There is no replacement for. experience.

Transcription

1 Leading the way in iron replacement therapy There is no replacement for experience.

2 Leading the way in iron replacement therapy There s no replacement for options A trusted name in iron replacement for 2 years Millions of patients treated with American Regent iron replacement products Treatment options to meet the needs of your patients Injectafer Broadly available for a range of patients in the outpatient and inpatient settings Single dose of 2 or more doses 75 mg (2 doses separated by at least 7 days) 1 mg to 4 mg, depending upon the indication Indication Iron deficiency anemia (IDA) in adult patients who have non-dialysis dependent chronic kidney disease (NDD-CKD) IDA in patients with peritoneal-dialysis dependent (PDD) or hemodialysis dependent (HDD) CKD IDA in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron IDA of various etiologies, which may include*: GI disorders OB/GYN disorders Cancer Heart failure Post-gastric bypass Injectafer (ferric carboxymaltose injection) (iron sucrose injection, USP) Recommended cumulative doses Number of administrations for recommended cumulative dose (for non-dialysis dependent CKD) Total cumulative dose not to exceed 15 mg of iron per course (maximum dose) Usual total treatment course is 1 mg IV push Yes Yes IV infusion Yes, over at least 15 minutes to to Yes, over 15 minutes to 2.5 hours, depending on dose Indicated for pediatric patients (age 2 years and older) with HDD-CKD for iron maintenance treatment or with NDD-CKD or PDD-CKD who are on erythropoietin therapy for iron maintenance treatment Dextran-free IV iron SELECTED SAFETY INFORMATION FOR INJECTAFER WARNINGS AND PRECAUTIONS Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been lifethreatening 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 3 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. 2 SELECTED SAFETY INFORMATION FOR VENOFER WARNINGS AND PRECAUTIONS Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been lifethreatening and fatal, have been reported in patients receiving. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop immediately. Monitor patients for signs and symptoms of hypersensitivity during and after administration for at least 3 minutes and until clinically stable following completion of the infusion. Only administer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous iron preparations occur within 3 minutes of the completion of the infusion. *Injectafer and are not indicated to treat these conditions. For adult patients weighing less than 5 kg (11 lb), give each dose as 15 mg/kg body weight for a total cumulative dose not to exceed 15 mg of iron per course of treatment. When administered via IV infusion, dilute up to 75 mg of iron in no more than 25 ml of sterile.9% sodium chloride injection, USP, such that the concentration of the infusion is not <2 mg of iron per ml and administer over at least 15 minutes. When administered as a slow IV push, give at the rate of approximately 1 mg (2 ml) per minute. Please see attached Full Prescribing Information for Injectafer and. 3

3 An outpatient case for Injectafer An inpatient case for Robin s* inflammatory bowel disease may have impaired the absorption of her oral iron therapy LAB RESULTS Hb 1.5 g/dl Michael* is a CKD patient who was hospitalized after experiencing complications LAB RESULTS Hb 9.8 g/dl Name/age Robin H, 41 Ferritin 15.8 ng/ml Name/age Michael A, 72 Ferritin 88. ng/ml 4 Diagnosis Weight Medication history IDA secondary to inflammatory bowel disease 159 lb/72.1 kg The #1 IV iron in oncology and gastroenterology clinics Although Robin was fully compliant with her course of oral iron therapy (ferrous sulfate, 325 mg TID), her Hb level only increased by.5 g/dl Only Injectafer provides up to 15 mg of iron in just 2 administrations of up to 75 mg, separated by at least 7 days Two administration options IV infusion or slow IV push The ONLY dextran-free IV iron for adult patients with IDA from etiologies other than CKD 72-hour stability SELECTED SAFETY INFORMATION FOR INJECTAFER ADVERSE REACTIONS TSAT 11.6% When added to an infusion bag containing.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 Up to 5% more iron (15 mg) in the form of Injectafer may be administered in only 2 administrations Compared with iron sucrose, which has a recommended cumulative dose of 1 mg in 5 administrations in patients with NDD-CKD over a 14-day period *Note: The individuals depicted in this brochure are fictional and for illustrative purposes only. Based on IMS DDD MG Sales (July 215 to December 215). For adult patients weighing less than 5 kg (11 lb), give each dose as 15 mg/kg body weight for a total cumulative dose not to exceed 15 mg of iron per course of treatment. When administered via IV infusion, dilute up to 75 mg of iron in no more than 25 ml of sterile.9% sodium chloride injection, USP, such that the concentration of the infusion is not <2 mg of iron per ml and administer over at least 15 minutes. When administered as a slow IV push, give at the rate of approximately 1 mg (2 ml) per minute. º IMS Health Sales Data Data on file. PSUR (Periodic Safety Update Report), February 216. Luitpold Pharmaceuticals, Inc. Shirley, NY. In 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 75 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 15 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.