Multiminerals

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Multiminerals uses

Multiminerals consists of Calcium (Calcium Citrate), Chromium (Chromium Chloride), Copper (Copper Gluconate), Iodine (Kelp), Iron (Ferrous Proteinate), Magnesium (Magnesium Oxide), Manganese (Manganese HVP Chelate), Potassium (Potassium HVP Chelate), Selenium (Yeast), Zinc (Zinc HVP Chelate).

Calcium (Calcium Citrate):


1 INDICATIONS AND USAGE

Multiminerals (Calcium (Calcium Citrate)) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

- Calcium acetate is a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. (1)

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of Multiminerals (Calcium (Calcium Citrate)) acetate for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal.

- Starting dose is 2 capsules with each meal. (2)

- Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. (2)

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Multiminerals (Calcium (Calcium Citrate)) acetate capsule.

- Capsule: 667 mg Multiminerals (Calcium (Calcium Citrate)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Multiminerals ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Multiminerals (Calcium (Calcium Citrate)) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with Multiminerals (Calcium (Calcium Citrate)), including Multiminerals (Calcium (Calcium Citrate)) acetate. Avoid the use of Multiminerals (Calcium (Calcium Citrate)) supplements, including Multiminerals (Calcium (Calcium Citrate)) based nonprescription antacids, concurrently with Multiminerals (Calcium (Calcium Citrate)) acetate.

An overdose of Multiminerals (Calcium (Calcium Citrate)) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Multiminerals (Calcium (Calcium Citrate)) levels twice weekly. Should hypercalcemia develop, reduce the Multiminerals (Calcium (Calcium Citrate)) acetate dosage, or discontinue the treatment, depending on the severity of hypercalcemia

More severe hypercalcemia (Ca >12 mg/dL) is associated with confusion, delirium, stupor and coma. Severe hypercalcemia can be treated by acute hemodialysis and discontinuing Multiminerals (Calcium (Calcium Citrate)) acetate therapy.

Mild hypercalcemia (10.5 to 11.9 mg/dL) may be asymptomatic or manifest as constipation, anorexia, nausea, and vomiting. Mild hypercalcemia is usually controlled by reducing the Multiminerals (Calcium (Calcium Citrate)) acetate dose or temporarily discontinuing therapy. Decreasing or discontinuing Vitamin D therapy is recommended as well.

Chronic hypercalcemia may lead to vascular calcification and other soft-tissue calcification. Radiographic evaluation of suspected anatomical regions may be helpful in early detection of soft tissue calcification. The long term effect of Multiminerals (Calcium (Calcium Citrate)) acetate on the progression of vascular or soft tissue calcification has not been determined.

Hypercalcemia (>11 mg/dL) was reported in 16% of patients in a 3 month study of solid dose formulation of Multiminerals (Calcium (Calcium Citrate)) acetate; all cases resolved upon lowering the dose or discontinuing treatment.

Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg2/dL2.

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

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6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

- The most common (>10%) adverse reactions are hypercalcemia, nausea and vomiting. (6.1)

- In clinical studies, patients have occasionally experienced nausea during Multiminerals (Calcium (Calcium Citrate)) acetate therapy. (6)

To report SUSPECTED ADVERSE REACTIONS, contact West-Ward Pharmaceuticals Corp. at 1-800-962-8364 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In clinical studies, Multiminerals (Calcium (Calcium Citrate)) acetate has been generally well tolerated.

Multiminerals (Calcium (Calcium Citrate)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Multiminerals (Calcium (Calcium Citrate)) acetate was studied in a two week double-blind, placebo-controlled, cross-over study with 69 enrolled ESRD hemodialysis patients. Adverse reactions (>2% on treatment) from these trials are presented in Table 1.


Preferred Term


Total adverse reactions reported for Multiminerals (Calcium (Calcium Citrate)) acetate

N=167

N (%)


3 month, open label study of Multiminerals (Calcium (Calcium Citrate)) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Multiminerals (Calcium (Calcium Citrate)) acetate

N=69


Multiminerals (Calcium (Calcium Citrate)) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Multiminerals (Calcium (Calcium Citrate)) concentration could reduce the incidence and severity of Multiminerals (Calcium (Calcium Citrate)) acetate-induced hypercalcemia. Isolated cases pruritus have been reported, which may represent allergic reactions.

6.2 Postmarketing Experience

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.

The following additional adverse reactions have been identified during post-approval of Multiminerals (Calcium (Calcium Citrate)) acetate: dizziness, edema, and weakness.

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7 DRUG INTERACTIONS

The drug interaction of Multiminerals ) acetate is characterized by the potential of Multiminerals (Calcium (Calcium Citrate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Multiminerals (Calcium (Calcium Citrate)) acetate may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism.

There are no empirical data on avoiding drug interactions between Multiminerals (Calcium (Calcium Citrate)) acetate and most concomitant drugs. When administering an oral medication with Multiminerals (Calcium (Calcium Citrate)) acetate where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after Multiminerals (Calcium (Calcium Citrate)) acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of Multiminerals (Calcium (Calcium Citrate)) acetate.

- Calcium acetate may decrease the bioavailability of tetracyclines or fluoroquinolones. (7)

- When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after Multiminerals (Calcium (Calcium Citrate)) acetate or consider monitoring blood levels of the drug. (7)

7.1 Ciprofloxacin

In a study of 15 healthy subjects, a co-administered single dose of 4 Multiminerals (Calcium (Calcium Citrate)) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Multiminerals ) acetate capsules contains Multiminerals (Calcium (Calcium Citrate)) acetate. Animal reproduction studies have not been conducted with Multiminerals (Calcium (Calcium Citrate)) acetate, and there are no adequate and well controlled studies of Multiminerals (Calcium (Calcium Citrate)) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Multiminerals (Calcium (Calcium Citrate)) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Multiminerals (Calcium (Calcium Citrate)) levels is important for maternal and fetal well being. Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. Multiminerals (Calcium (Calcium Citrate)) acetate treatment, as recommended, is not expected to harm a fetus if maternal Multiminerals (Calcium (Calcium Citrate)) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Multiminerals (Calcium (Calcium Citrate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Multiminerals ) Acetate Capsules contains Multiminerals (Calcium (Calcium Citrate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Multiminerals (Calcium (Calcium Citrate)) acetate is not expected to harm an infant, provided maternal serum Multiminerals (Calcium (Calcium Citrate)) levels are appropriately monitored.

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

Clinical studies of Multiminerals (Calcium (Calcium Citrate)) acetate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other clinical experience has not identified differences in responses 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.

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10 OVERDOSAGE

Administration of Multiminerals (Calcium (Calcium Citrate)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Multiminerals (Calcium (Calcium Citrate)) acetate acts as a phosphate binder. Its chemical name is Multiminerals (Calcium (Calcium Citrate)) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:


Each white opaque/blue opaque capsule contains 667 mg of Multiminerals (Calcium (Calcium Citrate)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Multiminerals (Calcium (Calcium Citrate)), polyethylene glycol 8000 and magnesium stearate. Each capsule shell contains: black monogramming ink, FD&C Blue #1, FD&C Red #3, gelatin and titanium dioxide. The black monogramming ink contains: ammonium hydroxide, iron oxide black, isopropyl alcohol, n-butyl alcohol, propylene glycol and shellac glaze.

Multiminerals (Calcium (Calcium Citrate)) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

Patients with ESRD retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum Multiminerals ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Multiminerals (Calcium (Calcium Citrate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Multiminerals (Calcium (Calcium Citrate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Multiminerals (Calcium (Calcium Citrate)) acetate from pharmaceutical dosage forms is systemically absorbed up to approximately 40% under fasting conditions and up to approximately 30% under nonfasting conditions. This range represents data from both healthy subjects and renal dialysis patients under various conditions.

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Multiminerals (Calcium (Calcium Citrate)) acetate.

14 CLINICAL STUDIES

Effectiveness of Multiminerals (Calcium (Calcium Citrate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Multiminerals (Calcium (Calcium Citrate)) acetate solid oral dosage form.

Ninety-one patients with end-stage renal disease who were undergoing hemodialysis and were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a 1 week phosphate binder washout period contributed efficacy data to an open-label, non-randomized study.

The patients received Multiminerals (Calcium (Calcium Citrate)) acetate 667 mg tablets at each meal for a period of 12 weeks. The initial starting dose was 2 tablets per meal for 3 meals a day, and the dose was adjusted as necessary to control serum phosphorus levels. The average final dose after 12 weeks of treatment was 3.4 tablets per meal. Although there was a decrease in serum phosphorus, in the absence of a control group the true magnitude of effect is uncertain.

The data presented in Table 2 demonstrate the efficacy of Multiminerals (Calcium (Calcium Citrate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Multiminerals (Calcium (Calcium Citrate)) levels are also presented.


* Ninety-one patients completed at least 6 weeks of the study.

