Nestosule-MV Drops

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Nestosule-MV Drops uses

Nestosule-MV Drops consists of Beta-Carotene, Iron (Ferric Ammonium Citrate), L-Lysine Hydrochloride, Manganese (Manganese Sulfate), Potassium Sulfate, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B3 (Niacinamide), Vitamin B5 (D-Panthenol), Vitamin B6, Vitamin C, Vitamin D, Vitamin H (Biotin), Zinc.

Iron (Ferric Ammonium Citrate):


1 INDICATIONS AND USAGE

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is indicated for the treatment of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) deficiency anemia in patients with chronic kidney disease (CKD).

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is an Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) replacement product indicated for the treatment of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Nestosule-MV Drops ) must only be administered intravenously either by slow injection or by infusion. The dosage of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is expressed in mg of elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)). Each mL contains 20 mg of elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)).

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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) should be administered early during the dialysis session. The usual total treatment course of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is 1000 mg. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) treatment may be repeated if Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

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

Administer Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)), 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. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) treatment may be repeated if Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) in a maximum of 250 mL of 0.9% NaCl. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) treatment may be repeated if Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) maintenance treatment

The dosing for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) maintenance treatment: Administer Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) maintenance treatment

The dosing for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) maintenance treatment: Administer Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) treatment may be repeated if necessary.

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3 DOSAGE FORMS AND STRENGTHS

  • 10 mL single-use vial / 200 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 5 mL single-use vial / 100 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 2.5 mL single-use vial / 50 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL)
  • 10 mL single-use vial / 200 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)
  • 5 mL single-use vial / 100 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)
  • 2.5 mL single-use vial / 50 mg elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (20 mg/mL) (3)

4 CONTRAINDICATIONS

  • Known hypersensitivity to Nestosule-MV Drops (Iron (Ferric Ammonium Citrate))
  • Known hypersensitivity to Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

Nestosule-MV Drops ) may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)). Hypotension following administration of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) may be related to the rate of administration and/or total dose administered .

5.3 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) Overload

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

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6 ADVERSE REACTIONS

The following serious adverse reactions associated with Nestosule-MV Drops ) are described in other sections .

  • The most common adverse reactions (≥2%) following the administration of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops ) has been documented in six clinical trials involving 231 patients with HDD-CKD, 139 patients with NDD-CKD and 75 patients with PDD-CKD. Treatment-emergent adverse reactions reported by ≥ 2% of treated patients in the six clinical trials for which the rate for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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
Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) Oral Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) therapy and were reported to be intolerant (defined as precluding further use of that Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) product). When these patients were treated with Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) there were no occurrences of adverse reactions that precluded further use of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) .

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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) maintenance treatment with Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 0.5 mg/kg, 53% (25/47) of the patients receiving Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 1.0 mg/kg, and 55% (26/47) of the patients receiving Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 2.0 mg/kg.

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness of Nestosule-MV Drops ) for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

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

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

Clinical studies of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)), 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) in humans. Excessive dosages of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) may lead to accumulation of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) in storage sites potentially leading to hemosiderosis. Do not administer Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) to patients with Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) sucrose.

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (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 Nestosule-MV Drops ).

14.1 Study A: Hemodialysis Dependent-Chronic Kidney Disease (HDD–CKD)

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

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)), who were off intravenous Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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
Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (n=69 Historical Control (n=18) Nestosule-MV Drops (Iron (Ferric Ammonium Citrate))

(n=73)

Historical Control

(n=18)

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate))

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

A statistically significantly greater proportion of Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) subjects (35/79; 44.3%) compared to oral Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) to patients with PDD-CKD receiving an erythropoietin alone without Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) or Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) / 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) / 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) / 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: Nestosule-MV Drops ) Maintenance Treatment Dosing in Pediatric Patients Ages 2 years and Older with Chronic Kidney Disease

Study F was a randomized, open-label, dose-ranging study for Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) (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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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 Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) 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

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Nestosule-MV Drops (Iron (Ferric Ammonium Citrate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

L-Lysine Hydrochloride:


Nestosule-MV Drops (L-Lysine Hydrochloride) (abbreviated as Lys or K) is an О±-amino acid with the chemical formula HO2CCH(CH2)4NH2. This amino acid is an essential amino acid, which means that humans cannot synthesize it. Its codons are AAA and AAG.L-Lysine is a base, as are arginine and histidine. The Оµ-amino group often participates in hydrogen bonding and as a general base in catalysis. Common posttranslational modifications include methylation of the Оµ-amino group, giving methyl-, dimethyl-, and trimethyllysine. The latter occurs in calmodulin. Other posttranslational modifications include acetylation. Collagen contains hydroxylysine which is derived from lysine by lysyl hydroxylase. O-Glycosylation of lysine residues in the endoplasmic reticulum or Golgi apparatus is used to mark certain proteins for secretion from the cell.

