Important Information about Feraheme® (ferumoxytol) Injection

WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS
Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving Feraheme.  Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest.

Efficacy and safety in trials

Feraheme raised mean Hgb 1 g/dL with 1 g of IV iron in 35 days1

Feraheme raised mean Hgb 1 g/dL with only 1 g of IV iron

In clinical trials of adult patients with CKD who were nondialysis dependent (NDD):

  • Two 510-mg doses of Feraheme raised mean Hgb by 1.2 g/dL (± 1.3, standard deviation [SD]; P ≤ 0.001) in clinical trial 1 and by 0.8 g/dL (± 1.2, SD; P ≤ 0.001) in clinical trial 2 vs baseline at day 351
  • Following completion of the controlled phase of the trials, 69 patients received 2 additional 510-mg IV injections of Feraheme for a total cumulative dose of 2.04 g. On day 35 following the additional injections, 70% of these patients experienced an increase in Hgb and iron parameters (TSAT and ferritin)1
  • 1 g is the most commonly recommended full therapeutic dose of IV iron2,3

Learn more about the trial design and the efficacy and safety of Feraheme in trials.*

* The safety and efficacy of Feraheme were also evaluated in patients on dialysis.1

Important Safety Information1

  • Fatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving Feraheme. Other adverse reactions potentially associated with hypersensitivity have occurred (pruritus, rash, urticaria, and wheezing). These reactions have occurred following the first dose or subsequent doses in patients in whom a previous Feraheme dose was tolerated

Efficacy trials in CKD patients not dependent on dialysis1,4

Pivotal trials design: ferumoxytol vs oral iron
  • The efficacy and safety of Feraheme were studied in 2 randomized, active-controlled, open-label pivotal trials vs oral iron (ferrous fumarate)1,†
    • Feraheme was administered as two 510-mg IV single doses, with the second injection administered 3 to 8 days after the first injection1
    • Oral iron was administered as a total daily dose of 200 mg elemental iron for 21 days1,4
    • Primary end point: mean change in Hgb; baseline to day 351,4
  • Key inclusion criteria4
    • ≥ 18 years of age; CKD stages 1 to 5; Hgb ≤ 11.0 g/dL; TSAT ≤ 30%; serum ferritin ≤ 600 ng/mL

Important Safety Information1

  • Only administer Feraheme when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity, including monitoring of blood pressure and pulse, during and after Feraheme administration for at least 30 minutes and until clinically stable following completion of each infusion

The safety and efficacy of Feraheme were also evaluated in patients on dialysis.1

Feraheme was proven to increase mean Hgb in patients with CKD who were NDD in 2 pivotal trials vs oral iron1,5,‡,§

Trial 1: mean change in Hgb levels from baseline with Feraheme or oral iron1,5
Feraheme was proven to increase mean Hgb. Trial 1: mean change in Hgb levels from baseline with Feraheme vs oral iron
  • Mean Hgb increased by 1.2 g/dL in patients with CKD who were NDD1,5,‡
  • Evaluated in 303 patients with CKD stages 1 to 5 who were NDD5
  • Increase vs baseline at day 35 (P ≤ 0.001)1
  • TSAT levels1:
    • Feraheme 9.8% at baseline and 19.0% at day 35
    • Oral iron 10.4% at baseline and 10.7% at day 35

n values represent the ITT population. Actual n values used in analyses may vary depending on missing values, thus decreasing the n.1

§As demonstrated in 2 randomized, active-controlled, open-label pivotal trials in which 303 patients with CKD stages 1 to 5 who were NDD (Trial 1) and 304 patients with CKD stages 1 to 5 who were NDD (Trial 2) were randomized 3:1 to treatment with Feraheme or oral iron. Feraheme was administered as two 510-mg doses; most patients received their second Feraheme injection 3 to 8 days after the first injection. Oral iron (ferrous fumarate) was administered as a total daily dose of 200-mg elemental iron for 21 days.1,5

