Ferrlecit® is used to replete the total body content of iron. Iron is critical for normal hemoglobin synthesis to maintain oxygen transport. Additionally, iron is necessary for metabolism and synthesis of DNA and various enzymatic processes.
The total body iron content of an adult ranges from 2 to 4 grams. Approximately 2/3 is in hemoglobin and 1/3 in reticuloendothelial storage (bone marrow, spleen, liver) and ferritin. The body highly conserves iron (daily loss of 0.03%) requiring supplementation of about 1 mg/day to replenish losses in healthy, non-menstruating adults. The etiology of iron deficiency in hemodialysis patients is varied and can include increased iron utilization (e.g., from erythropoietin therapy), blood loss (e.g., from fistula, retention in dialyzer, hematologic testing, menses), decreased dietary intake or absorption, surgery, iron sequestration due to inflammatory process, and malignancy. The administration of exogenous erythropoietin increases red blood cell production and iron utilization. The increased iron utilization and blood losses in the hemodialysis patient may lead to absolute or functional iron deficiency. Iron deficiency is absolute when hematologic indicators of iron stores are low. Patients with functional iron deficiency do not meet laboratory criteria for absolute iron deficiency but demonstrate an increase in hemoglobin/ hematocrit or a decrease in erythropoietin dosage with stable hemoglobin /hematocrit when parenteral iron is administered.
Study A was a three-center, randomized, open-label study of the safety and efficacy of two doses of Ferrlecit® administered intravenously to iron-deficient hemodialysis patients. The study included both a dose-response concurrent control and an historical control. Enrolled patients received a test dose of Ferrlecit® (25 mg of elemental iron) and were then randomly assigned to receive Ferrlecit® at cumulative doses of either 500mg (low dose) or 1000mg (high dose) of elemental iron. Ferrlecit® was given to both dose groups in eight divided doses during sequential dialysis sessions (a period of 16 to 17 days). At each dialysis session, patients in the low-dose group received Ferrlecit® 62.5 mg of elemental iron over 30 minutes, and those in the high-dose group received Ferrlecit® 125mg of elemental iron over 60 minutes. The primary endpoint was the change in hemoglobin from baseline to the last available observation through Day 40.
Eligibility for this study included chronic hemodialysis patients with a hemoglobin below 10 g/dl (or hematocrit at or below 30%) and either serum ferritin below 200 ng/ml or iron saturation below 18%. Exclusion criteria included significant underlying disease or inflammatory conditions or an erythropoietin (EPO) requirement of greater than 10,000 units three times per week. Parenteral iron and red cell transfusion were not allowed for two months before the study. Oral iron and red cell transfusion were not allowed during the study for Ferrlecit®-treated patients.
The historical control population consisted of 25 chronic hemodialysis patients who received only oral iron supplementation for 14 months and did not receive red cell transfusion. All patients had stable EPO doses and hematocrit values for at least two months before initiation of oral iron therapy.
The evaluated population consisted of 39 patients in the low-dose Ferrlecit® group, 44 patients in the high-dose Ferrlecit® group, and 25 historical control patients.
The mean baseline hemoglobin and hematocrit were similar between treatment and historical control patients: 9.8 g/dl and 29% and 9.6 g/dl and 29% in low- and high-dose Ferrlecit® treated patients, respectively, and 9.4 g/dl and 29% in historical control patients. Baseline serum iron saturation was 20% in the low-dose group, 16% in the high-dose group, and 14% in the historical control. Baseline serum ferritin was 106 ng/ml in the low-dose group, 88 ng/ml in the high-dose group, and 606 ng/ml in the historical control. Patients in the high-dose Ferrlecit® group achieved significantly higher increases in hemoglobin and hematocrit than either patients in the low-dose Ferrlecit® group or patients in the historical control group (oral iron). Patients in the low-dose Ferrlecit® group did not achieve significantly higher increases in hemoglobin and hematocrit than patients receiving oral iron.
Side effects include flushing and hypotension, and hypersensitivity.