Infaglobin Drops

Iron (Ferrous Gluconate):

• 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
• Infaglobin Drops (Iron (Ferrous Gluconate)) reviews

1 INDICATIONS AND USAGE

Infaglobin Drops (Iron (Ferrous Gluconate)) is indicated for the treatment of Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency anemia in patients with chronic kidney disease (CKD).

Infaglobin Drops (Iron (Ferrous Gluconate)) is an Infaglobin Drops (Iron (Ferrous Gluconate)) replacement product indicated for the treatment of Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Infaglobin Drops ) must only be administered intravenously either by slow injection or by infusion. The dosage of Infaglobin Drops (Iron (Ferrous Gluconate)) is expressed in mg of elemental Infaglobin Drops (Iron (Ferrous Gluconate)). Each mL contains 20 mg of elemental Infaglobin Drops (Iron (Ferrous Gluconate)).

2.1 Adult Patients with Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD)

Administer Infaglobin Drops (Iron (Ferrous Gluconate)) 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. Infaglobin Drops (Iron (Ferrous Gluconate)) should be administered early during the dialysis session. The usual total treatment course of Infaglobin Drops (Iron (Ferrous Gluconate)) is 1000 mg. Infaglobin Drops (Iron (Ferrous Gluconate)) treatment may be repeated if Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency reoccurs.

2.2 Adult Patients with Non-Dialysis Dependent-Chronic Kidney Disease

Administer Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)), 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. Infaglobin Drops (Iron (Ferrous Gluconate)) treatment may be repeated if Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) in a maximum of 250 mL of 0.9% NaCl. Infaglobin Drops (Iron (Ferrous Gluconate)) treatment may be repeated if Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment

The dosing for Infaglobin Drops (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment: Administer Infaglobin Drops (Iron (Ferrous Gluconate)) 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. Infaglobin Drops (Iron (Ferrous Gluconate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment

The dosing for Infaglobin Drops (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment: Administer Infaglobin Drops (Iron (Ferrous Gluconate)) 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. Infaglobin Drops (Iron (Ferrous Gluconate)) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

• 10 mL single-use vial / 200 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL)
• 5 mL single-use vial / 100 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL)
• 2.5 mL single-use vial / 50 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL)

• 10 mL single-use vial / 200 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL) (3)
• 5 mL single-use vial / 100 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL) (3)
• 2.5 mL single-use vial / 50 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

• Known hypersensitivity to Infaglobin Drops (Iron (Ferrous Gluconate))

• Known hypersensitivity to Infaglobin Drops (Iron (Ferrous Gluconate)) (4)

5 WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Infaglobin Drops ) administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Infaglobin Drops (Iron (Ferrous Gluconate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
• Hypotension: Infaglobin Drops (Iron (Ferrous Gluconate)) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Infaglobin Drops (Iron (Ferrous Gluconate)). (5.2)
• Infaglobin Drops (Iron (Ferrous Gluconate)) Overload: Regularly monitor hematologic responses during Infaglobin Drops (Iron (Ferrous Gluconate)) therapy. Do not administer Infaglobin Drops (Iron (Ferrous Gluconate)) to patients with Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)). 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 Infaglobin Drops (Iron (Ferrous Gluconate)) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Infaglobin Drops (Iron (Ferrous Gluconate)) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Infaglobin Drops (Iron (Ferrous Gluconate)) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Infaglobin Drops (Iron (Ferrous Gluconate)) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

Infaglobin Drops ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Infaglobin Drops (Iron (Ferrous Gluconate)). Hypotension following administration of Infaglobin Drops (Iron (Ferrous Gluconate)) may be related to the rate of administration and/or total dose administered .

5.3 Infaglobin Drops (Iron (Ferrous Gluconate)) Overload

Excessive therapy with parenteral Infaglobin Drops (Iron (Ferrous Gluconate)) can lead to excess storage of Infaglobin Drops (Iron (Ferrous Gluconate)) with the possibility of iatrogenic hemosiderosis. All adult and pediatric patients receiving Infaglobin Drops (Iron (Ferrous Gluconate)) require periodic monitoring of hematologic and Infaglobin Drops (Iron (Ferrous Gluconate)) parameters (hemoglobin, hematocrit, serum ferritin and transferrin saturation). Do not administer Infaglobin Drops (Iron (Ferrous Gluconate)) to patients with evidence of Infaglobin Drops (Iron (Ferrous Gluconate)) overload. Transferrin saturation (TSAT) values increase rapidly after intravenous administration of Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose; do not perform serum Infaglobin Drops (Iron (Ferrous Gluconate)) measurements for at least 48 hours after intravenous dosing .