ANOVA of difference in values at pre-study and study completion.

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Multiminerals (Calcium (Calcium Citrate)) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Multiminerals (Calcium (Calcium Citrate)) increased 9% during the study mostly in the first month of the study.

Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Patients were randomized to receive Multiminerals (Calcium (Calcium Citrate)) acetate or placebo, and each continued to receive the same number of tablets as had been individually established during the previous study. Following 2 weeks of treatment, patients switched to the alternative therapy for an additional 2 weeks.

The phosphate binding effect of Multiminerals (Calcium (Calcium Citrate)) acetate is shown in the Table 3.


* ANOVA of Multiminerals (Calcium (Calcium Citrate)) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Multiminerals (Calcium (Calcium Citrate)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Multiminerals (Calcium (Calcium Citrate)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


Overall, 2 weeks of treatment with Multiminerals (Calcium (Calcium Citrate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Multiminerals (Calcium (Calcium Citrate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Multiminerals (Calcium (Calcium Citrate)) Acetate Capsules

667 mg capsule is supplied as a white opaque/blue opaque capsule, imprinted with “54 215” on the cap and body.

NDC 0615-2303-39: Blistercards of 30 Capsules

NDC 0615-2303-30: Unit-dose Boxes of 30 Capsules

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

Inform patients to take Multiminerals (Calcium (Calcium Citrate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Multiminerals (Calcium (Calcium Citrate)) supplements including nonprescription antacids. Inform the patients about the symptoms of hypercalcemia [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ].

Advise patients who are taking an oral medication where reduction in the bioavailability of that medication would have clinically significant effect on its safety or efficacy to take the drug one hour before or three hours after Multiminerals (Calcium (Calcium Citrate)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Copper (Copper Gluconate):



Water-Resistant Protection Without Bandaging

Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Multiminerals (Copper (Copper Gluconate)) Naphthenate.

For Animal Use Only.

INDICATIONS:

ThrushTox® is indicated in the treatment of thrush in horses and ponies.

GENERAL DIRECTIONS:

Clean the hoof thoroughly, removing debris and necrotic material prior to application of Multiminerals (Copper (Copper Gluconate))®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Multiminerals (Copper (Copper Gluconate))® onto hair since contact with Multiminerals (Copper (Copper Gluconate))® may cause some hair loss. Do not contaminate feed.

NOTE: Multiminerals (Copper (Copper Gluconate))® is easily removed from hands, clothing and surfaces with light grade fuel oil or any type of lighter fluid.

CONTAINS FOIL SEAL – REMOVE BEFORE USE.

SHAKE WELL BEFORE USE.

To report suspected adverse reactions or to obtain technical assistance, call 1-800-650-4899.

ACTIVE INGREDIENT:

Multiminerals (Copper (Copper Gluconate)) Naphthenate...37.5% w/w

INACTIVE INGREDIENTS:

Inert Ingredients...62.5% w/w

Total... 100.0%

CAUTION:

Do not use in horses intended for human consumption.

CAUTION: COMBUSTIBLE MIXTURE.

Use in a well-ventilated place. Avoid fire, flame, sparks or heaters.

If swallowed, do not induce vomiting, call physician immediately. Avoid breathing vapor. Avoid contact with skin and eyes.

KEEP OUT OF REACH OF CHILDREN AND PETS.

STORAGE:

Store at controlled room temperature 15º to 30ºC (59º to 86ºF). Keep container tightly closed when not in use.

Manufactured for:

Aspen Veterinary Resources,® Ltd.

Liberty, MO 64068, USA

FC163FP 11/13

Manufactured by:

First Priority, Inc.

Elgin, IL 60123-1146, USA

NET CONTENTS:

16 OZ (473 mL)

ANADA 200-304, Approved by FDA

Image of 473 mL bottle/case label

Iodine (Kelp):


Multiminerals ) Tincture 7%

Directions:


Topical Antiseptic

Use full Strength for superficial cuts, wounds, abrasions, insect bites and bruises on the skin of animals. Apply Multiminerals (Iodine (Kelp)) with a swab.

If necessary, clip hair around the area being treated and clean with soap and water.

Apply Multiminerals (Iodine (Kelp)) Tincture 7% only once daily. Dilute product 3 to 1 if repeating application.

Do not apply under bandage.

Irritation may occur if used on tender skin areas. If redness, irritation, or swelling persists or increases, discontinue use and consult a veterinarian.


Storage:

Store at 2-30 degrees C (36-86 degrees F).

