important safety information billing and coding … · the treatment of iron deﬁciency anemia...

INDICATIONSInjectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of iron deficiency anemia (IDA) in adult patients:•who have intolerance to or have had unsatisfactory response to oral iron

or•who have non-dialysis dependent chronic kidney disease

CONTRAINDICATIONSInjectafer® is contraindicated in patients with hypersensitivity to Injectafer® or any of its inactive components.

Billing and Coding Guide

®

Please see attached Full Prescribing Information for Injectafer® andImportant Safety Information on Page 5.

American Regent® is a registered trademark of Luitpold Pharmaceuticals, Inc.Injectafer® and the Injectafer® logo are trademarks of Vifor (International), Inc., Switzerland.Injectafer® is manufactured under license from Vifor (International), Inc., Switzerland.

©2015 American Regent, Inc. FCM195 Iss. 7/2015

®

Please see Full Prescribing Information for Injectafer® enclosed in the pocket of this guide, and the Important Safety Information inside.

Current ICD-9-CM Code† Corresponding ICD-10-CM Code‡

Code Description Code Description

555.0-550.9

Regional Enteritis of the small intestine

K50.00- K50.919

Crohn's disease [regional enteritis]

556.0-556.9 Ulcerative Colitis K51.0-

K51.919 Ulcerative Colitis

579.0 Celiac Disease K90.0 Celiac Disease

579.8 Other specified intestinal malabsorption

K90.4Malabsorption due to intolerance not elsewhere classified

K90.89 Other intestinal malabsorption

579.9 Unspecified intestinal malabsorption K90.9 Intestinal malabsorption

unspecified

585.1 Chronic Kidney Disease, Stage 1 N18.1 Chronic Kidney Disease, Stage 1





585.6 End Stage Renal Disease N18.6 End Stage Renal Disease

585.9 Chronic Kidney Disease, Unspecified N18.9 Chronic Kidney Disease,

Unspecified

995.29 Unspecified adverse effect of other drug medicinal & biologic substance

T454X5A Adverse effect of iron and its compounds initial encounter

626.2 Excessive or frequent menstruation N92.0

Excessive and frequent menstruation with regular cycle

626.4 Irregular menstrual cycleN92.5 Other specified irregular

menstruation

N92.6 Irregular menstruation, unspecified

*Secondary code suggestions only; appropriate codes not limited to those listed above. Injectafer is indicated to treat IDA; it is not indicated to treat the above listed underlying conditions.

†International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)‡International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)

The information provided is for educational purposes only. The health care provider is fully responsible for billing and coding determinations.

Choose a Code Speci�c to Your IDA Patient’s Underlying Condition*

INDICATIONSInjectafer® (ferric carboxymaltose injection) 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, and in adult patients with non-dialysis dependent chronic kidney disease.

IMPORTANT SAFETY INFORMATIONCONTRAINDICATIONSInjectafer® is contraindicated in patients with hypersensitivity to Injectafer® or any of its inactive components.WARNINGS AND PRECAUTIONSSerious 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 signi�cant 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.

In clinical studies, hypertension was reported in 3.8% (67/1775) of subjects. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/ 1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer® administration.

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 REACTIONSIn two randomized clinical studies, a total of 1775 patients were exposed to Injectafer®, 15 mg/kg of body weight, up to a single maximum 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 reported by ≥2% of Injectafer®-treated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.0%).

The following serious adverse reactions have been most commonly reported from the post-marketing spontaneous reports: urticaria, dyspnea, pruritus, tachycardia, erythema, pyrexia, chest discomfort, chills, angioedema, back pain, arthralgia, and syncope.

Please see Full Prescribing Information for Injectafer® inside pocket.

SELECTED SAFETY INFORMATION FOR INJECTAFER®WARNINGS AND PRECAUTIONSSerious 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 signi�cant 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.

Please see attached Full Prescribing Information for Injectafer® andImportant Safety Information on Page 5.

J Code Product Indications

J1439 Injection, ferric carboxymaltose, 1 mg

Injectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of IDA in adult patients:

• who have intolerance to or have had unsatisfactory response to oral iron

or • who have non-dialysis dependent chronic

kidney disease

J Code

For more information, please visit Injectafer.com

FOR BILLING AND CODING ASSISTANCE, PLEASE CONTAC T:

IV Iron Reimbursement Hotline1-877-4-IV-IRON (1-877-448-4766)Monday through Friday between 9:00 AM and 8:00 PM, ET

Required Billing and Coding

* Healthcare Common Procedure Coding System.† Current Procedural Terminology (CPT). CPT codes® 2015 American Medical Association (AMA). All rights reserved. CPT is

a trademark of the AMA. No fee schedules, basic units, relative values, or related listings are included in the CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use.

*International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)†International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)

Code Type Code Description

Product Package Code

National Drug Code (NDC) 00517-0650-01 Injectafer 750 mg iron/15 mL single use vial

Product Speci�c Billing Code

HCPCS* J1439 Injection, ferric carboxymaltose 1 mg

Drug Administration Codes

CPT®†

96374or

96365

Therapeutic, prophylactic or diagnostic injection (specify substance or drug) Intravenous Push single or initial substance drug

Intravenous infusion for therapy, prophylaxis, or diagnosis (specify substance or drug); initial up to 1 hr

Current ICD-9-CM Code* Corresponding ICD-10-CM Code†


280.0 Iron deficiency anemia secondary to blood loss (chronic) D50.0 Iron deficiency anemia

secondary to blood loss (chronic)

280.1 Iron deficiency anemia secondary to dietary iron intake D50.8 Other iron deficiency anemias

280.8 Other specified iron deficiency anemias

D50.1 Sideropenic dysphagia

D50.8 Other iron deficiency anemias

280.9 Unspecified iron deficiency anemia D50.9 Iron deficiency anemia,

unspecified

285.21 Anemia in chronic kidney disease D63.1 Anemia in chronic kidney disease

285.22 Anemia in neoplastic disease D63.0 Anemia in neoplastic disease

285.29 Anemia of other chronic disease D63.8 Anemia in other chronic diseases classified elsewhere

285.3 Antineoplastic chemotherapy induced anemia

D64.81 Antineoplastic chemotherapy induced anemia

Required Product and Administration Codes

IDA-Related Diagnosis Codes: Choose a Primary Code

SELECTED SAFETY INFORMATION FOR INJECTAFER®WARNINGS AND PRECAUTIONSSerious 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 signi�cant 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.


J Code Product Indications

J1439 Injection, ferric carboxymaltose, 1 mg

Injectafer® (ferric carboxymaltose injection) is an iron replacement product indicated for the treatment of IDA in adult patients:

• who have intolerance to or have had unsatisfactory response to oral iron

or • who have non-dialysis dependent chronic

kidney disease

J Code

For more information, please visit Injectafer.com

FOR BILLING AND CODING ASSISTANCE, PLEASE CONTAC T:

IV Iron Reimbursement Hotline1-877-4-IV-IRON (1-877-448-4766)Monday through Friday between 9:00 AM and 8:00 PM, ET

Required Billing and Coding

* Healthcare Common Procedure Coding System.† Current Procedural Terminology (CPT). CPT codes® 2015 American Medical Association (AMA). All rights reserved. CPT is

a trademark of the AMA. No fee schedules, basic units, relative values, or related listings are included in the CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use.

*International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)†International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM)

Code Type Code Description

Product Package Code

National Drug Code (NDC) 00517-0650-01 Injectafer 750 mg iron/15 mL single use vial

Product Speci�c Billing Code

HCPCS* J1439 Injection, ferric carboxymaltose 1 mg

Drug Administration Codes

CPT®†

96374or

96365

Therapeutic, prophylactic or diagnostic injection (specify substance or drug) Intravenous Push single or initial substance drug

Intravenous infusion for therapy, prophylaxis, or diagnosis (specify substance or drug); initial up to 1 hr

Current ICD-9-CM Code* Corresponding ICD-10-CM Code†


280.0 Iron deficiency anemia secondary to blood loss (chronic) D50.0 Iron deficiency anemia

secondary to blood loss (chronic)

280.1 Iron deficiency anemia secondary to dietary iron intake D50.8 Other iron deficiency anemias

280.8 Other specified iron deficiency anemias

D50.1 Sideropenic dysphagia

D50.8 Other iron deficiency anemias

280.9 Unspecified iron deficiency anemia D50.9 Iron deficiency anemia,

unspecified

285.21 Anemia in chronic kidney disease D63.1 Anemia in chronic kidney disease

285.22 Anemia in neoplastic disease D63.0 Anemia in neoplastic disease

285.29 Anemia of other chronic disease D63.8 Anemia in other chronic diseases classified elsewhere

285.3 Antineoplastic chemotherapy induced anemia

D64.81 Antineoplastic chemotherapy induced anemia

Required Product and Administration Codes

IDA-Related Diagnosis Codes: Choose a Primary Code





®

Please see Full Prescribing Information for Injectafer® enclosed in the pocket of this guide and the Important Safety Information inside.



®




555.0-550.9


K50.00- K50.919









unspecified








Unspecified






menstruation
















®




®




555.0-550.9


K50.00- K50.919









unspecified








Unspecified






menstruation











Please see attached Full Prescribing Information for Injectafer®.




Billing and CodingGuide

®



©2015 American Regent, Inc. FCM195EM Iss. 07/2015

®

Please see attached Full Prescribing Information for Injectafer® andthe Important Safety Information on Page 5.



555.0-550.9


K50.00- K50.919









unspecified








Unspecified






menstruation












651 S ML King Jr Ave • Waukegan, IL 60085 • Phone 847.336.4200 • Fax 847.360.4924complete packaging | individual solutionsSM

Product Information Specified Colors

P/N: J/N:Cust:Size:

Proof A7/26/2013

Approved By

Name

Date

OK to Print New Proof Required

This proof is to show size, copy placement andcolor break. Actual colors will be matched onpress to: PMS Book, On_Demand Solutions FourColor Book, On _Demand Solutions IndichromePlus Book and/or approved Color Standards.

