Vitarose

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Vitarose uses

• 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
• Vitarose reviews

1 INDICATIONS AND USAGE

Vitarose is indicated for the treatment of Vitarose deficiency anemia in patients with chronic kidney disease (CKD).

Vitarose is an Vitarose replacement product indicated for the treatment of Vitarose deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Vitarose must only be administered intravenously either by slow injection or by infusion. The dosage of Vitarose is expressed in mg of elemental Vitarose. Each mL contains 20 mg of elemental Vitarose.

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

Administer Vitarose 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. Vitarose should be administered early during the dialysis session. The usual total treatment course of Vitarose is 1000 mg. Vitarose treatment may be repeated if Vitarose deficiency reoccurs.

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

Administer Vitarose 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 Vitarose, 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. Vitarose treatment may be repeated if Vitarose deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Vitarose 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 Vitarose in a maximum of 250 mL of 0.9% NaCl. Vitarose treatment may be repeated if Vitarose deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Vitarose maintenance treatment

The dosing for Vitarose replacement treatment in pediatric patients with HDD-CKD has not been established.

For Vitarose maintenance treatment: Administer Vitarose 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. Vitarose treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Vitarose maintenance treatment

The dosing for Vitarose replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Vitarose maintenance treatment: Administer Vitarose 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. Vitarose treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

• 10 mL single-use vial / 200 mg elemental Vitarose (20 mg/mL)
• 5 mL single-use vial / 100 mg elemental Vitarose (20 mg/mL)
• 2.5 mL single-use vial / 50 mg elemental Vitarose (20 mg/mL)

• 10 mL single-use vial / 200 mg elemental Vitarose (20 mg/mL) (3)
• 5 mL single-use vial / 100 mg elemental Vitarose (20 mg/mL) (3)
• 2.5 mL single-use vial / 50 mg elemental Vitarose (20 mg/mL) (3)

4 CONTRAINDICATIONS

• Known hypersensitivity to Vitarose

• Known hypersensitivity to Vitarose (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

Vitarose may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Vitarose. Hypotension following administration of Vitarose may be related to the rate of administration and/or total dose administered .

5.3 Vitarose Overload

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

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Vitarose are described in other sections .

• The most common adverse reactions (≥2%) following the administration of Vitarose 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 Vitarose 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 Vitarose 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 Vitarose therapy and were reported to be intolerant (defined as precluding further use of that Vitarose product). When these patients were treated with Vitarose there were no occurrences of adverse reactions that precluded further use of Vitarose .

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

A total of 5 (11%) subjects in the Vitarose 0.5 mg/kg group, 10 (21%) patients in the Vitarose 1.0 mg/kg group, and 10 (21%) patients in the Vitarose 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 Vitarose. 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 Vitarose 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 Vitarose injection. Reactions have occurred following the first dose or subsequent doses of Vitarose. 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 Vitarose have not been studied. However, Vitarose may reduce the absorption of concomitantly administered oral Vitarose 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, Vitarose sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Vitarose and revealed no evidence of harm to the fetus due to Vitarose sucrose. Because animal reproductive studies are not always predictive of human response, Vitarose should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness of Vitarose for Vitarose replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Vitarose for Vitarose maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Vitarose 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 ]

Vitarose has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

Clinical studies of Vitarose 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 Vitarose, 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 Vitarose in humans. Excessive dosages of Vitarose may lead to accumulation of Vitarose in storage sites potentially leading to hemosiderosis. Do not administer Vitarose to patients with Vitarose overload.

Toxicities in single-dose studies in mice and rats, at intravenous Vitarose 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

Following intravenous administration of Vitarose, Vitarose sucrose is dissociated into Vitarose and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Vitarose containing 1,510 mg of sucrose and 100 mg of Vitarose in 12 healthy adults, 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Vitarose 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 Vitarose sucrose containing 500 to 700 mg of Vitarose in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Vitarose was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Vitarose have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

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

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

Vitarose sucrose at intravenous doses up to 15 mg/kg/day of elemental Vitarose (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 Vitarose.

14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease

Study A was a multicenter, open-label, historically-controlled study in 101 patients with HDD-CKD (77 patients with Vitarose treatment and 24 in the historical control group) with Vitarose deficiency anemia. Eligibility criteria for Vitarose 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.

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

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

Vitarose is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Vitarose, each 5 mL vial contains 100 mg elemental Vitarose, and each 2.5 mL vial contains 50 mg elemental Vitarose.

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: Vitarose, when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Vitarose per mL, or undiluted (20 mg elemental Vitarose 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: Vitarose, 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 Vitarose 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 Vitarose 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 Vitarose administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Vitarose is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx^®

IN2340

MG #15727

Vitarose pharmaceutical active ingredients containing related brand and generic drugs:

• Iron (Iron Sucrose)

Vitarose available forms, composition, doses:

• Injectable; Injection; Iron (Iron Sucrose) 20 mg / ml

Vitarose destination | category:

• Human:
• Antianemics
• Vitamins and minerals (pre and post natal)

Vitarose Anatomical Therapeutic Chemical codes:

• B03A - Iron preparations

Vitarose pharmaceutical companies:

• Solitaire Pharmacia

References

1. "Iron". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
2. "Iron". http://www.drugbank.ca/drugs/DB0159... (accessed August 28, 2018).
3. "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

Depending on the reaction of the Vitarose after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Vitarose 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.

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.

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The information was verified by Dr. Rachana Salvi, MD Pharmacology