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DRUGS & SUPPLEMENTS
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Vitaferro
What are the side effects you encounter while taking this medicine? |
Vitaferro uses
Vitaferro consists of Iron (Ferrous Chloride), Iron (Ferrous Sulfate).Iron (Ferrous Chloride):
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Vitaferro (Iron (Ferrous Chloride)) is indicated for the treatment of Vitaferro (Iron (Ferrous Chloride)) deficiency anemia in patients with chronic kidney disease (CKD).
Vitaferro (Iron (Ferrous Chloride)) is an Vitaferro (Iron (Ferrous Chloride)) replacement product indicated for the treatment of Vitaferro (Iron (Ferrous Chloride)) deficiency anemia in patients with chronic kidney disease (CKD). (1)
2 DOSAGE AND ADMINISTRATION
Vitaferro ) must only be administered intravenously either by slow injection or by infusion. The dosage of Vitaferro (Iron (Ferrous Chloride)) is expressed in mg of elemental Vitaferro (Iron (Ferrous Chloride)). Each mL contains 20 mg of elemental Vitaferro (Iron (Ferrous Chloride)).
| Population | Dose | |
| Adult patients | Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) | 100 mg slow intravenous injection or infusion |
| Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) | 200 mg slow intravenous injection or infusion | |
| Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) | 300 mg or 400 mg intravenous infusion | |
| Pediatric patients | HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) | 0.5 mg/kg slow intravenous injection or infusion |
2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)
Administer Vitaferro (Iron (Ferrous Chloride)) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. Vitaferro (Iron (Ferrous Chloride)) should be administered early during the dialysis session. The usual total treatment course of Vitaferro (Iron (Ferrous Chloride)) is 1000 mg. Vitaferro (Iron (Ferrous Chloride)) treatment may be repeated if Vitaferro (Iron (Ferrous Chloride)) deficiency reoccurs.
2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease
Administer Vitaferro (Iron (Ferrous Chloride)) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Vitaferro (Iron (Ferrous Chloride)), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Vitaferro (Iron (Ferrous Chloride)) treatment may be repeated if Vitaferro (Iron (Ferrous Chloride)) deficiency reoccurs.
2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease
Administer Vitaferro (Iron (Ferrous Chloride)) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Vitaferro (Iron (Ferrous Chloride)) in a maximum of 250 mL of 0.9% NaCl. Vitaferro (Iron (Ferrous Chloride)) treatment may be repeated if Vitaferro (Iron (Ferrous Chloride)) deficiency reoccurs.
2.4 Pediatric Patients with HDD-CKD for Vitaferro (Iron (Ferrous Chloride)) maintenance treatment
The dosing for Vitaferro (Iron (Ferrous Chloride)) replacement treatment in pediatric patients with HDD-CKD has not been established.
For Vitaferro (Iron (Ferrous Chloride)) maintenance treatment: Administer Vitaferro (Iron (Ferrous Chloride)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Vitaferro (Iron (Ferrous Chloride)) treatment may be repeated if necessary.
2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Vitaferro (Iron (Ferrous Chloride)) maintenance treatment
The dosing for Vitaferro (Iron (Ferrous Chloride)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For Vitaferro (Iron (Ferrous Chloride)) maintenance treatment: Administer Vitaferro (Iron (Ferrous Chloride)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Vitaferro (Iron (Ferrous Chloride)) treatment may be repeated if necessary.
3 DOSAGE FORMS AND STRENGTHS
- 10 mL single-use vial / 200 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL)
- 5 mL single-use vial / 100 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL)
- 2.5 mL single-use vial / 50 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL)
- 10 mL single-use vial / 200 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL) (3)
- 5 mL single-use vial / 100 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL) (3)
- 2.5 mL single-use vial / 50 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL) (3)
4 CONTRAINDICATIONS
- Known hypersensitivity to Vitaferro (Iron (Ferrous Chloride))
- Known hypersensitivity to Vitaferro (Iron (Ferrous Chloride)) (4)
5 WARNINGS AND PRECAUTIONS
- Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Vitaferro ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Vitaferro (Iron (Ferrous Chloride)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
- Hypotension: Vitaferro (Iron (Ferrous Chloride)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Vitaferro (Iron (Ferrous Chloride)). (5.2)
- Vitaferro (Iron (Ferrous Chloride)) Overload: Regularly monitor hematologic responses during Vitaferro (Iron (Ferrous Chloride)) therapy. Do not administer Vitaferro (Iron (Ferrous Chloride)) to patients with Vitaferro (Iron (Ferrous Chloride)) overload. (5.3)
5.1 Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Vitaferro (Iron (Ferrous Chloride)). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Vitaferro (Iron (Ferrous Chloride)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Vitaferro (Iron (Ferrous Chloride)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Vitaferro (Iron (Ferrous Chloride)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Vitaferro (Iron (Ferrous Chloride)) preparations occur within 30 minutes of the completion of the infusion .
5.2 Hypotension
Vitaferro ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Vitaferro (Iron (Ferrous Chloride)). Hypotension following administration of Vitaferro (Iron (Ferrous Chloride)) may be related to the rate of administration and/or total dose administered .
5.3 Vitaferro (Iron (Ferrous Chloride)) Overload
Excessive therapy with parenteral Vitaferro (Iron (Ferrous Chloride)) can lead to excess storage of Vitaferro (Iron (Ferrous Chloride)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Vitaferro (Iron (Ferrous Chloride)) require periodic monitoring of hematologic and Vitaferro (Iron (Ferrous Chloride)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Vitaferro (Iron (Ferrous Chloride)) to patients with evidence of Vitaferro (Iron (Ferrous Chloride)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Vitaferro (Iron (Ferrous Chloride)) sucrose; do not perform serum Vitaferro (Iron (Ferrous Chloride)) measurements for at least 48 hours after intravenous dosing .
6 ADVERSE REACTIONS
The following serious adverse reactions associated with Vitaferro ) are described in other sections .
