`•
`
`
`-------------------------------CONTRAINDICATIONS-----------------------------
`
`
`
`
`Hypersensitivity to Injectafer or any of its inactive components. (4)
`
`-----------------------WARNINGS AND PRECAUTIONS-----------------------
`
`• Hypersensitivity reactions: Observe for signs and symptoms of
`
`
`
`
`
`
`
`
`
`
`
`
`hypersensitivity during and after Injectafer administration for at least 30
`
`
`minutes and until clinically stable following completion of each
`
`administration. (5.1)
`• Hypertension: Monitor patients closely for signs and symptoms of
`
`
`
`
`hypertension following each Injectafer administration. (5.2)
`
`
`
`
`
`
`
`------------------------------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
`1-800-FDA-1088
`or
`1-800-734-9236
`at
`or FDA
`at
`
`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.
`
`
`
`
` 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
`
`
`----------------------------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
`
`•
`
`response to oral iron;
`
`who have non-dialysis dependent chronic kidney disease.
`
`
`----------------------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)
`
`
`---------------------DOSAGE FORMS AND STRENGTHS---------------------
`
`
`
`
`
`
`Injection: 750 mg iron / 15 mL single-dose vial. (3)
`____________________________________________________________________________________________________________
`
`
`
`
`
`Revised: 01/2018
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`
`10 OVERDOSAGE
`
`
`
`11 DESCRIPTION
`
`INDICATIONS AND USAGE
`1
`
`
`
`12 CLINICAL PHARMACOLOGY
`
`2 DOSAGE AND ADMINISTRATION
`
`
`
`12.1 Mechanism of Action
`
`3 DOSAGE FORMS AND STRENGTHS
`
`
`
`12.2 Pharmacodynamics
`
`4 CONTRAINDICATIONS
`
`
`
`12.3 Pharmacokinetics
`
`5 WARNINGS AND PRECAUTIONS
`
`
`
`13 NONCLINICAL TOXICOLOGY
`
`5.1 Hypersensitivity Reactions
`
`
`
`
`
`
`13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility
`
`5.2 Hypertension
`
`
`
`14 CLINICAL STUDIES
`
`
`5.3
`Laboratory Test Alterations
`
`
`
`
`
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to
`
`6 ADVERSE REACTIONS
`
`
`
`
`
`Oral Iron or Have Had Unsatisfactory Response to Oral Iron
`
`
`
`6.1 Adverse Reactions in Clinical Trials
`
`
`
`14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis
`
`
`
`6.2
`Post-marketing Experience
`
`Dependent Chronic Kidney Disease
`
`7 DRUG INTERACTIONS
`
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`8 USE IN SPECIFIC POPULATIONS
`
`
`
`17 PATIENT COUNSELING INFORMATION
`
`8.1
`Pregnancy
`
`
`
`8.2
`Lactation
`
`
`
`
`
`
`
`* Sections or subsections omitted from the full prescribing information are not
`8.4
`Pediatric Use
`
`
`
`8.5 Geriatric Use
`listed.
`___________________________________________________________________________________________________________________________________
`
`
`
`
`
`
`Reference ID: 4212697
`
`
`
` 1
`
`
`
`
`
` FULL PRESCRIBING INFORMATION
`
`
`
`INDICATIONS AND USAGE
`1
`
`
`
`
`Injectafer is indicated for the treatment of iron deficiency anemia in adult patients:
`
`
`
`
`
`
`• who have intolerance to oral iron or have had unsatisfactory response to oral iron;
`
`
`
`
`• who have non-dialysis dependent chronic kidney disease.
`
`
`
`
`
`DOSAGE AND ADMINISTRATION
`2
`
`
`
`
`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.
`
`
`
`
`
`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.
`
`
`
`
`The dosage of Injectafer is expressed in mg of elemental iron. Each mL of Injectafer
`
`
`
`
`contains 50 mg of elemental iron. Injectafer treatment may be repeated if iron deficiency
`
`anemia reoccurs.
`
`
`
`
`Administer Injectafer intravenously, either as an undiluted slow intravenous push or by
`
`
`
`
`infusion. When administering as a slow intravenous push, give at the rate of
`
`
`
`approximately 100 mg (2 mL) per minute. 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-use only. Any unused drug remaining after injection must
`
`
`
`
`be discarded.
`
`
`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.
`
`
`
`3
`
`
`Injection: 750 mg iron / 15 mL single-dose vial
`
`
`
`
`CONTRAINDICATIONS
`4
`
`
`Hypersensitivity to Injectafer or any of its components [see Warnings and Precautions
`
`
`
`
`(5.1)].
`
`DOSAGE FORMS AND STRENGTHS
`
`
`Reference ID: 4212697
`
`
`
` 2
`
`
`
`
`
`
`
`
`WARNINGS AND PRECAUTIONS
`
`
`5
`
`
`
`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 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)].
