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Prevalence of IDA

Iron deficiency affects well over 50% of CKD patients with anemia21

In 2002, Hsu et al analyzed data from the Third National Health and Nutrition Examination Survey (NHANES III) (n=15,837) and found low iron indices to be frequently present at all levels of reduced creatinine clearance (CrCl).21

  • More than 50% of chronic kidney disease (CKD) patients with anemia were iron deficient, as indicated by serum ferritin <100 ng/mL or transferrin saturation (TSAT) <20%

Percentage of anemic CKD patients with iron deficiency21

Adapted from Hsu et al. J Am Soc Nephrol. 2002.21

A more recent retrospective analysis published by Fishbane et al (n=34,782) in 2009 expanded on the study published by Hsu et al and found that low levels of iron were present in most patients with reduced CrCl, suggesting that iron deficiency may be common in non-dialysis dependent chronic kidney disease (NDD-CKD) patients.33

  • Previous studies have also found low iron indices at all levels of reduced CrCl. However, data were collected prior to widespread use of erythropoiesis stimulating agents (ESAs) and prior to publication of the first National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI™) guidelines21
  • The purpose of the analysis from Fishbane et al was to more fully examine the distribution of serum ferritin and transferrin saturation (TSAT) among individuals with CKD evaluated by the NHANES program33
  • By thoroughly analyzing NHANES III data (1988-1994) and subsequent NHANES 2-year data sets (1999 to 2000, 2001 to 2002, and 2003 to 2004), Fishbane et al found that33:
    • Low iron tests—indicated by serum ferritin <100 ng/mL or TSAT <20%—were present in approximately 59% of men and approximately 73% of women with NDD-CKD, Stages 3 to 5 (CrCl <60 mL/min)33
    • The percentage of patients with low iron tests did not significantly differ between CKD Stages 3, 4, or 5 (P=NS)33

Percentage of NDD-CKD patients with low iron tests by CKD stage for combined NHANES cohorts33

Adapted from Fishbane et al. J Am Soc Nephrol. 2009.33

Additional findings from Fishbane et al
In addition to a high prevalence of iron deficiency, the study found that33:

  • Risk for anemia was generally unrelated to quartiles of mean serum ferritin
  • Probability of anemia increased with progressively lower quartiles of TSAT
  • Divergence between serum ferritin and TSAT may be due to the effects of inflammation
    • Analysis demonstrated a trend of increasing levels of C-reactive protein—an inflammatory marker—in CKD patients Stages 3 to 5

Findings of low levels of iron tests in the majority of CKD patients were further supported in a study by Gotloib et al.22

In 2006, Gotloib and colleagues evaluated 47 CKD patients with hemoglobin (Hgb) <12 g/dL who also showed evidence of low iron.

  • Patients underwent sternal bone marrow biopsy
  • 98%, or 46 of 47 patients, had no evidence of iron deposits in bone marrow, indicating severe iron deficiency

Anemia awareness is important because of the high prevalence of anemia in CKD. It is especially important to identify anemia and its causes early to select appropriate treatment.

NS=not significant.
KDOQI is a trademark of the National Kidney Foundation.

For the treatment of iron deficiency anemia (IDA) in adults with chronic kidney disease (CKD)

Important Safety Information for Feraheme (ferumoxytol) Injection

Indication and contraindication

Feraheme (ferumoxytol) Injection is indicated for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. Feraheme is contraindicated in patients with known hypersensitivity to Feraheme or any of its components.

Warnings and precautions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Feraheme. Observe patients for signs and symptoms of hypersensitivity during and after Feraheme administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer the drug when personnel and therapies are immediately available for the treatment of anaphylaxis and other hypersensitivity reactions. Anaphylactic-type reactions, presenting with cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, and unresponsiveness have been reported in the post-marketing experience. In clinical studies, 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 subjects. 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 injection. 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

In clinical trials, the most commonly occurring adverse reactions in Feraheme treated patients versus oral iron treated patients reported in ≥ 2% of chronic kidney disease patients were diarrhea (4.0% vs. 8.2%), nausea (3.1% vs. 7.5%), dizziness (2.6% vs. 1.8%), hypotension (2.5% vs. 0.4%), constipation (2.1% vs. 5.7%) and peripheral edema (2.0% vs. 3.2%). In clinical trials, adverse reactions leading to treatment discontinuation and occurring in 2 or more Feraheme treated patients included hypotension, infusion site swelling, increased serum ferritin level, chest pain, diarrhea, dizziness, ecchymosis, pruritus, chronic renal failure, and urticaria.

Post-marketing safety experience

The following adverse reactions have been identified during post-approval use of Feraheme. 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 serious adverse reactions have been reported from the post-marketing spontaneous reports with Feraheme: life-threatening anaphylactic-type reactions, cardiac/cardiorespiratory arrest, clinically significant hypotension, syncope, unresponsiveness, loss of consciousness, tachycardia/rhythm abnormalities, angioedema, ischemic myocardial events, congestive heart failure, pulse absent, and cyanosis. These adverse reactions have occurred up to 30 minutes after the administration of Feraheme injection. Reactions have occurred following the first dose or subsequent doses of Feraheme.