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Infaglobin Drops ) are described in other sections .

• The most common adverse reactions (≥2%) following the administration of Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops ) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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.

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 Infaglobin Drops (Iron (Ferrous Gluconate)) therapy and were reported to be intolerant (defined as precluding further use of that Infaglobin Drops (Iron (Ferrous Gluconate)) product). When these patients were treated with Infaglobin Drops (Iron (Ferrous Gluconate)) there were no occurrences of adverse reactions that precluded further use of Infaglobin Drops (Iron (Ferrous Gluconate)) .

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 Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment with Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Infaglobin Drops (Iron (Ferrous Gluconate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Infaglobin Drops (Iron (Ferrous Gluconate)) 2.0 mg/kg.

A total of 5 (11%) subjects in the Infaglobin Drops (Iron (Ferrous Gluconate)) 0.5 mg/kg group, 10 (21%) patients in the Infaglobin Drops (Iron (Ferrous Gluconate)) 1.0 mg/kg group, and 10 (21%) patients in the Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)). 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) injection. Reactions have occurred following the first dose or subsequent doses of Infaglobin Drops (Iron (Ferrous Gluconate)). 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 Infaglobin Drops (Iron (Ferrous Gluconate)) have not been studied. However, Infaglobin Drops (Iron (Ferrous Gluconate)) may reduce the absorption of concomitantly administered oral Infaglobin Drops (Iron (Ferrous Gluconate)) 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, Infaglobin Drops ) sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (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 Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose. Because animal reproductive studies are not always predictive of human response, Infaglobin Drops (Iron (Ferrous Gluconate)) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose is excreted in human milk. Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Infaglobin Drops (Iron (Ferrous Gluconate)) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Infaglobin Drops ) for Infaglobin Drops (Iron (Ferrous Gluconate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Infaglobin Drops (Iron (Ferrous Gluconate)) for Infaglobin Drops (Iron (Ferrous Gluconate)) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Infaglobin Drops (Iron (Ferrous Gluconate)) 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)]

Infaglobin Drops (Iron (Ferrous Gluconate)) has not been studied in patients younger than 2 years of age.

In a country where Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Infaglobin Drops (Iron (Ferrous Gluconate)) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)), 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 Infaglobin Drops (Iron (Ferrous Gluconate)) in humans. Excessive dosages of Infaglobin Drops (Iron (Ferrous Gluconate)) may lead to accumulation of Infaglobin Drops (Iron (Ferrous Gluconate)) in storage sites potentially leading to hemosiderosis. Do not administer Infaglobin Drops (Iron (Ferrous Gluconate)) to patients with Infaglobin Drops (Iron (Ferrous Gluconate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Infaglobin Drops (Iron (Ferrous Gluconate)) 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

Infaglobin Drops (Iron (Ferrous Gluconate)) (iron sucrose injection, USP), an Infaglobin Drops (Iron (Ferrous Gluconate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Infaglobin Drops (Iron (Ferrous Gluconate)) (III)-hydroxide in sucrose for intravenous use. Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) polymerization and m is the number of sucrose molecules associated with the Infaglobin Drops (Iron (Ferrous Gluconate)) (III)-hydroxide.

Each mL contains 20 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) as Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose in water for injection. Infaglobin Drops (Iron (Ferrous Gluconate)) is available in 10 mL single-use vials (200 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) per 10 mL), 5 mL single-use vials (100 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) 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

Infaglobin Drops ) is an aqueous complex of poly-nuclear Infaglobin Drops (Iron (Ferrous Gluconate)) (III)-hydroxide in sucrose. Following intravenous administration, Infaglobin Drops (Iron (Ferrous Gluconate)) is dissociated into Infaglobin Drops (Iron (Ferrous Gluconate)) and sucrose and the Infaglobin Drops (Iron (Ferrous Gluconate)) is transported as a complex with transferrin to target cells including erythroid precursor cells. The Infaglobin Drops (Iron (Ferrous Gluconate)) in the precursor cells is incorporated into hemoglobin as the cells mature into red blood cells.