258024LUITPOLD PHARMACEUTICALS INC

Cyan Magenta Yellow Black

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Injectafer is indicated for the treatment of iron deficiency anemia in adultpatients:• who have intolerance to oral iron or have had unsatisfactory response to

oral iron;• who have non-dialysis dependent chronic kidney disease.2 DOSAGE AND ADMINISTRATIONFor patients weighing 50 kg (110lb) or more: Give Injectafer in two dosesseparated by at least 7 days. Give each dose as 750 mg for a total cumulativedose not to exceed 1500 mg of iron per course.For patients weighing less than 50 kg (110lb): Give Injectafer in two dosesseparated by at least 7 days. Give each dose as 15 mg/kg body weight for atotal cumulative dose not to exceed 1500 mg of iron per course.The dosage of Injectafer is expressed in mg of elemental iron. Each mL ofInjectafer contains 50 mg of elemental iron. Injectafer treatment may berepeated if iron deficiency anemia reoccurs.Administer Injectafer intravenously, either as an undiluted slow intravenouspush or by infusion. When administering as a slow intravenous push, give atthe rate of approximately 100 mg (2 mL) per minute. When administered viainfusion, 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 isnot 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, Injectafersolution is physically and chemically stable for 72 hours when stored at roomtemperature. To maintain stability, do not dilute to concentrations less than2 mg iron/mL.Inspect parenteral drug products visually for the absence of particulatematter and discoloration prior to administration. The product contains nopreservatives. Each vial of Injectafer is intended for single-use only. Anyunused drug remaining after injection must be discarded.Avoid extravasation of Injectafer since brown discoloration of the extravasationsite may be long lasting. Monitor for extravasation. If extravasation occurs,discontinue the Injectafer administration at that site.

3 DOSAGE FORMS AND STRENGTHS

750 mg iron / 15 mL single-use vial

4 CONTRAINDICATIONS

Hypersensitivity to Injectafer or any of its components [see Warnings andPrecautions (5.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity ReactionsSerious hypersensitivity reactions, including anaphylactic-type reactions,some of which have been life-threatening and fatal, have been reported inpatients receiving Injectafer. Patients may present with shock, clinicallysignificant hypotension, loss of consciousness, and/or collapse. Monitorpatients for signs and symptoms of hypersensitivity during and afterInjectafer administration for at least 30 minutes and until clinically stablefollowing completion of the infusion. Only administer Injectafer whenpersonnel and therapies are immediately available for the treatment ofserious hypersensitivity reactions. [see Adverse Reactions (6.1 and 6.2)].

HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to useInjectafer safely and effectively. See full prescribing information forInjectafer.INJECTAFER® (ferric carboxymaltose injection)For intravenous useInitial U.S. Approval: 2013------------------------------INDICATIONS AND USAGE------------------------------Injectafer is an iron replacement product indicated for the treatment of irondeficiency 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 (110lb) or more: Give Injectafer in twodoses separated by at least 7 days. Give each dose as 750 mg for a totalcumulative dose of 1500 mg of iron per course.For patients weighing less than 50 kg (110lb): Give Injectafer in two dosesseparated 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)

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions5.2 Hypertension5.3 Laboratory Test Alterations

6 ADVERSE REACTIONS6.1 Adverse Reactions in Clinical Trials6.2 Post-marketing Experience

7 DRUG INTERACTIONS8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use

--------------------------DOSAGE FORMS AND STRENGTHS-----------------------750 mg iron / 15 mL single-use vial. (3)-------------------------------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 least30 minutes and until clinically stable following completion of eachadministration. (5.1)

• Hypertension: Monitor patients closely for signs and symptoms ofhypertension 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 at1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.------------------------USE IN SPECIFIC POPULATIONS----------------------------• Nursing Mothers: Exercise caution when administered to a nursing

woman. (8.3)See 17 for PATIENT COUNSELING INFORMATION and FDA-approvedpatient labeling.

Revised: July 2013

10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility

14 CLINICAL STUDIES14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to

Oral Iron or Have Had Unsatisfactory Response to Oral Iron14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis

Dependent Chronic Kidney Disease16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing informationare not listed.

In clinical trials, serious anaphylactic/anaphylactoid reactions were reportedin 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severeadverse reactions potentially associated with hypersensitivity which included,but not limited to, pruritus, rash, urticaria, wheezing, or hypotension werereported in 1.5% (26/1775) of these subjects.5.2 HypertensionIn clinical studies, hypertension was reported in 3.8% (67/1,775) of subjectsin clinical trials 1 and 2. Transient elevations in systolic blood pressure,sometimes occurring with facial flushing, dizziness, or nausea were observedin 6% (106/1,775) of subjects in these two clinical trials. These elevationsgenerally occurred immediately after dosing and resolved within 30 minutes.Monitor patients for signs and symptoms of hypertension following eachInjectafer administration [see Dosage and Administration (2)].5.3 Laboratory Test AlterationsIn the 24 hours following administration of Injectafer, laboratory assays mayoverestimate serum iron and transferrin bound iron by also measuring theiron in Injectafer.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in othersections 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 TrialsBecause clinical trials are conducted under widely varying conditions, theadverse reaction rates observed cannot be directly compared to rates in otherclinical 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 upto a maximum single dose of 750 mg of iron on two occasions separated byat least 7 days up to a cumulative dose of 1500 mg of iron.Adverse reactions reported by ≥ 1% of treated patients are shown in thefollowing table.Table 1. Adverse reactions reported in ≥ 1% of Study Patients in Clinical Trials1 and 2

Term Injectafer

(N=1775)%

PooledComparatorsa

(N=1783)%

Oraliron

(N=253)%

Nausea 7.2 1.8 1.2Hypertension 3.8 1.9 0.4Flushing/Hot Flush 3.6 0.2 0.0Blood Phosphorus Decrease 2.1 0.1 0.0Dizziness 2.0 1.2 0.0Vomiting 1.7 0.5 0.4Injection Site Discoloration 1.4 0.3 0.0Headache 1.2 0.9 0.0Alanine AminotransferaseIncrease 1.1 0.2 0.0

Dysgeusia 1.1 2.1 0.0Hypotension 1.0 1.9 0.0Constipation 0.5 0.9 3.2

a Includes oral iron and all formulations of IV iron other than Injectafer

INJE

CTAF

ER®

(ferr

ic c

arbo

xym

alto

se in

ject

ion)

RQ105200

Other adverse reactions reported by ≥ 0.5% of treated patients includeabdominal pain, diarrhea, gamma glutamyl transferase increased, injectionsite pain/irritation, rash, paraesthesia, sneezing. Transient decreases inlaboratory blood phosphorus levels (< 2 mg/dL) have been observed in 27%(440/1638) patients in clinical trials.6.2 Post-marketing ExperienceBecause these reactions are reported voluntarily from a population of uncertainsize, it is not always possible to reliably estimate their frequency or establish acausal relationship to drug exposure. The following serious adverse reactionshave been most commonly reported from the post-marketing spontaneousreports with Injectafer: urticaria, dyspnea, pruritis, tachycardia, erythema,pyrexia, chest discomfort, chills, angioedema, back pain, arthralgia, andsyncope. One case of hypophosphatemic osteomalacia was reported ina subject who received 500 mg of Injectafer every 2 weeks for a total of16 weeks. Partial recovery followed discontinuation of Injectafer.

7 DRUG INTERACTIONS

Formal drug interaction studies have not been performed with Injectafer.

8 USE IN SPECIFIC POPULATIONS

8.1 PregnancyPregnancy Category CRisk SummaryAdequate and well controlled studies in pregnant women have not beenconducted. However, animal reproduction studies have been conducted withferric carboxymaltose. In these studies, administration of ferric carboxymaltoseto rabbits during the period of organogenesis caused fetal malformations andincreased 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 beenestablished for Injectafer. However, all pregnancies, regardless of exposure toany drug, has a background rate of 2 to 4% for major malformations, and 15to 20% for pregnancy loss. Injectafer should be used during pregnancy only ifthe potential benefit justifies the potential risk to the fetus.Animal DataAdministration of ferric carboxymaltose to rats as a one-hour intravenousinfusion up to 30 mg/kg/day iron on gestation days 6 to 17 did not result inadverse 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 gestationdays 6 to 19 at iron doses of 4.5, 9, 13.5, and 18 mg/kg/day. Malformationswere seen starting at the daily dose of 9 mg/kg (23% of the human weeklydose of 750 mg). Spontaneous abortions occurred starting at the daily irondose of 4.5 mg/kg (12% of the human weekly dose based on body surfacearea). Pre-implantation loss was at the highest dose. Adverse embryofetaleffects were observed in the presence of maternal toxicity.A pre- and post-natal development study was conducted in rats at intravenousdoses up to 18 mg/kg/day of iron (approximately 23% of the weekly humandose of 750 mg on a body surface area basis). There were no adverse effectson survival of offspring, their behavior, sexual maturation or reproductiveparameters.8.3 Nursing MothersA study to determine iron concentrations in breast milk after administration ofInjectafer (n=11) or oral ferrous sulfate (n=14) was conducted in 25 lactatingwomen with postpartum iron deficiency anemia. Mean breast milk iron levelswere higher in lactating women receiving Injectafer than in lactating womenreceiving oral ferrous sulfate.8.4 Pediatric UseSafety and effectiveness have not been established in pediatric patients.8.5 Geriatric UseOf the 1775 subjects in clinical studies of Injectafer, 50% were 65 years andover, while 25% were 75 years and over. No overall differences in safety oreffectiveness were observed between these subjects and younger subjects,and other reported clinical experience has not identified differences inresponses between the elderly and younger patients, but greater sensitivity ofsome older individuals cannot be ruled out.

10 OVERDOSAGEExcessive dosages of Injectafer may lead to accumulation of iron in storagesites potentially leading to hemosiderosis. A patient who received Injectafer18,000 mg over 6 months developed hemosiderosis with multiple jointdisorder, walking disability and asthenia . Hypophosphatemic osteomalaciawas reported in a patient who received Injectafer 4000 mg over 4 months.Partial recovery followed discontinuation of Injectafer. [see Post-marketingExperience (6.2)].

11 DESCRIPTION

Ferric carboxymaltose, an iron replacement product, is an iron carbohydratecomplex with the chemical name of polynuclear iron (III) hydroxide4(R)-(poly-(1→4)-O-a-D-glucopyranosyl)-oxy-2(R),3(S),5(R),6-tetrahydroxy-hexanoate. It has a relative molecular weight of approximately150,000 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:

651 S M

L King Jr A

ve • Waukegan, IL 60085 • P

hone 847.336.4200 • Fax 847.360.4924co

mp

lete packag

ing

| ind

ividu

al solu

tion

sS

M

Pro

du

ct Info

rmatio

nS

pecified

Co

lors

P/N: J/N:C

ust:Size:

Pro

of A

7/26/2013A

pp

roved

By

Nam

e

DateO

K to PrintN

ew Proof R

equired

This proof is to show size, copy placem

ent andcolor break. Actual colors w

ill be matched on

press to: PMS Book, O

n_Dem

and Solutions FourC

olor Book, On _D

emand Solutions Indichrom

ePlus Book and/or approved C

olor Standards.

