Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have non-dialysis dependent chronic kidney disease.

EFFICACY & SAFETY

Review the data from pivotal trial 2 (REPAIR-IDA): Injectafer vs IV iron SoC in non-dialysis dependent chronic kidney disease (NDD-CKD)
  • Study design for pivotal trial 21*

    A randomized, active-controlled, multicenter, noninferiority, open-label trial comparing the safety and efficacy of Injectafer with IV iron sucrose in patients with IDA and NDD-CKD.

    Primary
    efficacy endpoint:

    Mean change from baseline Hb to highest observed Hb at any time between baseline and end of treatment (day 56) or time of intervention.

    Key secondary
    efficacy endpoints:

    • Proportion of subjects achieving an increase in Hb of ≥1 g/dL at any time between baseline and day 56
    • Mean change from baseline to highest observed ferritin and TSAT between baseline and day 56

    Primary
    composite safety endpoint§:

    Proportion of patients experiencing at least one treatment-emergent adverse event included in a primary composite safety endpoint, beginning on or after the first dose of randomized treatment.II

    Pivotal trial 2 for Injectafer included patients with iron intolerance, drug allergy, and hypotension1

    *Patients in this study received Injectafer by IV push.1 14 patients randomized to Injectafer and 9 patients randomized to iron sucrose were withdrawn prior to receiving study drug. The efficacy analysis was 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 analysis population comprised all participants who received a randomly assigned treatment dose. IIIncluded: all-cause death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, chronic heart failure requiring hospitalization or medical intervention, cardiac arrhythmia, and hyper- or hypotensive events as defined per protocol.

TRIAL 2 (REPAIR-IDA): INJECTAFER VS IV IRON SoC IN NDD-CKD

Injectafer demonstrated hemoglobin (Hb) improvement

  • Noninferiority of Injectafer compared with iron sucrose was demonstrated in patients with NDD-CKD1

Greater absolute increase in Hb1

Primary endpoint

Hb: Mean change from baseline to highest value between baseline and day 56 or time of intervention

No significant difference was shown at the primary composite safety endpoint1

Primary composite safety endpoint
Injectafer (n=1276) Iron sucrose (n=1285)
Patients meeting endpoint 175 (13.7%) 156 (12.1%)
A significant difference in the
number of protocol-defined,

predominantly transient
hypertensive episodes was
observed
Patient episodes 95 (7.45%) 56 (4.36%)

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

Injectafer showed greater improvements in ferritin and TSAT

Mean ferritin and TSAT values at each scheduled visit1,3

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

Ferritin: Mean value at each scheduled visit

Ferritin: Mean change at each scheduled visit

TSAT: Mean value at each scheduled visit

TSAT: Mean change at each
scheduled visit

In a post hoc analysis, fewer patients taking Injectafer required retreatment4II

2x as many patients receiving Iron sucrose required retreatment
Retreatment between days 56 and 90 (safety population)
Injectafer 1500 mg (n=1276) Iron sucrose 1000 mg (n=1285)
Patients retreated 71 (5.6%) 142 (11.1%)
||P<0.001 SD=standard deviation. IIPlease note that this was a post hoc analysis; therefore, the limitations of the data must be considered, and the results should be interpreted with caution and in the context of the overall trial results.

References:

  1. Onken JE, Bregman DB, Harrington RA, et al. Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrol Dial Transplant. 2014;29(4):833-842.
  2. Injectafer [package insert]. Shirley, NY: American Regent, Inc.; April 2021.
  3. Data on file. Daiichi Sankyo Inc., Basking Ridge, NJ.
  4. Koch TA, Myers J, Goodnough LT. Intravenous iron therapy in patients with iron deficiency anemia: dosing considerations. Anemia. 2015. doi:10.1155/2015/763576.
  • IMPORTANT SAFETY INFORMATION


    INDICATIONS

    Injectafer® (ferric carboxymaltose injection) is indicated for the treatment of iron deficiency anemia (IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have 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

    Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, 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.

    Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.

    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.

    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.

    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 [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%); dizziness (2.1%); and vomiting (2%).

    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 (rarely reported event); 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 patients who have intolerance to oral iron or have had unsatisfactory response to oral iron, or who have 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

Symptomatic hypophosphatemia requiring clinical intervention has been reported in patients at risk of low serum phosphate in the postmarketing setting. These cases have occurred mostly after repeated exposure to Injectafer in patients with no reported history of renal impairment. Possible risk factors for hypophosphatemia include a history of gastrointestinal disorders associated with malabsorption of fat-soluble vitamins or phosphate, 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.

Monitor serum phosphate levels in patients at risk for low serum phosphate who require a repeat course of treatment.

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.

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.

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 [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%); dizziness (2.1%); and vomiting (2%).

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 (rarely reported event); 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

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