Ferrlecit Information
Ferrlecit (Sodium) Indications And Usage
Ferrlecit (Sodium) is indicated for the treatment of iron deficiency anemia in adult patients and in pediatric patients age 6 years and older with chronic kidney disease receiving hemodialysis who are receiving supplemental epoetin therapy.
Ferrlecit (Sodium) Dosage And Administration
The dosage of Ferrlecit (Sodium) is expressed in terms of mg of elemental iron. Each 5 mL sterile, single-use ampule or vial contains 62.5 mg of elemental iron (12.5 mg/mL).
Do not mix Ferrlecit (Sodium) with other medications, or add to parenteral nutrition solutions for intravenous infusion. The compatibility of Ferrlecit (Sodium) with intravenous infusion vehicles other than 0.9% sodium chloride has not been evaluated. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever the solution and container permit. If diluted, use immediately.
Ferrlecit (Sodium) treatment may be repeated if iron deficiency reoccurs.
Ferrlecit (Sodium) Dosage Forms And Strengths
Ferrlecit (Sodium) is available as a single use ampule or vial, containing 62.5 mg of elemental iron in 5 mL volume.
Ferrlecit (Sodium) Warnings And Precautions
In the single-dose, post-marketing, safety study one patient experienced a life-threatening hypersensitivity reaction (diaphoresis, nausea, vomiting, severe lower back pain, dyspnea, and wheezing for 20 minutes) following Ferrlecit (Sodium) administration. Among 1,097 patients who received Ferrlecit (Sodium) in this study, there were 9 patients (0.8%) who had an adverse reaction that, in the view of the investigator, precluded further Ferrlecit (Sodium) administration. These included one life-threatening reaction, six allergic reactions (pruritus x2, facial flushing, chills, dyspnea/chest pain, and rash), and two other reactions (hypotension and nausea). Another 2 patients experienced (0.2%) allergic reactions not deemed to represent drug intolerance (nausea/malaise and nausea/dizziness) following Ferrlecit (Sodium) administration.
Ferrlecit (Sodium) contains benzyl alcohol as a preservative. Benzyl alcohol has been associated with serious adverse events and death in pediatric patients. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low-birth weight infants may be more likely to develop toxicity
Ferrlecit (Sodium) Adverse Reactions
The following serious adverse reactions are discussed in greater detail in other sections of the labeling:
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
The most commonly reported adverse reactions (≥10%) in adult patients were nausea, vomiting and/or diarrhea, injection site reaction, hypotension, cramps, hypertension, dizziness, abnormal erythrocytes (e.g., changes in morphology, color, or number of red blood cells), dyspnea, chest pain, leg cramps and pain. In patients 6 to 15 years of age the most common adverse reactions (≥10%) were hypotension, headache, hypertension, tachycardia and vomiting.
In the single-dose, postmarketing safety study, 11% of patients who received Ferrlecit (Sodium) and 9.4% of patients who received placebo reported adverse reactions. The most frequent adverse reactions following Ferrlecit (Sodium) were: hypotension (2%), nausea, vomiting and/or diarrhea (2%), pain (0.7%), hypertension (0.6%), allergic reaction (0.5%), chest pain (0.5%), pruritus (0.5%), and back pain (0.4%). The following additional events were reported in two or more patients: hypertonia, nervousness, dry mouth, and hemorrhage.
In the multiple-dose, open-label surveillance study, 28% of the patients received concomitant angiotensin converting enzyme inhibitor (ACEi) therapy. The incidences of both drug intolerance or suspected allergic events following first dose Ferrlecit (Sodium) administration were 1.6% in patients with concomitant ACEi use compared to 0.7% in patients without concomitant ACEi use. The patient with a life-threatening event was not on ACEi therapy. One patient had facial flushing immediately on Ferrlecit (Sodium) exposure. No hypotension occurred and the event resolved rapidly and spontaneously without intervention other than drug withdrawal.
The following additional adverse reactions have been identified with the use of Ferrlecit (Sodium) from postmarketing spontaneous reports: anaphylactic-type reactions, shock, loss of consciousness, convulsion, skin discoloration, pallor, phlebitis, dysgeusia, and hypoesthesia.
Individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events based on information from postmarketing spontaneous reports. These adverse events included hypotension, nausea, vomiting, abdominal pain, diarrhea, dizziness, dyspnea, urticaria, chest pain, paresthesia, and peripheral swelling.
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.