258024LU

ITPOLD

PHAR

MAC

EUTIC

ALS INC

Cyan

Magenta

Yellow

Black


1INDICATIONS AND USAGE

Injectaferis

indicatedfor

thetreatm

entof

irondeficiency

anemia

inadult

patients:•

who

haveintolerance

tooraliron

orhavehad

unsatisfactoryresponse

tooral iron;

•who

havenon-dialysis

dependentchronickidney

disease.2

DOSAGE AND ADMINISTRATION

Forpatients

weighing

50kg

(110lb)or

more:

GiveInjectafer

intwodoses

separatedby

atleast7days.

Giveeach

doseas

750mgfora

totalcumulative

dosenotto

exceed1500

mgofiron

percourse.For

patientsweighing

lessthan

50kg

(110lb):Give

Injectaferin

twodoses

separatedby

atleast7days.Give

eachdose

as15

mg/kg

bodyweightfor

atotalcum

ulativedose

nottoexceed

1500mgofiron

percourse.The

dosageof

Injectaferis

expressedin

mgof

elementaliron.Each

mLof

Injectafercontains

50mgof

elemental

iron.Injectafer

treatment

may

berepeated

ifirondeficiency

anemiareoccurs.

Administer

Injectaferintravenously,either

asan

undilutedslow

intravenouspush

orbyinfusion.W

henadm

inisteringas

aslow

intravenouspush,give

atthe

rateofapproxim

ately100

mg(2

mL)perm

inute.When

administered

viainfusion,dilute

upto

750mgofiron

inno

more

than250

mLofsterile

0.9%sodium

chlorideinjection,USP,such

thattheconcentration

oftheinfusion

isnotless

than2mgofiron

permLand

administeroveratleast15

minutes.

When

addedto

aninfusion

bagcontaining

0.9%sodium

chlorideinjection,

USP,atconcentrationsranging

from2mgto

4mgofiron

permL,Injectafer

solutionisphysically

andchem

icallystable

for72hours

when

storedatroom

temperature.To

maintain

stability,donot

diluteto

concentrationsless

than2mgiron/m

L.Inspect

parenteraldrug

productsvisually

forthe

absenceof

particulatematter

anddiscoloration

priorto

administration.

Theproduct

containsno

preservatives.Each

vialof

Injectaferis

intendedfor

single-useonly.

Anyunused

drugrem

ainingafterinjection

mustbe

discarded.Avoid

extravasationofInjectafersince

browndiscoloration

oftheextravasation

sitemay

belong

lasting.Monitor

forextravasation.Ifextravasation

occurs,discontinue

theInjectaferadm

inistrationatthatsite.

3DOSAGE FORM

S AND STRENGTHS

750mgiron

/15mLsingle-use

vial

4CONTRAINDICATIONS

Hypersensitivityto

Injectaferor

anyof

itscom

ponents[see

Warnings

andPrecautions (5.1)].

5W

ARNINGS AND PRECAUTIONS

5.1Hypersensitivity Reactions

Serioushypersensitivity

reactions,including

anaphylactic-typereactions,

some

ofwhich

havebeen

life-threateningand

fatal,havebeen

reportedin

patientsreceiving

Injectafer.Patients

may

presentw

ithshock,

clinicallysignificant

hypotension,loss

ofconsciousness,

and/orcollapse.

Monitor

patientsfor

signsand

symptom

sof

hypersensitivityduring

andafter

Injectaferadministration

foratleast30m

inutesand

untilclinicallystable

following

completion

ofthe

infusion.Only

administer

Injectaferw

henpersonnel

andtherapies

areim

mediately

availablefor

thetreatm

entof

serioushypersensitivity

reactions.[see

AdverseReactions

(6.1and

6.2)].

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 useInitial U.S. Approval: 2013------------------------------INDICATIONS

ANDUSAGE------------------------------

Injectafer is an iron replacement product indicated for the treatm

ent of irondeficiency anem

ia in adult patients:•

who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis


disease.-------------------------DOSAGE AND ADM

INISTRATION---------------------------Forpatients

weighing

50kg

(110lb)ormore:

GiveInjectaferin

two

dosesseparated

byatleast7

days.Give

eachdose

as750

mgfora

totalcum

ulativedose

of1500mgofiron

percourse.Forpatients

weighing

lessthan

50kg

(110lb):Give

Injectaferintwodoses

separatedby

atleast7days

andgive

eachdose

as15

mg/kg

bodyweight.

Injectafertreatmentm

aybe

repeatedifiron

deficiencyanem

iareoccurs.(2)



2DOSAGE AND ADM

INISTRATION3

DOSAGE FORMS AND STRENGTHS

4CONTRAINDICATIONS

5W

ARNINGS AND PRECAUTIONS5.1

HypersensitivityReactions

5.2Hypertension

5.3Laboratory

TestAlterations6

ADVERSE REACTIONS6.1

AdverseReactions

inClinicalTrials

6.2Post-m

arketingExperience

7DRUG INTERACTIONS

8USE IN SPECIFIC POPULATIONS8.1

Pregnancy8.3

NursingMothers

8.4Pediatric

Use8.5

GeriatricUse

--------------------------DOSAGEFORM

SAND

STRENGTHS-----------------------750

mgiron

/15mLsingle-use

vial.(3)-------------------------------CONTRAINDICATIONS---------------------------------Hypersensitivity

toInjectaferorany

ofitsinactive

components.(4)

------------------------WARNINGS AND PRECAUTIONS----------------------------

•Hypersensitivity reactions:Observe

forsignsand

symptom

sof


andafterInjectaferadm

inistrationforatleast

30minutes

anduntilclinically

stablefollow

ingcom

pletionofeach

administration.(5.1)

•Hypertension:M

onitorpatientsclosely

forsignsand

symptom

sof

hypertensionfollow

ingeach

Injectaferadministration.(5.2)

------------------------------ADVERSE REACTIONS----------------------------------The

mostcom

mon

adversereactions

(≥2%

)arenausea,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 orwww.fda.gov/m

edwatch.

------------------------USE IN SPECIFIC POPULATIONS----------------------------•

NursingMothers:Exercise

cautionwhen

administered

toanursing

wom

an.(8.3)See 17 for PATIENT COUNSELING INFORM

ATION and FDA-approvedpatient labeling.

Revised: July 2013

10OVERDOSAGE

11DESCRIPTION

12CLINICAL PHARM

ACOLOGY12.1

Mechanism

ofAction12.2

Pharmacodynam

ics12.3

Pharmacokinetics

13NONCLINICAL TOXICOLOGY13.1

Carcinogenesis,Mutagenesis,and

Impairm

entofFertility14

CLINICAL STUDIES14.1

Trial1:IronDeficiency

AnemiainPatients

Who

areIntolerantto

OralIronorHave

HadUnsatisfactory

Responseto

OralIron14.2


AnemiainPatients

with

Non-DialysisDependentChronic

KidneyDisease

16HOW

SUPPLIED/STORAGE AND HANDLING17

PATIENT COUNSELING INFORMATION

*Sectionsorsubsections

omitted

fromthe

fullprescribinginform

ationare

notlisted.

Inclinicaltrials,serious

anaphylactic/anaphylactoidreactions

were

reportedin

0.1%(2/1775)

ofsubjects

receivingInjectafer.

Otherserious

orsevere

adversereactions

potentiallyassociated

with

hypersensitivitywhich

included,but

notlim

itedto,

pruritus,rash,

urticaria,wheezing,

orhypotension

were

reportedin1.5%

(26/1775)ofthesesubjects.

5.2Hypertension

Inclinicalstudies,hypertension

was

reportedin3.8%

(67/1,775)ofsubjectsin

clinicaltrials

1and

2.Transient

elevationsin

systolicblood

pressure,som

etimes

occurringwith

facialflushing,dizziness,ornauseawere

observedin

6%(106/1,775)

ofsubjects

inthese

twoclinicaltrials.

Theseelevations

generallyoccurred

immediately

afterdosingand

resolvedwithin

30minutes.

Monitor

patientsfor

signsand

symptom

sof

hypertensionfollow

ingeach


[seeDosage and Adm

inistration(2)].

5.3Laboratory Test Alterations

Inthe

24hours

following

administration

ofInjectafer,laboratoryassays

may

overestimate

serumiron

andtransferrin

boundiron

byalso

measuring

theiron

inInjectafer.

6ADVERSE REACTIONS

Thefollow

ingadverse

reactionsare

discussedin

greaterdetail

inother

sectionsofthe

labeling:•


[seeW

arnings and Precautions(5.1)]

•Hypertension

[seeW


•Laboratory

TestAlterations[see

Warnings and Precautions

(5.3)]6.1

Adverse Reactions in Clinical TrialsBecause

clinicaltrials

areconducted

underwidely

varyingconditions,

theadverse

reactionrates

observedcannotbe

directlycom

paredto

ratesinother

clinicaltrialsand

may

notreflecttherates

observedinclinicalpractice.

Intworandom

izedclinicalstudies

[Studies1and

2,SeeClinicalStudies

(14)],atotalof1,775

patientswere

exposedto

Injectafer15mg/kg

bodyweightup

toamaxim

umsingle

doseof750

mgofiron

ontwooccasions

separatedby

atleast7days

upto

acum

ulativedose

of1500mgofiron.

Adversereactions

reportedby

≥1%

oftreated

patientsare

shownin

thefollow

ingtable.

Table1.

Adversereactions

reportedin

≥1%

ofStudyPatients

inClinicalTrials

1 and 2

TermInjectafer

(N=1775)%

PooledCom

paratorsa

(N=1783)%

Oraliron

(N=253)%

Nausea7.2

1.81.2

Hypertension3.8

1.90.4

Flushing/HotFlush3.6

0.20.0

BloodPhosphorus

Decrease2.1

0.10.0

Dizziness2.0

1.20.0

Vomiting

1.70.5

0.4Injection

SiteDiscoloration

1.40.3

0.0Headache

1.20.9

0.0Alanine Am

inotransferaseIncrease

1.10.2

0.0

Dysgeusia1.1

2.10.0

Hypotension1.0

1.90.0

Constipation0.5

0.93.2


INJECTAFER®

(ferric carboxymaltose injection)

RQ105200

Otheradverse

reactionsreported

by≥

0.5%of

treatedpatients

includeabdom

inalpain,

diarrhea,gam

maglutam

yltransferase

increased,injection

sitepain/irritation,

rash,paraesthesia,

sneezing.Transient

decreasesin

laboratoryblood

phosphoruslevels

(<2mg/dL)have

beenobserved

in27%

(440/1638)patientsinclinicaltrials.