Indication: Supplemental Nestosule-MV Drops (L-Lysine Hydrochloride) has putative anti-herpes simplex virus activity. There is preliminary research suggesting that it may have some anti-osteoporotic activity.

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

Manganese (Manganese Sulfate):


INDICATIONS AND USAGE

Nestosule-MV Drops (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).

Administration helps to maintain Nestosule-MV Drops (Manganese (Manganese Sulfate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Nestosule-MV Drops (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.

Liver and/or biliary tract dysfunction may require omission or reduction of copper and Nestosule-MV Drops (Manganese (Manganese Sulfate)) doses because these elements are primarily eliminated in the bile.

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

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

PRECAUTIONS

General

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

Nestosule-MV Drops ) 0.1 mg/mL (Manganese Chloride Injection, USP) should only be used in conjunction with a pharmacy directed admixture program using aseptic technique in a laminar flow environment; it should be used promptly and in a single operation without any repeated penetrations. Solution contains no preservatives; discard unused portion immediately after admixture procedure is completed.

Laboratory Tests

Serum Nestosule-MV Drops (Manganese (Manganese Sulfate)) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Nestosule-MV Drops ) 0.1 mg/mL (Manganese Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nestosule-MV Drops (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C.

Animal reproduction studies have not been conducted with Nestosule-MV Drops (Manganese (Manganese Sulfate)) chloride. It is also not known whether Nestosule-MV Drops (Manganese (Manganese Sulfate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Nestosule-MV Drops (Manganese (Manganese Sulfate)) chloride should be given to a pregnant woman only if clearly indicated.

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Nestosule-MV Drops (Manganese (Manganese Sulfate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Nestosule-MV Drops (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) contains 0.1 mg manganese/mL and is administered intravenously only after dilution. The additive should be administered in a volume of fluid not less than 100 mL. For the adult receiving TPN, the suggested additive dosage for Nestosule-MV Drops (Manganese (Manganese Sulfate)) is 0.15 to 0.8 mg/day (1.5 to 8 mL/day). For pediatric patients, a dosage of 2 to 10 mcg manganese/kg/day (0.02 to 0.1 mL/kg/day) is recommended.

Periodic monitoring of Nestosule-MV Drops (Manganese (Manganese Sulfate)) plasma levels is suggested as a guideline for subsequent administration.

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

HOW SUPPLIED

Nestosule-MV Drops (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).

Store at 20 to 25°C (68 to 77°F)

Revised: November, 2009

Printed in USA EN-2320

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0104


Potassium Sulfate:



Nestosule-MV Drops (Potassium Sulfate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Nestosule-MV Drops (Potassium Sulfate) chloride containing 1500 mg of microencapsulated Nestosule-MV Drops (Potassium Sulfate) chloride, USP equivalent to 20 mEq of Nestosule-MV Drops (Potassium Sulfate) in a tablet.

These formulations are intended to slow the release of Nestosule-MV Drops (Potassium Sulfate) so that the likelihood of a high localized concentration of Nestosule-MV Drops (Potassium Sulfate) chloride within the gastrointestinal tract is reduced.

Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Nestosule-MV Drops (Potassium Sulfate) chloride, and the structural formula is KCl. Nestosule-MV Drops (Potassium Sulfate) chloride, USP occurs as a white, granular powder or as colorless crystals. It is odorless and has a saline taste. Its solutions are neutral to litmus. It is freely soluble in water and insoluble in alcohol.

Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Nestosule-MV Drops (Potassium Sulfate) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq begin disintegrating into microencapsulated crystals within seconds and completely disintegrates within 1 minute. The microencapsulated crystals are formulated to provide an extended release of Nestosule-MV Drops (Potassium Sulfate) chloride.

