Lycimin Tonic for Children with Iron

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Lycimin Tonic for Children with Iron uses

Lycimin Tonic for Children with Iron consists of Iron, Lysine Hydrochloride, Vitamin B.

Iron:


1 INDICATIONS AND USAGE

Lycimin Tonic for Children with Iron (Iron) is indicated for the treatment of Lycimin Tonic for Children with Iron (Iron) deficiency anemia in patients with chronic kidney disease (CKD).

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

2 DOSAGE AND ADMINISTRATION

Lycimin Tonic for Children with Iron must only be administered intravenously either by slow injection or by infusion. The dosage of Lycimin Tonic for Children with Iron (Iron) is expressed in mg of elemental Lycimin Tonic for Children with Iron (Iron). Each mL contains 20 mg of elemental Lycimin Tonic for Children with Iron (Iron).

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 Lycimin Tonic for Children with Iron (Iron) 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. Lycimin Tonic for Children with Iron (Iron) should be administered early during the dialysis session. The usual total treatment course of Lycimin Tonic for Children with Iron (Iron) is 1000 mg. Lycimin Tonic for Children with Iron (Iron) treatment may be repeated if Lycimin Tonic for Children with Iron (Iron) deficiency reoccurs.

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

Administer Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron), 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. Lycimin Tonic for Children with Iron (Iron) treatment may be repeated if Lycimin Tonic for Children with Iron (Iron) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) in a maximum of 250 mL of 0.9% NaCl. Lycimin Tonic for Children with Iron (Iron) treatment may be repeated if Lycimin Tonic for Children with Iron (Iron) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Lycimin Tonic for Children with Iron (Iron) maintenance treatment

The dosing for Lycimin Tonic for Children with Iron (Iron) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Lycimin Tonic for Children with Iron (Iron) maintenance treatment: Administer Lycimin Tonic for Children with Iron (Iron) 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. Lycimin Tonic for Children with Iron (Iron) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Lycimin Tonic for Children with Iron (Iron) maintenance treatment

The dosing for Lycimin Tonic for Children with Iron (Iron) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Lycimin Tonic for Children with Iron (Iron) maintenance treatment: Administer Lycimin Tonic for Children with Iron (Iron) 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. Lycimin Tonic for Children with Iron (Iron) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Lycimin Tonic for Children with Iron (Iron) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Lycimin Tonic for Children with Iron (Iron)
  • Known hypersensitivity to Lycimin Tonic for Children with Iron (Iron) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

Lycimin Tonic for Children with Iron may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Lycimin Tonic for Children with Iron (Iron). Hypotension following administration of Lycimin Tonic for Children with Iron (Iron) may be related to the rate of administration and/or total dose administered .

5.3 Lycimin Tonic for Children with Iron (Iron) Overload

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

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6 ADVERSE REACTIONS

The following serious adverse reactions associated with Lycimin Tonic for Children with Iron are described in other sections .

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

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

A total of 5 (11%) subjects in the Lycimin Tonic for Children with Iron (Iron) 0.5 mg/kg group, 10 (21%) patients in the Lycimin Tonic for Children with Iron (Iron) 1.0 mg/kg group, and 10 (21%) patients in the Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron). 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 Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) injection. Reactions have occurred following the first dose or subsequent doses of Lycimin Tonic for Children with Iron (Iron). 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.

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7 DRUG INTERACTIONS

Drug interactions involving Lycimin Tonic for Children with Iron (Iron) have not been studied. However, Lycimin Tonic for Children with Iron (Iron) may reduce the absorption of concomitantly administered oral Lycimin Tonic for Children with Iron (Iron) 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, Lycimin Tonic for Children with Iron sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Lycimin Tonic for Children with Iron (Iron) (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 Lycimin Tonic for Children with Iron (Iron) sucrose. Because animal reproductive studies are not always predictive of human response, Lycimin Tonic for Children with Iron (Iron) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Lycimin Tonic for Children with Iron (Iron) sucrose is excreted in human milk. Lycimin Tonic for Children with Iron (Iron) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Lycimin Tonic for Children with Iron (Iron) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Lycimin Tonic for Children with Iron for Lycimin Tonic for Children with Iron (Iron) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

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

Lycimin Tonic for Children with Iron (Iron) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

Clinical studies of Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron), 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.

