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 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 is in reticuloendothelial (RE) storage (bone marrow, spleen, liver) bound to intracellular 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 blood loss and/or increased iron utilization (e.g., from epoetin therapy). The administration of exogenous epoetin 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 hematological 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 epoetin dosage with stable hemoglobin/ hematocrit when parenteral iron is administered.

Pharmacokinetics

Multiple sequential single dose intravenous pharmacokinetic studies were performed on 14 healthy iron-deficient volunteers. Entry criteria included hemoglobin ≥ 10.5 gm/dL and transferrin saturation ≤ 15% (TSAT) or serum ferritin value ≤ 20 ng/mL. In the first stage, each subject was randomized 1:1 to undiluted Ferrlecit® injection of either 125 mg/hr or 62.5 mg/0.5 hr (2.1 mg/min). Five days after the first stage, each subject was re-randomized 1:1 to undiluted Ferrlecit® injection of either 125 mg/7 min or 62.5 mg/4 min ( > 15.5 mg/min).

Peak drug levels (Cmax) varied significantly by dosage and by rate of administration with the highest Cmax observed in the regimen in which 125 mg was administered in 7 minutes (19.0 mg/L). The initial volume of distribution (V_Ferr) of 6 L corresponds well to calculated blood volume. V_Ferr did not vary by dosage or rate of administration. The terminal elimination half-life (λ_z-HL) for drug bound iron was approximately 1 hour. λ_z-HL varied by dose but not by rate of administration. The shortest value (0.85 h) occurred in the 62.5 mg/4 min regimen; the longest value (1.45 h) occurred in the 125 mg/7 min regimen. Total clearance of Ferrlecit® was 3.02 to 5.35 L/h. There was no significant variation by rate of administration. The AUC for Ferrlecit® bound iron varied by dose from 17.5 mg-h/L (62.5 mg) to 35.6 mg-h/L (125 mg). There was no significant variation by rate of administration. Approximately 80% of drug bound iron was delivered to transferrin as a mononuclear ionic iron species within 24 hours of administration in each dosage regimen. Direct movement of iron from Ferrlecit® to transferrin was not observed. Mean peak transferrin saturation did not exceed 100% and returned to near baseline by 40 hours after administration of each dosage regimen.

Pediatrics: Single dose intravenous pharmacokinetic analyses were performed on 48 iron-deficient pediatric hemodialysis patients. Twenty-two patients received 1.5 mg/kg Ferrlecit® and 26 patients received 3.0 mg/kg Ferrlecit® (maximum dose 125 mg). The mean Cmax, AUC_0-∞, and terminal elimination half-life values for the 22 patients who received a 1.5 mg/kg dose were 12.9 mg/L, 95.0 mg•hr/L,and 2.0 hours, respectively. The mean Cmax, AUC_0-∞, and terminal elimination half-life values for the 26 patients who received a 3.0 mg/kg dose were 22.8 mg/L, 170.9 mg•hr/L, and 2.5 hours, respectively.

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