`
`
`
`
`
`5.3 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
`
`
`
`
`The following adverse reactions are discussed in greater detail in other sections of the
`
`labeling:
`
`
`
`Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
`
`
`•
`
`
`
`Hypertension [see Warnings and Precautions (5.2)]
`
`
`•
`
`
`
`Laboratory Test Alterations [see Warnings and Precautions (5.3)]
`
`
`
`•
`
`
`
`6.1 Adverse Reactions in Clinical Trials
`
`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.
`
`
`
`ADVERSE REACTIONS
`
`Reference ID: 4212697
`
`
`
` 3
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Adverse reactions reported by ≥ 1% of treated patients are shown in the following table.
`
`
`
` Table 1. Adverse reactions reported in ≥ 1% of Study Patients in Clinical Trials 1 and 2
`
`
`
` Injectafer
`
`
`
`
` Oral
` Pooled
`
`
`
` Comparatorsa
`
` iron
`Term
`
`
`
`
`(N=1783)
`(N=1775)
`
`
`
` (N=253)
`
`
`
` %
` %
` %
` Nausea
`
` 7.2
`
`
` 1.8
`
` 1.2
` Hypertension
`
`
` 3.8
`
` 1.9
`
` 0.4
` Flushing/Hot Flush
`
` 3.6
`
` 0.2
`
` 0.0
`
`
` 2.1
`
` 0.1
`
` 0.0
` Blood Phosphorus Decrease
`
` 2.0
`
` 1.2
`
` 0.0
`
` Dizziness
`
` 1.7
`
` 0.5
`
` 0.4
`
` Vomiting
`
` 1.4
`
` 0.3
`
` 0.0
` Injection Site Discoloration
`
` 1.2
`
` 0.9
`
` 0.0
`
` Headache
`
` 1.1
`
` 0.2
`
` 0.0
` Alanine Aminotransferase Increase
`
` 1.1
`
` 2.1
`
` 0.0
`
` Dysgeusia
`
` 1.0
`
` 1.9
`
` 0.0
`
` Hypotension
`
` 0.5
`
` 0.9
`
` 3.2
`
` Constipation
` a Includes oral iron and all formulations of IV iron other than Injectafer
`
`
`Other adverse reactions reported by ≥ 0.5% of treated patients include abdominal pain,
`
`diarrhea, gamma glutamyl transferase increased, injection site pain/irritation, rash,
`
`
`paraesthesia, sneezing. Transient decreases in laboratory blood phosphorus levels (< 2
`
`
`
`
`mg/dL) have been observed in 27% (440/1638) patients in clinical trials.
`
`
`
`
`
`6.2 Post-marketing Experience
`
`
`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 serious adverse reactions have been most commonly
`
`
`reported from the post-marketing spontaneous reports with Injectafer: urticaria, dyspnea,
`
`
`
`pruritis, tachycardia, erythema, pyrexia, chest discomfort, chills, angioedema, back pain,
`
`
`arthralgia, and syncope. One case of hypophosphatemic osteomalacia was reported in a
`
`
`
`
`
`
`subject who received 500 mg of Injectafer every 2 weeks for a total of 16 weeks. Partial
`
`
`recovery followed discontinuation of Injectafer.
`
`
`8
`
`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 (IDA) 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
`
` 4
`
`
`USE IN SPECIFIC POPULATIONS
`
`
`
`Reference ID: 4212697
`
`
`
`
`
`
`
` 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.
`
`
`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
`
`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 a 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.
`
`
`Reference ID: 4212697
`
`
`
` 5
`
`
`
`
`
`
`
`
`
`
`
` 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.
`
`
`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.
`
`[see Adverse Reactions (6.2)].
`
`
`
`
`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→4)-O-α-D
`
`
`
`
`
`a
`glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate.
`has
`It
`relative
`
`
`molecular weight of approximately 150,000 Da corresponding to the following empirical
`
`formula:
`
`
`
`[FeOx(OH)y(H2O)z]n [{(C6H10O5)m (C6H12O7)}l]k,
`
`where n ≈ 103, m ≈ 8, l≈ 11, and k ≈ 4
`
`
`
`
`
`
`
`
`(l represents the mean branching degree of the ligand).
`
`
`
`The chemical structure is presented below:
`
`
`
`
`
`
`Reference ID: 4212697
`
`
`
` 6
`
`
`
`
`
`
`
`CLINICAL PHARMACOLOGY
`
`
`
`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-use 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
`
`
`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% after 24 days 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.
`
`
`
`
`
`
`Reference ID: 4212697
`
`
`
` 7
`
`
`
`
`
`
`
`
`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
`
`
`
`
`
`in vitro mammalian cell mutation assay
`
`
`lymphocytes,
`lymphoma
`in mouse
`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.
`
`CLINICAL STUDIES
`14
`
`
`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.
`
`
`
`
`14.1 Trial 1: Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron or
`
`
`
`
`Have Had Unsatisfactory Response to Oral 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,
`
`
`
`ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mL when transferrin saturation (TSAT) ≤ 30%.