%). 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. Diagnosis Weight Iron replacement therapy The top selling IV iron in the US every year since 23 º Over 2 million patients treated with over 417 million units prescribed worldwide Wide formulary acceptance for in-hospital use Multiple dosage strengths and dosing options available May be administered as a slow IV push over 2-5 minutes Stable for 7 days Chronic kidney disease and IDA. Patient was admitted to the hospital after experiencing shortness of breath, swelling in his legs, and persistent wheezing 166 lb/75.3 kg Scheduled to receive an IV iron replacement goal of 1 mg in divided doses, each administered as an IV push to minimize fluid intake Syringe stability: When diluted with.9% NaCl at concentrations ranging from 2 mg to 1 mg of elemental iron per ml, or undiluted (2 mg elemental iron per ml) and stored in a plastic syringe, has been found to be physically and chemically stable for 7 days at controlled room temperature (25 C ± 2 C) and under refrigeration (4 C ± 2 C) Intravenous admixture stability: When added to intravenous infusion bags (PVC or non-pvc) containing.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental iron per ml, has been found to be physically and chemically stable for 7 days at controlled room temperature (25 C ± 2 C) SELECTED SAFETY INFORMATION FOR VENOFER ADVERSE REACTIONS TSAT 17.4% The most common adverse reactions ( 2%) following the administration of are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain and peripheral edema. Additional adverse reactions include infusion site pain or burning, graft complications, and nasopharyngitis, sinusitis, upper respiratory tract infections and pharyngitis. In pediatric patients, more than 5% of the patients experienced at least one treatment-emergent reaction. The most common adverse reactions ( 2%) were headache, respiratory tract viral infection, peritonitis, vomiting, pyrexia, dizziness, cough, renal transplant, nausea, arteriovenous fistula thrombosis, hypotension and hypertension. Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation. Please see attached Full Prescribing Information for Injectafer and. 5

4 INDICATIONS 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, and in adult patients with non-dialysis dependent chronic kidney disease. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components. WARNINGS AND PRECAUTIONS 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 3 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.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. To report adverse events, please contact American Regent at You may also contact the FDA at or 1-8-FDA-188. Please see attached Full Prescribing Information for Injectafer and. 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% (16/1775) of subjects. These elevations generally occurred immediately after dosing and resolved within 3 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 REACTIONS In 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 75 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 15 mg of iron. Adverse reactions reported by 2% of Injectafertreated patients were nausea (7.2%); hypertension (3.8%); flushing/hot flush (3.6%); blood phosphorus decrease (2.1%); and dizziness (2.%). 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. INDICATION (iron sucrose injection, USP) is indicated for the treatment of iron deficiency anemia in patients with chronic kidney disease. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS is contraindicated in patients with known hypersensitivity to. WARNINGS AND PRECAUTIONS Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop immediately. Monitor patients for signs and symptoms of hypersensitivity during and after administration for at least 3 minutes and until clinically stable following completion of the infusion. Only administer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous iron preparations occur within 3 minutes of the completion of the infusion. may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of. Hypotension following administration of may be related to rate of administration and/or total dose delivered. Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving require periodic monitoring of hematologic and iron parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer to patients with evidence of iron overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of iron sucrose; do not perform serum iron measurements for at least 48 hours after intravenous dosing. ADVERSE REACTIONS The most common adverse reactions ( 2%) following the administration of are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain and peripheral edema. Additional adverse reactions include infusion site pain or burning, graft complications, and nasopharyngitis, sinusitis, upper respiratory tract infections and pharyngitis. In pediatric patients, more than 5% of the patients experienced at least one treatment-emergent reaction. The most common adverse reactions ( 2%) were headache, respiratory tract viral infection, peritonitis, vomiting, pyrexia, dizziness, cough, renal transplant, nausea, arteriovenous fistula thrombosis, hypotension and hypertension. In post-marketing safety studies of in 1,51 patients with HDD-CKD, adverse reactions reported by >1% were cardiac failure congestive, sepsis and dysgeusia. Because adverse reactions from post-marketing experience 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. In addition to potential serious hypersensitivity reactions, the following adverse reactions have been identified during post-approval use of : bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, bradycardia and chromaturia. Symptoms associated with total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema and cardiovascular collapse. These adverse reactions have occurred up to 3 minutes after the administration of injections. Reactions have occurred following the first dose or subsequent doses of. Slowing the infusion rate may alleviate symptoms. Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation. 6 7

5 Trusted options for your adult IDA patients Which option is appropriate for your patients? The #1 IV iron in oncology and gastroenterology clinics* Over a decade of clinical experience The only dextran-free IV iron for adult patients with IDA from etiologies other than CKD Over 75 patients treated in clinical trials worldwide The market leader for the treatment of IDA in CKD (dialysis and non-dialysis dependent) Consistently the #1 selling IV iron in the US Wide formulary acceptance for in-hospital use Approved in 7 countries worldwide INDICATIONS FOR INJECTAFER Injectafer is an iron replacement product indicated for the treatment of iron deficiency anemia in adult patients: who have intolerance to or have had unsatisfactory response to oral iron or who have non-dialysis dependent chronic kidney disease INDICATION FOR VENOFER is indicated for the treatment of iron deficiency anemia in patients with chronic kidney disease. CONTRAINDICATIONS FOR VENOFER is contraindicated in patients with known hypersensitivity to. CONTRAINDICATIONS FOR INJECTAFER Injectafer is contraindicated in patients with hypersensitivity to Injectafer or any of its inactive components. *Based on IMS DDD MG Sales (July 215 to December 215). Data on file. PSUR (Periodic Safety Update Report), February 216. Luitpold Pharmaceuticals, Inc. Shirley, NY. Initial US approval: 2. Data on file. IMS Sales Data Please see attached Full Prescribing Information and the Important Safety Information inside for Injectafer and. American Regent is a registered trademark of Luitpold Pharmaceuticals, Inc. Injectafer and the Injectafer logo are trademarks of Vifor (International), Inc., Switzerland. and the logo are trademarks of Vifor (International), Inc., Switzerland. Injectafer and are manufactured under license from Vifor (International), Inc., Switzerland. 216 American Regent, Inc. PP-IN-US-15 Iss. 4/216

6 DOSAGE FORMS AND STRENGTHS Other adverse reactions reported by.5% of treated patients include In the 24 hours following administration of Injectafer, laboratory assays may 75 mg iron / 15 ml single-use vial. (3) overestimate serum iron and transferrin bound iron by also measuring the Safety and effectiveness have not been established in pediatric patients. iron CONTRAINDICATIONS in Injectafer. 8.5 laboratory Geriatric blood Use phosphorus levels (< 2 mg/dl) have been observed in 27% Hypersensitivity to Injectafer or any of its inactive components. (4) Of (44/1638) the 1775 patients subjects in in clinical trials. studies of Injectafer, 5% were 65 years and 6 ADVERSE REACTIONS WARNINGS AND PRECAUTIONS over, while 25% were 75 years and over. No overall differences in safety or The Hypersensitivity following adverse reactions: Observe are discussed for signs in and greater symptoms detail of in other effectiveness were observed between these subjects and younger subjects, sections hypersensitivity of the labeling: during and after Injectafer administration for at least and other reported clinical experience has not identified differences in 3 Hypersensitivity minutes and until Reactions clinically [see stable Warnings following and Precautions completion of (5.1)] each responses between the elderly and younger patients, but greater sensitivity of administration. Hypertension [see (5.1) Warnings and Precautions (5.2)] some older individuals cannot be ruled out. 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. For intravenous use Initial U.S. Approval: 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 5 kg (11lb) or more: Give Injectafer in two doses separated by at least 7 days. Give each dose as 75 mg for a total cumulative dose of 15 mg of iron per course. For patients weighing less than 5 kg (11lb): 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) FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactions 5.2 Hypertension 5.3 Laboratory Test Alterations 6 ADVERSE REACTIONS 6.1 Adverse Reactions in Clinical Trials 7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.5 Geriatric Use FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE RQ152 In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in.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% (16/1,775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 3 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration [see Dosage and Administration (2)]. 5.3 Laboratory Test Alterations * Sections or subsections omitted from the full prescribing information are not listed. 14 CLINICAL STUDIES 14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron 14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent Chronic Kidney Disease 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 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. 2 DOSAGE AND ADMINISTRATION For patients weighing 5 kg (11lb) or more: Give Injectafer in two doses separated by at least 7 days. Give each dose as 75 mg for a total cumulative dose not to exceed 15 mg of iron per course. For patients weighing less than 5 kg (11lb): 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 15 mg of iron per course. The dosage of Injectafer is expressed in mg of elemental iron. Each ml of Injectafer contains 5 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 1 mg (2 ml) per minute. When administered via infusion, dilute up to 75 mg of iron in no more than 25 ml of sterile.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.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. 1 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 1 Pharmacodynamics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility DOSAGE FORMS AND STRENGTHS 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 least 3 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 at or FDA at 1-8-FDA-188 or USE IN SPECIFIC POPULATIONS Nursing Mothers: Exercise caution when administered to a nursing woman. (8.3) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: July OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 1 Pharmacodynamics 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, and Impairment of Fertility 14 CLINICAL STUDIES 14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron 14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent Chronic Kidney Disease 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION * Sections or subsections omitted from the full prescribing information are not listed. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in.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% (16/1,775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 3 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 ADVERSE REACTIONS 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 75 mg of iron on two occasions separated by at least 7 days up to a cumulative dose of 15 mg of iron. 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 3 DOSAGE FORMS AND STRENGTHS Term Injectafer Pooled Oral Comparators a iron 75 mg iron / 15 ml single-use vial (N=1775) (N=1783) (N=253) 4 CONTRAINDICATIONS % % % Nausea Hypersensitivity to Injectafer or any of its components [see Warnings and Hypertension Precautions (5.1)]. Flushing/Hot Flush WARNINGS AND PRECAUTIONS Blood Phosphorus Decrease Hypersensitivity Reactions Dizziness Serious hypersensitivity reactions, including anaphylactic-type reactions, Vomiting some of which have been life-threatening and fatal, have been reported in Injection Site Discoloration.3. patients receiving Injectafer. Patients may present with shock, clinically Headache significant hypotension, loss of consciousness, and/or collapse. Monitor Alanine Aminotransferase patients for signs and symptoms of hypersensitivity during and after Increase Injectafer administration for at least 3 minutes and until clinically stable Dysgeusia following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of Hypotension Constipation serious hypersensitivity reactions. [see Adverse Reactions (6.1 and 6.2)]. a Includes oral iron and all formulations of IV iron other than Injectafer RQ152 any drug, has a background rate of 2 to 4% for major malformations, and 15 to 2% for pregnancy loss. Injectafer should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data Administration of ferric carboxymaltose to rats as a one-hour intravenous infusion up to 3 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryofetal findings. This daily dose in rats is approximately 4% of the human weekly dose of 75 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 75 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 embryofetal 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 75 mg on a body surface area basis). There were no adverse effects on survival of offspring, their behavior, sexual maturation or reproductive parameters. A study to determine iron concentrations in breast milk after administration of Injectafer (n=11) or oral ferrous sulfate (n=14) was conducted in 25 lactating women with postpartum iron deficiency anemia. Mean breast milk iron levels were higher in lactating women receiving Injectafer than in lactating women receiving oral ferrous sulfate. established for Injectafer. However, all pregnancies, regardless of exposure to Revised: July 213 patient labeling. Pregnancy Category C Risk Summary Adequate and well controlled studies in pregnant women have not been conducted. However, animal reproduction studies have been conducted with ferric carboxymaltose. In these studies, administration of ferric carboxymaltose to rabbits during the period of organogenesis caused fetal malformations and increased implantation loss at maternally toxic doses of approximately 12% to 23% of the human weekly dose of 75 mg (based on body surface area). The incidence of major malformations in human pregnancies has not been DOSAGE FORMS AND STRENGTHS 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 least 3 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 at or FDA at 1-8-FDA-188 or USE IN SPECIFIC POPULATIONS Nursing Mothers: Exercise caution when administered to a nursing woman. (8.3) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved 8 USE IN SPECIFIC POPULATIONS Formal drug interaction studies have not been performed with Injectafer. 7 DRUG INTERACTIONS pyrexia, chest discomfort, chills, angioedema, back pain, arthralgia, and syncope. One case of hypophosphatemic osteomalacia was reported in a subject who received 5 mg of Injectafer every 2 weeks for a total of 16 weeks. Partial recovery followed discontinuation of Injectafer. Other adverse reactions reported by.5% of treated patients include laboratory blood phosphorus levels (< 2 mg/dl) have been observed in 27% (44/1638) patients in clinical trials. have been most commonly reported from the post-marketing spontaneous reports with Injectafer: urticaria, dyspnea, pruritis, tachycardia, erythema, Other adverse reactions reported by.5% of treated patients include laboratory blood phosphorus levels (< 2 mg/dl) have been observed in 27% (44/1638) patients in clinical trials. 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 5 mg of Injectafer every 2 weeks for a total of 16 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 Pregnancy Category C Risk Summary Adequate and well controlled studies in pregnant women have not been conducted. However, animal reproduction studies have been conducted with ferric carboxymaltose. In these studies, administration of ferric carboxymaltose to rabbits during the period of organogenesis caused fetal malformations and increased implantation loss at maternally toxic doses of approximately 12% to 23% of the human weekly dose of 75 mg (based on body surface area). The incidence of major malformations in human pregnancies has not been established for Injectafer. However, all pregnancies, regardless of exposure to any drug, has a background rate of 2 to 4% for major malformations, and 15 to 2% for pregnancy loss. Injectafer should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data Administration of ferric carboxymaltose to rats as a one-hour intravenous infusion up to 3 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryofetal findings. This daily dose in rats is approximately 4% of the human weekly dose of 75 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 75 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 embryofetal 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 75 mg on a body surface area basis). There were no adverse effects on survival of offspring, their behavior, sexual maturation or reproductive parameters. A study to determine iron concentrations in breast milk after administration of Injectafer (n=11) or oral ferrous sulfate (n=14) was conducted in 25 lactating women with postpartum iron deficiency anemia. Mean breast milk iron levels were higher in lactating women receiving Injectafer than in lactating women receiving oral ferrous sulfate. Safety and effectiveness have not been established in pediatric patients. 8.5 Geriatric Use Of the 1775 subjects in clinical studies of Injectafer, 5% 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. 1 OVERDOSAGE Excessive dosages of Injectafer may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. A patient who received Injectafer 18, mg over 6 months developed hemosiderosis with multiple joint disorder, walking disability and asthenia. Hypophosphatemic osteomalacia was reported in a patient who received Injectafer 4 mg over 4 months. Partial recovery followed discontinuation of Injectafer. [see Post-marketing Experience (6.2)]. 11 DESCRIPTION RQ152 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-a-D-glucopyranosyl)-oxy-2(R),3(S),5(R),6- tetrahydroxy-hexanoate. It has a relative molecular weight of approximately 15, Da corresponding to the following empirical formula: [FeO x (OH) y (H 2 O) z ] n [{(C 6 H 1 O 5 ) m (C 6 H 12 O 7 )} l ] k, where n 1 3,m 8, l 11, and k 4 (l represents the mean branching degree of the ligand). The chemical structure is presented below:

7 l nous ive at d via.9% 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)] Other adverse reactions reported by.5% of treated patients include Safety and effectiveness have not been established in pediatric patients. 8.5 laboratory Geriatric blood Use phosphorus levels (< 2 mg/dl) have been observed in 27% Of (44/1638) the 1775 patients subjects in in clinical trials. studies of Injectafer, 5% 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. 6 ADVERSE REACTIONS L of ay be iron in Injectafer. oses for a oses lative Injectafer is a dark brown, sterile, aqueous, isotonic colloidal solution for intravenous injection. Each ml contains 5 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 Vial closure is not made with natural rubber latex. 12 CLINICAL PHARMACOLOGY Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron. 1 Pharmacodynamics Using positron emission tomography (PET) it was demonstrated that red cell uptake of 59 Fe and 52 Fe 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. After administration of a single dose of Injectafer of 1 to 1 mg of iron in iron deficient patients, maximum iron levels 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. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with ferric carboxymaltose. Ferric carboxymaltose was not genotoxic in the following genetic toxicology studies: in vitro microbial mutagenesis (Ames) assay, in vitro chromosome aberration test in human lymphocytes, in vitro mammalian cell mutation assay in mouse lymphoma L5178Y/TK+/- cells, in vivo mouse micronucleus test at single intravenous doses up to 5 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 3 mg/kg. Animals were dosed 3 times per week (on Days, 3, and 7). There was no effect on mating function, fertility or early embryonic development. The dose of 3 mg/kg in animals is approximately 4% of the human dose of 75 mg based on body surface area. 14 CLINICAL STUDIES 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 75 mg of iron on two occasions separated by at least 7 days up to a cumulative dose of 15 mg of iron Trial 1: Iron Deficiency Anemia in Patients Who Are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron Trial 1 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 1 ng/ml or ferritin 3 ng/ml when transferrin saturation (TSAT) 3%. Cohort 1 subjects were randomized to Injectafer or oral iron for 14 more days. Cohort 2 subjects were randomized to Injectafer or another IV iron per standard of care [9% of subjects received iron sucrose]. The mean age of study patients was 43 years (range, 18 to 94); 94% were female; 42% were Caucasian, 32% were African American, 24% were Hispanic, and 2% were other races. The primary etiologies of iron deficiency anemia were heavy uterine bleeding (47%) and gastrointestinal disorders (17%). Table 2 shows the baseline and the change in hemoglobin from baseline to highest value between baseline and Day 35 or time of intervention. Table 2. Mean Change in Hemoglobin From Baseline to the Highest Value Between Day 35 or Time of Intervention (Modified Intent to Treat Population) Hemoglobin (g/dl) Mean (SD) Injectafer (N=244) Cohort 1 Cohort 2 Oral Iron Injectafer (N=251) (N=245) IV SC a (N=237) Baseline 1.6 (1.) 1.6 (1.) 9.1 (1.6) 9. (1.5) Highest Value 1 (1.1) 1 (1.2) 12. (1.2) 11.2 () Change (from baseline to highest value) se to adult RQ152 In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in.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% (16/1,775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 3 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 * Sections or subsections omitted from the full prescribing information are not listed Carcinogenesis, Mutagenesis, and Impairment of Fertility 14 CLINICAL STUDIES 14.1 Trial 1: Iron Deficiency Anemia in Patients Who are Intolerant to Oral Iron or Have Had Unsatisfactory Response to Oral Iron 14.2 Trial 2: Iron Deficiency Anemia in Patients with Non-Dialysis Dependent Chronic Kidney Disease 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION any drug, has a background rate of 2 to 4% for major malformations, and 15 to 2% for pregnancy loss. Injectafer should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal Data Administration of ferric carboxymaltose to rats as a one-hour intravenous infusion up to 3 mg/kg/day iron on gestation days 6 to 17 did not result in adverse embryofetal findings. This daily dose in rats is approximately 4% of the human weekly dose of 75 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 75 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 embryofetal 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 75 mg on a body surface area basis). There were no adverse effects on survival of offspring, their behavior, sexual maturation or reproductive parameters. A study to determine iron concentrations in breast milk after administration of Injectafer (n=11) or oral ferrous sulfate (n=14) was conducted in 25 lactating women with postpartum iron deficiency anemia. Mean breast milk iron levels were higher in lactating women receiving Injectafer than in lactating women receiving oral ferrous sulfate. 1.6 (1.2).8 (.8) 2.9 (1.6) () p-value.1.1 SD=standard deviation; a : Intravenous iron per standard of care Increases from baseline in mean ferritin (264.2 ± ng/ml in Cohort 1 and ± 21 ng/ml in Cohort 2), and transferrin saturation (13 ± 16% in Cohort 1 and 2 ± 15% in Cohort 2) were observed at Day 35 in Injectafertreated patients Trial 2: Iron Deficiency Anemia in Patients with Non Dialysis Dependent Chronic Kidney Disease Trial 2 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 1 ng/ml or ferritin 3 ng/ml when transferrin saturation (TSAT) 3%. Study patients were randomized to either Injectafer or. 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. 1 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 1 Pharmacodynamics 13 NONCLINICAL TOXICOLOGY Table 3. Mean Change in Hemoglobin From Baseline to the Highest Value Between Baseline and Day 56 or Time of Intervention (Modified Intent to Treat Population) Hemoglobin (g/dl) Mean (SD) Injectafer (N=1249) (N=1244) Baseline (.8) (.8) Highest Value 1 (1.2) 1 (1.1) Change (from baseline to highest 1.1 (1.).9 (.92) value) Treatment Difference (95% CI).21 (.13,.28) Increases from baseline in mean ferritin (734.7 ± ng/ml), and transferrin saturation (3 ± 17%) were observed at Day 56 in Injectafer-treated patients. 