12.2 Pharmacodynamics

Following intravenous administration, Infaglobin Drops (Iron (Ferrous Gluconate)) is dissociated into Infaglobin Drops (Iron (Ferrous Gluconate)) and sucrose. In 22 patients undergoing hemodialysis and receiving erythropoietin (recombinant human erythropoietin) therapy treated with Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose containing 100 mg of Infaglobin Drops (Iron (Ferrous Gluconate)), three times weekly for three weeks, significant increases in serum Infaglobin Drops (Iron (Ferrous Gluconate)) and serum ferritin and significant decreases in total Infaglobin Drops (Iron (Ferrous Gluconate)) binding capacity occurred four weeks from the initiation of Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose treatment.

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Infaglobin Drops ), its Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Infaglobin Drops (Iron (Ferrous Gluconate)) containing 100 mg of Infaglobin Drops (Iron (Ferrous Gluconate)) labeled with ⁵²Fe/⁵⁹Fe in patients with Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency showed that a significant amount of the administered Infaglobin Drops (Iron (Ferrous Gluconate)) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Infaglobin Drops (Iron (Ferrous Gluconate)) trapping compartment.

Following intravenous administration of Infaglobin Drops (Iron (Ferrous Gluconate)), Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose is dissociated into Infaglobin Drops (Iron (Ferrous Gluconate)) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Infaglobin Drops (Iron (Ferrous Gluconate)) containing 1,510 mg of sucrose and 100 mg of Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose containing 500 to 700 mg of Infaglobin Drops (Iron (Ferrous Gluconate)) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Infaglobin Drops (Iron (Ferrous Gluconate)) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Infaglobin Drops (Iron (Ferrous Gluconate)) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Infaglobin Drops (Iron (Ferrous Gluconate)), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Infaglobin Drops (Iron (Ferrous Gluconate)) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Infaglobin Drops (Iron (Ferrous Gluconate)), the half-life of total serum Infaglobin Drops (Iron (Ferrous Gluconate)) 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.

Infaglobin Drops (Iron (Ferrous Gluconate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose.

Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Infaglobin Drops (Iron (Ferrous Gluconate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (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 Infaglobin Drops ).

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 Infaglobin Drops (Iron (Ferrous Gluconate)) treatment and 24 in the historical control group) with Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency anemia. Eligibility criteria for Infaglobin Drops (Iron (Ferrous Gluconate)) 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.

Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)), who were off intravenous Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.

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 Infaglobin Drops (Iron (Ferrous Gluconate)) in 23 patients with Infaglobin Drops (Iron (Ferrous Gluconate)) deficiency and HDD-CKD who had been discontinued from Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)). Exclusion criteria were similar to those in studies A and B. Infaglobin Drops (Iron (Ferrous Gluconate)) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) versus Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) (325 mg ferrous sulfate three times daily for 56 days); or Infaglobin Drops (Iron (Ferrous Gluconate)) (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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) group.

A statistically significantly greater proportion of Infaglobin Drops (Iron (Ferrous Gluconate)) subjects (35/79; 44.3%) compared to oral Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) to patients with PDD-CKD receiving an erythropoietin alone without Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) or Infaglobin Drops (Iron (Ferrous Gluconate)) (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 Infaglobin Drops (Iron (Ferrous Gluconate)) / 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 Infaglobin Drops (Iron (Ferrous Gluconate)) / 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 Infaglobin Drops (Iron (Ferrous Gluconate)) / 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: Infaglobin Drops ) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) (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 Infaglobin Drops (Iron (Ferrous Gluconate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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

Infaglobin Drops ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)), each 5 mL vial contains 100 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)), and each 2.5 mL vial contains 50 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) (20 mg/mL).