- The most common adverse reactions (≥2%) following the administration of Vitaferro (Iron (Ferrous Chloride)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Adverse Reactions in Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
Adverse Reactions in Adults Patients with CKD
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of Vitaferro ) has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Vitaferro (Iron (Ferrous Chloride)) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.
| * EPO=Erythropoietin | |||||
| Adverse Reactions (Preferred Term) | HDD-CKD | NDD-CKD | PDD-CKD | ||
| Vitaferro (Iron (Ferrous Chloride)) | Vitaferro (Iron (Ferrous Chloride)) | Oral Vitaferro (Iron (Ferrous Chloride)) | Vitaferro (Iron (Ferrous Chloride)) | EPO* Only | |
| (N=231) | (N=139) | (N=139) | (N=75) | (N=46) | |
| % | % | % | % | % | |
| Subjects with any adverse reaction | 78.8 | 76.3 | 73.4 | 72.0 | 65.2 |
| Ear and Labyrinth Disorders | |||||
| Ear Pain | 0 | 2.2 | 0.7 | 0 | 0 |
| Eye Disorders | |||||
| Conjunctivitis | 0.4 | 0 | 0 | 2.7 | 0 |
| Gastrointestinal Disorders | |||||
| Abdominal pain | 3.5 | 1.4 | 2.9 | 4.0 | 6.5 |
| Diarrhea | 5.2 | 7.2 | 10.1 | 8.0 | 4.3 |
| Dysgeusia | 0.9 | 7.9 | 0 | 0 | 0 |
| Nausea | 14.7 | 8.6 | 12.2 | 5.3 | 4.3 |
| Vomiting | 9.1 | 5.0 | 8.6 | 8.0 | 2.2 |
| General Disorders and | |||||
| Administration Site Conditions | |||||
| Asthenia | 2.2 | 0.7 | 2.2 | 2.7 | 0 |
| Chest pain | 6.1 | 1.4 | 0 | 2.7 | 0 |
| Feeling abnormal | 3.0 | 0 | 0 | 0 | 0 |
| Infusion site pain or burning | 0 | 5.8 | 0 | 0 | 0 |
| Injection site extravasation | 0 | 2.2 | 0 | 0 | 0 |
| Peripheral edema | 2.6 | 7.2 | 5.0 | 5.3 | 10.9 |
| Pyrexia | 3.0 | 0.7 | 0.7 | 1.3 | 0 |
| Infections and Infestations | |||||
| Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis | 2.6 | 2.2 | 4.3 | 16.0 | 4.3 |
| Injury, Poisoning and Procedural | |||||
| Complications | |||||
| Graft complication | 9.5 | 1.4 | 0 | 0 | 0 |
| Metabolism and Nutrition Disorders | |||||
| Fluid overload | 3.0 | 1.4 | 0.7 | 1.3 | 0 |
| Gout | 0 | 2.9 | 1.4 | 0 | 0 |
| Hyperglycemia | 0 | 2.9 | 0 | 0 | 2.2 |
| Hypoglycemia | 0.4 | 0.7 | 0.7 | 4.0 | 0 |
| Musculoskeletal and Connective | |||||
| Tissue Disorders | |||||
| Arthralgia | 3.5 | 1.4 | 2.2 | 4.0 | 4.3 |
| Back pain | 2.2 | 2.2 | 3.6 | 1.3 | 4.3 |
| Muscle cramp | 29.4 | 0.7 | 0.7 | 2.7 | 0 |
| Myalgia | 0 | 3.6 | 0 | 1.3 | 0 |
| Pain in extremity | 5.6 | 4.3 | 0 | 2.7 | 6.5 |
| Nervous System Disorders | |||||
| Dizziness | 6.5 | 6.5 | 1.4 | 1.3 | 4.3 |
| Headache | 12.6 | 2.9 | 0.7 | 4.0 | 0 |
| Respiratory, Thoracic and | |||||
| Mediastinal Disorders | |||||
| Cough | 3.0 | 2.2 | 0.7 | 1.3 | 0 |
| Dyspnea | 3.5 | 5.8 | 1.4 | 1.3 | 2.2 |
| Nasal congestion | 0 | 1.4 | 2.2 | 1.3 | 0 |
| Skin and Subcutaneous | |||||
| Tissue Disorders | |||||
| Pruritus | 3.9 | 2.2 | 4.3 | 2.7 | 0 |
| Vascular Disorders | |||||
| Hypertension | 6.5 | 6.5 | 4.3 | 8.0 | 6.5 |
| Hypotension | 39.4 | 2.2 | 0.7 | 2.7 | 2.2 |
One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous Vitaferro (Iron (Ferrous Chloride)) therapy and were reported to be intolerant (defined as precluding further use of that Vitaferro (Iron (Ferrous Chloride)) product). When these patients were treated with Vitaferro (Iron (Ferrous Chloride)) there were no occurrences of adverse reactions that precluded further use of Vitaferro (Iron (Ferrous Chloride)) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for Vitaferro (Iron (Ferrous Chloride)) maintenance treatment with Vitaferro (Iron (Ferrous Chloride)) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Vitaferro (Iron (Ferrous Chloride)) 0.5 mg/kg, 53% (25/47) of the patients receiving Vitaferro (Iron (Ferrous Chloride)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Vitaferro (Iron (Ferrous Chloride)) 2.0 mg/kg.
A total of 5 (11%) subjects in the Vitaferro (Iron (Ferrous Chloride)) 0.5 mg/kg group, 10 (21%) patients in the Vitaferro (Iron (Ferrous Chloride)) 1.0 mg/kg group, and 10 (21%) patients in the Vitaferro (Iron (Ferrous Chloride)) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).
6.2 Adverse Reactions from Post-Marketing Experience
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.
In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.
The following adverse reactions have been identified during post-approval use of Vitaferro (Iron (Ferrous Chloride)). 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: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.
Symptoms associated with Vitaferro (Iron (Ferrous Chloride)) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Vitaferro (Iron (Ferrous Chloride)) injection. Reactions have occurred following the first dose or subsequent doses of Vitaferro (Iron (Ferrous Chloride)). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.