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10 OVERDOSAGE

No data are available regarding overdosage of Lycimin Tonic for Children with Iron (Iron) in humans. Excessive dosages of Lycimin Tonic for Children with Iron (Iron) may lead to accumulation of Lycimin Tonic for Children with Iron (Iron) in storage sites potentially leading to hemosiderosis. Do not administer Lycimin Tonic for Children with Iron (Iron) to patients with Lycimin Tonic for Children with Iron (Iron) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Lycimin Tonic for Children with Iron (Iron) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

Lycimin Tonic for Children with Iron (Iron) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) sucrose.

Lycimin Tonic for Children with Iron (Iron) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Lycimin Tonic for Children with Iron (Iron) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Lycimin Tonic for Children with Iron (Iron) sucrose at intravenous doses up to 15 mg/kg/day of elemental Lycimin Tonic for Children with Iron (Iron) (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 Lycimin Tonic for Children with Iron.

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 Lycimin Tonic for Children with Iron (Iron) treatment and 24 in the historical control group) with Lycimin Tonic for Children with Iron (Iron) deficiency anemia. Eligibility criteria for Lycimin Tonic for Children with Iron (Iron) 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.

Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron), who were off intravenous Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) 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
Lycimin Tonic for Children with Iron (Iron) (n=69 Historical Control (n=18) Lycimin Tonic for Children with Iron (Iron)

(n=73)

Historical Control

(n=18)

Lycimin Tonic for Children with Iron (Iron)

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

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

Lycimin Tonic for Children with Iron is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Lycimin Tonic for Children with Iron (Iron), each 5 mL vial contains 100 mg elemental Lycimin Tonic for Children with Iron (Iron), and each 2.5 mL vial contains 50 mg elemental Lycimin Tonic for Children with Iron (Iron) (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: Lycimin Tonic for Children with Iron (Iron), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Lycimin Tonic for Children with Iron (Iron) per mL, or undiluted (20 mg elemental Lycimin Tonic for Children with Iron (Iron) 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: Lycimin Tonic for Children with Iron (Iron), 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 Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) 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 Lycimin Tonic for Children with Iron (Iron) administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Lycimin Tonic for Children with Iron (Iron) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

Lysine Hydrochloride:


BOXED WARNING

Pharmacy Bulk Package

Not For Direct Infusion

DESCRIPTION

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% Amino Acids Injection in a Pharmacy Bulk Package is a sterile, clear, nonpyrogenic solution of essential and nonessential amino acids for intravenous infusion in parenteral nutrition following appropriate dilution.

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% in a Pharmacy Bulk Package is not for direct infusion. It is a sterile dosage from which contains several single doses for use in a pharmacy admixture program in the preparation of intravenous parenteral fluids.

Each 100 mL contains:


Essential Amino Acids


Lycimin Tonic for Children with Iron (Lysine Hydrochloride) (from Lycimin Tonic for Children with Iron (Lysine Hydrochloride) Acetate, USP)……………………………………................1.18


