural rubber latex.
`
`12
`
`CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose,
`a carbohydrate polymer that releases iron.
`
`12.2 Pharmacodynamics
`Using positron emission tomography (PET) it was demonstrated that red cell uptake of
`59Fe and 52Fe from Injectafer ranged from 61% to 99%. In patients with iron deficiency,
`red cell uptake of radio-labeled iron ranged from 91% to 99% at 24 days after Injectafer
`dose. In patients with renal anemia, red cell uptake of radio-labeled iron ranged from
`61% to 84% at 24 days after Injectafer dose.
`
`12.3 Pharmacokinetics
`After administration of a single dose of Injectafer of 100 to 1000 mg of iron in iron
`deficient patients, maximum iron concentration of 37 μg/mL to 333 μg/mL were obtained
`respectively after 15 minutes to 1.21 hours post dose. The volume of distribution was
`estimated to be 3 L.
`
`The iron injected or infused was rapidly cleared from the plasma, the terminal half-life
`ranged from 7 to 12 hours. Renal elimination of iron was negligible.
`
`NONCLINICAL TOXICOLOGY
`13
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`Carcinogenicity studies have not been performed with ferric carboxymaltose.
`
`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.
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`Reference ID: 4563426
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`14
`
`CLINICAL STUDIES
`
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron
`or Have Had Unsatisfactory Response to Oral Iron
`
`The safety and efficacy of Injectafer for treatment of iron deficiency anemia were
`evaluated in two randomized, open-label, controlled clinical trials (Trial 1 and Trial 2).
`In these two trials, Injectafer was administered at a dose of 15 mg/kg body weight up to a
`maximum single dose of 750 mg of iron on two occasions separated by at least 7 days up
`to a cumulative dose of 1500 mg of iron.
`
`Trial 1: A Multi-center, Randomized, Active Controlled Study to Investigate the Efficacy
`and Safety of Intravenous Ferric Carboxymaltose (FCM) in Patients with Iron Deficiency
`Anemia (IDA), (NCT00982007) was a randomized, open-label, controlled clinical study
`in patients with iron deficiency anemia who had an unsatisfactory response to oral iron
`(Cohort 1) or who were intolerant to oral iron (Cohort 2) during the 14-day oral iron run-
`in period. Inclusion criteria prior to randomization included hemoglobin (Hb) <12 g/dL,
`(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:87)(cid:76)(cid:81)(cid:3)(cid:148)(cid:3)(cid:20)(cid:19)(cid:19)(cid:3)(cid:81)(cid:74)(cid:18)(cid:80)(cid:47)(cid:3)(cid:82)(cid:85)(cid:3)(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:87)(cid:76)(cid:81)(cid:3)(cid:148)(cid:3)(cid:22)(cid:19)(cid:19)(cid:3)(cid:81)(cid:74)(cid:18)(cid:80)(cid:47)(cid:3)(cid:90)(cid:75)(cid:72)(cid:81)(cid:3)(cid:87)(cid:85)(cid:68)(cid:81)(cid:86)(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:81)(cid:3)(cid:86)(cid:68)(cid:87)(cid:88)(cid:85)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3)(cid:11)(cid:55)(cid:54)(cid:36)(cid:55)(cid:12)(cid:3)(cid:148)(cid:3)(cid:22)(cid:19)(cid:8)(cid:17)(cid:3)
`Cohort 1 subjects were randomized to Injectafer or oral iron for 14 more days. Cohort 2
`subjects were randomized to Injectafer or another IV iron per standard of care [90% of
`subjects received iron sucrose]. The mean age of study patients was 43 years (range, 18
`to 94); 94% were female; 42% were Caucasian, 32% were African American, 24% were
`Hispanic, and 2% were other races. The primary etiologies of iron deficiency anemia
`were heavy uterine bleeding (47%) and gastrointestinal disorders (17%).
`
`Table 2 shows the baseline and the change in hemoglobin from baseline to highest value
`between baseline and Day 35 or time of intervention.
`
`Table 2. Mean Change in Hemoglobin From Baseline to the Highest Value
`Between Day 35 or Time of Intervention (Modified Intent-to-Treat Population)
`Hemoglobin (g/dL)
`Cohort 1
`Cohort 2
`Mean (SD)
`Injectafer
`Injectafer
`(N=244)
`(N=245)
`10.6 (1.0)
`9.1 (1.6)
`
`Oral Iron
`(N=251)
`10.6 (1.0)
`
`Baseline
`
`IV SCa
`(N=237)
`9.0 (1.5)
`
`Highest Value
`
`12.2 (1.1)
`
`11.4 (1.2)
`
`12.0 (1.2)
`
`11.2 (1.3)
`
`Change (from baseline to
`highest value)
`
`1.6 (1.2)
`
`0.8 (0.8)
`
`2.9 (1.6)
`
`2.2 (1.3)
`
`0.001
`p-value
`SD=standard deviation; a: Intravenous iron per standard of care
`
`0.001
`
`Increases from baseline in mean ferritin (264.2 ± 224.2 ng/mL in Cohort 1 and 218.2 ±
`211.4 ng/mL in Cohort 2), and transferrin saturation (13 ± 16% in Cohort 1 and 20 ±
`15% in Cohort 2) were observed at Day 35 in Injectafer-treated patients.
`
`Reference ID: 4563426
`
`9
`
`