7 DRUG INTERACTIONS
Drug interactions involving Vitaferro (Iron (Ferrous Chloride)) have not been studied. However, Vitaferro (Iron (Ferrous Chloride)) may reduce the absorption of concomitantly administered oral Vitaferro (Iron (Ferrous Chloride)) preparations.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Vitaferro ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Vitaferro (Iron (Ferrous Chloride)) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Vitaferro (Iron (Ferrous Chloride)) sucrose. Because animal reproductive studies are not always predictive of human response, Vitaferro (Iron (Ferrous Chloride)) should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether Vitaferro (Iron (Ferrous Chloride)) sucrose is excreted in human milk. Vitaferro (Iron (Ferrous Chloride)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Vitaferro (Iron (Ferrous Chloride)) is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of Vitaferro ) for Vitaferro (Iron (Ferrous Chloride)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of Vitaferro (Iron (Ferrous Chloride)) for Vitaferro (Iron (Ferrous Chloride)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Vitaferro (Iron (Ferrous Chloride)) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]
Vitaferro (Iron (Ferrous Chloride)) has not been studied in patients younger than 2 years of age.
In a country where Vitaferro (Iron (Ferrous Chloride)) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Vitaferro (Iron (Ferrous Chloride)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Vitaferro (Iron (Ferrous Chloride)) or any other drugs could be established.
8.5 Geriatric Use
Clinical studies of Vitaferro (Iron (Ferrous Chloride)) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Vitaferro (Iron (Ferrous Chloride)), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
No data are available regarding overdosage of Vitaferro (Iron (Ferrous Chloride)) in humans. Excessive dosages of Vitaferro (Iron (Ferrous Chloride)) may lead to accumulation of Vitaferro (Iron (Ferrous Chloride)) in storage sites potentially leading to hemosiderosis. Do not administer Vitaferro (Iron (Ferrous Chloride)) to patients with Vitaferro (Iron (Ferrous Chloride)) overload.
Toxicities in single-dose studies in mice and rats, at intravenous Vitaferro (Iron (Ferrous Chloride)) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.
11 DESCRIPTION
Vitaferro (Iron (Ferrous Chloride)) (iron sucrose injection, USP), an Vitaferro (Iron (Ferrous Chloride)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Vitaferro (Iron (Ferrous Chloride)) (III)-hydroxide in sucrose for intravenous use. Vitaferro (Iron (Ferrous Chloride)) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:
[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)
where: n is the degree of Vitaferro (Iron (Ferrous Chloride)) polymerization and m is the number of sucrose molecules associated with the Vitaferro (Iron (Ferrous Chloride)) (III)-hydroxide.
Each mL contains 20 mg elemental Vitaferro (Iron (Ferrous Chloride)) as Vitaferro (Iron (Ferrous Chloride)) sucrose in water for injection. Vitaferro (Iron (Ferrous Chloride)) is available in 10 mL single-use vials (200 mg elemental Vitaferro (Iron (Ferrous Chloride)) per 10 mL), 5 mL single-use vials (100 mg elemental Vitaferro (Iron (Ferrous Chloride)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Vitaferro (Iron (Ferrous Chloride)) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Vitaferro ) is an aqueous complex of poly-nuclear Vitaferro (Iron (Ferrous Chloride)) (III)-hydroxide in sucrose. Following intravenous administration, Vitaferro (Iron (Ferrous Chloride)) is dissociated into Vitaferro (Iron (Ferrous Chloride)) and sucrose and the Vitaferro (Iron (Ferrous Chloride)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Vitaferro (Iron (Ferrous Chloride)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
12.2 Pharmacodynamics
Following intravenous administration, Vitaferro (Iron (Ferrous Chloride)) is dissociated into Vitaferro (Iron (Ferrous Chloride)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Vitaferro (Iron (Ferrous Chloride)) sucrose containing 100 mg of Vitaferro (Iron (Ferrous Chloride)), three times weekly for three weeks, significant increases in serum Vitaferro (Iron (Ferrous Chloride)) and serum ferritin and significant decreases in total Vitaferro (Iron (Ferrous Chloride)) binding capacity occurred four weeks from the initiation of Vitaferro (Iron (Ferrous Chloride)) sucrose treatment.
12.3 Pharmacokinetics
In healthy adults administered intravenous doses of Vitaferro ), its Vitaferro (Iron (Ferrous Chloride)) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Vitaferro (Iron (Ferrous Chloride)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Vitaferro (Iron (Ferrous Chloride)) containing 100 mg of Vitaferro (Iron (Ferrous Chloride)) labeled with 52Fe/59Fe in patients with Vitaferro (Iron (Ferrous Chloride)) deficiency showed that a significant amount of the administered Vitaferro (Iron (Ferrous Chloride)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Vitaferro (Iron (Ferrous Chloride)) trapping compartment.
Following intravenous administration of Vitaferro (Iron (Ferrous Chloride)), Vitaferro (Iron (Ferrous Chloride)) sucrose is dissociated into Vitaferro (Iron (Ferrous Chloride)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Vitaferro (Iron (Ferrous Chloride)) containing 1,510 mg of sucrose and 100 mg of Vitaferro (Iron (Ferrous Chloride)) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Vitaferro (Iron (Ferrous Chloride)) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Vitaferro (Iron (Ferrous Chloride)) sucrose containing 500 to 700 mg of Vitaferro (Iron (Ferrous Chloride)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Vitaferro (Iron (Ferrous Chloride)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Vitaferro (Iron (Ferrous Chloride)) have not been studied.
Pharmacokinetics in Pediatric Patients
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of Vitaferro (Iron (Ferrous Chloride)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Vitaferro (Iron (Ferrous Chloride)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Vitaferro (Iron (Ferrous Chloride)), the half-life of total serum Vitaferro (Iron (Ferrous Chloride)) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.
Vitaferro (Iron (Ferrous Chloride)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Vitaferro (Iron (Ferrous Chloride)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with Vitaferro (Iron (Ferrous Chloride)) sucrose.
Vitaferro (Iron (Ferrous Chloride)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Vitaferro (Iron (Ferrous Chloride)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
Vitaferro (Iron (Ferrous Chloride)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Vitaferro (Iron (Ferrous Chloride)) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.
14 CLINICAL STUDIES
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Vitaferro ).
14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Vitaferro (Iron (Ferrous Chloride)) treatment and 24 in the historical control group) with Vitaferro (Iron (Ferrous Chloride)) deficiency anemia. Eligibility criteria for Vitaferro (Iron (Ferrous Chloride)) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.