6.2Post-m

arketing ExperienceBecause

thesereactions

arereported

voluntarilyfrom

apopulation

ofuncertainsize,itis

notalways

possibletoreliably

estimate

theirfrequencyorestablish

acausalrelationship

todrug

exposure.Thefollow

ingserious

adversereactions

havebeen

most

commonly

reportedfrom

thepost-m

arketingspontaneous

reportswith

Injectafer:urticaria,

dyspnea,pruritis,

tachycardia,erythem

a,pyrexia,

chestdiscom

fort,chills,

angioedema,

backpain,

arthralgia,and

syncope.One

caseof

hypophosphatemic

osteomalacia

was

reportedin

asubject

who

received500

mgof

Injectaferevery

2weeks

foratotal

of16

weeks.Partialrecovery

followed

discontinuationofInjectafer.

7DRUG INTERACTIONS

Formaldrug

interactionstudies

havenotbeen

performed

with

Injectafer.

8USE IN SPECIFIC POPULATIONS

8.1Pregnancy

PregnancyCategory

CRisk

Summ

aryAdequate

andwell

controlledstudies

inpregnant

wom

enhave

notbeen

conducted.However,anim

alreproductionstudies

havebeen

conductedwith

ferriccarboxymaltose.In

thesestudies,administration

offerriccarboxymaltose

torabbits

duringthe

periodoforganogenesis

causedfetalm

alformations

andincreased

implantation

lossatm

aternallytoxic

dosesofapproxim

ately12%

to23%

ofthehum

anweekly

doseof750

mg(based

onbody

surfacearea).

Theincidence

ofmajor

malform

ationsin

human

pregnancieshas

notbeen

establishedforInjectafer.How

ever,allpregnancies,regardlessofexposure

toany

drug,hasabackground

rateof2

to4%

formajorm

alformations,and

15to

20%forpregnancy

loss.Injectafershouldbe

usedduring

pregnancyonly

ifthe

potentialbenefitjustifiesthe

potentialriskto

thefetus.

Animal Data

Administration

offerric

carboxymaltose

torats

asaone-hour

intravenousinfusion

upto

30mg/kg/day

ironon

gestationdays

6to

17did

notresultinadverse

embryofetalfindings.This

dailydose

inrats

isapproxim

ately40%

ofthehum

anweekly

doseof750

mgbased

onbody

surfacearea.In

rabbits,ferric

carboxymaltose

was

administered

asaone-hour

infusionon

gestationdays

6to

19atiron

dosesof4.5,9,13.5,and

18mg/kg/day.M

alformations

were

seenstarting

atthedaily

doseof9

mg/kg

(23%ofthe

human

weekly

doseof750

mg).Spontaneous

abortionsoccurred

startingatthe

dailyiron

doseof4.5

mg/kg

(12%ofthe

human

weekly

dosebased

onbody

surfacearea).

Pre-implantation

losswas

atthe

highestdose.

Adverseem

bryofetaleffects

were

observedinthe

presenceofm

aternaltoxicity.Apre-and

post-nataldevelopmentstudy

was

conductedinrats

atintravenousdoses

upto

18mg/kg/day

ofiron(approxim

ately23%

oftheweekly

human

doseof750

mgon

abody

surfacearea

basis).Therewere

noadverse

effectson

survivalof

offspring,their

behavior,sexual

maturation

orreproductive

parameters.

8.3Nursing M

othersAstudy

todeterm

ineiron

concentrationsinbreastm

ilkafteradm

inistrationof

Injectafer(n=11)ororalferroussulfate

(n=14)was

conductedin25

lactatingwom

enwith

postpartumiron

deficiencyanem

ia.Mean

breastmilk

ironlevels

were

higherin

lactatingwom

enreceiving

Injectaferthan

inlactating

wom

enreceiving

oralferroussulfate.

8.4Pediatric Use

Safetyand

effectivenesshave

notbeenestablished

inpediatric

patients.8.5

Geriatric UseOfthe

1775subjects

inclinicalstudies

ofInjectafer,50%were

65years

andover,w

hile25%

were

75years

andover.No

overalldifferencesin

safetyor

effectivenesswere

observedbetw

eenthese

subjectsand

youngersubjects,

andother

reportedclinical

experiencehas

notidentified

differencesin

responsesbetw

eenthe

elderlyand

youngerpatients,butgreatersensitivityof

someolderindividuals

cannotberuled

out.

10OVERDOSAGE

Excessivedosages

ofInjectafermay

leadto

accumulation

ofironin

storagesites

potentiallyleading

tohem

osiderosis.Apatientw

horeceived

Injectafer18,000

mg

over6

months

developedhem

osiderosiswith

multiple

jointdisorder,

walking

disabilityand

asthenia.Hypophosphatem

icosteom

alaciawas

reportedin

apatient

who

receivedInjectafer

4000mgover

4months.

Partialrecoveryfollow

eddiscontinuation

ofInjectafer.

[seePost-m

arketingExperience (6.2)].

11DESCRIPTION

Ferriccarboxym

altose,aniron

replacementproduct,is

aniron

carbohydratecom

plexwith

thechem

icalnam

eof

polynucleariron

(III)hydroxide

4(R)-(poly-(1→

4)-O-a

-D-glucopyranosyl)-oxy-2(R

),3(S),5(R

),6-tetrahydroxy-hexanoate.It

hasarelative

molecular

weight

ofapproxim

ately150,000

Dacorresponding

tothe

following

empiricalform

ula:[FeO

x (OH)y (H2 O)z ]n [{(C

6 H10 O

5 )m(C

6 H12 O

7 )}l ]k ,

where

n≈10

3,m≈8,l≈

11,andk≈4

(lrepresentsthe

mean

branchingdegree

oftheligand).

Thechem

icalstructureispresented

below:

651 S M

L King Jr A


hone 847.336.4200 • Fax 847.360.4924co

mp

lete packag

ing

| ind

ividu

al solu

tion

sS

M

Pro

du

ct Info

rmatio

nS

pecified

Co

lors

P/N: J/N:C

ust:Size:

Pro

of A

7/26/2013A

pp

roved

By

Nam

e

DateO

K to PrintN

ew Proof R

equired



ill be matched on


n_Dem

and Solutions FourC

olor Book, On _D



olor Standards.

258024LU

ITPOLD

PHAR

MAC

EUTIC

ALS INC

Cyan

Magenta

Yellow

Black



Injectaferis

indicatedfor

thetreatm

entof

irondeficiency

anemia

inadult

patients:•

who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis


disease.2


Forpatients

weighing

50kg

(110lb)or

more:

GiveInjectafer

intwodoses

separatedby

atleast7days.

Giveeach

doseas

750mgfora

totalcumulative

dosenotto

exceed1500

mgofiron

percourse.For

patientsweighing

lessthan

50kg

(110lb):Give

Injectaferin

twodoses

separatedby

atleast7days.Give

eachdose

as15

mg/kg

bodyweightfor

atotalcum

ulativedose

nottoexceed

1500mgofiron

percourse.The

dosageof

Injectaferis

expressedin

mgof

elementaliron.Each

mLof

Injectafercontains

50mgof

elemental

iron.Injectafer

treatment

may

berepeated

ifirondeficiency

anemiareoccurs.

Administer


asan

undilutedslow

intravenouspush

orbyinfusion.W

henadm

inisteringas

aslow


atthe

rateofapproxim

ately100

mg(2

mL)perm

inute.When

administered

viainfusion,dilute

upto

750mgofiron

inno

more

than250

mLofsterile

0.9%sodium



oftheinfusion

isnotless

than2mgofiron

permLand


minutes.

When

addedto

aninfusion

bagcontaining

0.9%sodium

chlorideinjection,


from2mgto

4mgofiron

permL,Injectafer


andchem

icallystable

for72hours

when

storedatroom

temperature.To

maintain

stability,donot

diluteto

concentrationsless

than2mgiron/m

L.Inspect

parenteraldrug

productsvisually

forthe

absenceof

particulatematter

anddiscoloration

priorto

administration.

Theproduct

containsno

preservatives.Each

vialof

Injectaferis

intendedfor

single-useonly.

Anyunused

drugrem


mustbe

discarded.Avoid


browndiscoloration

oftheextravasation

sitemay

belong

lasting.Monitor


occurs,discontinue

theInjectaferadm


3DOSAGE FORM

S AND STRENGTHS

750mgiron

/15mLsingle-use

vial

4CONTRAINDICATIONS

Hypersensitivityto

Injectaferor

anyof

itscom

ponents[see

Warnings


5W




reactions,including


some

ofwhich

havebeen

life-threateningand

fatal,havebeen

reportedin

patientsreceiving

Injectafer.Patients

may

presentw

ithshock,


hypotension,loss

ofconsciousness,

and/orcollapse.

Monitor

patientsfor

signsand

symptom

sof


andafter


foratleast30m

inutesand


following

completion

ofthe

infusion.Only

administer

Injectaferw

henpersonnel

andtherapies

areim

mediately

availablefor

thetreatm

entof


reactions.[see

AdverseReactions

(6.1and

6.2)].







ANDUSAGE------------------------------




who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis




weighing

50kg

(110lb)ormore:

GiveInjectaferin

two

dosesseparated

byatleast7

days.Give

eachdose

as750

mgfora

totalcum

ulativedose

of1500mgofiron


weighing

lessthan

50kg

(110lb):Give


separatedby

atleast7days

andgive

eachdose

as15

mg/kg

bodyweight.


aybe

repeatedifiron

deficiencyanem

iareoccurs.(2)



2DOSAGE AND ADM

INISTRATION3


4CONTRAINDICATIONS

5W



5.2Hypertension

5.3Laboratory

TestAlterations6


AdverseReactions

inClinicalTrials

6.2Post-m

arketingExperience

7DRUG INTERACTIONS


Pregnancy8.3

NursingMothers

8.4Pediatric

Use8.5

GeriatricUse

--------------------------DOSAGEFORM

SAND

STRENGTHS-----------------------750

mgiron

/15mLsingle-use


toInjectaferorany

ofitsinactive

components.(4)



forsignsand

symptom

sof




30minutes

anduntilclinically

stablefollow

ingcom

pletionofeach


•Hypertension:M


forsignsand

symptom

sof

hypertensionfollow

ingeach



mostcom

mon

adversereactions

(≥2%



dizziness(6.1)



edwatch.



cautionwhen

administered

toanursing

wom



Revised: July 2013

10OVERDOSAGE

11DESCRIPTION

12CLINICAL PHARM

ACOLOGY12.1

Mechanism

ofAction12.2

Pharmacodynam

ics12.3

Pharmacokinetics



Impairm

entofFertility14



AnemiainPatients

Who

areIntolerantto

OralIronorHave

HadUnsatisfactory

Responseto

OralIron14.2


AnemiainPatients

with


KidneyDisease

16HOW




omitted

fromthe


ationare

notlisted.



were

reportedin

0.1%(2/1775)

ofsubjects


Otherserious

orsevere

adversereactions


with


included,but

notlim

itedto,

pruritus,rash,

urticaria,wheezing,

orhypotension

were

reportedin1.5%


5.2Hypertension


was

reportedin3.8%


clinicaltrials

1and

2.Transient

elevationsin

systolicblood

pressure,som

etimes

occurringwith


observedin

6%(106/1,775)

ofsubjects

inthese

twoclinicaltrials.