Ferrlecit (Sodium) Drug Interactions
Drug-drug interactions involving Ferrlecit (Sodium) have not been studied. Ferrlecit (Sodium) may reduce the absorption of concomitantly administered oral iron preparations.
Ferrlecit (Sodium) Overdosage
The Ferrlecit (Sodium) iron complex is not dialyzable.
No data is available regarding overdose of Ferrlecit (Sodium) in humans. Excessive dosages of Ferrlecit (Sodium) may lead to accumulation of iron in storage sites potentially leading to hemosiderosis. Do not administer Ferrlecit (Sodium) to patients with iron overload [see ].
Individual doses exceeding 125 mg may be associated with a higher incidence and/or severity of adverse events [see ].
Ferrlecit (Sodium) at elemental iron doses of 125 mg/kg, 78.8 mg/kg, 62.5 mg/kg and 250 mg/kg caused deaths in mice, rats, rabbits, and dogs respectively. The major symptoms of acute toxicity were decreased activity, staggering, ataxia, increases in the respiratory rate, tremor, and convulsions.
Ferrlecit (Sodium) Description
Ferrlecit (Sodium) (sodium ferric gluconate complex in sucrose injection), an iron replacement product, is a stable macromolecular complex with an apparent molecular weight on gel chromatography of 289,000 – 440,000 daltons. The macromolecular complex is negatively charged at alkaline pH and is present in solution with sodium cations. The product has a deep red color indicative of ferric oxide linkages. The chemical name is D-Gluconic acid, iron (3+) sodium salt.
The structural formula is considered to be [NaFeO(CHO)(CH0)5]
Each sterile, single-use ampule or vial of 5 mL of Ferrlecit (Sodium) for intravenous injection contains 62.5 mg (12.5 mg/mL) of elemental iron as the sodium salt of a ferric ion carbohydrate complex in an alkaline aqueous solution with approximately 20% sucrose w/v (195 mg/mL) in water for injection, pH 7.7 – 9.7.
Each mL contains 9 mg of benzyl alcohol as an inactive ingredient.
Ferrlecit (Sodium) Clinical Pharmacology
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 (Sodium) 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 (Sodium) injection of either 125 mg/7 min or 62.5 mg/4 min (>15.5 mg/min).
Peak drug levels (C) varied significantly by dosage and by rate of administration with the highest C observed in the regimen in which 125 mg was administered in 7 minutes (19.0 mg/L). The terminal elimination half-life for drug bound iron was approximately 1 hour. Half-life varied by dose but not by rate of administration. Half-life values were 0.85 and 1.45 hours for the 62.5 mg/4 min and 125 mg/7 min regimens, respectively. Total clearance of Ferrlecit (Sodium) was 3.02 to 5.35 L/h. The AUC for Ferrlecit (Sodium) bound iron varied by dose from 17.5 mg-h/L (62.5 mg) to 35.6 mg-h/L (125 mg). 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 (Sodium) to transferrin was not observed. Mean peak transferrin saturation returned to near baseline by 40 hours after administration of each dosage regimen.
Ferrlecit (Sodium) Clinical Studies
Two clinical studies (Studies A and B) were conducted in adults and one clinical study was conducted in pediatric patients (Study C) to assess the efficacy and safety of Ferrlecit (Sodium) .
Study A
Study A was a three-center, randomized, open-label study of the safety and efficacy of two doses of Ferrlecit (Sodium) 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 (Sodium) (25 mg of elemental iron) and were then randomly assigned to receive Ferrlecit (Sodium) at cumulative doses of either 500 mg (low dose) or 1000 mg (high dose) of elemental iron. Ferrlecit (Sodium) 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 (Sodium) 62.5 mg of elemental iron over 30 minutes, and those in the high-dose group received Ferrlecit (Sodium) 125 mg 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 32%) and either serum ferritin below 100 ng/mL or transferrin saturation below 18%. Exclusion criteria included significant underlying disease or inflammatory conditions or an epoetin 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 (Sodium) -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 epoetin 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 (Sodium) (sodium ferric gluconate complex in sucrose injection) group (50% female, 50% male; 74% white, 18% black, 5% Hispanic, 3% Asian; mean age 54 years, range 22–83 years), 44 patients in the high-dose Ferrlecit (Sodium) group (50% female, 48% male, 2% unknown; 75% white, 11% black, 5% Hispanic, 7% other, 2% unknown; mean age 56 years, range 20–87 years), and 25 historical control patients (68% female, 32% male; 40% white, 32% black, 20% Hispanic, 4% Asian, 4% unknown; mean age 52 years, range 25–84 years).