Vitaferro (Iron (Ferrous Chloride)) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Vitaferro (Iron (Ferrous Chloride)), who were off intravenous Vitaferro (Iron (Ferrous Chloride)) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.
Patients in the Vitaferro (Iron (Ferrous Chloride)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
| **p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates. | ||||||
| Efficacy parameters | End of treatment | 2 week follow-up | 5 week follow-up | |||
| Vitaferro (Iron (Ferrous Chloride)) (n=69 | Historical Control (n=18) | Vitaferro (Iron (Ferrous Chloride)) (n=73) | Historical Control (n=18) | Vitaferro (Iron (Ferrous Chloride)) (n=71) | Historical Control (n=15) | |
| Hemoglobin (g/dL) | 1.0 ± 0.12** | 0.0 ± 0.21 | 1.3 ± 0.14** | -0.6 ± 0.24 | 1.2 ± 0.17* | -0.1 ± 0.23 |
| Hematocrit (%) | 3.1 ± 0.37** | -0.3 ± 0.65 | 3.6 ± 0.44** | -1.2 ± 0.76 | 3.3 ± 0.54 | 0.2 ± 0.86 |
Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).
14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease
Study B was a multicenter, open label study of Vitaferro (Iron (Ferrous Chloride)) in 23 patients with Vitaferro (Iron (Ferrous Chloride)) deficiency and HDD-CKD who had been discontinued from Vitaferro (Iron (Ferrous Chloride)) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.
All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.
14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease
Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Vitaferro (Iron (Ferrous Chloride)). Exclusion criteria were similar to those in studies A and B. Vitaferro (Iron (Ferrous Chloride)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Vitaferro (Iron (Ferrous Chloride)) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.
The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.
14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Vitaferro (Iron (Ferrous Chloride)) versus Vitaferro (Iron (Ferrous Chloride)) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Vitaferro (Iron (Ferrous Chloride)) (325 mg ferrous sulfate three times daily for 56 days); or Vitaferro (Iron (Ferrous Chloride)) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Vitaferro (Iron (Ferrous Chloride)) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Vitaferro (Iron (Ferrous Chloride)) group.
A statistically significantly greater proportion of Vitaferro (Iron (Ferrous Chloride)) subjects (35/79; 44.3%) compared to oral Vitaferro (Iron (Ferrous Chloride)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Vitaferro (Iron (Ferrous Chloride)) to patients with PDD-CKD receiving an erythropoietin alone without Vitaferro (Iron (Ferrous Chloride)) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Vitaferro (Iron (Ferrous Chloride)) or Vitaferro (Iron (Ferrous Chloride)) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Vitaferro (Iron (Ferrous Chloride)) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.
Patients in the Vitaferro (Iron (Ferrous Chloride)) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Vitaferro (Iron (Ferrous Chloride)) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).
14.6 Study F: Vitaferro ) Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease
Study F was a randomized, open-label, dose-ranging study for Vitaferro (Iron (Ferrous Chloride)) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Vitaferro (Iron (Ferrous Chloride)) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Vitaferro (Iron (Ferrous Chloride)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Vitaferro (Iron (Ferrous Chloride)) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Vitaferro (Iron (Ferrous Chloride)) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
16 HOW SUPPLIED/storage and handling
16.1 How Supplied
Vitaferro ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Vitaferro (Iron (Ferrous Chloride)), each 5 mL vial contains 100 mg elemental Vitaferro (Iron (Ferrous Chloride)), and each 2.5 mL vial contains 50 mg elemental Vitaferro (Iron (Ferrous Chloride)) (20 mg/mL).
| NDC-0517-2310-05 | 200 mg/10 mL Single-Use Vial | Packages of 5 |
| NDC-0517-2310-10 | 200 mg/10 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-01 | 100 mg/5 mL Single-Use Vial | Individually Boxed |
| NDC-0517-2340-10 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-25 | 100 mg/5 mL Single-Use Vial | Packages of 25 |
| NDC-0517-2340-99 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-10 | 50 mg/2.5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-25 | 50 mg/2.5 mL Single-Use Vial | Packages of 25 |
16.2 Stability and Storage
Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.
Syringe Stability: Vitaferro (Iron (Ferrous Chloride)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Vitaferro (Iron (Ferrous Chloride)) per mL, or undiluted (20 mg elemental Vitaferro (Iron (Ferrous Chloride)) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).
Intravenous Admixture Stability: Vitaferro (Iron (Ferrous Chloride)), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Vitaferro (Iron (Ferrous Chloride)) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).
Do not dilute to concentrations below 1 mg/mL.
Do not mix Vitaferro (Iron (Ferrous Chloride)) with other medications or add to parenteral nutrition solutions for intravenous infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.
17 PATIENT COUNSELING INFORMATION
Prior to Vitaferro (Iron (Ferrous Chloride)) administration:
- Question patients regarding any prior history of reactions to parenteral Vitaferro (Iron (Ferrous Chloride)) products
- Advise patients of the risks associated with Vitaferro (Iron (Ferrous Chloride))
- Advise patients to report any symptoms of hypersensitivity that may develop during and following Vitaferro (Iron (Ferrous Chloride)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
Vitaferro (Iron (Ferrous Chloride)) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
PREMIERProRx®
IN2340
MG #15727
Iron (Ferrous Sulfate):
- Indications and usage
- Dosage and administration
- Dosage forms and strengths
- Contraindications
- Warnings and precautions
- Adverse reactions
- Drug interactions
- Use in specific populations
- Overdosage
- Description
- Clinical pharmacology
- Nonclinical toxicology
- Clinical studies
- How supplied/storage and handling
- Patient counseling information
1 INDICATIONS AND USAGE
Vitaferro (Iron (Ferrous Sulfate)) is indicated for the treatment of Vitaferro (Iron (Ferrous Sulfate)) deficiency anemia in patients with chronic kidney disease (CKD).