g


Leucine, USP……………………………………………………………..............1.04


g


Phenylalanine, USP……………………………………........................................1.04


g


Valine, USP……………………………………………………………..................960


mg


Isoleucine, USP………………………………………............................................749


mg


Methionine, USP………………………………………..........................................749


mg


Threonine, USP………………………………………............................................749


mg


Tryptophan, USP………………………………………..........................................250


mg


Nonessential Amino Acids


Alanine, USP…………………………………………..........................................2.17


g


Arginine, USP………………………………………….........................................1.47


g


Glycine, USP…………………………………………..........................................1.04


g


Histidine, USP………………………………………….........................................894


mg


Proline, USP…………………………………………………………….................894


mg


Glutamic Acid…………………………………………..........................................749


mg


Serine, USP……………………………………………..........................................592


mg


Aspartic Acid, USP……………………………………..........................................434


mg


Tyrosine, USP…………………………………………............................................39


mg


Sodium Metabisulfite, NF added……………………………………………...............30


mg


Water for Injection, USP……………………………………………………...................


qs


Essential Amino Acids……………………………………………………….............6.7


g


Nonessential Amino Acids………………………………………………….................8.3


g


Total Amino Acids…………………………………………………………...............15.0


g


Total Nitrogen………………………………………………………………..............2.37


g


Acetate*…………………………………………………….........................................151


mEq/L


Osmolarity (calculated)…………………………………….......................................1388


mOsmol/L


pH……………………………………………………………………………....................5.6(5.2-6.0)


*Acetate from Lycimin Tonic for Children with Iron (Lysine Hydrochloride) Acetate, USP and acetic acid used for pH adjustment.


The formulas for the individual amino acids are as follows:

Formulas for individual amino acids

CLINICAL PHARMACOLOGY

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% Amino Acids Injection providesseventeen crystalline amino acids. This completely utilizable substrate promotesprotein synthesis and wound healing and reduces the rate of protein catabolism.

A.Total Parenteral Nutrition (Central Infusion)

When enteralfeeding is inadvisable, Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% given by central venousinfusion in combination with energy sources, vitamins, trace elements andelectrolytes, will completely satisfy the requirements for weight maintenanceor weight gain, depending upon the dose selected. The energy component inparenteral nutrition by central infusion may be derived solely from dextroseor may be provided by a combination of dextrose and intravenous fat emulsion. The addition of intravenous fat emulsion provides essential fatty acids andpermits a dietary balance of fat and carbohydrate, at the same time offeringthe option of reducing the dextrose load and/or increasing the total caloricinput. An adequate energy supply is essential for optimal utilization of aminoacids.

B. Total Parenteral Nutrition (Peripheral Infusion)

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%can also be administered as part of a total parenteral nutrition program byperipheral vein when the enteral route is inadvisable and use of the centralvenous catheter is contraindicated.

Reduction of proteinloss can be achieved by use of diluted Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% in combinationwith dextrose or with dextrose and intravenous fat emulsion by peripheralinfusion. Complete peripheral intravenous nutrition can be achieved in patientswith low caloric requirements by a Lycimin Tonic for Children with Iron (Lysine Hydrochloride)®15%-dextrose-fatregimen.

INDICATIONS AND USAGE

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% is indicated as an amino acid(nitrogen) source in parenteral nutrition regimens. This use is appropriatewhen the enteral route is inadvisable, inadequate or not possible, as when:

-Gastrointestinal absorption is impaired by obstruction, inflammatory diseaseor its complications, or antineoplastic therapy;

-Bowel rest is needed because of gastrointestinal surgery or its complicationssuch as ileus, fistulae or anastomotic leaks;

-Tube feeding methods alone cannot provide adequate nutrition.

CONTRAINDICATIONS

This solution should not be used in patients in hepatic coma,severe renal failure, metabolic disorders involving impaired nitrogen utilizationor hypersensitivity to one or more amino acids.

WARNINGS

Administration of amino acids solutions at excessive ratesor to patients with hepatic insufficiency may result in plasma amino acidimbalances, hyperammonemia, prerenal azotemia, stupor and coma. Conservativedoses of amino acids should be given to these patients, dictated by the nutritionalstatus of the patient. Should symptoms of hyperammonemia develop, amino acidadministration should be discontinued and the patient’s clinical statusre-evaluated.

Contains sodium metabisulfite, a sulfitethat may cause allergic-type reactions including anaphylactic symptoms andlife-threatening or less severe asthmatic episodes in certain susceptiblepeople. The overall prevalence of sulfite sensitivity in the general populationis unknown and probably low.

Sulfite sensitivity isseen more frequently in asthmatic than in nonasthmatic people.

WARNING: This product contains aluminum that maybe toxic. Aluminum may reach toxic levels with prolonged parenteral administrationif kidney function is impaired. Premature neonates are particularly at riskbecause their kidneys are immature, and they require large amounts of calciumand phosphate solutions, which contain aluminum.

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

PRECAUTIONS

A. GENERAL

It is essential to provide adequate calories concurrently if parenterally administered amino acids are to be retained by the body and utilized for protein synthesis.

The administration of Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% Amino Acids Injection as part of total parenteral nutrition (TPN) with large volumes of hyperosmotic fluids requires periodic monitoring of the patient for signs of hyperosmolarity, hyperglycemia, glycosuria and hypertriglyceridemia.

During parenteral nutrition with concentrated dextrose and amino acids solutions, essential fatty acid deficiency syndrome may develop but may not be clinically apparent. Early demonstration of this condition can only be accomplished by gas liquid chromatographic analysis of plasma lipids. The syndrome may be prevented or corrected by appropriate treatment with intravenous fat emulsions.

For complete nutritional support, TPN regimens must also include multiple vitamins and trace elements. Potentially incompatible ions such as calcium and phosphate may be added to alternate infusate bottles to avoid precipitation. Although the metabolizable acetate ion in Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% diminishes the risk of acidosis, the physician must be alert to the potential appearance of this disorder.

Initiation and termination of infusions of TPN fluids must be gradual to permit adjustment of endogenous insulin release.

Undiluted Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% should not be administered peripherally. When administered centrally, it should be diluted with appropriate diluents, e.g., dextrose, electrolytes and other nutrient components, to at least half strength. See DOSAGE AND ADMINISTRATION.

Caution against volume overload should be exercised.

Drug product contains no more than 25 mcg/L of aluminum.

B. Laboratory Tests

Infusion of Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% without concomitant infusion of an adequate number of non-protein calories may result in elevated BUN. Monitoring of BUN is required and the balance between Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% and the calorie source may require adjustment. Frequent clinical evaluations and laboratory determinations are required to prevent the complications which may occur during the administration of solutions used in TPN. Laboratory tests should include blood glucose, serum electrolytes, liver and kidney function, serum osmolarity, blood ammonia, serum protein, pH, hematocrit, WBC and urinary glucose. When Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% is combined with electrolytes, care should be used in administering this solution to patients with congestive heart failure, renal failure, edema, adrenal hyperactivity, acid-base imbalance and those receiving diuretics or antihypertensive therapy. Total volume infused should be closely monitored. Serum electrolytes should be monitored daily in these patients.

C. Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies with Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

D. Pregnancy Category C

Animal reproduction studies have not been conducted with Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%. It is also not known whether Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% should be given to a pregnant woman only if clearly needed.

E. Nursing Mothers

Caution should be exercised when Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% is administered to a nursing woman.

F. Pediatric Use

Safety and effectiveness of Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% Amino Acids Injection in pediatric patients have not been established by adequate and well-controlled studies. However, the use of amino acids injections in pediatric patients as an adjunct in the offsetting of nitrogen loss or in the treatment of negative nitrogen balance is referenced in the medical literature.

G. Special Precautions for Central Infusion

TPN delivered by indwelling catheter through a central or large peripheral vein is a special technique requiring a team effort by physician, nurse and pharmacist. The responsibility for administering this therapy should be confined to those trained in the procedures and alert to signs of complications. Complications known to occur from the placement of central venous catheter are pneumothorax, hemothorax, hydrothorax, artery puncture and transection, injury to the brachial plexus, malposition of the catheter, formation of arteriovenous fistula, phlebitis, thrombosis, and air/catheter emboli. The risk of sepsis is present during intravenous therapy, especially when using central venous catheters for prolonged periods. It is imperative that the preparation of admixtures and the placement and care of the catheters be accomplished under controlled aseptic conditions.