Theseelevations

generallyoccurred

immediately

afterdosingand

resolvedwithin

30minutes.

Monitor

patientsfor

signsand

symptom

sof

hypertensionfollow

ingeach


[seeDosage and Adm

inistration(2)].


Inthe

24hours

following

administration


may

overestimate

serumiron

andtransferrin

boundiron

byalso

measuring

theiron

inInjectafer.

6ADVERSE REACTIONS

Thefollow

ingadverse

reactionsare

discussedin

greaterdetail

inother

sectionsofthe

labeling:•


[seeW


•Hypertension

[seeW


•Laboratory

TestAlterations[see


(5.3)]6.1


clinicaltrials

areconducted

underwidely

varyingconditions,

theadverse

reactionrates

observedcannotbe

directlycom

paredto

ratesinother

clinicaltrialsand

may

notreflecttherates


Intworandom

izedclinicalstudies

[Studies1and


(14)],atotalof1,775

patientswere

exposedto

Injectafer15mg/kg

bodyweightup

toamaxim

umsingle

doseof750

mgofiron

ontwooccasions

separatedby

atleast7days

upto

acum

ulativedose

of1500mgofiron.

Adversereactions

reportedby

≥1%

oftreated

patientsare

shownin

thefollow

ingtable.

Table1.

Adversereactions

reportedin

≥1%

ofStudyPatients

inClinicalTrials

1 and 2

TermInjectafer

(N=1775)%

PooledCom

paratorsa

(N=1783)%

Oraliron

(N=253)%

Nausea7.2

1.81.2

Hypertension3.8

1.90.4


0.20.0

BloodPhosphorus

Decrease2.1

0.10.0

Dizziness2.0

1.20.0

Vomiting

1.70.5

0.4Injection

SiteDiscoloration

1.40.3

0.0Headache

1.20.9

0.0Alanine Am


1.10.2

0.0

Dysgeusia1.1

2.10.0

Hypotension1.0

1.90.0

Constipation0.5

0.93.2


INJECTAFER®


RQ105200

Otheradverse

reactionsreported

by≥

0.5%of

treatedpatients

includeabdom

inalpain,

diarrhea,gam

maglutam

yltransferase

increased,injection


rash,paraesthesia,

sneezing.Transient

decreasesin

laboratoryblood

phosphoruslevels

(<2mg/dL)have

beenobserved

in27%


6.2Post-m


thesereactions

arereported

voluntarilyfrom

apopulation


notalways

possibletoreliably

estimate


acausalrelationship

todrug

exposure.Thefollow

ingserious

adversereactions

havebeen

most

commonly

reportedfrom

thepost-m

arketingspontaneous

reportswith


dyspnea,pruritis,

tachycardia,erythem

a,pyrexia,

chestdiscom

fort,chills,

angioedema,

backpain,

arthralgia,and

syncope.One

caseof

hypophosphatemic

osteomalacia

was

reportedin

asubject

who

received500

mgof

Injectaferevery

2weeks

foratotal

of16


followed


7DRUG INTERACTIONS

Formaldrug

interactionstudies

havenotbeen

performed

with

Injectafer.


8.1Pregnancy

PregnancyCategory

CRisk

Summ

aryAdequate

andwell

controlledstudies

inpregnant

wom

enhave

notbeen



havebeen

conductedwith




torabbits

duringthe


causedfetalm

alformations

andincreased

implantation

lossatm

aternallytoxic

dosesofapproxim

ately12%

to23%

ofthehum

anweekly

doseof750

mg(based

onbody

surfacearea).

Theincidence

ofmajor

malform

ationsin

human

pregnancieshas

notbeen



toany

drug,hasabackground

rateof2

to4%

formajorm

alformations,and

15to

20%forpregnancy


usedduring

pregnancyonly

ifthe


potentialriskto

thefetus.

Animal Data

Administration

offerric

carboxymaltose

torats

asaone-hour

intravenousinfusion

upto

30mg/kg/day

ironon

gestationdays

6to

17did

notresultinadverse


dailydose

inrats

isapproxim

ately40%

ofthehum

anweekly

doseof750

mgbased

onbody

surfacearea.In

rabbits,ferric

carboxymaltose

was

administered

asaone-hour

infusionon

gestationdays

6to

19atiron


18mg/kg/day.M

alformations

were

seenstarting

atthedaily

doseof9

mg/kg

(23%ofthe

human

weekly

doseof750

mg).Spontaneous

abortionsoccurred

startingatthe

dailyiron

doseof4.5

mg/kg

(12%ofthe

human

weekly

dosebased

onbody

surfacearea).

Pre-implantation

losswas

atthe

highestdose.

Adverseem

bryofetaleffects

were

observedinthe

presenceofm



was

conductedinrats

atintravenousdoses

upto

18mg/kg/day

ofiron(approxim

ately23%

oftheweekly

human

doseof750

mgon

abody

surfacearea

basis).Therewere

noadverse

effectson

survivalof

offspring,their

behavior,sexual

maturation

orreproductive

parameters.

8.3Nursing M

othersAstudy

todeterm

ineiron


ilkafteradm

inistrationof


(n=14)was

conductedin25

lactatingwom

enwith

postpartumiron

deficiencyanem

ia.Mean

breastmilk

ironlevels

were

higherin

lactatingwom

enreceiving

Injectaferthan

inlactating

wom

enreceiving

oralferroussulfate.

8.4Pediatric Use

Safetyand

effectivenesshave

notbeenestablished

inpediatric

patients.8.5

Geriatric UseOfthe

1775subjects

inclinicalstudies


65years

andover,w

hile25%

were

75years

andover.No


safetyor

effectivenesswere

observedbetw

eenthese

subjectsand

youngersubjects,

andother

reportedclinical

experiencehas

notidentified

differencesin

responsesbetw

eenthe

elderlyand



cannotberuled

out.

10OVERDOSAGE

Excessivedosages

ofInjectafermay

leadto

accumulation

ofironin

storagesites

potentiallyleading

tohem


horeceived

Injectafer18,000

mg

over6

months

developedhem

osiderosiswith

multiple

jointdisorder,

walking

disabilityand


icosteom

alaciawas

reportedin

apatient

who

receivedInjectafer

4000mgover

4months.


eddiscontinuation

ofInjectafer.

[seePost-m


11DESCRIPTION

Ferriccarboxym

altose,aniron


aniron

carbohydratecom

plexwith

thechem

icalnam

eof

polynucleariron

(III)hydroxide

4(R)-(poly-(1→

4)-O-a


),3(S),5(R


hasarelative

molecular

weight

ofapproxim

ately150,000

Dacorresponding

tothe

following

empiricalform

ula:[FeO

x (OH)y (H2 O)z ]n [{(C

6 H10 O

5 )m(C

6 H12 O

7 )}l ]k ,

where

n≈10

3,m≈8,l≈

11,andk≈4

(lrepresentsthe

mean

branchingdegree

oftheligand).

Thechem


below:

1100 Venture Court • Suite 100 • Carrollton, Texas 75006 • Phone 972.478.6400 • Fax 972.478.6401651 S ML King Jr Ave • Waukegan, IL 60085 • Phone 847.336.4200 • Fax 847.360.4924

complete packaging | individual solutionsSM

Product Information Specified Colors

P/N: J/N:Cust:Size:

Proof A7/26/2013

Approved By

Name

Date

We must have signed proof before we can begin production.

OK to Print New Proof Required

This proof is to show size, copy placement andcolor break. Actual colors will be matched onpress to: PMS Book, On_Demand Solutions FourColor Book, On _Demand Solutions IndichromePlus Book and/or approved Color Standards.

258024LUITPOLD PHARMACEUTICALS INC

Black

Injectafer (ferric carboxymaltose injection) is a dark brown, sterile, aqueous,isotonic colloidal solution for intravenous injection. Each mL contains 50 mgiron as ferric carboxymaltose in water for injection. Injectafer is available in15 mL single-use vials. Sodium hydroxide and/or hydrochloric acid may havebeen 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 ActionFerric carboxymaltose is a colloidal iron (III) hydroxide in complex withcarboxymaltose, a carbohydrate polymer that releases iron.

12.2 PharmacodynamicsUsing positron emission tomography (PET) it was demonstrated that red celluptake of 59Fe and 52Fe from Injectafer ranged from 61% to 99%. In patientswith iron deficiency, red cell uptake of radio-labeled iron ranged from 91% to99% at 24 days after Injectafer dose. In patients with renal anemia red celluptake of radio-labeled iron ranged from 61% to 84% after 24 days Injectaferdose.

12.3 PharmacokineticsAfter administration of a single dose of Injectafer of 100 to 1000 mg of iron iniron deficient patients, maximum iron levels of 37 μg/mL to 333 μg/mL wereobtained respectively after 15 minutes to 1.21 hours post dose. The volume ofdistribution was estimated to be 3 L.The iron injected or infused was rapidly cleared from the plasma, the terminalhalf-life ranged from 7 to 12 hours. Renal elimination of iron was negligible.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of FertilityCarcinogenicity studies have not been performed with ferric carboxymaltose.Ferric carboxymaltose was not genotoxic in the following genetic toxicologystudies: in vitro microbial mutagenesis (Ames) assay, in vitro chromosomeaberration test in human lymphocytes, in vitro mammalian cell mutation assayin mouse lymphoma L5178Y/TK+/- cells, in vivo mouse micronucleus test atsingle intravenous doses up to 500 mg/kg.In a combined male and female fertility study, ferric carboxymaltose wasadministered intravenously over one hour to male and female rats at irondoses 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 embryonicdevelopment. The dose of 30 mg/kg in animals is approximately 40% of thehuman dose of 750 mg based on body surface area.

