Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult and pediatric patients 1 year of age and older who have either intolerance or an unsatisfactory response to oral iron, or adult patients who have non-dialysis dependent chronic kidney disease. Injectafer is also indicated for iron deficiency in adult patients with heart failure and New York Heart Association class II/III to improve exercise capacity.

The first & only FDA-approved IV iron to treat iron deficiency in adult patients with heart failure1-6

(With New York Heart Association class II/III, to improve exercise capacity)

Detecting and diagnosing iron deficiency vs iron deficiency anemia

Iron deficiency, anemia and iron deficiency anemia are 3 different conditions1

The symptoms of iron deficiency (ID) and iron deficiency anemia (IDA) are often nonspecific and may be underdiagnosed. Some patients may be asymptomatic.2,3

Common signs and symptoms may include:4

  • Fatigue icon

    Fatigue

  • Weakness icon

    Weakness

  • Dizziness icon

    Dizziness

  • Shortness of breath icon

    Shortness of breath

Other signs and symptoms:

  • headache
  • chest pain
  • pale skin
  • arrhythmia
  • lightheadedness
  • brittle nails
  • coldness in extremities
  • pica (craving nonfood items such as dirt or ice)

The signs and symptoms of ID and IDA can overlap with those of other conditions2,5-7

  • Many HF symptoms can look like iron deficiency, such as: dyspnea, fatigue, and heart palpitations. It’s important to obtain lab values for key iron deficiency indices.6,8-10
*Injectafer is not indicated to treat the symptoms of IDA.11

It is important to routinely test patients who are at risk for ID and IDA for low iron stores, even when they aren't exhibiting symptoms2

3 key indices for evaluating ID and IDA12,13

Hemoglobin (Hb): Hb production requires sufficient levels of stored iron and adequate TSAT.14

Ferritin: When the body requires more iron than the diet provides, ferritin supplies a reservoir from which iron can be metabolized.15

Transferrin saturation (TSAT): Transferrin transports iron throughout the body so it can be used to produce Hb. TSAT is decreased in patients with chronic iron deficiency.14,16

3 Key indices for evaluating ID & IDA showing Hemoglobin, Ferritin, and Transferrin saturation

Normal levels in healthy patients*

Adults

Hb17

M 13.5 g/dL-17.5 g/dL13

F 12.0 g/dL-15.5 g/dL13

Ferritin1

M 40 ng/mL-300 ng/mL14

F 20 ng/mL-200 ng/mL14

TSAT18

M 20%-50%8

F 20%-50%8

Pediatrics

Hb19

M 10.5 g/dL-16 g/dL11

F 10.5 g/dL-16 g/dL11

Ferritin19

M 36 ng/mL-311 ng/mL1

F 36 ng/mL-92 ng/mL1

TSAT19

M 15%-44%12‡

F 11%-44%12‡

It may also be important to test for total iron-binding capacity (TIBC) to diagnose IDA.14
Normal values for TIBC range from:

  • 240 μg/dL to 450 μg/dL in healthy adult patients18
  • 268 μg/dL to 570 μg/dL in healthy male pediatric patients20
  • 268 μg/dL to 564 μg/dL in healthy female pediatric patients20

Please note TIBC values were not measured in pivotal trials for Injectafer.

When diagnosing ID look for:

Ferritin levels below 100 ng/mL8

OR

Ferritin levels between 100 ng/mL to 300 ng/mL, if TSAT is <20%8

*Normal lab values may vary based on patient characteristics/comorbidities and by laboratory. Injectafer is not indicated to treat patients with CKD who are on dialysis or patients with anemia of chronic disease. For adult patients with CKD and anemia, guidelines issued by the National Kidney Foundation (NKF) recommend IV iron for patients with a TSAT ≤30% and ferritin ≤500 ng/mL. Consult the NKF guidelines for a complete list of recommendations for lab values when starting treatment.7,21 7 months-2 years: 10.5 g/dL-14 g/dL; 3-6 years: 11.5 g/dL-14.5 g/dL; 7-12 years: 11.5 g/dL-15.5 g/dL; 13-18 years: 13 g/dL-16 g/dL (male),12 g/dL-16 g/dL (female).19 §1 -5 years: 36 ng/mL-84 ng/mL; >6 years: 36 ng/mL-311 ng/mL (male), 36 ng/mL-92 ng/mL (female).19 II0 -11 years: 15%-39%; 12-17 years: 16%-44% (male), 11%-44% (female).19