Vitaferro (Iron (Ferrous Sulfate)) is an Vitaferro (Iron (Ferrous Sulfate)) replacement product indicated for the treatment of Vitaferro (Iron (Ferrous Sulfate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)
2 DOSAGE AND ADMINISTRATION
Vitaferro ) must only be administered intravenously either by slow injection or by infusion. The dosage of Vitaferro (Iron (Ferrous Sulfate)) is expressed in mg of elemental Vitaferro (Iron (Ferrous Sulfate)). Each mL contains 20 mg of elemental Vitaferro (Iron (Ferrous Sulfate)).
| Population | Dose | |
| Adult patients | Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1) | 100 mg slow intravenous injection or infusion |
| Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2) | 200 mg slow intravenous injection or infusion | |
| Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3) | 300 mg or 400 mg intravenous infusion | |
| Pediatric patients | HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5) | 0.5 mg/kg slow intravenous injection or infusion |
2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)
Administer Vitaferro (Iron (Ferrous Sulfate)) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. Vitaferro (Iron (Ferrous Sulfate)) should be administered early during the dialysis session. The usual total treatment course of Vitaferro (Iron (Ferrous Sulfate)) is 1000 mg. Vitaferro (Iron (Ferrous Sulfate)) treatment may be repeated if Vitaferro (Iron (Ferrous Sulfate)) deficiency reoccurs.
2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease
Administer Vitaferro (Iron (Ferrous Sulfate)) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Vitaferro (Iron (Ferrous Sulfate)), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Vitaferro (Iron (Ferrous Sulfate)) treatment may be repeated if Vitaferro (Iron (Ferrous Sulfate)) deficiency reoccurs.
2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease
Administer Vitaferro (Iron (Ferrous Sulfate)) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Vitaferro (Iron (Ferrous Sulfate)) in a maximum of 250 mL of 0.9% NaCl. Vitaferro (Iron (Ferrous Sulfate)) treatment may be repeated if Vitaferro (Iron (Ferrous Sulfate)) deficiency reoccurs.
2.4 Pediatric Patients with HDD-CKD for Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment
The dosing for Vitaferro (Iron (Ferrous Sulfate)) replacement treatment in pediatric patients with HDD-CKD has not been established.
For Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment: Administer Vitaferro (Iron (Ferrous Sulfate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Vitaferro (Iron (Ferrous Sulfate)) treatment may be repeated if necessary.
2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment
The dosing for Vitaferro (Iron (Ferrous Sulfate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.
For Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment: Administer Vitaferro (Iron (Ferrous Sulfate)) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Vitaferro (Iron (Ferrous Sulfate)) treatment may be repeated if necessary.
3 DOSAGE FORMS AND STRENGTHS
- 10 mL single-use vial / 200 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL)
- 5 mL single-use vial / 100 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL)
- 2.5 mL single-use vial / 50 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL)
- 10 mL single-use vial / 200 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL) (3)
- 5 mL single-use vial / 100 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL) (3)
- 2.5 mL single-use vial / 50 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL) (3)
4 CONTRAINDICATIONS
- Known hypersensitivity to Vitaferro (Iron (Ferrous Sulfate))
- Known hypersensitivity to Vitaferro (Iron (Ferrous Sulfate)) (4)
5 WARNINGS AND PRECAUTIONS
- Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Vitaferro ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Vitaferro (Iron (Ferrous Sulfate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
- Hypotension: Vitaferro (Iron (Ferrous Sulfate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Vitaferro (Iron (Ferrous Sulfate)). (5.2)
- Vitaferro (Iron (Ferrous Sulfate)) Overload: Regularly monitor hematologic responses during Vitaferro (Iron (Ferrous Sulfate)) therapy. Do not administer Vitaferro (Iron (Ferrous Sulfate)) to patients with Vitaferro (Iron (Ferrous Sulfate)) overload. (5.3)
5.1 Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Vitaferro (Iron (Ferrous Sulfate)). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Vitaferro (Iron (Ferrous Sulfate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Vitaferro (Iron (Ferrous Sulfate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Vitaferro (Iron (Ferrous Sulfate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Vitaferro (Iron (Ferrous Sulfate)) preparations occur within 30 minutes of the completion of the infusion .
5.2 Hypotension
Vitaferro ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Vitaferro (Iron (Ferrous Sulfate)). Hypotension following administration of Vitaferro (Iron (Ferrous Sulfate)) may be related to the rate of administration and/or total dose administered .
5.3 Vitaferro (Iron (Ferrous Sulfate)) Overload
Excessive therapy with parenteral Vitaferro (Iron (Ferrous Sulfate)) can lead to excess storage of Vitaferro (Iron (Ferrous Sulfate)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Vitaferro (Iron (Ferrous Sulfate)) require periodic monitoring of hematologic and Vitaferro (Iron (Ferrous Sulfate)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Vitaferro (Iron (Ferrous Sulfate)) to patients with evidence of Vitaferro (Iron (Ferrous Sulfate)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Vitaferro (Iron (Ferrous Sulfate)) sucrose; do not perform serum Vitaferro (Iron (Ferrous Sulfate)) measurements for at least 48 hours after intravenous dosing .
6 ADVERSE REACTIONS
The following serious adverse reactions associated with Vitaferro ) are described in other sections .
- The most common adverse reactions (≥2%) following the administration of Vitaferro (Iron (Ferrous Sulfate)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Adverse Reactions in Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.
Adverse Reactions in Adults Patients with CKD
Adverse Reactions in Adult Patients with CKD
The frequency of adverse reactions associated with the use of Vitaferro ) has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Vitaferro (Iron (Ferrous Sulfate)) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.