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: Infaglobin Drops (Iron (Ferrous Gluconate)), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Infaglobin Drops (Iron (Ferrous Gluconate)) per mL, or undiluted (20 mg elemental Infaglobin Drops (Iron (Ferrous Gluconate)) 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: Infaglobin Drops (Iron (Ferrous Gluconate)), 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) 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 Infaglobin Drops (Iron (Ferrous Gluconate)) administration:

• Question patients regarding any prior history of reactions to parenteral Infaglobin Drops (Iron (Ferrous Gluconate)) products
• Advise patients of the risks associated with Infaglobin Drops (Iron (Ferrous Gluconate))
• Advise patients to report any symptoms of hypersensitivity that may develop during and following Infaglobin Drops (Iron (Ferrous Gluconate)) administration, such as rash, itching, dizziness, light-headedness, swelling, and breathing problems [see Warnings and Precautions (5)]

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Infaglobin Drops (Iron (Ferrous Gluconate)) is manufactured under license from Vifor (International) Inc., Switzerland.

PremierProRx^® is a trademark of Premier, Inc., used under license.

PREMIERProRx^®

IN2340

MG #15727

Vitamin A:

• Dosage and administration
• Warning
• Clinical pharmacology
• Dietary supplementation
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Infaglobin Drops (Vitamin A) reviews

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

WARNING

KEEP OUT OF THE REACH OF CHILDREN.

In case of accidental overdose, seek professional assistance or contact a Poison Control Center immediately.

Other Ingredients: Artificial cherry flavor, artificial grape flavor, ascorbic acid, cholecalciferol, compressible sugar, D&C Red #7 calcium lake, FD&C Blue #1 aluminum lake, FD&C Yellow #6 aluminum lake, folic acid, magnesium stearate, microcrystalline cellulose, natural and artificial orange flavor, niacinamide, polyethylene glycol, pyridoxine HCl, riboflavin, sodium ascorbate, sodium fluoride, stearic acid, sucralose, thiamine HCl, Infaglobin Drops (Vitamin A) acetate, vitamin B12 and vitamin E acetate.

Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.

CLINICAL PHARMACOLOGY

Significant decrease in the incidence of dental caries can be linked to the fluoridation of the water supply (1ppm fluoride) during the period of tooth development.

Infaglobin Drops (Vitamin A) Tablets provide sodium fluoride and ten essential vitamins in a chewable tablet. Because the tablets are chewable, they provide a topical as well as systemic source of fluoride. Hydroxyapatite is the principal crystal for all calcified tissue in the human body. The fluoride ion reacts with the Hydroxyapatite in the tooth as it is formed to produce the more caries-resistant crystal, fluorapatite.

The reaction may be expressed by the equation:

Three stages of fluoride deposition in tooth enamel can be distinguished:

• Small amounts (reflecting the low levels of fluoride in tissue fluids) are incorporated into the enamel crystals while they are being formed.
• After enamel has been laid down, fluoride deposition continues in the surface enamel. Diffusion of fluoride from the surface inward is apparently restricted.
• After eruption, the surface enamel acquires fluoride from the water, food, supplementary fluoride and smaller amounts of saliva.

DIETARY SUPPLEMENTATION

Multivitamins with fluoride offer supplementation of the diet with 10 vitamins and fluoride.

WARNINGS

AS IN THE CASE OF ALL MEDICATIONS, KEEP OUT OF THE REACH OF CHILDREN. This tablet should be chewed. This product, as with all chewable tablets are not recommended for children under the age of 4 due to risk of choking.

PRECAUTIONS

The suggested dose of Infaglobin Drops (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Infaglobin Drops (Vitamin A) Tablets

• Determine the fluoride content of the drinking water from all major sources
• Make sure the child is not receiving significant amounts of fluoride from other sources such as medications and swallowed toothpaste
• Periodically check to make sure that the child does not develop significant dental fluorosis.

ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

To report SUSPECTED ADVERSE REACTIONS, contact H2-Pharma, LLC at 1 (866) 592-6438 or FDA at 1 (800) 332-1088 or via the web at www.fda.gov/medwatch/index.html for voluntary reporting of adverse reactions.

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

HOW SUPPLIED

Infaglobin Drops Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Infaglobin Drops (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Infaglobin Drops (Vitamin A) Tablets 1.0 mg are available as orange, red and purple chewable tablets imprinted with "153" in 100 tablet bottles.

STORAGE

Store at controlled room temperature 20ºC-25ºC (68º-77ºF), excursions permitted between 15º-30ºC (59º-86ºF).