Inactive Ingredients: Colloidal silicon dioxide, crospovidone, diethyl phthalate, ethyl-cellulose, microcrystalline cellulose.

CLINICAL PHARMACOLOGY

The Nestosule-MV Drops (Potassium Sulfate) ion is the principal intracellular cation of most body tissues. Nestosule-MV Drops (Potassium Sulfate) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of Nestosule-MV Drops (Potassium Sulfate) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

Nestosule-MV Drops (Potassium Sulfate) is a normal dietary constituent and under steady-state conditions the amount of Nestosule-MV Drops (Potassium Sulfate) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Nestosule-MV Drops (Potassium Sulfate) is 50 to 100 mEq per day.

Nestosule-MV Drops (Potassium Sulfate) depletion will occur whenever the rate of Nestosule-MV Drops (Potassium Sulfate) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Nestosule-MV Drops (Potassium Sulfate) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Nestosule-MV Drops (Potassium Sulfate) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Nestosule-MV Drops (Potassium Sulfate) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Nestosule-MV Drops (Potassium Sulfate) depletion may produce weakness, fatigue, disturbances or cardiac rhythm (primarily ectopic beats), prominent U-waves in the electrocardiogram, and in advanced cases, flaccid paralysis and/or impaired ability to concentrate urine.

If Nestosule-MV Drops (Potassium Sulfate) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Nestosule-MV Drops (Potassium Sulfate) in the form of high Nestosule-MV Drops (Potassium Sulfate) food or Nestosule-MV Drops (Potassium Sulfate) chloride may be able to restore normal Nestosule-MV Drops (Potassium Sulfate) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Nestosule-MV Drops (Potassium Sulfate) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Nestosule-MV Drops (Potassium Sulfate) replacement should be accomplished with Nestosule-MV Drops (Potassium Sulfate) salts other than the chloride, such as Nestosule-MV Drops (Potassium Sulfate) bicarbonate, Nestosule-MV Drops (Potassium Sulfate) citrate, Nestosule-MV Drops (Potassium Sulfate) acetate, or Nestosule-MV Drops (Potassium Sulfate) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Nestosule-MV Drops (Potassium Sulfate) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Nestosule-MV Drops (Potassium Sulfate) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

1. For the treatment of patients with hypokalemia with or without metabolic alkalosis, in digitalis intoxication, and in patients with hypokalemic familial periodic paralysis. If hypokalemia is the result of diuretic therapy, consideration should be given to the use of a lower dose of diuretic, which may be sufficient without leading to hypokalemia.

2. For the prevention of hypokalemia in patients who would be at particular risk if hypokalemia were to develop, eg, digitalized patients or patients with significant cardiac arrhythmias.

The use of Nestosule-MV Drops (Potassium Sulfate) salts in patients receiving diuretics for uncomplicated essential hypertension is often unnecessary when such patients have a normal dietary pattern and when low doses of the diuretic are used. Serum Nestosule-MV Drops (Potassium Sulfate) should be checked periodically, however, and if hypokalemia occurs, dietary supplementation with potassium-containing foods may be adequate to control milder cases. In more severe cases, and if dose adjustment of the diuretic is ineffective or unwarranted, supplementation with Nestosule-MV Drops (Potassium Sulfate) salts may be indicated.

CONTRAINDICATIONS

Nestosule-MV Drops (Potassium Sulfate) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Nestosule-MV Drops (Potassium Sulfate) concentration in such patients can produce cardiac arrest. Hyperkalemia may complicate any of the following conditions: chronic renal failure, systemic acidosis, such as diabetic acidosis, acute dehydration, extensive tissue breakdown as in severe burns, adrenal insufficiency, or the administration of a potassium-sparing diuretic (eg, spironolactone, triamterene, amiloride) (see OVERDOSAGE ).