Learn about treatment options for both iron deficiency and iron deficiency anemia.22,23

A wide variety of patient types should be tested for iron deficiency and iron deficiency anemia

Published studies and available data from postmarketing reports with IV Injectafer are insufficient to assess the risk for pregnant women of major birth defects and miscarriage. #Defined in reference as serum ferritin <100 ng/mL or TSAT <20%. Authors concluded this remarkably high prevalence might indicate these indices may not be specific enough and may falsely identify too many patients as iron deficient.26

References:

  1. Iron-deficiency anemia. National Heart, Lung, and Blood Institute website. https://www.nhlbi.nih.gov/health-topics/iron-deficiency-anemia. Accessed April 29, 2021.
  2. Iron-deficiency anemia. Mayo Clinic website. https://www.mayoclinic.org/diseases-conditions/iron-deficiency-anemia/symptoms-causes/syc-20355034. Accessed April 29, 2021.
  3. Dumitru I. Heart failure clinical presentation. Medscape website. http://emedicine.medscape.com/article/163062-clinical. Updated March 2, 2021. Accessed April 29, 2021.
  4. Top Doctors®, United Kingdom. Iron Deficiency. Accessed June 29, 2022. https://www.topdoctors.co.uk/medical-dictionary/iron- deficiency#
  5. Anand IS, Chandrashekhar Y, Ferrari R, Poole-Wilson PA, Harris PC. Pathogenesis of oedema in chronic severe anaemia: studies of body water and sodium, renal function, haemodynamic variables, and plasma hormones. Br Heart J. 1993;70(4):357-362.
  6. Colorectal cancer symptoms. Cancer Treatment Centers of America® website. https://www.cancercenter.com/cancer-types/colorectal-cancer/symptoms. Accessed April 29, 2021.
  7. Injectafer®. Package insert. American Regent, Inc.; 2023.
  8. Kotze MJ, van Velden DP, van Rensburg SJ, Erasmus R. Pathogenic mechanisms underlying iron deficiency and iron overload: new insights for clinical application. EJIFCC. 2009;20(2):108-123.
  9. Kaitha S, Bashir M, Ali T. Iron deficiency anemia in inflammatory bowel disease. World J Gastrointest Pathophysiol. 2015;6(3):62-72.
  10. Iron-deficiency anemia. American Society of Hematology website. https://www.hematology.org/education/patients/anemia/iron-deficiency. Accessed April 29, 2021.
  11. Ferritin blood test. Medline Plus website. https://medlineplus.gov/ency/article/003490.htm. Updated April 2, 2021. Accessed April 13, 2021.
  12. Transferrin saturation. Medscape website. http://emedicine.medscape.com/article/2087960-overview#a2. Accessed May 10, 2021.
  13. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(17):e263-e421. doi.org/10.1016/j.jacc.2021.12.012
  14. Staff hemoglobin test. Mayo Clinic website. https://www.mayoclinic.org/tests-procedures/hemoglobin-test/about/pac-20385075. Accessed May 11, 2021.
  15. Serum iron test. MedlinePlus website. https://medlineplus.gov/ency/article/003488.htm. Accessed May 10, 2021.
  16. Total iron binding capacity. MedlinePlus website. https://medlineplus.gov/ency/article/003489.htm. Accessed May 10, 2021.
  17. Andropoulos DB. Appendix B: pediatric normal laboratory values. In: Gregory GA, Andropoulos DB, eds. Gregory’s Pediatric Anesthesia. 5th ed. Blackwell Publishing Ltd; 2012:1300-1315.
  18. Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. 2013;24(7):1886-1892.
  19. Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010;7(11):599-610.
  20. Fishbane S, Pollack S, Feldman Hl, Joffe MM. Iron indices in chronic kidney disease in the National Health and Nutritional Examination Survey 1988-2004. Clin J Am Soc Nephrol. 2009;4(1):57-61.
  21. Your guide to anemia. National Heart, Lung, and Blood Institute website. https://www.nhlbi.nih.gov/sites/default/files/publications/11-7629.pdf. Published September 2011. Accessed April 13, 2021.
  22. Ebner N, von Haehling S. Why is iron deficiency recognised as an important comorbidity in heart failure? Card Fail Rev. 2019;5(3):173-175. doi:10.15420/cfr.2019.9.2
  • IMPORTANT SAFETY INFORMATION


    INDICATIONS

    Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult and pediatric patients 1 year of age and older who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have non-dialysis dependent chronic kidney disease. Injectafer is also indicated for iron deficiency in adult patients with heart failure and New York Heart Association class II/III to improve exercise capacity.