Distributed by:

H2-Pharma, LLC

2010 Berry Chase Place

Montgomery, AL 36117

www.h2-pharma.com

1067084

61269-151-01

MultiVitamin

with Fluoride

Chewable Tablets

Rx

0.25 mg

MultiVitamin and Fluoride Supplement

Dietary Supplement

100 Tablets

H²pharma

Vitamin B12:

• Pharmacological action
• Pharmacokinetics
• Why is Infaglobin Drops prescribed?
• Dosage and administration
• Infaglobin Drops (Vitamin B12) side effects, adverse reactions
• Infaglobin Drops contraindications
• Infaglobin Drops using during pregnancy and breastfeeding
• Special instructions
• Infaglobin Drops (Vitamin B12) drug interactions
• Infaglobin Drops (Vitamin B12) reviews

Pharmacological action

Infaglobin Drops refers to a group of water-soluble vitamins. It has high biological activity. Infaglobin Drops (Vitamin B12) is necessary for normal hematopoiesis (promotes maturation of erythrocytes). Involved in the processes of transmethylation, hydrogen transport, synthesis of methionine, nucleic acids, choline, creatine. Contributes to the accumulation in erythrocytes of compounds containing sulfhydryl groups. Has a beneficial effect on liver function and the nervous system. Activates the coagulation of blood in high doses causes an increase in the activity of thromboplastin and prothrombin.

Pharmacokinetics

After oral administration Infaglobin Drops (Vitamin B12) absorbed from the gastrointestinal tract. Metabolized in the tissues, becoming a co-enzyme form - adenosylcobalamin which is the active form of cyanocobalamin. Excreted in bile and urine.

Why is Infaglobin Drops prescribed?

Anemia due to B12-deficiency conditions; in the complex therapy for iron and posthemorrhagic anemia; aplastic anemia caused by toxic substances and drugs; liver disease (hepatitis, cirrhosis); funicular myelosis; polyneuritis, radiculitis, neuralgia, amyotrophic lateral sclerosis; children cerebral palsy, Down syndrome, peripheral nerve injury; skin diseases (psoriasis, photodermatosis, herpetiformis dermatitis, neurodermatitis); to prevent and treat symptoms of deficiency of Infaglobin Drops (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Infaglobin Drops is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Infaglobin Drops (Vitamin B12) deficiency is introduced on 100-200 mcg in 2 days. In anemia with symptoms of funicular myelosis and megalocytic anemia with diseases of the nervous system - 400-500 micrograms in the first 7 days daily, then 1 time every 5-7 days. In the period of remission in the absence of events funicular myelosis maintenance dose - 100 mcg 2 times a month, in the presence of neurological symptoms - at 200-400 mcg 2-4 times a month. In acute post-hemorrhagic anemia and iron anemia by 30-100 mcg 2-3 times a week. When aplastic anemia (especially in children) - 100 micrograms before clinical improvement. When nutritional anemia in infants and preterm - 30 mcg / day during 15 days.

In diseases of the central and peripheral nervous system and neurological diseases with a pain syndrome is administered in increasing doses - 200-500 mcg, with the improvement in the state - 100 mcg / day. The course of treatment with Infaglobin Drops (Vitamin B12) is 2 weeks. In traumatic lesions of peripheral nervous system - at 200-400 mcg every other day for 40-45 days.

When hepatitis and cirrhosis - 30-60 mcg / day or 100 mg every other day for 25-40 days.

Dystrophy in young children, Down syndrome and cerebral palsy - by 15-30 mcg every other day.

When funicular myelosis, amyotrophic lateral sclerosis can be introduced into the spinal canal at 15-30 mcg, gradually increasing the dose of 200-250 micrograms.

In radiation sickness, diabetic neuropathy, sprue - by 60-100 mcg daily for 20-30 days.

When deficiency of Infaglobin Drops (Vitamin B12) to prevent - IV or IM for 1 mg 1 time a month; for treatment - IV or IM for 1 mg daily for 1-2 weeks, the maintenance dose is 1-2 mg IV or IM from 1 per week, up to 1 per month. Duration of treatment is determined individually.

Infaglobin Drops (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

Cardiovascular system: rarely - pain in the heart, tachycardia.

Allergic reactions: rarely - urticaria.