| * EPO=Erythropoietin | |||||
| Adverse Reactions (Preferred Term) | HDD-CKD | NDD-CKD | PDD-CKD | ||
| Vitaferro (Iron (Ferrous Sulfate)) | Vitaferro (Iron (Ferrous Sulfate)) | Oral Vitaferro (Iron (Ferrous Sulfate)) | Vitaferro (Iron (Ferrous Sulfate)) | EPO* Only | |
| (N=231) | (N=139) | (N=139) | (N=75) | (N=46) | |
| % | % | % | % | % | |
| Subjects with any adverse reaction | 78.8 | 76.3 | 73.4 | 72.0 | 65.2 |
| Ear and Labyrinth Disorders | |||||
| Ear Pain | 0 | 2.2 | 0.7 | 0 | 0 |
| Eye Disorders | |||||
| Conjunctivitis | 0.4 | 0 | 0 | 2.7 | 0 |
| Gastrointestinal Disorders | |||||
| Abdominal pain | 3.5 | 1.4 | 2.9 | 4.0 | 6.5 |
| Diarrhea | 5.2 | 7.2 | 10.1 | 8.0 | 4.3 |
| Dysgeusia | 0.9 | 7.9 | 0 | 0 | 0 |
| Nausea | 14.7 | 8.6 | 12.2 | 5.3 | 4.3 |
| Vomiting | 9.1 | 5.0 | 8.6 | 8.0 | 2.2 |
| General Disorders and | |||||
| Administration Site Conditions | |||||
| Asthenia | 2.2 | 0.7 | 2.2 | 2.7 | 0 |
| Chest pain | 6.1 | 1.4 | 0 | 2.7 | 0 |
| Feeling abnormal | 3.0 | 0 | 0 | 0 | 0 |
| Infusion site pain or burning | 0 | 5.8 | 0 | 0 | 0 |
| Injection site extravasation | 0 | 2.2 | 0 | 0 | 0 |
| Peripheral edema | 2.6 | 7.2 | 5.0 | 5.3 | 10.9 |
| Pyrexia | 3.0 | 0.7 | 0.7 | 1.3 | 0 |
| Infections and Infestations | |||||
| Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis | 2.6 | 2.2 | 4.3 | 16.0 | 4.3 |
| Injury, Poisoning and Procedural | |||||
| Complications | |||||
| Graft complication | 9.5 | 1.4 | 0 | 0 | 0 |
| Metabolism and Nutrition Disorders | |||||
| Fluid overload | 3.0 | 1.4 | 0.7 | 1.3 | 0 |
| Gout | 0 | 2.9 | 1.4 | 0 | 0 |
| Hyperglycemia | 0 | 2.9 | 0 | 0 | 2.2 |
| Hypoglycemia | 0.4 | 0.7 | 0.7 | 4.0 | 0 |
| Musculoskeletal and Connective | |||||
| Tissue Disorders | |||||
| Arthralgia | 3.5 | 1.4 | 2.2 | 4.0 | 4.3 |
| Back pain | 2.2 | 2.2 | 3.6 | 1.3 | 4.3 |
| Muscle cramp | 29.4 | 0.7 | 0.7 | 2.7 | 0 |
| Myalgia | 0 | 3.6 | 0 | 1.3 | 0 |
| Pain in extremity | 5.6 | 4.3 | 0 | 2.7 | 6.5 |
| Nervous System Disorders | |||||
| Dizziness | 6.5 | 6.5 | 1.4 | 1.3 | 4.3 |
| Headache | 12.6 | 2.9 | 0.7 | 4.0 | 0 |
| Respiratory, Thoracic and | |||||
| Mediastinal Disorders | |||||
| Cough | 3.0 | 2.2 | 0.7 | 1.3 | 0 |
| Dyspnea | 3.5 | 5.8 | 1.4 | 1.3 | 2.2 |
| Nasal congestion | 0 | 1.4 | 2.2 | 1.3 | 0 |
| Skin and Subcutaneous | |||||
| Tissue Disorders | |||||
| Pruritus | 3.9 | 2.2 | 4.3 | 2.7 | 0 |
| Vascular Disorders | |||||
| Hypertension | 6.5 | 6.5 | 4.3 | 8.0 | 6.5 |
| Hypotension | 39.4 | 2.2 | 0.7 | 2.7 | 2.2 |
One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous Vitaferro (Iron (Ferrous Sulfate)) therapy and were reported to be intolerant (defined as precluding further use of that Vitaferro (Iron (Ferrous Sulfate)) product). When these patients were treated with Vitaferro (Iron (Ferrous Sulfate)) there were no occurrences of adverse reactions that precluded further use of Vitaferro (Iron (Ferrous Sulfate)) .
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)
In a randomized, open-label, dose-ranging trial for Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment with Vitaferro (Iron (Ferrous Sulfate)) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Vitaferro (Iron (Ferrous Sulfate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Vitaferro (Iron (Ferrous Sulfate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Vitaferro (Iron (Ferrous Sulfate)) 2.0 mg/kg.
A total of 5 (11%) subjects in the Vitaferro (Iron (Ferrous Sulfate)) 0.5 mg/kg group, 10 (21%) patients in the Vitaferro (Iron (Ferrous Sulfate)) 1.0 mg/kg group, and 10 (21%) patients in the Vitaferro (Iron (Ferrous Sulfate)) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).
6.2 Adverse Reactions from Post-Marketing Experience
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.
In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.
The following adverse reactions have been identified during post-approval use of Vitaferro (Iron (Ferrous Sulfate)). 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: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.
Symptoms associated with Vitaferro (Iron (Ferrous Sulfate)) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Vitaferro (Iron (Ferrous Sulfate)) injection. Reactions have occurred following the first dose or subsequent doses of Vitaferro (Iron (Ferrous Sulfate)). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.
Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.
7 DRUG INTERACTIONS
Drug interactions involving Vitaferro (Iron (Ferrous Sulfate)) have not been studied. However, Vitaferro (Iron (Ferrous Sulfate)) may reduce the absorption of concomitantly administered oral Vitaferro (Iron (Ferrous Sulfate)) preparations.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
Pregnancy Category B
There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Vitaferro ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Vitaferro (Iron (Ferrous Sulfate)) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Vitaferro (Iron (Ferrous Sulfate)) sucrose. Because animal reproductive studies are not always predictive of human response, Vitaferro (Iron (Ferrous Sulfate)) should be used during pregnancy only if clearly needed.
8.3 Nursing Mothers
It is not known whether Vitaferro (Iron (Ferrous Sulfate)) sucrose is excreted in human milk. Vitaferro (Iron (Ferrous Sulfate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Vitaferro (Iron (Ferrous Sulfate)) is administered to a nursing woman.
8.4 Pediatric Use
Safety and effectiveness of Vitaferro ) for Vitaferro (Iron (Ferrous Sulfate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.