    IMPORTANT SAFETY INFORMATION

    CONTRAINDICATIONS

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

    WARNINGS AND PRECAUTIONS

    Symptomatic Hypophosphatemia

    Symptomatic hypophosphatemia with serious outcomes including osteomalacia and fractures requiring clinical intervention has been reported in patients treated with Injectafer in the post-marketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. However, symptomatic hypophosphatemia has been reported after one dose. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, inflammatory bowel disease, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency, and malnutrition. In most cases, hypophosphatemia resolved within three months.

    Correct pre-existing hypophosphatemia prior to initiating therapy with Injectafer. Monitor serum phosphate levels in patients at risk for chronic low serum phosphate. Check serum phosphate levels prior to a repeat course of treatment in patients at risk for low serum phosphate and in any patient who receives a second course of therapy within three months. Treat hypophosphatemia as medically indicated.

    Hypersensitivity Reactions

    Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.

    Hypertension

    In clinical studies, hypertension was reported in 4% (67/1775) of subjects in clinical trials 1 and 2. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.

    Laboratory Test Alterations

    In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.

    ADVERSE REACTIONS

    Adults

    In two randomized clinical studies [Studies 1 and 2], a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a maximum single dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by >2% of Injectafer-treated patients were nausea (7.2%); hypertension (4%); flushing (4%); injection site reactions (3%); erythema (3%); hypophosphatemia (2.1%); and dizziness (2.1%).

    Pediatric

    The safety of Injectafer in pediatric patients was evaluated in Study 3. Study 3 was a randomized, active-controlled study in which 40 patients (1 to 12 years of age: 10 patients, 12 to 17 years of age: 30 patients) received Injectafer 15 mg/kg to a maximum single dose of 750 mg (whichever was smaller) on Days 0 and 7 for a maximum total dose of 1500 mg; 38 patients evaluable for safety in the control arm received an age-dependent formulation of oral ferrous sulfate for 28 days. The median age of patients who received Injectafer was 14.5 years (range, 1-17); 83% were female; 88% White and 13% Black. The most common adverse reactions (≥4%) were hypophosphatemia (13%), injection site reactions (8%), rash (8%), headache (5%), and vomiting (5%).

    Patients with Iron Deficiency and Heart Failure

    The safety of Injectafer was evaluated in adult patients with iron deficiency and heart failure in randomized controlled trials FAIR-HF (NCT00520780), CONFIRM-HF (NCT01453608) and AFFIRM-AHF (NCT02937454) in which 1016 patients received Injectafer versus 857 received placebo. The overall safety profile of Injectafer was consistent across the studied indications.

    Post-Marketing Experience

    The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia; nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria; pregnancy: fetal bradycardia.

    CLINICAL CONSIDERATIONS IN PREGNANCY

    Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.

    Severe adverse reactions, including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.


    Please see Full Prescribing Information

IMPORTANT SAFETY INFORMATION


INDICATIONS

Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult and pediatric patients 1 year of age and older who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have non-dialysis dependent chronic kidney disease. Injectafer is also indicated for iron deficiency in adult patients with heart failure and New York Heart Association class II/III to improve exercise capacity.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

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

WARNINGS AND PRECAUTIONS

Symptomatic Hypophosphatemia

Symptomatic hypophosphatemia with serious outcomes including osteomalacia and fractures requiring clinical intervention has been reported in patients treated with Injectafer in the post-marketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. However, symptomatic hypophosphatemia has been reported after one dose. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, inflammatory bowel disease, concurrent or prior use of medications that affect proximal renal tubular function, hyperparathyroidism, vitamin D deficiency, and malnutrition. In most cases, hypophosphatemia resolved within three months.