14 CLINICAL STUDIES

The safety and efficacy of Injectafer for treatment of iron deficiency anemiawere evaluated in two randomized, open-label, controlled clinical trials (Trial1 and Trial 2). In these two trials, Injectafer was administered at a dose of15 mg/kg body weight up to a maximum single dose of 750 mg of ironon two occasions separated by at least 7 days up to a cumulative dose of1500 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 IronTrial 1 was a randomized, open-label, controlled clinical study in patientswith 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 dayoral iron run-in period. Inclusion criteria prior to randomization includedhemoglobin (Hb) <12 g/dL, ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mL whentransferrin saturation (TSAT) ≤ 30%. Cohort 1 subjects were randomized toInjectafer or oral iron for 14 more days. Cohort 2 subjects were randomizedto Injectafer or another IV iron per standard of care [90% of subjects receivediron sucrose]. The mean age of study patients was 43 years (range, 18 to94); 94% were female; 42% were Caucasian, 32% were African American,24% were Hispanic, and 2% were other races. The primary etiologies of irondeficiency anemia were heavy uterine bleeding (47%) and gastrointestinaldisorders (17%).Table 2 shows the baseline and the change in hemoglobin from baseline tohighest value between baseline and Day 35 or time of intervention.Table 2. Mean Change in Hemoglobin From Baseline to the HighestValue Between Day 35 or Time of Intervention (Modified Intent‑to‑TreatPopulation)

Hemoglobin (g/dL)Mean (SD)

Cohort 1 Cohort 2Injectafer(N=244)

Oral Iron(N=251)

Injectafer(N=245)

IV SCa

(N=237)

Baseline 10.6 (1.0) 10.6 (1.0) 9.1 (1.6) 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 tohighest value) 1.6 (1.2) 0.8 (0.8) 2.9 (1.6) 2.2 (1.3)

p-value 0.001 0.001SD=standard deviation; a: Intravenous iron per standard of careIncreases from baseline in mean ferritin (264.2 ± 224.2 ng/mL in Cohort 1and 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‑DialysisDependent Chronic Kidney DiseaseTrial 2 was a randomized, open-label, controlled clinical study in patients withnon-dialysis dependent chronic kidney disease. Inclusion criteria includedhemoglobin (Hb) ≤ 11.5 g/dL, ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mLwhen transferrin saturation (TSAT) ≤ 30%. Study patients were randomizedto 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 AfricanAmerican, 18% Hispanics, and 2% were other races.Table 3 shows the baseline and the change in hemoglobin from baseline tohighest value between baseline and Day 56 or time of intervention.

Table 3. Mean Change in Hemoglobin From Baseline to theHighest 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 10.3 (0.8) 10.3 (0.8)Highest Value 11.4 (1.2) 11.3 (1.1)Change (from baseline to highestvalue) 1.1 (1.0) 0.9 (0.92)

Treatment Difference (95% CI) 0.21 (0.13, 0.28)

Increases from baseline in mean ferritin (734.7 ± 337.8 ng/mL), and transferrinsaturation (30 ± 17%) were observed at Day 56 in Injectafer-treated patients.

16 HOW SUPPLIED/STORAGE AND HANDLING

NDC 0517-0650-01 750 mg iron/15 mL Single-Use Vial Individually boxedNDC 0517-0650-02 750 mg iron/15 mL Single-Use Vial Packages of 2Store 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

• Question patients regarding any prior history of reactions toparenteral 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 andbreathing problems [see Warnings and Precautions (5)]

Injectafer is manufactured under license from Vifor (International) Inc,Switzerland.

AMERICANREGENT, INC.SHIRLEY, NY 11967

Patient InformationINJECTAFER (ferric carboxymaltose injection)

Please read this information carefully before taking thismedication. This summary does not tell you everythingabout INJECTAFER. Speak with your doctor or healthcareprofessional if there is something you do not understand or ifyou would like to learn more about INJECTAFER. Your doctoror healthcare professional is your best source of informationabout this medicine.What is INJECTAFER?Iron is a mineral that the body needs to produce red bloodcells. When the body does not get enough iron, it cannotproduce the number of normal red blood cells needed to keepyou in good health. This condition is called iron deficiency(iron shortage) or iron deficiency anemia.INJECTAFER is used to treat iron deficiency anemia. Irondeficiency anemia may be caused by several medicalconditions including heavy menstrual bleeding, pregnancy,childbirth, inflammatory bowel disease, other malabsorptiondiseases, bariatric surgery, or chronic kidney disease.General information about using INJECTAFER safely andeffectivelyInjectable iron is administered only by or under the supervisionof your health care professional.Serious or life threatening allergic reactions have beenreported with intravenous iron products. Tell your healthcare professional if you have ever had any unusual or allergicreaction to any IV iron.Patients should report to their healthcare professional anysigns and symptoms of an allergic reaction to INJECTAFER, inparticular rashes, shortness of breath and wheezing.Iron is not easily eliminated from the body, and its build upmay be lead to a condition called iron overload which may beharmful. Certain medical conditions such as liver disease mayalso make you more likely to develop iron overload. Ask yourdoctor or healthcare professional.Who should not take INJECTAFER?You should not be given INJECTAFER if you have anemia thatis not caused by iron deficiency, or if you have iron overload.If you are pregnant or plan to become pregnant please notifyyour doctor or healthcare professional. They will decidewhether it is safe for you to receive INJECTAFER.How should I take INJECTAFER?INJECTAFER is administered intravenously (into your vein) byyour doctor or healthcare professional in two doses.What should I avoid while taking INJECTAFER?You should not take iron supplements by mouth if youare receiving iron injections. Tell your doctor about allthe medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

What are the possible side effects of INJECTAFER?The side effects of INJECTAFER are infrequent, usuallymild and generally do not cause patients to stop treatment.The most common side effects are nausea, injection sitereactions (including pain or bruising at the injection site),asymptomatic reductions in blood phosphorus, flushing,headache, hypertension, dizziness, and increased alanineaminotransferase. Potentially long lasting brown staining ofskin near injection site may occur.These are not all the possible side effects of INJECTAFER. Formore information ask your doctor or healthcare professional.Talk to your doctor if you think you have side effects fromtaking INJECTAFER.

651 S M

L King Jr A


hone 847.336.4200 • Fax 847.360.4924co

mp

lete packag

ing

| ind

ividu

al solu

tion

sS

M

Pro

du

ct Info

rmatio

nS

pecified

Co

lors

P/N: J/N:C

ust:Size:

Pro

of A

7/26/2013A

pp

roved

By

Nam

e

DateO

K to PrintN

ew Proof R

equired



ill be matched on


n_Dem

and Solutions FourC

olor Book, On _D



olor Standards.

258024LU

ITPOLD

PHAR

MAC

EUTIC

ALS INC

Cyan

Magenta

Yellow

Black



Injectaferis

indicatedfor

thetreatm

entof

irondeficiency

anemia

inadult

patients:•

who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis


disease.2


Forpatients

weighing

50kg

(110lb)or

more:

GiveInjectafer

intwodoses

separatedby

atleast7days.

Giveeach

doseas

750mgfora

totalcumulative

dosenotto

exceed1500

mgofiron

percourse.For

patientsweighing

lessthan

50kg

(110lb):Give

Injectaferin

twodoses

separatedby

atleast7days.Give

eachdose

as15

mg/kg

bodyweightfor

atotalcum

ulativedose

nottoexceed

1500mgofiron

percourse.The

dosageof

Injectaferis

expressedin

mgof

elementaliron.Each

mLof

Injectafercontains

50mgof

elemental

iron.Injectafer

treatment

may

berepeated

ifirondeficiency

anemiareoccurs.

Administer


asan

undilutedslow

intravenouspush

orbyinfusion.W

henadm

inisteringas

aslow


atthe

rateofapproxim

ately100

mg(2

mL)perm

inute.When

administered

viainfusion,dilute

upto

750mgofiron

inno

more

than250

mLofsterile

0.9%sodium



oftheinfusion

isnotless

than2mgofiron

permLand


minutes.

When

addedto

aninfusion

bagcontaining

0.9%sodium

chlorideinjection,


from2mgto

4mgofiron

permL,Injectafer


andchem

icallystable

for72hours

when

storedatroom

temperature.To

maintain

stability,donot

diluteto

concentrationsless

than2mgiron/m

L.Inspect

parenteraldrug

productsvisually

forthe

absenceof

particulatematter

anddiscoloration

priorto

administration.

Theproduct

containsno

preservatives.Each

vialof

Injectaferis

intendedfor

single-useonly.

Anyunused

drugrem


mustbe

discarded.Avoid


browndiscoloration

oftheextravasation

sitemay

belong

lasting.Monitor


occurs,discontinue

theInjectaferadm


3DOSAGE FORM

S AND STRENGTHS

750mgiron

/15mLsingle-use

vial

4CONTRAINDICATIONS

Hypersensitivityto

Injectaferor

anyof

itscom

ponents[see

Warnings


5W




reactions,including


some

ofwhich

havebeen

life-threateningand

fatal,havebeen

reportedin

patientsreceiving

Injectafer.Patients

may

presentw

ithshock,


hypotension,loss

ofconsciousness,

and/orcollapse.

Monitor

patientsfor

signsand

symptom

sof


andafter


foratleast30m

inutesand


following

completion

ofthe

infusion.Only

administer

Injectaferw

henpersonnel

andtherapies

areim

mediately

availablefor

thetreatm

entof


reactions.[see

AdverseReactions

(6.1and

6.2)].