Infaglobin Drops contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Infaglobin Drops using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

When stenocardia should be used with caution in a single dose of Infaglobin Drops 100 mcg. During treatment should regularly monitor the blood picture and coagulation. It is unacceptable to enter in the same syringe with cyanocobalamin solutions of thiamine and pyridoxine.

Infaglobin Drops (Vitamin B12) drug interactions

In an application of Infaglobin Drops (Vitamin B12) with hormonal contraceptives for oral administration may decrease the concentration of cyanocobalamin in plasma.

In an application with anticonvulsant drugs decreased cyanocobalamin absorption from the gut.

In an Infaglobin Drops (Vitamin B12) application with neomycin, aminosalicylic acid, colchicine, cimetidine, ranitidine, drugs potassium decreased cyanocobalamin absorption from the gut.

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

When parenteral application of chloramphenicol may decrease the hematopoietic effects of cyanocobalamin with anemia.

Pharmaceutical incompatibility

Contained in the molecule of cyanocobalamin cobalt ion contributes to the destruction of ascorbic acid, thiamine bromide, riboflavin in one solution.

Zinc Gluconate:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Infaglobin Drops (Zinc Gluconate) reviews

INDICATIONS AND USAGE

Infaglobin Drops (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Infaglobin Drops (Zinc Gluconate) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Infaglobin Drops (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Infaglobin Drops (Zinc Gluconate) doses because these elements are primarily eliminated in the urine.

WARNING: This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphate solutions, which contain aluminum.

Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

PRECAUTIONS

General

Do not use unless the solution is clear and the seal is intact.

Zinc 1 mg/mL should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Infaglobin Drops (Zinc Gluconate) from a bolus injection. Administration of Infaglobin Drops (Zinc Gluconate) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Infaglobin Drops (Zinc Gluconate) are suggested as a guideline for subsequent Infaglobin Drops (Zinc Gluconate) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Infaglobin Drops 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Infaglobin Drops (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Infaglobin Drops chloride. It is also not known whether Infaglobin Drops (Zinc Gluconate) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Infaglobin Drops (Zinc Gluconate) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

An evaluation of current literature revealed no clinical experience identifying differences in response between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Single intravenous doses of 1 to 2 mg zinc/kg body weight have been given to adult leukemic patients without toxic manifestations. However, acute toxicity was reported in an adult when 10 mg Infaglobin Drops (Zinc Gluconate) was infused over a period of one hour on each of four consecutive days. Profuse sweating, decreased level of consciousness, blurred vision, tachycardia (140/min), and marked hypothermia (94.2° F) on the fourth day were accompanied by a serum Infaglobin Drops (Zinc Gluconate) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Infaglobin Drops (Zinc Gluconate) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Infaglobin Drops (Zinc Gluconate) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Infaglobin Drops (Zinc Gluconate) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Infaglobin Drops (Zinc Gluconate) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Infaglobin Drops (Zinc Gluconate) toxicity.

DOSAGE AND ADMINISTRATION

Infaglobin Drops (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) contains 1 mg zinc/mL and is administered intravenously only after dilution. The additive should be diluted prior to administration in a volume of fluid not less than 100 mL. For the metabolically stable adult receiving TPN, the suggested intravenous dosage is 2.5 to 4 mg zinc/day (2.5 to 4 mL/day). An additional 2 mg zinc/day (2 mL/day) is suggested for acute catabolic states. For the stable adult with fluid loss from the small bowel, an additional 12.2 mg zinc/liter of small bowel fluid lost (12.2 mL/liter of small bowel fluid lost), or an additional 17.1 mg zinc/kg of stool or ileostomy output (17.1 mL/kg of stool or ileostomy output) is recommended. Frequent monitoring of Infaglobin Drops (Zinc Gluconate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Infaglobin Drops (Zinc Gluconate).

For full term infants and children up to 5 years of age, 100 mcg zinc/kg/day (0.1 mL/kg/day) is recommended. For premature infants (birth weight less than 1500 g) up to 3 kg in body weight, 300 mcg zinc/kg/day (0.3 mL/kg/day) is suggested.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. See PRECAUTIONS.

HOW SUPPLIED

Infaglobin Drops (Zinc Gluconate) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Infaglobin Drops (Zinc Gluconate)

1 mg/mL

Infaglobin Drops (Zinc Gluconate) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA