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)

EFFICACY & SAFETY

Review the data from pivotal trial 1: Injectafer vs oral iron and vs intravenous (IV) iron standard of care (SoC) in various etiologies
  • Study design for pivotal trial 11: Injectafer vs oral iron and vs IV iron SoC

    A randomized, open-label, multicenter study evaluating the efficacy and safety of Injectafer in adult patients with iron deficiency anemia (IDA) of any etiology.1*

    Unsatisfactory response to oral iron (hemoglobin (Hb) increase <1 g/dL) after a 14 day run-in of oral iron

    COHORT 1

    Randomized 1:1

    Intolerant to oral iron after a 14 day run-in of oral iron, or inappropriate for oral iron

    COHORT 2

    Randomized 1:1

    Primary
    efficacy endpoint

    Mean change in Hb from baseline to highest observed value between baseline and day 35 or time of intervention in Cohort 1.

    Key secondary
    efficacy endpoints

    • Mean change from baseline to highest observed Hb at any time between baseline and day 35 or time of intervention in Cohort 2
    • Proportion of subjects achieving a Hb level >12 g/dL at any time between baseline and day 35 or time of intervention
    • Mean change in Hb, ferritin, and Transferrin Saturation (TSAT) from baseline to each scheduled visit

    Primary
    composite safety endpoint

    Proportion of study participants experiencing at least 1 treatment-emergent adverse event included as components of a composite safety endpoint.§

    • Treatment-emergent adverse events included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure (CHF), arrhythmias, and protocol-defined hypotension or hypertension

    Pivotal trial 1 for Injectafer included subjects with iron intolerance and/or drug allergy

    *Participants who responded adequately to oral iron during run-in (Hb increase ≥1 g/dL) were not randomized. Subjects inappropriate for oral iron were defined as either those who were intolerant of oral iron during the run-in phase or those in whom the baseline Hb measurement was sufficiently low as to require rapid repletion of iron stores to minimize the risk of eventual blood transfusion. These patients were not included in the indication for Injectafer. The efficacy analyses were performed on the modified intent-to-treat (mITT) population, which included all patients who received at least 1 dose of randomized treatment and had at least 1 post-baseline Hb assessment. §The safety population consisted of all subjects who received a dose of randomized treatment. All safety analyses were performed with the safety population.

TRIAL 1, COHORT 1: INJECTAFER VS ORAL IRON IN PATIENTS WITH IDA OF VARIOUS ETIOLOGIES

Injectafer provided a significantly greater increase in hemoglobin (Hb)1

  • Cohort 1 consisted of patients with iron deficiency anemia (IDA) who did not have a satisfactory response to oral iron in a 14-­day run-­in period1
  • Injectafer was compared to oral iron in patients with IDA of various etiologies1

Injectafer provided a significantly greater increase in Hb1

Primary endpoint1,2

Hb: Mean change in absolute value from baseline to highest value between baseline and day 35 or time of intervention

Injectafer helped more patients achieve a Hb target of >12 g/dL1

Secondary endpoint (secondary efficacy
endpoints were not powered for superiority)

Hb: Percentage of patients reaching a Hb level >12 g/dL at any time between baseline and day 35 or time of an intervention

SD=standard deviation

Injectafer arm showed greater improvements in ferritin and Transferrin Saturation (TSAT)1

Secondary endpoints (secondary efficacy endpoints were not powered for superiority)

Ferritin: Mean change from baseline to
day 35 or time of intervention

TSAT: Mean change from baseline to
day 35 or time of intervention

P=0.001

The diminished iron stores, as seen by ferritin and TSAT levels in the oral iron arm of this study, suggest that iron loss outpaced iron supplementation1

Primary composite safety endpoint1
Injectafer (n=246) Oral iron (n=253)
Patients meeting endpoint 7 (2.9%) 4 (1.6%)
  • The most commonly observed components of the composite safety endpoint were protocol-defined hypertension (4 participants in Cohort 1, Injectafer arm) and death due to any cause (2 participants in Cohort 1, oral iron arm).1

In clinical trials 1 and 2 for Injectafer, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer2

TRIAL 1, COHORT 2: INJECTAFER VS IV IRON SoC in patients with IDA of various etiologies who tolerated oral iron poorly or who were inappropriate for treatment with oral iron1

Injectafer provided a greater increase in Hb1

  • Cohort 2 consisted of patients who tolerated oral iron poorly or were inappropriate for treatment with oral iron1
  • 90% of patients randomized to IV iron SoC received iron sucrose1

Injectafer provided a greater increase in Hb

Secondary endpoint (secondary efficacy
endpoints were not powered for superiority)1,2

Hb: Mean change in absolute value from baseline to highest value between baseline and day 35 or time of intervention

Proportion of patients achieving a Hb target of >12 g/dL1||Post hoc comparison1

Secondary endpoint (secondary efficacy
endpoints were not powered for superiority)

Hb: Percentage of patients reaching Hb level >12 g/dL between baseline and day 35 or time of a intervention

Injectafer arm showed greater improvements in ferritin and TSAT1

Secondary endpoints (secondary efficacy endpoints were not powered for superiority)1,2

Ferritin: Mean change from baseline to
day 35 or time of intervention

TSAT: Mean change from baseline to
day 35 or time of intervention

P=0.001

No significant difference was shown in the primary composite safety endpoint1

Primary composite safety endpoint1
Injectafer (n=253) IV iron SoC (n=245)
Patients meeting endpoint 10 (4.0%) 12 (4.9%)
  • The most commonly observed component of the composite safety endpoint was protocol-defined hypertension (7 participants in Cohort 2, Injectafer arm; 6 participants in Cohort 2, IV iron SoC arm)

In clinical trials 1 and 2 for Injectafer, serious anaphylactic/anaphylactoid reactions were reported in 0.1% (2/1775) of subjects receiving Injectafer2

References:

  1. Onken JE, Bregman DB, Harrington RA, et al. A multicenter, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia. Transfusion. 2014;54(2):306-315.
  2. Injectafer®. Package insert. American Regent, Inc.; 2023.
  • 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