ANDUSAGE------------------------------




who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis




weighing

50kg

(110lb)ormore:

GiveInjectaferin

two

dosesseparated

byatleast7

days.Give

eachdose

as750

mgfora

totalcum

ulativedose

of1500mgofiron


weighing

lessthan

50kg

(110lb):Give


separatedby

atleast7days

andgive

eachdose

as15

mg/kg

bodyweight.


aybe

repeatedifiron

deficiencyanem

iareoccurs.(2)



2DOSAGE AND ADM

INISTRATION3


4CONTRAINDICATIONS

5W



5.2Hypertension

5.3Laboratory

TestAlterations6


AdverseReactions

inClinicalTrials

6.2Post-m

arketingExperience

7DRUG INTERACTIONS


Pregnancy8.3

NursingMothers

8.4Pediatric

Use8.5

GeriatricUse

--------------------------DOSAGEFORM

SAND

STRENGTHS-----------------------750

mgiron

/15mLsingle-use


toInjectaferorany

ofitsinactive

components.(4)



forsignsand

symptom

sof




30minutes

anduntilclinically

stablefollow

ingcom

pletionofeach


•Hypertension:M


forsignsand

symptom

sof

hypertensionfollow

ingeach



mostcom

mon

adversereactions

(≥2%



dizziness(6.1)



edwatch.



cautionwhen

administered

toanursing

wom



Revised: July 2013

10OVERDOSAGE

11DESCRIPTION

12CLINICAL PHARM

ACOLOGY12.1

Mechanism

ofAction12.2

Pharmacodynam

ics12.3

Pharmacokinetics



Impairm

entofFertility14



AnemiainPatients

Who

areIntolerantto

OralIronorHave

HadUnsatisfactory

Responseto

OralIron14.2


AnemiainPatients

with


KidneyDisease

16HOW




omitted

fromthe


ationare

notlisted.



were

reportedin

0.1%(2/1775)

ofsubjects


Otherserious

orsevere

adversereactions


with


included,but

notlim

itedto,

pruritus,rash,

urticaria,wheezing,

orhypotension

were

reportedin1.5%


5.2Hypertension


was

reportedin3.8%


clinicaltrials

1and

2.Transient

elevationsin

systolicblood

pressure,som

etimes

occurringwith


observedin

6%(106/1,775)

ofsubjects

inthese

twoclinicaltrials.

Theseelevations

generallyoccurred

immediately

afterdosingand

resolvedwithin

30minutes.

Monitor

patientsfor

signsand

symptom

sof

hypertensionfollow

ingeach


[seeDosage and Adm

inistration(2)].


Inthe

24hours

following

administration


may

overestimate

serumiron

andtransferrin

boundiron

byalso

measuring

theiron

inInjectafer.

6ADVERSE REACTIONS

Thefollow

ingadverse

reactionsare

discussedin

greaterdetail

inother

sectionsofthe

labeling:•


[seeW


•Hypertension

[seeW


•Laboratory

TestAlterations[see


(5.3)]6.1


clinicaltrials

areconducted

underwidely

varyingconditions,

theadverse

reactionrates

observedcannotbe

directlycom

paredto

ratesinother

clinicaltrialsand

may

notreflecttherates


Intworandom

izedclinicalstudies

[Studies1and


(14)],atotalof1,775

patientswere

exposedto

Injectafer15mg/kg

bodyweightup

toamaxim

umsingle

doseof750

mgofiron

ontwooccasions

separatedby

atleast7days

upto

acum

ulativedose

of1500mgofiron.

Adversereactions

reportedby

≥1%

oftreated

patientsare

shownin

thefollow

ingtable.

Table1.

Adversereactions

reportedin

≥1%

ofStudyPatients

inClinicalTrials

1 and 2

TermInjectafer

(N=1775)%

PooledCom

paratorsa

(N=1783)%

Oraliron

(N=253)%

Nausea7.2

1.81.2

Hypertension3.8

1.90.4


0.20.0

BloodPhosphorus

Decrease2.1

0.10.0

Dizziness2.0

1.20.0

Vomiting

1.70.5

0.4Injection

SiteDiscoloration

1.40.3

0.0Headache

1.20.9

0.0Alanine Am


1.10.2

0.0

Dysgeusia1.1

2.10.0

Hypotension1.0

1.90.0

Constipation0.5

0.93.2


INJECTAFER®


RQ105200

Otheradverse

reactionsreported

by≥

0.5%of

treatedpatients

includeabdom

inalpain,

diarrhea,gam

maglutam

yltransferase

increased,injection


rash,paraesthesia,

sneezing.Transient

decreasesin

laboratoryblood

phosphoruslevels

(<2mg/dL)have

beenobserved

in27%


6.2Post-m


thesereactions

arereported

voluntarilyfrom

apopulation


notalways

possibletoreliably

estimate


acausalrelationship

todrug

exposure.Thefollow

ingserious

adversereactions

havebeen

most

commonly

reportedfrom

thepost-m

arketingspontaneous

reportswith


dyspnea,pruritis,

tachycardia,erythem

a,pyrexia,

chestdiscom

fort,chills,

angioedema,

backpain,

arthralgia,and

syncope.One

caseof

hypophosphatemic

osteomalacia

was

reportedin

asubject

who

received500

mgof

Injectaferevery

2weeks

foratotal

of16


followed


7DRUG INTERACTIONS

Formaldrug

interactionstudies

havenotbeen

performed

with

Injectafer.


8.1Pregnancy

PregnancyCategory

CRisk

Summ

aryAdequate

andwell

controlledstudies

inpregnant

wom

enhave

notbeen



havebeen

conductedwith




torabbits

duringthe


causedfetalm

alformations

andincreased

implantation

lossatm

aternallytoxic

dosesofapproxim

ately12%

to23%

ofthehum

anweekly

doseof750

mg(based

onbody

surfacearea).

Theincidence

ofmajor

malform

ationsin

human

pregnancieshas

notbeen



toany

drug,hasabackground

rateof2

to4%

formajorm

alformations,and

15to

20%forpregnancy


usedduring

pregnancyonly

ifthe


potentialriskto

thefetus.

Animal Data

Administration

offerric

carboxymaltose

torats

asaone-hour

intravenousinfusion

upto

30mg/kg/day

ironon

gestationdays

6to

17did

notresultinadverse


dailydose

inrats

isapproxim

ately40%

ofthehum

anweekly

doseof750

mgbased

onbody

surfacearea.In

rabbits,ferric

carboxymaltose

was

administered

asaone-hour

infusionon

gestationdays

6to

19atiron


18mg/kg/day.M

alformations

were

seenstarting

atthedaily

doseof9

mg/kg

(23%ofthe

human

weekly

doseof750

mg).Spontaneous

abortionsoccurred

startingatthe

dailyiron

doseof4.5

mg/kg

(12%ofthe

human

weekly

dosebased

onbody

surfacearea).

Pre-implantation

losswas

atthe

highestdose.

Adverseem

bryofetaleffects

were

observedinthe

presenceofm



was

conductedinrats

atintravenousdoses

upto

18mg/kg/day

ofiron(approxim

ately23%

oftheweekly

human

doseof750

mgon

abody

surfacearea

basis).Therewere

noadverse

effectson

survivalof

offspring,their

behavior,sexual

maturation

orreproductive

parameters.

8.3Nursing M

othersAstudy

todeterm

ineiron


ilkafteradm

inistrationof


(n=14)was

conductedin25

lactatingwom

enwith

postpartumiron

deficiencyanem

ia.Mean

breastmilk

ironlevels

were

higherin

lactatingwom

enreceiving

Injectaferthan

inlactating

wom

enreceiving

oralferroussulfate.

8.4Pediatric Use

Safetyand

effectivenesshave

notbeenestablished

inpediatric

patients.8.5

Geriatric UseOfthe

1775subjects

inclinicalstudies


65years

andover,w

hile25%

were

75years

andover.No


safetyor

effectivenesswere

observedbetw

eenthese

subjectsand

youngersubjects,

andother

reportedclinical

experiencehas

notidentified

differencesin

responsesbetw

eenthe

elderlyand



cannotberuled

out.

10OVERDOSAGE

Excessivedosages

ofInjectafermay

leadto

accumulation

ofironin

storagesites

potentiallyleading

tohem


horeceived

Injectafer18,000

mg

over6

months

developedhem

osiderosiswith

multiple

jointdisorder,

walking

disabilityand


icosteom

alaciawas

reportedin

apatient

who

receivedInjectafer

4000mgover

4months.


eddiscontinuation

ofInjectafer.

[seePost-m


11DESCRIPTION

Ferriccarboxym

altose,aniron


aniron

carbohydratecom

plexwith

thechem

icalnam

eof

polynucleariron

(III)hydroxide

4(R)-(poly-(1→

4)-O-a


),3(S),5(R


hasarelative

molecular

weight

ofapproxim

ately150,000

Dacorresponding

tothe

following

empiricalform

ula:[FeO

x (OH)y (H2 O)z ]n [{(C

6 H10 O

5 )m(C

6 H12 O

7 )}l ]k ,

where

n≈10

3,m≈8,l≈

11,andk≈4

(lrepresentsthe

mean

branchingdegree

oftheligand).

Thechem


below:

651 S M

L King Jr A


hone 847.336.4200 • Fax 847.360.4924co

mp

lete packag

ing

| ind

ividu

al solu

tion

sS

M

Pro

du

ct Info

rmatio

nS

pecified

Co

lors

P/N: J/N:C

ust:Size:

Pro

of A

7/26/2013A

pp

roved

By

Nam

e

DateO

K to PrintN

ew Proof R

equired



ill be matched on


n_Dem

and Solutions FourC

olor Book, On _D



olor Standards.

258024LU

ITPOLD

PHAR

MAC

EUTIC

ALS INC

Cyan

Magenta

Yellow

Black



Injectaferis

indicatedfor

thetreatm

entof

irondeficiency

anemia

inadult

patients:•

who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis


disease.2


Forpatients

weighing

50kg

(110lb)or

more:

GiveInjectafer

intwodoses

separatedby

atleast7days.

Giveeach

doseas

750mgfora

totalcumulative

dosenotto

exceed1500

mgofiron

percourse.For

patientsweighing

lessthan

50kg

(110lb):Give

Injectaferin

twodoses

separatedby

atleast7days.Give

eachdose

as15

mg/kg

bodyweightfor

atotalcum

ulativedose

nottoexceed

1500mgofiron

percourse.The

dosageof

Injectaferis

expressedin

mgof

elementaliron.Each

mLof

Injectafercontains

50mgof

elemental

iron.Injectafer

treatment

may

berepeated

ifirondeficiency

anemiareoccurs.

Administer


asan

undilutedslow

intravenouspush

orbyinfusion.W

henadm

inisteringas

aslow


atthe

rateofapproxim

ately100

mg(2

mL)perm

inute.When

administered

viainfusion,dilute

upto

750mgofiron

inno

more

than250

mLofsterile

0.9%sodium



oftheinfusion

isnotless

than2mgofiron

permLand


minutes.

When

addedto

aninfusion

bagcontaining

0.9%sodium

chlorideinjection,


from2mgto

4mgofiron

permL,Injectafer


andchem

icallystable

for72hours

when

storedatroom

temperature.To

maintain

stability,donot

diluteto

concentrationsless

than2mgiron/m

L.Inspect

parenteraldrug

productsvisually

forthe

absenceof

particulatematter

anddiscoloration

priorto

administration.