Controlled-release formulations of Nestosule-MV Drops (Potassium Sulfate) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Nestosule-MV Drops (Potassium Sulfate) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Nestosule-MV Drops (Potassium Sulfate) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Nestosule-MV Drops (Potassium Sulfate) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

In patients with impaired mechanisms for excreting Nestosule-MV Drops (Potassium Sulfate), the administration of Nestosule-MV Drops (Potassium Sulfate) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Nestosule-MV Drops (Potassium Sulfate) by the intravenous route but may also occur in patients given Nestosule-MV Drops (Potassium Sulfate) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Nestosule-MV Drops (Potassium Sulfate) salts in patients with chronic renal disease, or any other condition which impairs Nestosule-MV Drops (Potassium Sulfate) excretion, requires particularly careful monitoring of the serum Nestosule-MV Drops (Potassium Sulfate) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Nestosule-MV Drops (Potassium Sulfate) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Nestosule-MV Drops (Potassium Sulfate) retention by inhibiting aldosterone production. Nestosule-MV Drops (Potassium Sulfate) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Nestosule-MV Drops (Potassium Sulfate) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Nestosule-MV Drops (Potassium Sulfate) chloride are associated with an increased frequency of small bowel lesions (40-50 per 100,000 patient years) compared to sustained release wax matrix formulations (less than one per 100,000 patient years). Because of the lack of extensive marketing experience with microencapsulated products, a comparison between such products and wax matrix or enteric-coated products is not available. Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Nestosule-MV Drops (Potassium Sulfate) chloride and thus to minimize the possibility of a high local concentration of Nestosule-MV Drops (Potassium Sulfate) near the gastrointestinal wall.

Prospective trials have been conducted in normal human volunteers in which the upper gastrointestinal tract was evaluated by endoscopic inspection before and after 1 week of solid oral Nestosule-MV Drops (Potassium Sulfate) chloride therapy. The ability of this model to predict events occurring in usual clinical practice is unknown. Trials which approximated usual clinical practice did not reveal any clear differences between the wax matrix and microencapsulated dosage forms. In contrast, there was a higher incidence of gastric and duodenal lesions in subjects receiving a high dose of a wax matrix controlled-release formulation under conditions which did not resemble usual or recommended clinical practice (ie, 96 mEq per day in divided doses of Nestosule-MV Drops (Potassium Sulfate) chloride administered to fasted patients, in the presence of an anticholinergic drug to delay gastric emptying). The upper gastrointestinal lesions observed by endoscopy were asymptomatic and were not accompanied by evidence of bleeding (Hemoccult testing). The relevance of these findings to the usual conditions (ie, non-fasting, no anticholinergic agent, smaller doses) under which controlled-release Nestosule-MV Drops (Potassium Sulfate) chloride products are used is uncertain; epidemiologic studies have not identified an elevated risk, compared to microencapsulated products, for upper gastrointestinal lesions in patients receiving wax matrix formulations. Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq should be discontinued immediately and the possibility of ulceration, obstruction, or perforation should be considered if severe vomiting, abdominal pain, distention, or gastrointestinal bleeding occurs.

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Nestosule-MV Drops (Potassium Sulfate) salt such as Nestosule-MV Drops (Potassium Sulfate) bicarbonate, Nestosule-MV Drops (Potassium Sulfate) citrate, Nestosule-MV Drops (Potassium Sulfate) acetate, or Nestosule-MV Drops (Potassium Sulfate) gluconate.

PRECAUTIONS

General

The diagnosis of Nestosule-MV Drops depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Nestosule-MV Drops (Potassium Sulfate) depletion. In interpreting the serum Nestosule-MV Drops (Potassium Sulfate) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Nestosule-MV Drops (Potassium Sulfate) while acute acidosis per se can increase the serum Nestosule-MV Drops (Potassium Sulfate) concentration into the normal range even in the presence of a reduced total body Nestosule-MV Drops (Potassium Sulfate). The treatment of Nestosule-MV Drops (Potassium Sulfate) depletion, particularly in the presence of cardiac disease, renal disease, or acidosis requires careful attention to acid-base balance and appropriate monitoring of serum electrolytes, the electrocardiogram, and the clinical status of the patient.

Information for Patients

Physicians should consider reminding the patient of the following: To take each dose with meals and with a full glass of water or other liquid. To take each dose without crushing, chewing, or sucking the tablets. If those patients are having difficulty swallowing whole tablets, they may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:

    1. Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).

    2. Allow approximately 2 minutes for the tablet(s) to disintegrate.

    3. Stir for about half a minute after the tablet(s) has disintegrated.

    4. Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.