Safety and effectiveness of Vitaferro (Iron (Ferrous Sulfate)) for Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Vitaferro (Iron (Ferrous Sulfate)) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]
Vitaferro (Iron (Ferrous Sulfate)) has not been studied in patients younger than 2 years of age.
In a country where Vitaferro (Iron (Ferrous Sulfate)) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Vitaferro (Iron (Ferrous Sulfate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Vitaferro (Iron (Ferrous Sulfate)) or any other drugs could be established.
8.5 Geriatric Use
Clinical studies of Vitaferro (Iron (Ferrous Sulfate)) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Vitaferro (Iron (Ferrous Sulfate)), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
10 OVERDOSAGE
No data are available regarding overdosage of Vitaferro (Iron (Ferrous Sulfate)) in humans. Excessive dosages of Vitaferro (Iron (Ferrous Sulfate)) may lead to accumulation of Vitaferro (Iron (Ferrous Sulfate)) in storage sites potentially leading to hemosiderosis. Do not administer Vitaferro (Iron (Ferrous Sulfate)) to patients with Vitaferro (Iron (Ferrous Sulfate)) overload.
Toxicities in single-dose studies in mice and rats, at intravenous Vitaferro (Iron (Ferrous Sulfate)) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.
11 DESCRIPTION
Vitaferro (Iron (Ferrous Sulfate)) (iron sucrose injection, USP), an Vitaferro (Iron (Ferrous Sulfate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Vitaferro (Iron (Ferrous Sulfate)) (III)-hydroxide in sucrose for intravenous use. Vitaferro (Iron (Ferrous Sulfate)) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:
[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)
where: n is the degree of Vitaferro (Iron (Ferrous Sulfate)) polymerization and m is the number of sucrose molecules associated with the Vitaferro (Iron (Ferrous Sulfate)) (III)-hydroxide.
Each mL contains 20 mg elemental Vitaferro (Iron (Ferrous Sulfate)) as Vitaferro (Iron (Ferrous Sulfate)) sucrose in water for injection. Vitaferro (Iron (Ferrous Sulfate)) is available in 10 mL single-use vials (200 mg elemental Vitaferro (Iron (Ferrous Sulfate)) per 10 mL), 5 mL single-use vials (100 mg elemental Vitaferro (Iron (Ferrous Sulfate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Vitaferro (Iron (Ferrous Sulfate)) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Vitaferro ) is an aqueous complex of poly-nuclear Vitaferro (Iron (Ferrous Sulfate)) (III)-hydroxide in sucrose. Following intravenous administration, Vitaferro (Iron (Ferrous Sulfate)) is dissociated into Vitaferro (Iron (Ferrous Sulfate)) and sucrose and the Vitaferro (Iron (Ferrous Sulfate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Vitaferro (Iron (Ferrous Sulfate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.
12.2 Pharmacodynamics
Following intravenous administration, Vitaferro (Iron (Ferrous Sulfate)) is dissociated into Vitaferro (Iron (Ferrous Sulfate)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Vitaferro (Iron (Ferrous Sulfate)) sucrose containing 100 mg of Vitaferro (Iron (Ferrous Sulfate)), three times weekly for three weeks, significant increases in serum Vitaferro (Iron (Ferrous Sulfate)) and serum ferritin and significant decreases in total Vitaferro (Iron (Ferrous Sulfate)) binding capacity occurred four weeks from the initiation of Vitaferro (Iron (Ferrous Sulfate)) sucrose treatment.
12.3 Pharmacokinetics
In healthy adults administered intravenous doses of Vitaferro ), its Vitaferro (Iron (Ferrous Sulfate)) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Vitaferro (Iron (Ferrous Sulfate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Vitaferro (Iron (Ferrous Sulfate)) containing 100 mg of Vitaferro (Iron (Ferrous Sulfate)) labeled with 52Fe/59Fe in patients with Vitaferro (Iron (Ferrous Sulfate)) deficiency showed that a significant amount of the administered Vitaferro (Iron (Ferrous Sulfate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Vitaferro (Iron (Ferrous Sulfate)) trapping compartment.
Following intravenous administration of Vitaferro (Iron (Ferrous Sulfate)), Vitaferro (Iron (Ferrous Sulfate)) sucrose is dissociated into Vitaferro (Iron (Ferrous Sulfate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Vitaferro (Iron (Ferrous Sulfate)) containing 1,510 mg of sucrose and 100 mg of Vitaferro (Iron (Ferrous Sulfate)) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Vitaferro (Iron (Ferrous Sulfate)) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Vitaferro (Iron (Ferrous Sulfate)) sucrose containing 500 to 700 mg of Vitaferro (Iron (Ferrous Sulfate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Vitaferro (Iron (Ferrous Sulfate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Vitaferro (Iron (Ferrous Sulfate)) have not been studied.
Pharmacokinetics in Pediatric Patients
Pharmacokinetics in Pediatric Patients
In a single-dose PK study of Vitaferro (Iron (Ferrous Sulfate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Vitaferro (Iron (Ferrous Sulfate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Vitaferro (Iron (Ferrous Sulfate)), the half-life of total serum Vitaferro (Iron (Ferrous Sulfate)) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.
Vitaferro (Iron (Ferrous Sulfate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Vitaferro (Iron (Ferrous Sulfate)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies have not been performed with Vitaferro (Iron (Ferrous Sulfate)) sucrose.
Vitaferro (Iron (Ferrous Sulfate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Vitaferro (Iron (Ferrous Sulfate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.
Vitaferro (Iron (Ferrous Sulfate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Vitaferro (Iron (Ferrous Sulfate)) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.
14 CLINICAL STUDIES
Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Vitaferro ).
14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)
Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Vitaferro (Iron (Ferrous Sulfate)) treatment and 24 in the historical control group) with Vitaferro (Iron (Ferrous Sulfate)) deficiency anemia. Eligibility criteria for Vitaferro (Iron (Ferrous Sulfate)) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.
Vitaferro (Iron (Ferrous Sulfate)) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Vitaferro (Iron (Ferrous Sulfate)), who were off intravenous Vitaferro (Iron (Ferrous Sulfate)) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.