Theproduct

containsno

preservatives.Each

vialof

Injectaferis

intendedfor

single-useonly.

Anyunused

drugrem


mustbe

discarded.Avoid


browndiscoloration

oftheextravasation

sitemay

belong

lasting.Monitor


occurs,discontinue

theInjectaferadm


3DOSAGE FORM

S AND STRENGTHS

750mgiron

/15mLsingle-use

vial

4CONTRAINDICATIONS

Hypersensitivityto

Injectaferor

anyof

itscom

ponents[see

Warnings


5W




reactions,including


some

ofwhich

havebeen

life-threateningand

fatal,havebeen

reportedin

patientsreceiving

Injectafer.Patients

may

presentw

ithshock,


hypotension,loss

ofconsciousness,

and/orcollapse.

Monitor

patientsfor

signsand

symptom

sof


andafter


foratleast30m

inutesand


following

completion

ofthe

infusion.Only

administer

Injectaferw

henpersonnel

andtherapies

areim

mediately

availablefor

thetreatm

entof


reactions.[see

AdverseReactions

(6.1and

6.2)].







ANDUSAGE------------------------------




who

haveintolerance

tooraliron

orhavehad


tooral iron;

•who

havenon-dialysis




weighing

50kg

(110lb)ormore:

GiveInjectaferin

two

dosesseparated

byatleast7

days.Give

eachdose

as750

mgfora

totalcum

ulativedose

of1500mgofiron


weighing

lessthan

50kg

(110lb):Give


separatedby

atleast7days

andgive

eachdose

as15

mg/kg

bodyweight.


aybe

repeatedifiron

deficiencyanem

iareoccurs.(2)



2DOSAGE AND ADM

INISTRATION3


4CONTRAINDICATIONS

5W



5.2Hypertension

5.3Laboratory

TestAlterations6


AdverseReactions

inClinicalTrials

6.2Post-m

arketingExperience

7DRUG INTERACTIONS


Pregnancy8.3

NursingMothers

8.4Pediatric

Use8.5

GeriatricUse

--------------------------DOSAGEFORM

SAND

STRENGTHS-----------------------750

mgiron

/15mLsingle-use


toInjectaferorany

ofitsinactive

components.(4)



forsignsand

symptom

sof




30minutes

anduntilclinically

stablefollow

ingcom

pletionofeach


•Hypertension:M


forsignsand

symptom

sof

hypertensionfollow

ingeach



mostcom

mon

adversereactions

(≥2%



dizziness(6.1)



edwatch.



cautionwhen

administered

toanursing

wom



Revised: July 2013

10OVERDOSAGE

11DESCRIPTION

12CLINICAL PHARM

ACOLOGY12.1

Mechanism

ofAction12.2

Pharmacodynam

ics12.3

Pharmacokinetics



Impairm

entofFertility14



AnemiainPatients

Who

areIntolerantto

OralIronorHave

HadUnsatisfactory

Responseto

OralIron14.2


AnemiainPatients

with


KidneyDisease

16HOW




omitted

fromthe


ationare

notlisted.



were

reportedin

0.1%(2/1775)

ofsubjects


Otherserious

orsevere

adversereactions


with


included,but

notlim

itedto,

pruritus,rash,

urticaria,wheezing,

orhypotension

were

reportedin1.5%


5.2Hypertension


was

reportedin3.8%


clinicaltrials

1and

2.Transient

elevationsin

systolicblood

pressure,som

etimes

occurringwith


observedin

6%(106/1,775)

ofsubjects

inthese

twoclinicaltrials.

Theseelevations

generallyoccurred

immediately

afterdosingand

resolvedwithin

30minutes.

Monitor

patientsfor

signsand

symptom

sof

hypertensionfollow

ingeach


[seeDosage and Adm

inistration(2)].


Inthe

24hours

following

administration


may

overestimate

serumiron

andtransferrin

boundiron

byalso

measuring

theiron

inInjectafer.

6ADVERSE REACTIONS

Thefollow

ingadverse

reactionsare

discussedin

greaterdetail

inother

sectionsofthe

labeling:•


[seeW


•Hypertension

[seeW


•Laboratory

TestAlterations[see


(5.3)]6.1


clinicaltrials

areconducted

underwidely

varyingconditions,

theadverse

reactionrates

observedcannotbe

directlycom

paredto

ratesinother

clinicaltrialsand

may

notreflecttherates


Intworandom

izedclinicalstudies

[Studies1and


(14)],atotalof1,775

patientswere

exposedto

Injectafer15mg/kg

bodyweightup

toamaxim

umsingle

doseof750

mgofiron

ontwooccasions

separatedby

atleast7days

upto

acum

ulativedose

of1500mgofiron.

Adversereactions

reportedby

≥1%

oftreated

patientsare

shownin

thefollow

ingtable.

Table1.

Adversereactions

reportedin

≥1%

ofStudyPatients

inClinicalTrials

1 and 2

TermInjectafer

(N=1775)%

PooledCom

paratorsa

(N=1783)%

Oraliron

(N=253)%

Nausea7.2

1.81.2

Hypertension3.8

1.90.4


0.20.0

BloodPhosphorus

Decrease2.1

0.10.0

Dizziness2.0

1.20.0

Vomiting

1.70.5

0.4Injection

SiteDiscoloration

1.40.3

0.0Headache

1.20.9

0.0Alanine Am


1.10.2

0.0

Dysgeusia1.1

2.10.0

Hypotension1.0

1.90.0

Constipation0.5

0.93.2


INJECTAFER®


RQ105200

Otheradverse

reactionsreported

by≥

0.5%of

treatedpatients

includeabdom

inalpain,

diarrhea,gam

maglutam

yltransferase

increased,injection


rash,paraesthesia,

sneezing.Transient

decreasesin

laboratoryblood

phosphoruslevels

(<2mg/dL)have

beenobserved

in27%


6.2Post-m


thesereactions

arereported

voluntarilyfrom

apopulation


notalways

possibletoreliably

estimate


acausalrelationship

todrug

exposure.Thefollow

ingserious

adversereactions

havebeen

most

commonly

reportedfrom

thepost-m

arketingspontaneous

reportswith


dyspnea,pruritis,

tachycardia,erythem

a,pyrexia,

chestdiscom

fort,chills,

angioedema,

backpain,

arthralgia,and

syncope.One

caseof

hypophosphatemic

osteomalacia

was

reportedin

asubject

who

received500

mgof

Injectaferevery

2weeks

foratotal

of16


followed


7DRUG INTERACTIONS

Formaldrug

interactionstudies

havenotbeen

performed

with

Injectafer.


8.1Pregnancy

PregnancyCategory

CRisk

Summ

aryAdequate

andwell

controlledstudies

inpregnant

wom

enhave

notbeen



havebeen

conductedwith




torabbits

duringthe


causedfetalm

alformations

andincreased

implantation

lossatm

aternallytoxic

dosesofapproxim

ately12%

to23%

ofthehum

anweekly

doseof750

mg(based

onbody

surfacearea).

Theincidence

ofmajor

malform

ationsin

human

pregnancieshas

notbeen



toany

drug,hasabackground

rateof2

to4%

formajorm

alformations,and

15to

20%forpregnancy


usedduring

pregnancyonly

ifthe


potentialriskto

thefetus.

Animal Data

Administration

offerric

carboxymaltose

torats

asaone-hour

intravenousinfusion

upto

30mg/kg/day

ironon

gestationdays

6to

17did

notresultinadverse


dailydose

inrats

isapproxim

ately40%

ofthehum

anweekly

doseof750

mgbased

onbody

surfacearea.In

rabbits,ferric

carboxymaltose

was

administered

asaone-hour

infusionon

gestationdays

6to

19atiron


18mg/kg/day.M

alformations

were

seenstarting

atthedaily

doseof9

mg/kg

(23%ofthe

human

weekly

doseof750

mg).Spontaneous

abortionsoccurred

startingatthe

dailyiron

doseof4.5

mg/kg

(12%ofthe

human

weekly

dosebased

onbody

surfacearea).

Pre-implantation

losswas

atthe

highestdose.

Adverseem

bryofetaleffects

were

observedinthe

presenceofm



was

conductedinrats

atintravenousdoses

upto

18mg/kg/day

ofiron(approxim

ately23%

oftheweekly

human

doseof750

mgon

abody

surfacearea

basis).Therewere

noadverse

effectson

survivalof

offspring,their

behavior,sexual

maturation

orreproductive

parameters.

8.3Nursing M

othersAstudy

todeterm

ineiron


ilkafteradm

inistrationof


(n=14)was

conductedin25

lactatingwom

enwith

postpartumiron

deficiencyanem

ia.Mean

breastmilk

ironlevels

were

higherin

lactatingwom

enreceiving

Injectaferthan

inlactating

wom

enreceiving

oralferroussulfate.

8.4Pediatric Use

Safetyand

effectivenesshave

notbeenestablished

inpediatric

patients.8.5

Geriatric UseOfthe

1775subjects

inclinicalstudies


65years

andover,w

hile25%

were

75years

andover.No


safetyor

effectivenesswere

observedbetw

eenthese

subjectsand

youngersubjects,

andother

reportedclinical

experiencehas

notidentified

differencesin

responsesbetw

eenthe

elderlyand



cannotberuled

out.

10OVERDOSAGE

Excessivedosages

ofInjectafermay

leadto

accumulation

ofironin

storagesites

potentiallyleading

tohem


horeceived

Injectafer18,000

mg

over6

months

developedhem

osiderosiswith

multiple

jointdisorder,

walking

disabilityand


icosteom

alaciawas

reportedin

apatient

who

receivedInjectafer

4000mgover

4months.


eddiscontinuation

ofInjectafer.

[seePost-m


11DESCRIPTION

Ferriccarboxym

altose,aniron


aniron

carbohydratecom

plexwith

thechem

icalnam

eof

polynucleariron

(III)hydroxide

4(R)-(poly-(1→

4)-O-a


),3(S),5(R


hasarelative

molecular

weight

ofapproxim

ately150,000

Dacorresponding

tothe

following

empiricalform

ula:[FeO

x (OH)y (H2 O)z ]n [{(C

6 H10 O

5 )m(C

6 H12 O

7 )}l ]k ,

where

n≈10

3,m≈8,l≈

11,andk≈4

(lrepresentsthe

mean

branchingdegree

oftheligand).

Thechem


below:

IN0650ADVIss. 7/2013

important safety information billing and coding … · the treatment of iron deﬁciency anemia...

Documents