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 (Sodium) -treated patients, respectively, and 9.4 g/dL and 29% in historical control patients. Baseline serum transferrin 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 (Sodium) group achieved significantly higher increases in hemoglobin and hematocrit than patients in the low-dose Ferrlecit (Sodium) group. See .
Study B
Study B was a single-center, non-randomized, open-label, historically-controlled, study of the safety and efficacy of variable, cumulative doses of intravenous Ferrlecit (Sodium) in iron-deficient hemodialysis patients. Ferrlecit (Sodium) administration was identical to Study A. The primary efficacy variable was the change in hemoglobin from baseline to the last available observation through Day 50.
Inclusion and exclusion criteria were identical to those of Study A as was the historical control population. Sixty-three patients were evaluated in this study: 38 in the Ferrlecit (Sodium) -treated group (37% female, 63% male; 95% white, 5% Asian; mean age 56 years, range 22– 84 years) and 25 in the historical control group (68% female, 32% male; 40% white, 32% black, 20% Hispanic, 4% Asian, 4% unknown; mean age 52 years, range 25–84 years).
Ferrlecit (Sodium) -treated patients were considered to have completed the study per protocol if they received at least eight Ferrlecit (Sodium) doses of either 62.5 mg or 125 mg of elemental iron. A total of 14 patients (37%) completed the study per protocol. Twelve (32%) Ferrlecit (Sodium) -treated patients received less than eight doses, and 12 (32%) patients had incomplete information on the sequence of dosing. Not all patients received Ferrlecit (Sodium) at consecutive dialysis sessions and many received oral iron during the study.
Baseline hemoglobin and hematocrit values were similar between the treatment and control groups, and were 9.1 g/dL and 27.3%, respectively, for Ferrlecit (Sodium) -treated patients. Serum iron studies were also similar between treatment and control groups, with the exception of serum ferritin, which was 606 ng/mL for historical control patients, compared to 77 ng/mL for Ferrlecit (Sodium) -treated patients.
In this patient population, only the Ferrlecit (Sodium) -treated group achieved increase in hemoglobin and hematocrit from baseline. See .
Study C
Study C was a multicenter, randomized, open-label study of the safety and efficacy of two Ferrlecit (Sodium) dose regimens (1.5 mg/kg or 3.0 mg/kg of elemental iron) administered intravenously to 66 iron-deficient (transferrin saturation
Ferrlecit (Sodium) at a dose of 1.5 mg/kg or 3.0 mg/kg (up to a maximum dose of 125 mg of elemental iron) in 25 mL 0.9% sodium chloride was infused intravenously over 1 hour during each hemodialysis session for eight sequential dialysis sessions. Thirty-two patients received the 1.5 mg/kg dosing regimen (47% male, 53% female; 66% Caucasian, 25% Hispanic, and 3% Black, Asian, or Other; mean age 12.3 years). Thirty-four patients received the 3.0 mg/kg dosing regimen (56% male, 44% female; 77% Caucasian, 12% Hispanic, 9% Black, and 3% Other; mean age 12.0 years).
The primary endpoint was the change in hemoglobin concentration from baseline to 2 weeks after last Ferrlecit (Sodium) administration. There was no significant difference between the treatment groups. Improvements in hematocrit, transferrin saturation, serum ferritin, and reticulocyte hemoglobin concentrations compared to baseline values were observed 2 weeks after the last Ferrlecit (Sodium) infusion in both the 1.5 mg/kg and 3.0 mg/kg treatment groups (Table 3).
The increased hemoglobin concentrations were maintained at 4 weeks after the last Ferrlecit (Sodium) infusion in both the 1.5 mg/kg and the 3.0 mg/kg Ferrlecit (Sodium) dose treatment groups.
Ferrlecit (Sodium) How Supplied/storage And Handling
NDC 0024-2791-50 for ampules
NDC 0024-2792-10 for vials
Ferrlecit (Sodium) is supplied in colorless glass ampules or vials. Each sterile, single-use ampule or vial contains 62.5 mg of elemental iron in 5 mL for intravenous use, packaged in cartons of 10 ampules or 10 vials.
Ferrlecit (Sodium) Patient Counseling Information
Prior to Ferrlecit (Sodium) administration:
Advise patients that Ferrlecit (Sodium) may reduce the absorption of concomitantly administered oral iron preparations [see ].
Ferrlecit (Sodium)
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