Patients in the Vitaferro (Iron (Ferrous Sulfate)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.
| **p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates. | ||||||
| Efficacy parameters | End of treatment | 2 week follow-up | 5 week follow-up | |||
| Vitaferro (Iron (Ferrous Sulfate)) (n=69 | Historical Control (n=18) | Vitaferro (Iron (Ferrous Sulfate)) (n=73) | Historical Control (n=18) | Vitaferro (Iron (Ferrous Sulfate)) (n=71) | Historical Control (n=15) | |
| Hemoglobin (g/dL) | 1.0 ± 0.12** | 0.0 ± 0.21 | 1.3 ± 0.14** | -0.6 ± 0.24 | 1.2 ± 0.17* | -0.1 ± 0.23 |
| Hematocrit (%) | 3.1 ± 0.37** | -0.3 ± 0.65 | 3.6 ± 0.44** | -1.2 ± 0.76 | 3.3 ± 0.54 | 0.2 ± 0.86 |
Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).
14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease
Study B was a multicenter, open label study of Vitaferro (Iron (Ferrous Sulfate)) in 23 patients with Vitaferro (Iron (Ferrous Sulfate)) deficiency and HDD-CKD who had been discontinued from Vitaferro (Iron (Ferrous Sulfate)) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.
All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.
14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease
Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Vitaferro (Iron (Ferrous Sulfate)). Exclusion criteria were similar to those in studies A and B. Vitaferro (Iron (Ferrous Sulfate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Vitaferro (Iron (Ferrous Sulfate)) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.
The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.
14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease
Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Vitaferro (Iron (Ferrous Sulfate)) versus Vitaferro (Iron (Ferrous Sulfate)) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Vitaferro (Iron (Ferrous Sulfate)) (325 mg ferrous sulfate three times daily for 56 days); or Vitaferro (Iron (Ferrous Sulfate)) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Vitaferro (Iron (Ferrous Sulfate)) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Vitaferro (Iron (Ferrous Sulfate)) group.
A statistically significantly greater proportion of Vitaferro (Iron (Ferrous Sulfate)) subjects (35/79; 44.3%) compared to oral Vitaferro (Iron (Ferrous Sulfate)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).
14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease
Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Vitaferro (Iron (Ferrous Sulfate)) to patients with PDD-CKD receiving an erythropoietin alone without Vitaferro (Iron (Ferrous Sulfate)) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Vitaferro (Iron (Ferrous Sulfate)) or Vitaferro (Iron (Ferrous Sulfate)) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Vitaferro (Iron (Ferrous Sulfate)) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.
Patients in the Vitaferro (Iron (Ferrous Sulfate)) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Vitaferro (Iron (Ferrous Sulfate)) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).
14.6 Study F: Vitaferro ) Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease
Study F was a randomized, open-label, dose-ranging study for Vitaferro (Iron (Ferrous Sulfate)) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Vitaferro (Iron (Ferrous Sulfate)) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Vitaferro (Iron (Ferrous Sulfate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Vitaferro (Iron (Ferrous Sulfate)) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Vitaferro (Iron (Ferrous Sulfate)) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.
16 HOW SUPPLIED/storage and handling
16.1 How Supplied
Vitaferro ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Vitaferro (Iron (Ferrous Sulfate)), each 5 mL vial contains 100 mg elemental Vitaferro (Iron (Ferrous Sulfate)), and each 2.5 mL vial contains 50 mg elemental Vitaferro (Iron (Ferrous Sulfate)) (20 mg/mL).
| NDC-0517-2310-05 | 200 mg/10 mL Single-Use Vial | Packages of 5 |
| NDC-0517-2310-10 | 200 mg/10 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-01 | 100 mg/5 mL Single-Use Vial | Individually Boxed |
| NDC-0517-2340-10 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2340-25 | 100 mg/5 mL Single-Use Vial | Packages of 25 |
| NDC-0517-2340-99 | 100 mg/5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-10 | 50 mg/2.5 mL Single-Use Vial | Packages of 10 |
| NDC-0517-2325-25 | 50 mg/2.5 mL Single-Use Vial | Packages of 25 |
16.2 Stability and Storage
Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.
Syringe Stability: Vitaferro (Iron (Ferrous Sulfate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Vitaferro (Iron (Ferrous Sulfate)) per mL, or undiluted (20 mg elemental Vitaferro (Iron (Ferrous Sulfate)) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).
Intravenous Admixture Stability: Vitaferro (Iron (Ferrous Sulfate)), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Vitaferro (Iron (Ferrous Sulfate)) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).
Do not dilute to concentrations below 1 mg/mL.
Do not mix Vitaferro (Iron (Ferrous Sulfate)) with other medications or add to parenteral nutrition solutions for intravenous infusion.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.
17 PATIENT COUNSELING INFORMATION
Prior to Vitaferro (Iron (Ferrous Sulfate)) administration:
- Question patients regarding any prior history of reactions to parenteral Vitaferro (Iron (Ferrous Sulfate)) products
- Advise patients of the risks associated with Vitaferro (Iron (Ferrous Sulfate))
- Advise patients to report any symptoms of hypersensitivity that may develop during and following Vitaferro (Iron (Ferrous Sulfate)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]
AMERICAN
REGENT, INC.
SHIRLEY, NY 11967
Vitaferro (Iron (Ferrous Sulfate)) is manufactured under license from Vifor (International) Inc., Switzerland.
PremierProRx® is a trademark of Premier, Inc., used under license.
PREMIERProRx®
IN2340
MG #15727
Vitaferro pharmaceutical active ingredients containing related brand and generic drugs:
Vitaferro available forms, composition, doses:
Vitaferro destination | category:
Vitaferro Anatomical Therapeutic Chemical codes:
Vitaferro pharmaceutical companies:
References
- "Iron". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
- "Iron". http://www.drugbank.ca/drugs/DB0159... (accessed August 28, 2018).
- "E1UOL152H7: The UNique Ingredient Identifier (UNII) is an alphanumeric substance identifier from the joint FDA/USP Substance Registration System (SRS).". https://www.fda.gov/ForIndustry/Dat... (accessed August 28, 2018).
Frequently asked Questions
Can i drive or operate heavy machine after consuming Vitaferro?Depending on the reaction of the Vitaferro after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Vitaferro not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Vitaferro addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Review
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The information was verified by Dr. Rachana Salvi, MD Pharmacology