`

`14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent
`Chronic Kidney Disease
`
`Trial 2: REPAIR-IDA, Randomized Evaluation of efficacy and safety of Ferric
`carboxymaltose in Patients with iron deficiency Anemia and Impaired Renal function,
`(NCT00981045) was a randomized, open-label, controlled clinical study in patients with
`non-dialysis dependent chronic kidney disease. Inclusion criteria included hemoglobin
`(cid:11)(cid:43)(cid:69)(cid:12)(cid:3)(cid:148)(cid:3)(cid:20)(cid:20)(cid:17)(cid:24)(cid:3)(cid:74)(cid:18)(cid:71)(cid:47)(cid:15)(cid:3)(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:87)(cid:76)(cid:81)(cid:3)(cid:148)(cid:3)(cid:20)(cid:19)(cid:19)(cid:3)(cid:81)(cid:74)(cid:18)(cid:80)(cid:47)(cid:3)(cid:82)(cid:85)(cid:3)(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:87)(cid:76)(cid:81)(cid:3)(cid:148)(cid:3)(cid:22)(cid:19)(cid:19)(cid:3)(cid:81)(cid:74)(cid:18)(cid:80)(cid:47)(cid:3)(cid:90)(cid:75)(cid:72)(cid:81)(cid:3)(cid:87)(cid:85)(cid:68)(cid:81)(cid:86)(cid:73)(cid:72)(cid:85)(cid:85)(cid:76)(cid:81)(cid:3)
`(cid:86)(cid:68)(cid:87)(cid:88)(cid:85)(cid:68)(cid:87)(cid:76)(cid:82)(cid:81)(cid:3)(cid:11)(cid:55)(cid:54)(cid:36)(cid:55)(cid:12)(cid:3)(cid:148)(cid:3)(cid:22)(cid:19)(cid:8)(cid:17) Study patients were randomized to either Injectafer or
`Venofer. The mean age of study patients was 67 years (range, 19 to 101); 64% were
`female; 54% were Caucasian, 26% were African American, 18% Hispanics, and 2% were
`other races.
`
`Table 3 shows the baseline and the change in hemoglobin from baseline to highest value
`between baseline and Day 56 or time of intervention.
`
`Table 3. Mean Change in Hemoglobin From Baseline to the Highest Value
`Between Baseline and Day 56 or Time of Intervention (Modified Intent-to-Treat
`Population)
`Hemoglobin (g/dL)
`Mean (SD)
`
`Injectafer
`(N=1249)
`
`Venofer
`(N=1244)
`
`Baseline
`
`Highest Value
`
`Change (from baseline to highest
`value)
`Treatment Difference (95% CI)
`
`10.3 (0.8)
`
`10.3 (0.8)
`
`11.4 (1.2)
`
`1.1 (1.0)
`
`11.3 (1.1)
`
`0.9 (0.92)
`
`0.21 (0.13, 0.28)
`
`Increases from baseline in mean f erritin (734.7 ± 337.8 ng/mL), and transferrin
`saturation (30 ± 17%) were observed prior to Day 56 in Injectafer-treated patients.
`
`16
`
`HOW SUPPLIED/STORAGE AND HANDLING
`
`NDC 0517-0650-01
`NDC 0517-0650-02
`
`750 mg iron/15 mL Single-Dose Vial
`750 mg iron/15 mL Single-Dose Vial
`
`Individually boxed
`Packages of 2
`
`Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to
`86°F). [See the USP controlled room temperature]. Do not freeze.
`
`17
`
`PATIENT COUNSELING INFORMATION
`
`Prior History of Reactions to Parenteral Iron Products
`Question patients regarding any prior history of reactions to parenteral iron products [see
`Warnings and Precautions (5.1)].
`
`Reference ID: 4563426
`
`10
`
`