Trial 2: mean change in Hgb levels from baseline with Feraheme or oral iron1,5
Feraheme was proven to increase mean Hgb. Trial 2: mean change in Hgb levels from baseline with Feraheme vs oral iron
  • Mean Hgb increased by 0.8 g/dL in patients with CKD who were NDD1,5,‖
  • Evaluated in 304 patients with CKD stages 1 to 5 who were NDD5
  • Increase vs baseline at day 35 (P ≤ 0.001)1
  • TSAT levels1:
    • Feraheme 11.3% at baseline and 21.1% at day 35
    • Oral iron 10.1% at baseline and 11.4% at day 35

Important Safety Information1

  • Patients with a history of multiple drug allergies may have a greater risk of anaphylaxis with parenteral iron products. Carefully consider the potential risks and benefits before administering Feraheme to these patients

n values represent the ITT population. Actual n values used in analyses may vary depending on missing values, thus decreasing the n.1

In clinical trials, the safety profile of Feraheme was evaluated in 1,726 subjects1

  • 0.2% of subjects (3/1,726) receiving Feraheme experienced serious hypersensitivity
    • Other adverse reactions potentially associated with hypersensitivity (eg, pruritus, rash, urticaria, or wheezing) were reported in 3.7% of subjects (63/1,726)
  • 1.9% of subjects (33/1,726) receiving Feraheme experienced hypotension, including 3 patients with serious hypotensive reactions
Adverse reactions reported in ≥ 1% of patients with CKD treated with Feraheme in 3 randomized, active-controlled, open-label studies
Diarrhea (4.0%), constipation (2.1%), and hypertension (1.0%) have also been reported in patients treated with Feraheme.

Evaluated in 3 randomized clinical trials in which 605 patients were exposed to 2 injections of 510 mg of Feraheme and a total of 280 patients were exposed to 200 mg/day of oral iron for 21 days; most patients received their second Feraheme injection 3 to 8 days after the first injection.1

In a noninferiority study, Feraheme demonstrated comparable efficacy to iron sucrose6

  • A randomized, open-label, active-controlled, multicenter clinical trial of 162 patients with IDA and CKD compared the efficacy and safety of Feraheme versus iron sucrose6
  • Feraheme was administered as two 510-mg injections for a total dose of 1.02 g6
  • Iron sucrose was administered as 1.0 g either by a slow injection or infusion (10 doses for dialysis patients; 5 doses for patients who were NDD)6
  • Feraheme raised mean Hgb by 0.8 g/dL; iron sucrose raised mean Hgb by 0.7 g/dL (difference = 0.1 g/dL [95% CI, -0.2 to 0.4])6
  • Adverse event profiles and rates were also similar between treatment groups6
    • In the Feraheme treatment group, the AESI was an anaphylactic-type reaction in 1 (1.3%) patient that resolved on the day of dosing
    • In the iron sucrose group, 5 (6.1%) patients experienced AESIs, including 6 AEs of hypotension and 1 AE of unresponsive to stimuli
#Adjusted for baseline Hgb and dialysis status.

 AESI: adverse event of special interest; AR: adverse reaction; CI: confidence interval; CKD: chronic kidney disease; Hgb: hemoglobin; IDA: iron deficiency anemia; ITT: intent to treat; IV: intravenous; TSAT: transferrin saturation.

 
Important Information about Feraheme® (ferumoxytol) Injection

WARNING: RISK FOR SERIOUS HYPERSENSITIVITY/ANAPHYLAXIS REACTIONS
Fatal and serious hypersensitivity reactions including anaphylaxis have occurred in patients receiving Feraheme. Initial symptoms may include hypotension, syncope, unresponsiveness, cardiac/cardiorespiratory arrest.

  • Only administer Feraheme when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions.
  • Observe for signs or symptoms of hypersensitivity reactions during and for at least 30 minutes following Feraheme infusion including monitoring of blood pressure and pulse during and after Feraheme administration.
  • Hypersensitivity reactions have occurred in patients in whom a previous Feraheme dose was tolerated.
Indication and Dosing

Feraheme is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD).

The recommended dose of Feraheme is an initial 510 mg dose followed by a second 510 mg dose 3 to 8 days later, each dose infused over at least 15 minutes while the patient is in a reclined or semi-reclined position.

