Injectafer

CLINICAL PHARMACOLOGY

Mechanism of Action

Ferric carboxymaltose is a colloidal iron (III) hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron.

Pharmacodynamics

Using positron emission tomography (PET) it was demonstrated that red cell uptake of 59Fe and 52Fe 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.

Pharmacokinetics

After administration of a single dose of Injectafer of 100 to 1000 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.

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 750 mg of iron on two occasions separated by at least 7 days up to a cumulative dose of 1500 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 ≤ 100 ng/mL or ferritin ≤ 300 ng/mL when transferrin saturation (TSAT) ≤ 30%. 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 [90% 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) Cohort 1 Cohort 2
Injectafer
(N=244)
Oral Iron
(N=251)
Injectafer
(N=245)
IV SCa
(N=237)
Baseline 10.6 (1.0) 10.6 (1.0) 9.1 (1.6) 9.0 (1.5)
Highest Value 12.2 (1.1) 11.4 (1.2) 12.0 (1.2) 11.2 (1.3)
Change (from baseline to highest value) 1.6 (1.2) 0.8 (0.8) 2.9 (1.6) 2.2 (1.3)
p-value 0.001 0.001
SD=standard deviation;
a Intravenous iron per standard of care

Increases from baseline in mean f erritin (264.2±224.2 ng/mL in Cohort 1 and 218.2 ±211.4 ng/mL in Cohort 2), and transferrin saturation (13±16% in Cohort 1 and 20±15% in Cohort) were observed at Day 35 in Injectafer-treated 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 nondialysis dependent chronic kidney disease. Inclusion criteria included hemoglobin (Hb) ≤ 11.5 g/dL, ferritin ≤ 100 ng/mL or ferritin ≤ 300 ng/mL when transferrin saturation (TSAT) ≤ 30%.Study patients were randomized to either Injectafer or Venofer. The mean age of study patients was 67 years (range, 19 to 96); 64% were female; 54% were Caucasian, 26% were 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.

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)
Venofer
(N=1244)
Baseline 10.3 (0.8) 10.3 (0.8)
Highest Value 11.4 (1.2) 11.3 (1.1)
Change (from baseline to highest value) 1.1 (1.0) 0.9 (0.92)
Treatment Difference (95% CI) 0.21 (0.13, 0.28)

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

Last reviewed on RxList: 8/7/2013
This monograph has been modified to include the generic and brand name in many instances.

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