    5. Add another 1 fluid ounce of water, swirl, and consume immediately.

    6. Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.


Aqueous suspension of Nestosule-MV Drops (Potassium Sulfate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

To take this medicine following the frequency and amount prescribed by the physician. This is especially important if the patient is also taking diuretics and/or digitalis preparations.

To check with the physician at once if tarry stools or other evidence of gastrointestinal bleeding is noticed.

Laboratory Tests

When blood is drawn for analysis of plasma Nestosule-MV Drops it is important to recognize that artifactual elevations can occur after improper venipuncture technique or as a result of in vitro hemolysis of the sample.

Drug Interactions

Potassium-sparing diuretics, angiotensin-converting enzyme inhibitors (see WARNINGS ).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Nestosule-MV Drops is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Nestosule-MV Drops (Potassium Sulfate) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Nestosule-MV Drops ion content of human milk is about 13 mEq per liter. Since oral Nestosule-MV Drops (Potassium Sulfate) becomes part of the body Nestosule-MV Drops (Potassium Sulfate) pool, so long as body Nestosule-MV Drops (Potassium Sulfate) is not excessive, the contribution of Nestosule-MV Drops (Potassium Sulfate) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of Nestosule-MV Drops (Potassium Sulfate) Chloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection; and it may be useful to monitor renal function.

ADVERSE REACTIONS

One of the most severe adverse effects is hyperkalemia (see CONTRAINDICATIONS , WARNINGS , and OVERDOSAGE ). There have also been reports of upper and lower gastrointestinal conditions including obstruction, bleeding, ulceration, and perforation (see CONTRAINDICATIONS and WARNINGS ). The most common adverse reactions to oral Nestosule-MV Drops (Potassium Sulfate) salts are nausea, vomiting, flatulence, abdominal pain/discomfort, and diarrhea. These symptoms are due to irritation of the gastrointestinal tract and are best managed by diluting the preparation further, taking the dose with meals or reducing the amount taken at one time.

OVERDOSAGE

The administration of oral Nestosule-MV Drops (Potassium Sulfate) salts to persons with normal excretory mechanisms for Nestosule-MV Drops (Potassium Sulfate) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Nestosule-MV Drops (Potassium Sulfate) is administered too rapidly intravenously, potentially fatal hyperkalemia can result (see CONTRAINDICATIONS and WARNINGS ). It is important to recognize that hyperkalemia is usually asymptomatic and may be manifested only by an increased serum Nestosule-MV Drops (Potassium Sulfate) concentration (6.5-8.0 mEq/L) and characteristic electrocardiographic changes (peaking of T-waves, loss of P-waves, depression of S-T segment, and prolongation of the QT-interval). Late manifestations include muscle paralysis and cardiovascular collapse from cardiac arrest (9-12 mEq/L).

Treatment measures for hyperkalemia include the following:

  • Patients should be closely monitored for arrhythmias and electrolyte changes.
  • Elimination of foods and medications containing Nestosule-MV Drops (Potassium Sulfate) and of any agents with potassium-sparing properties such as potassium-sparing diuretics, ARBS, ACE inhibitors, NSAIDS, certain nutritional supplements and many others.
  • Intravenous calcium gluconate if the patient is at no risk of developing digitalis toxicity.
  • Intravenous administration of 300 to 500 mL/hr of 10% dextrose solution containing 10-20 units of crystalline insulin per 1,000 mL.
  • Correction of acidosis, if present, with intravenous sodium bicarbonate.
  • Use of exchange resins, hemodialysis, or peritoneal dialysis.

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Nestosule-MV Drops (Potassium Sulfate) concentration can produce digitalis toxicity.

The extended release feature means that absorption and toxic effects may be delayed for hours.

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Nestosule-MV Drops (Potassium Sulfate) by the average adult is 50 to 100 mEq per day. Nestosule-MV Drops (Potassium Sulfate) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Nestosule-MV Drops (Potassium Sulfate) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Nestosule-MV Drops (Potassium Sulfate) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Nestosule-MV Drops (Potassium Sulfate) chloride.

Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

Patients having difficulty swallowing whole tablets may try one of the following alternate methods of administration:

  • Break the tablet in half, and take each half separately with a glass of water.
  • Prepare an aqueous (water) suspension as follows:
    • Place the whole tablet(s) in approximately 1/2 glass of water (4 fluid ounces).
    • Allow approximately 2 minutes for the tablet(s) to disintegrate.
    • Stir for about half a minute after the tablet(s) has disintegrated.
    • Swirl the suspension and consume the entire contents of the glass immediately by drinking or by the use of a straw.
    • Add another 1 fluid ounce of water, swirl, and consume immediately.
    • Then, add an additional 1 fluid ounce of water, swirl, and consume immediately.

Aqueous suspension of Nestosule-MV Drops (Potassium Sulfate) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Nestosule-MV Drops (Potassium Sulfate) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

Keep tightly closed. Store at controlled room temperature, 20°-25°C (68°-77°F).

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Nestosule-MV Drops (Potassium Sulfate) chloride 20 Meq

Vitamin B12:


Pharmacological action

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

Pharmacokinetics

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

Why is Nestosule-MV Drops prescribed?

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

Dosage and administration

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

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

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

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

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

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

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

Nestosule-MV Drops (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Nestosule-MV Drops contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Nestosule-MV Drops using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

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

Nestosule-MV Drops (Vitamin B12) drug interactions

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

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

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

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

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

Pharmaceutical incompatibility

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

Vitamin C:


Pharmacological action

Ascorbic acid is essential for the formation of intracellular collagen, is required to strengthen the structure of teeth, bones, and the capillary walls. Nestosule-MV Drops (Vitamin C) participates in redox reactions, the metabolism of tyrosine, converting folic acid into folinic acid, metabolism of carbohydrates, the synthesis of lipids and proteins, iron metabolism, processes of cellular respiration. Reduces the need for vitamins B1, B2, A, E, folic acid, pantothenic acid, enhances the body's resistance to infections; enhances iron absorption, contributing to its sequestration in reduced form. Nestosule-MV Drops (Vitamin C) has antioxidant properties.

With intravaginal application of ascorbic acid lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

Pharmacokinetics

After oral administration ascorbic acid is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.

The concentration of ascorbic acid in blood plasma in normal amounts to approximately 10-20 mg / ml.

The concentration of ascorbic acid in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.

Plasma protein binding is about 25%.

Ascorbic acid is reversibly oxidized to form dehydroascorbic acid, is metabolized with the formation of ascorbate-2-sulphate which is inactive and oxalic acid which is excreted in the urine.

Ascorbic acid taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.

Why is Nestosule-MV Drops prescribed?

For systemic use of Nestosule-MV Drops (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Nestosule-MV Drops (Vitamin C); providing increased need for Nestosule-MV Drops (Vitamin C) during growth, pregnancy, lactation, with heavy loads, fatigue and during recovery after prolonged severe illness; in winter with an increased risk of infectious diseases.

For intravaginal use: chronic or recurrent vaginitis (bacterial vaginosis, nonspecific vaginitis) caused by the anaerobic flora (due to changes in pH of the vagina) in order to normalize disturbed vaginal microflora.

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

For the prevention of deficiency conditions Nestosule-MV Drops dose is 25-75 mg / day, for the treatment - 250 mg / day or more in divided doses.

For intravaginal used ascorbic acid drugs in appropriate dosage forms.

Nestosule-MV Drops (Vitamin C) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

Allergic reaction: describes a few cases of skin reactions and manifestations of the respiratory system.

Urinary system: when used in high doses - hyperoxaluria and the formation of kidney stones of calcium oxalate.

Local reactions: with intravaginal application - a burning or itching in the vagina, increased mucous discharge, redness, swelling of the vulva. Other: sensation of heat.

Nestosule-MV Drops contraindications

Increased sensitivity to ascorbic acid.

Using during pregnancy and breastfeeding

The minimum daily requirement of ascorbic acid in the II and III trimester of pregnancy is about 60 mg.

Ascorbic acid crosses the placental barrier. It should be borne in mind that the fetus can adapt to high doses of ascorbic acid, which takes a pregnant woman, and then a newborn baby may develop the ascorbic disease as the reaction of cancel. Therefore, during pregnancy should not to take ascorbic acid in high doses, except in cases where the expected benefit outweighs the potential risk.