16 HOW SUPPLIED/STORAGE AND HANDLING NDC mg iron/15 ml Single-Use Vial Individually boxed NDC mg iron/15 ml Single-Use Vial Packages of 2 Store at 2 C to 25 C (68 F to 77 F); excursions permitted to 15 C to 3 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 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 ses ht. (2) or FDA at 1-8-FDA-188 or USE IN SPECIFIC POPULATIONS Nursing Mothers: Exercise caution when administered to a nursing woman. (8.3) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: July 213 Pregnancy Category C Risk Summary Adequate and well controlled studies in pregnant women have not been conducted. However, animal reproduction studies have been conducted with ferric carboxymaltose. In these studies, administration of ferric carboxymaltose to rabbits during the period of organogenesis caused fetal malformations and increased implantation loss at maternally toxic doses of approximately 12% to 23% of the human weekly dose of 75 mg (based on body surface area). The incidence of major malformations in human pregnancies has not been established for Injectafer. However, all pregnancies, regardless of exposure to IN65ADV Iss. 7/213 8 USE IN SPECIFIC POPULATIONS Formal drug interaction studies have not been performed with Injectafer. To report SUSPECTED ADVERSE REACTIONS, contact American Regent at 7 DRUG INTERACTIONS se to hypertension following each Injectafer administration. (5.2) ADVERSE REACTIONS The most common adverse reactions ( 2%) are nausea, hypertension, flushing, hypophosphatemia, and dizziness (6.1) administration. (5.1) Hypertension: Monitor patients closely for signs and symptoms of ron DOSAGE FORMS AND STRENGTHS 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 least 3 minutes and until clinically stable following completion of each Other adverse reactions reported by.5% of treated patients include laboratory blood phosphorus levels (< 2 mg/dl) have been observed in 27% (44/1638) patients in clinical trials. 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 5 mg of Injectafer every 2 weeks for a total of 16 weeks. Partial recovery followed discontinuation of Injectafer. Patient Information INJECTAFER Please read this information carefully before taking this medication. This summary does not tell you everything about INJECTAFER. Speak with your doctor or healthcare professional if there is something you do not understand or if you would like to learn more about INJECTAFER. Your doctor or healthcare professional is your best source of information about this medicine. What is INJECTAFER? RQ152 Iron is a mineral that the body needs to produce red blood cells. When the body does not get enough iron, it cannot produce the number of normal red blood cells needed to keep you in good health. This condition is called iron deficiency (iron shortage) or iron deficiency anemia. INJECTAFER is used to treat iron deficiency anemia. Iron deficiency anemia may be caused by several medical conditions including heavy menstrual bleeding, pregnancy, childbirth, inflammatory bowel disease, other malabsorption diseases, bariatric surgery, or chronic kidney disease. General information about using INJECTAFER safely and effectively Injectable iron is administered only by or under the supervision of your health care professional. Serious or life threatening allergic reactions have been reported with intravenous iron products. Tell your health care professional if you have ever had any unusual or allergic reaction to any IV iron. Patients should report to their healthcare professional any signs and symptoms of an allergic reaction to INJECTAFER, in particular rashes, shortness of breath and wheezing. Iron is not easily eliminated from the body, and its build up may be lead to a condition called iron overload which may be harmful. Certain medical conditions such as liver disease may also make you more likely to develop iron overload. Ask your doctor or healthcare professional. Who should not take INJECTAFER? You should not be given INJECTAFER if you have anemia that is not caused by iron deficiency, or if you have iron overload. If you are pregnant or plan to become pregnant please notify your doctor or healthcare professional. They will decide whether it is safe for you to receive INJECTAFER. How should I take INJECTAFER? INJECTAFER is administered intravenously (into your vein) by your doctor or healthcare professional in two doses. What should I avoid while taking INJECTAFER? You should not take iron supplements by mouth if you are receiving iron injections. Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. What are the possible side effects of INJECTAFER? The side effects of INJECTAFER are infrequent, usually mild and generally do not cause patients to stop treatment. The most common side effects are nausea, injection site reactions (including pain or bruising at the injection site), asymptomatic reductions in blood phosphorus, flushing, headache, hypertension, dizziness, and increased alanine aminotransferase. Potentially long lasting brown staining of skin near injection site may occur. These are not all the possible side effects of INJECTAFER. For more information ask your doctor or healthcare professional. Talk to your doctor if you think you have side effects from taking INJECTAFER.