`
`
`
`
`
`
`
`
`
`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.
`
`
`
`
`
`
`Reference ID: 4212697
`
`
`
` 8
`
`
`
`
`
`
`
` IV SCa
`
`
` (N=237)
`
` 9.0 (1.5)
`
`
`
` 11.2 (1.3)
`
`
`
`
`
` 2.2 (1.3)
`
`
`
`
`
`
`
`
`
` 0.001
`
` Table 2. Mean Change in Hemoglobin From Baseline to the Highest Value
`
`
`
` Between Day 35 or Time of Intervention (Modified Intent-to-Treat Population)
` Cohort 2
` Cohort 1
`
`
` Hemoglobin (g/dL)
`
` Mean (SD)
`
` Injectafer
`
` Oral Iron
`
` Injectafer
`
` (N=245)
`
`
` (N=244)
` (N=251)
`
` 9.1 (1.6)
`
` 10.6 (1.0)
`
` 10.6 (1.0)
`
`
`
`
`
`
`
` 12.0 (1.2)
`
`
` 12.2 (1.1)
`
` 11.4 (1.2)
`
`
`
`
`
`
` 2.9 (1.6)
`
`
`
` 1.6 (1.2)
` 0.8 (0.8)
`
`
`
`
`
`
`
`
` Baseline
`
`
`
`
`
`
`
`
`
`
`
`
` Highest Value
`
`
`
`Change (from baseline to
`
`
`highest value)
`
`
` 0.001
`
` p-value
`
` SD=standard deviation; a: Intravenous iron per standard of care
`
`
`
`
`
`
`
`
`
`
`
` 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.
`
`
`
`
`
`
`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
`
`(Hb) ≤ 11.5 g/dL, ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mL when transferrin
`
`
`
`
`
`
`
`
`
`
`saturation (TSAT) ≤ 30%. Study patients were randomized to either Injectafer or
`
`
`
`
`
`
`Venofer. The mean age of study patients was 67 years (range, 19 to 96); 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.
`
`
`
`
`
`Reference ID: 4212697
`
`
`
` 9
`
`
`
`
`
`
`
`
`
`
`
`
`
` 0.21 (0.13, 0.28)
`
`
` Highest Value
`
`Change (from baseline to highest
`
` value)
` Treatment Difference (95% CI)
`
`
`
`
`
`
`
`
`
`
`
` Increases from baseline in mean f erritin (734.7 ± 337.8 ng/mL), and transferrin
` saturation (30 ± 17%) were observed at Day 56 in Injectafer-treated patients.
`
`
`
`
`
`
`
`16
`
`
`NDC 0517-0650-01
`
`
`NDC 0517-0650-02
`
`
`
`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
`
`
`
`
`
`
`
`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)
`
` Baseline
`
`
`
`
` Injectafer
`
` (N=1249)
`
`
` 10.3 (0.8)
`
`
`
`
` 11.4 (1.2)
`
`
`
`
` 1.1 (1.0)
`
`
` Venofer
`
`
` (N=1244)
`
`
` 10.3 (0.8)
`
`
`
`
` 11.3 (1.1)
`
`
`
`
` 0.9 (0.92)
`
`
`HOW SUPPLIED/STORAGE AND HANDLING
`
`
`
`Individually boxed
`750 mg iron/15 mL Single-Dose Vial
`
`
`
`750 mg iron/15 mL Single-Dose Vial Packages of 2
`
`
`
`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 breathing problems [see Warnings and
`
`Precautions (5)].
`
`
`
`Injectafer is manufactured under license from Vifor (International) Inc, Switzerland.
`
`
`
`
`AMERICAN
`
`REGENT, INC.
`
`SHIRLEY, NY 11967
`
`
`IN0650
`
`RQ1052
`
`
`
`Reference ID: 4212697
`
`
`
` 10
`
`
`
`
`
`
`Patient Information
`
`INJECTAFER (in-jekt-a-fer)
`
`
`
`(ferric carboxymaltose injection)
`
`
`
`
`
`
`
`
`
`
`
`Reference ID: 4212697
`
`
`
`
`
`
`
` Revised: 01/2018
`
`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
`
`
`
`
`•
`
`• non-dialysis dependent chronic kidney disease
`
`
`
`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
`
`
` • have high blood pressure
`
`
`
`
`
` • are pregnant or plan to become pregnant. It is not known if INJECTAFER will harm your unborn baby.
`
` • are breastfeeding or plan to breastfeed. INJECTAFER passes into your breast milk. It is unknown whether
`
`
`
`
` 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:
`
`
` • 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.
` • 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:
`
`
`
`
`
` • nausea
` • high blood pressure
`
`
` flushing
`
` low levels of phosphorous in your blood
`
`•
`•
`
`
`
` • dizziness
`
` 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.
`
` Manufactured by:
`
`
` For more information go to www.TRADENAME.com or call 1-XXX-XXX-XXXX.
`
`
` This Patient Information has been approved by the U.S. Food and Drug Administration.
`
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`