Important Safety Information
Contraindications

Feraheme is contraindicated in patients with:

  • Known hypersensitivity to Feraheme or any of its components
  • History of allergic reaction to any intravenous iron product
Warnings and Precautions
  • Fatal and serious hypersensitivity reactions including anaphylaxis, presenting with cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, or unresponsiveness have occurred in patients receiving Feraheme. Other adverse reactions potentially associated with hypersensitivity have occurred (pruritus, rash, urticaria, and wheezing). These reactions have occurred following the first dose or subsequent doses in patients in whom a previous Feraheme dose was tolerated.
  • Patients with a history of multiple drug allergies may have a greater risk of anaphylaxis with parenteral iron products. Carefully consider the potential risks and benefits before administering Feraheme to these patients.
  • Only administer Feraheme when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Closely observe patients for signs and symptoms of hypersensitivity including monitoring of blood pressure and pulse during and after Feraheme administration for at least 30 minutes and until clinically stable following completion of each infusion.
  • In clinical studies predominantly in patients with CKD, serious hypersensitivity reactions were reported in 0.2% (3/1,726) of subjects receiving Feraheme. Other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria or wheezing) were reported in 3.7% (63/1,726) of these subjects. In other trials excluding patients with Stages 4 and 5 CKD, moderate to severe hypersensitivity reactions were reported in 2.6% (26/1,014) of patients treated with Feraheme.
  • In the post-marketing experience, fatal and serious anaphylactic type reactions presenting with cardiac/ cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported. Elderly patients with multiple or serious co-morbidities who experience hypersensitivity reactions and/or hypotension following administration of Feraheme may have more severe outcomes.
  • Severe adverse reactions of clinically significant hypotension have been reported in the post-marketing experience. In clinical studies, hypotension was reported in 1.9% (33/1,726) of subjects, including three patients with serious hypotensive reactions. Monitor for signs and symptoms of hypotension following each Feraheme administration.
  • Excessive therapy with parenteral iron can lead to excess storage of iron with the possibility of iatrogenic hemosiderosis. Patients should be regularly monitored for hematologic response during parenteral iron therapy, noting that lab assays may overestimate serum iron and transferrin bound iron values in the 24 hours following administration of Feraheme.
  • As a superparamagnetic iron oxide, Feraheme may transiently affect magnetic resonance diagnostic imaging studies for up to 3 months following the last Feraheme dose. Feraheme will not affect X-ray, CT, PET, SPECT, ultrasound, or nuclear imaging.
Adverse Reactions
  • The most common adverse reactions (≥ 2%) following the administration of Feraheme are diarrhea, nausea, dizziness, hypotension, constipation, and peripheral edema.
  • In clinical trials, adverse reactions leading to treatment discontinuation and occurring in ≥ 2 Feraheme-treated patients included hypotension, infusion site swelling, increased serum ferritin level, chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic renal failure, and urticaria.
  • The following additional serious adverse reactions have been reported from the post-marketing experience with Feraheme: tachycardia/rhythm abnormalities, angioedema, ischemic myocardial events, congestive heart failure, pulse absent, and cyanosis. These adverse reactions have usually occurred within 30 minutes after the administration of Feraheme. Reactions have occurred following the first dose or subsequent doses of Feraheme.

You may report an adverse event related to AMAG Pharmaceuticals’ products by calling 1-877-411-2510 or emailing amag@druginfo.com. If you prefer, you may contact the U.S. Food and Drug Administration (FDA) directly at fda.gov/medwatch or call 1-800-FDA-1088.

References: 1. Feraheme [package insert]. Waltham, MA: AMAG Pharmaceuticals, Inc; Mar 2015. 2. Ferrlecit [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; Mar 2015. 3. Venofer [package insert]. Shirley, NY: American Regent, Inc; 2012. 4. Spinowitz BS, Kausz AT, Baptista J, et al. Ferumoxytol for treating iron deficiency anemia in CKD. J Am Soc Nephrol. 2008;19(8):1599-1605. 5. Data on file, AMAG Pharmaceuticals, Inc. 6. Macdougall IC, Strauss WE, McLaughlin J, et al. A randomized comparison of ferumoxytol and iron sucrose for treating iron deficiency in anemia in patients with CKD. Clin J Am Soc Nephrol. 2014;9:705-712.