`

`Serious Hypersensitivity Reactions
`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 breathing problems [see Warnings and Precautions (5.1)].
`
`Injectafer is manufactured under license from Vifor (International) Inc, Switzerland.
`
`AMERICAN
`REGENT, INC.
`SHIRLEY, NY 11967
`
`IN0650
`RQ1052-A
`
`Reference ID: 4563426
`
`11
`
`

`

`Patient Information
`INJECTAFER (in-jekt-a-fer)
`(ferric carboxymaltose injection)
`What is INJECTAFER?
`INJECTAFER is a prescription iron replacement medicine used to treat iron deficiency anemia in adults who have:
`intolerance to oral iron or who have not responded well to treatment with oral iron, or
`(cid:120)
`non-dialysis dependent chronic kidney disease
`(cid:120)
`It is not known if INJECTAFER is safe and effective for use in children.
`Who should not receive INJECTAFER?
`Do not receive INJECTAFER if you are allergic to ferric carboxymaltose or any of the ingredients in INJECTAFER.
`See the end of this leaflet for a complete list of ingredients in INJECTAFER.
`Before receiving INJECTAFER, tell your healthcare provider about all of your medical conditions, including if
`you:
`have had an allergic reaction to iron given into your vein
`(cid:120)
`have high blood pressure
`(cid:120)
`are pregnant or plan to become pregnant. It is not known if INJECTAFER will harm your unborn baby.
`(cid:120)
`are breastfeeding or plan to breastfeed. INJECTAFER passes into your breast milk. It is unknown whether
`(cid:120)
`INJECTAFER would pose a risk to your baby. Talk to your healthcare provider about the best way to feed your
`baby during treatment with INJECTAFER.
`Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines,
`vitamins, and herbal supplements.
`How will I receive INJECTAFER?
`INJECTAFER is given intravenously (into your vein) by your healthcare provider in 2 doses at least 7 days apart.
`What are the possible side effects of INJECTAFER?
`INJECTAFER may cause serious side effects, including:
`(cid:120) Allergic (hypersensitivity) reactions. Serious life-threatening allergic reactions have happened in people who
`receive INJECTAFER. Other serious reactions including itching, hives, wheezing, and low blood pressure also
`have happened during treatment with INJECTAFER. Tell your healthcare provider if you have ever had any
`unusual or allergic reaction to any iron given by vein.
`(cid:120) High blood pressure (hypertension). High blood pressure, sometimes with face flushing, dizziness, or nausea,
`has happened during treatment with INJECTAFER. Your healthcare provider will check your blood pressure and
`check for any signs and symptoms of high blood pressure after you receive INJECTAFER.
`The most common side effects of INJECTAFER include:
`high blood pressure
`nausea
`(cid:120)
`(cid:120)
`low levels of phosphorous in your blood
`flushing
`(cid:120)
`(cid:120)
`dizziness
`(cid:120)
`These are not all the possible side effects of INJECTAFER.
`Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
`General information about INJECTAFER
`Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask
`your pharmacist or healthcare provider for information about INJECTAFER that is written for health professionals.
`
`What are the ingredients in INJECTAFER?
`Active ingredient: ferric carboxymaltose
`Inactive ingredients: water for injection. Sodium hydroxide and/or hydrochloric acid may have been added to adjust
`pH to 5.0-7.0.
`
`12
`
`Reference ID: 4563426
`
`

`

`AMERICAN
`REGENT, INC.
`SHIRLEY, NY 11967
`
`For more information go to www.injectafer.com or call 1-800-734-9236.
`This Patient Information has been approved by the U.S. Food and Drug Administration.
`
`Revised: 02/2020
`
`Reference ID: 4563426
`
`13
`
`

`

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