H. Admixtures

Admixtures should be prepared under a laminar flow hood using aseptic technique.

Admixtures should be stored under refrigeration and must be administered within 24 hours after removal from refrigerator.

Filters of less than 1.2 micron pore size must not be used with admixtures containing fat emulsion.

I. Do not administer unless solution is clear and the seal is intact.

IT IS ESSENTIAL THAT A CAREFULLY PREPARED PROTOCOL, BASED ON CURRENT MEDICAL PRACTICES, BE FOLLOWED, PREFERABLY BY AN EXPERIENCED TEAM.

ADVERSE REACTIONS

OVERDOSAGE

In the event of overhydration or solute overload, re-evaluatethe patient and institute appropriate corrective measures. See WARNINGS andPRECAUTIONS.

DOSAGE AND ADMINISTRATION

The appropriate daily dose of amino acids to be used withdextrose or with dextrose and intravenous fat emulsion will depend upon themetabolic status and clinical response of the patient as therapy proceeds. Doses which achieve nitrogen equilibrium or positive balance are the mostdesirable. The dosage on the first day should be approximately half the anticipatedoptimal dosage and should be increased gradually to minimize glycosuria; similarly,withdrawal should be accomplished gradually to avoid rebound hypoglycemia.

Fatemulsion coadministration should be considered when prolonged (more than 5days) parenteral nutrition is required in order to prevent essential fattyacid deficiency (EFAD). Serum lipids should be monitored for evidence of EFADin patients maintained on fat free TPN.

The amount administeredis dosed on the basis of amino acids/kg of body weight/day. In general, twoto three g/kg of body weight for neonates and infants with adequate caloriesare sufficient to satisfy protein needs and promote positive nitrogen balance. In pediatric patients, the final solution should not exceed twice normal serumosmolarity (718 mOsmol/L).

DIRECTIONSFOR PROPER USE OF PHARMACY BULK PACKAGE

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%in a Pharmacy Bulk Package is not intended for direct infusion. The containerclosure may be penetrated only once using a suitable sterile transfer deviceor dispensing set which allows measured dispensing of the contents. The PharmacyBulk Package is to be used only in a suitable work area such as a laminarflow hood (or an equivalent clean air compounding area). Once the closureis penetrated, the contents should be dispensed as soon as possible; the transferof contents must be completed within 4 hours of closure entry. The bottlemay be stored at room temperature (25°C) after the closure has been entered. Date and time of container entry should be noted in the area designated onthe container label.

When using Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%in patients with a need for fluid volume restriction, it can be diluted asfollows:


Volume


Amount


FinalConcentration


Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%


500 mL


75 g


7.5%


Dextrose 70%


250 mL


175 g


17.5%


Intralipid® 20%


250 mL


50 g


5.0%


This will provide 1395 kilocalories (kcal) per 1000 mLof admixture with a ratio of 118 non-protein calories per gram of nitrogenand an osmolarity of 1561 mOsmol/L.

In patients wherethe need for fluid restriction is not so marked, either of the following regimensmay be used dependent upon the energy needs of the patient.


Volume


Amount


FinalConcentration


Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%


500 mL


75 g


3.75%


Dextrose 50%


1000 mL


500 g


25%


Intralipid® 20%


500 mL


100 g


5%


This will provide 1500 kcal per 1000 mL of admixture witha ratio of 228 non-protein calories per gram of nitrogen and an osmolarityof 1633 mOsmol/L.