Correct pre-existing hypophosphatemia prior to initiating therapy with Injectafer. Monitor serum phosphate levels in patients at risk for chronic low serum phosphate. Check serum phosphate levels prior to a repeat course of treatment in patients at risk for low serum phosphate and in any patient who receives a second course of therapy within three months. Treat hypophosphatemia as medically indicated.

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Injectafer. Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. Monitor patients for signs and symptoms of hypersensitivity during and after Injectafer administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Injectafer when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. In clinical trials, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer. Other serious or severe adverse reactions potentially associated with hypersensitivity which included, but were not limited to, pruritus, rash, urticaria, wheezing, or hypotension were reported in 1.5% (26/1775) of these subjects.

Hypertension

In clinical studies, hypertension was reported in 4% (67/1775) of subjects in clinical trials 1 and 2. Transient elevations in systolic blood pressure, sometimes occurring with facial flushing, dizziness, or nausea were observed in 6% (106/1775) of subjects in these two clinical trials. These elevations generally occurred immediately after dosing and resolved within 30 minutes. Monitor patients for signs and symptoms of hypertension following each Injectafer administration.

Laboratory Test Alterations

In the 24 hours following administration of Injectafer, laboratory assays may overestimate serum iron and transferrin bound iron by also measuring the iron in Injectafer.

ADVERSE REACTIONS

Adults

In two randomized clinical studies [Studies 1 and 2], a total of 1775 patients were exposed to Injectafer, 15 mg/kg of body weight, up to a maximum single dose of 750 mg of iron on two occasions, separated by at least 7 days, up to a cumulative dose of 1500 mg of iron. Adverse reactions reported by >2% of Injectafer-treated patients were nausea (7.2%); hypertension (4%); flushing (4%); injection site reactions (3%); erythema (3%); hypophosphatemia (2.1%); and dizziness (2.1%).

Pediatric

The safety of Injectafer in pediatric patients was evaluated in Study 3. Study 3 was a randomized, active-controlled study in which 40 patients (1 to 12 years of age: 10 patients, 12 to 17 years of age: 30 patients) received Injectafer 15 mg/kg to a maximum single dose of 750 mg (whichever was smaller) on Days 0 and 7 for a maximum total dose of 1500 mg; 38 patients evaluable for safety in the control arm received an age-dependent formulation of oral ferrous sulfate for 28 days. The median age of patients who received Injectafer was 14.5 years (range, 1-17); 83% were female; 88% White and 13% Black. The most common adverse reactions (≥4%) were hypophosphatemia (13%), injection site reactions (8%), rash (8%), headache (5%), and vomiting (5%).

Patients with Iron Deficiency and Heart Failure

The safety of Injectafer was evaluated in adult patients with iron deficiency and heart failure in randomized controlled trials FAIR-HF (NCT00520780), CONFIRM-HF (NCT01453608) and AFFIRM-AHF (NCT02937454) in which 1016 patients received Injectafer versus 857 received placebo. The overall safety profile of Injectafer was consistent across the studied indications.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of Injectafer. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following adverse reactions have been reported from the post-marketing spontaneous reports with Injectafer: cardiac disorders: tachycardia; general disorders and administration site conditions: chest discomfort, chills, pyrexia; metabolism and nutrition disorders: hypophosphatemia; musculoskeletal and connective tissue disorders: arthralgia, back pain, hypophosphatemic osteomalacia; nervous system disorders: syncope; respiratory, thoracic and mediastinal disorders: dyspnea; skin and subcutaneous tissue disorders: angioedema, erythema, pruritus, urticaria; pregnancy: fetal bradycardia.

CLINICAL CONSIDERATIONS IN PREGNANCY

Untreated IDA in pregnancy is associated with adverse maternal outcomes such as postpartum anemia. Adverse pregnancy outcomes associated with IDA include increased risk for preterm delivery and low birth weight.

Severe adverse reactions, including circulatory failure (severe hypotension, shock including in the context of anaphylactic reaction) may occur in pregnant women with parenteral iron products (such as Injectafer) which may cause fetal bradycardia, especially during the second and third trimester.


Please see Full Prescribing Information