The minimum daily requirement during lactation is 80 mg. Ascorbic acid is excreted in breast milk. A mother's diet that contains adequate amounts of ascorbic acid, is sufficient to prevent deficiency in an infant. It is unknown whether dangerous to the child's mother use of ascorbic acid in high doses. Theoretically it is possible. Therefore, it is recommended not to exceed the maximum daily nursing mother needs to ascorbic acid, except when the expected benefit outweighs the potential risk.

Special instructions

Nestosule-MV Drops (Vitamin C) is used with caution in patients with hyperoxaluria, renal impairment, a history of instructions on urolithiasis. Because ascorbic acid increases iron absorption, its use in high doses can be dangerous in patients with hemochromatosis, thalassemia, polycythemia, leukemia, and sideroblastic anemia.

Patients with high content body iron should apply ascorbic acid in minimal doses.

Nestosule-MV Drops (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of ascorbic acid in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of ascorbic acid are contradictory. However, prolonged use of ascorbic acid should periodically monitor your blood glucose levels.

It is believed that the use of ascorbic acid in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in ascorbic acid in patients with advanced cancer.

Absorption of ascorbic acid decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Nestosule-MV Drops drug interactions

In an application with barbiturates, primidone increases the excretion of ascorbic acid in the urine.

With the simultaneous use of oral contraceptives reduces the concentration of ascorbic acid in blood plasma.

In an application of Nestosule-MV Drops (Vitamin C) with iron preparations ascorbic acid, due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Ascorbic acid in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of ascorbic acid by about a third.

Nestosule-MV Drops (Vitamin C) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of ascorbic acid increases the excretion of iron in patients receiving deferoxamine. In the application of ascorbic acid at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of ascorbic acid in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with ascorbic acid 500 mg 2 times / day.

May increase the concentration of ethinyl estradiol in the blood plasma in its simultaneous application in the oral contraceptives.

Nestosule-MV Drops in case of emergency / overdose

Symptoms: long-term use of large doses (more than 1 g) - headache, increased CNS excitability, insomnia, nausea, vomiting, diarrhea, gastritis giperatsidnyh, ultseratsiya gastrointestinal mucosa, inhibition of the function insular apparatus of the pancreas (hyperglycemia, glycosuria), hyperoxaluria, nephrolithiasis (calcium oxalate), damage to the glomerular apparatus of the kidneys, moderate thamuria (when receiving a dose of 600 mg / day).

Decrease capillary permeability (possibly deteriorating trophic tissues, increased blood pressure, hypercoagulability, the development of microangiopathy).

When IV administration in high doses - the threat of termination of pregnancy (due to estrogenemia), hemolysis of red blood cells.

Zinc:


INDICATIONS AND USAGE

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

CONTRAINDICATIONS

None known.

WARNINGS

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

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

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

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

PRECAUTIONS

General

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

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

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

Laboratory Tests

Periodic determinations of serum copper as well as Nestosule-MV Drops (Zinc) are suggested as a guideline for subsequent Nestosule-MV Drops (Zinc) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

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

Nursing Mothers

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

Pediatric Use

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

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

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

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

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

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

Calcium supplements may confer a protective effect against Nestosule-MV Drops (Zinc) toxicity.

DOSAGE AND ADMINISTRATION

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

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

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

HOW SUPPLIED

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

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004


© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Nestosule-MV Drops (Zinc)

1 mg/mL

Nestosule-MV Drops (Zinc) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Nestosule-MV Drops 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.


Nestosule-MV Drops 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.


Nestosule-MV Drops 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.


Nestosule-MV Drops 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.


Nestosule-MV Drops 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."ZINC INJECTABLE A 1MG/ML, SOLUTION INJECTABLE POUR PERFUSION (ZINC) INJECTION, SOLUTION [LABORATOIRE AGUETTANT]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."BETA CAROTENE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "beta-carotene". https://pubchem.ncbi.nlm.nih.gov/su... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Nestosule-MV Drops?

Depending on the reaction of the Nestosule-MV Drops after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Nestosule-MV Drops 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 Nestosule-MV Drops 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 Nestosule-MV Drops, 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 Nestosule-MV Drops 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. Rachana Salvi, MD Pharmacology

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