Volume


Amount


FinalConcentration


Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%


500 mL


75 g


3.75%


Dextrose 30%


1000 mL


300 g


15%


Intralipid® 10%


500 mL


50 g


2.5%


This will provide 935 kcal per 1000 mL of admixture witha ratio of 158 non-protein calories per gram of nitrogen and an osmolarityof 1128.5 mOsmol/L.

A. Total Parenteral Nutrition (CentralInfusion)

In unstressed adult patients with no unusualnitrogen losses, a minimum dosage of 0.1 gram nitrogen (4.2 mL of Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%)plus 4.4 grams (15 calories) of dextrose per kilogram of body weight per dayare required to achieve nitrogen balance and weight stability. Intravenousfat emulsion may be used as a partial substitute for dextrose. This regimenprovides a ratio of 150 non-protein calories per gram of nitrogen.

Forpatients stressed by surgery, trauma or sepsis, and those with unusual nitrogenlosses, the dosage required for maintenance may be as high as 0.3 to 0.4 gramsof nitrogen (13 to 17 mL Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%) per kilogram of bodyweight per day, with proportionate increases in non-protein calories. Periodicassessment of nitrogen balance of the individual patient is the best indicatorof proper dosage. Volume overload and glycosuria may be encountered at highdosage, and nitrogen balance may not be achieved in extremely hypermetabolicpatients under these constraints. Concomitant insulin administration may berequired to minimize glycosuria. Daily laboratory monitoring is essential.

Useof an infusion pump is advisable to maintain a steady infusion rate duringcentral venous infusion.

B. Peripheral Nutrition

Inpatients for whom central venous catheterization is not advisable, proteincatabolism can be reduced by peripheral use of diluted Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%plus non-protein calorie sources. Dilution of 250 mL Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15%in 750 mL of 10% dextrose will reduce the osmolarity to a level (724 mOsmol/L)which is more favorable to the maintenance of the integrity of the walls ofthe veins. Intravenous fat emulsion can be infused separately or simultaneously;if infused simultaneously the fat emulsion will provide a dilution effectupon the osmolarity while increasing the energy supply.

Parenteraldrug products should be inspected visually for particulate matter and discolorationprior to administration, whenever solution and container permit.

Toreduce the risk of bacterial contamination, all intravenous administrationsets should be replaced at least every 24 hours. Usage of admixtures mustbe initiated within 24 hours after mixing. If storage is necessary duringthis 24 hour period, admixtures must be refrigerated and completely used within24 hours of beginning administration.

HOW SUPPLIED

Lycimin Tonic for Children with Iron (Lysine Hydrochloride)® 15% Amino Acids Injection is suppliedas a Pharmacy Bulk Package in 500 mL containers.

500mL NDC 0409-0468-05

STORAGE

Store inthe closed carton; do not expose solution to light until ready for use. Exposureof pharmaceutical products to heat should be minimized. Avoid excessive heat. It is recommended that the product be stored at 20 to 25°C (68 to 77°F). Brief exposure to temperatures above25°C during transport and storage will not adversely affect the product. Solution that has been frozen must not be used.


©Hospira 2005


EN-1010


Hospira, Inc., Lake Forest, IL 60045 USA

RL-1450

Lycimin Tonic for Children with Iron pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Lycimin Tonic for Children with Iron available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Lycimin Tonic for Children with Iron destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Lycimin Tonic for Children with Iron Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Lycimin Tonic for Children with Iron pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."NOVAFERRUM PEDIATRIC DROPS (IRON) LIQUID [GENSAVIS PHARMACEUTICALS, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "Iron". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "Iron". http://www.drugbank.ca/drugs/DB0159... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Lycimin Tonic for Children with Iron?

Depending on the reaction of the Lycimin Tonic for Children with Iron after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Lycimin Tonic for Children with Iron 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 Lycimin Tonic for Children with Iron 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.

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Review

sdrugs.com conducted a study on Lycimin Tonic for Children with Iron, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Lycimin Tonic for Children with Iron consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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