Keep container away from heat and out of sunlight. Rinse empty container thoroughly and discard.


DANGER - Poison


Caution:

If swallowed, give starch paste, milk, bread, egg white, or

activated charcoal. A 5% solutions of sodium thiosulfate

(Photographic (“hypc”) may be administered orally at a

rate of 10 ml per kilogram of body weight.


Eye irritant: Use only as directed. Avoid contact with eyes. In case of contact, flush eyes immediately with tepid water for at least 15 minutes. Consult a physician.


Avoid contamination of food.


Not for use on burns, deep cuts, or body cavities.

Multiminerals ) Tincture 7%

image description

Iron (Ferrous Proteinate):


1 INDICATIONS AND USAGE

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

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

2 DOSAGE AND ADMINISTRATION

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

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

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

Administer Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)), 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. Multiminerals (Iron (Ferrous Proteinate)) treatment may be repeated if Multiminerals (Iron (Ferrous Proteinate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

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

2.4 Pediatric Patients with HDD-CKD for Multiminerals (Iron (Ferrous Proteinate)) maintenance treatment

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

For Multiminerals (Iron (Ferrous Proteinate)) maintenance treatment: Administer Multiminerals (Iron (Ferrous Proteinate)) 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. Multiminerals (Iron (Ferrous Proteinate)) treatment may be repeated if necessary.

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

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

For Multiminerals (Iron (Ferrous Proteinate)) maintenance treatment: Administer Multiminerals (Iron (Ferrous Proteinate)) 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. Multiminerals (Iron (Ferrous Proteinate)) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

  • Known hypersensitivity to Multiminerals (Iron (Ferrous Proteinate))
  • Known hypersensitivity to Multiminerals (Iron (Ferrous Proteinate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

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

5.3 Multiminerals (Iron (Ferrous Proteinate)) Overload

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

6 ADVERSE REACTIONS

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

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

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

A total of 5 (11%) subjects in the Multiminerals (Iron (Ferrous Proteinate)) 0.5 mg/kg group, 10 (21%) patients in the Multiminerals (Iron (Ferrous Proteinate)) 1.0 mg/kg group, and 10 (21%) patients in the Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)). 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 Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)) injection. Reactions have occurred following the first dose or subsequent doses of Multiminerals (Iron (Ferrous Proteinate)). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.

Injection site discoloration has been reported following extravasation. Assure stable intravenous access to avoid extravasation.

7 DRUG INTERACTIONS

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

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

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

Multiminerals (Iron (Ferrous Proteinate)) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

Clinical studies of Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

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

Toxicities in single-dose studies in mice and rats, at intravenous Multiminerals (Iron (Ferrous Proteinate)) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

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

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

Multiminerals (Iron (Ferrous Proteinate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Multiminerals (Iron (Ferrous Proteinate)) (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 Multiminerals ).

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 Multiminerals (Iron (Ferrous Proteinate)) treatment and 24 in the historical control group) with Multiminerals (Iron (Ferrous Proteinate)) deficiency anemia. Eligibility criteria for Multiminerals (Iron (Ferrous Proteinate)) 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.

Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)), who were off intravenous Multiminerals (Iron (Ferrous Proteinate)) 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 Multiminerals (Iron (Ferrous Proteinate)) 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
Multiminerals (Iron (Ferrous Proteinate)) (n=69 Historical Control (n=18) Multiminerals (Iron (Ferrous Proteinate))

(n=73)

Historical Control

(n=18)

Multiminerals (Iron (Ferrous Proteinate))

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

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

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Multiminerals (Iron (Ferrous Proteinate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

Magnesium (Magnesium Oxide):



Multiminerals (Magnesium (Magnesium Oxide)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is a sterile solution of Multiminerals (Magnesium (Magnesium Oxide)) sulfate heptahydrate in Water for Injection, USP administered by the intravenous or intramuscular routes as an electrolyte replenisher or anticonvulsant. Must be diluted before intravenous use. May contain sulfuric acid and/or sodium hydroxide for pH adjustment. The pH is 5.5 to 7.0. The 50% concentration has an osmolarity of 4.06 mOsmol/mL (calc.).

The solution contains no bacteriostat, antimicrobial agent or added buffer (except for pH adjustment) and is intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded with the entire unit.

Multiminerals (Magnesium (Magnesium Oxide)) Sulfate, USP heptahydrate is chemically designated MgSO4 - 7H2O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

The plastic syringe is molded from a specially formulated polypropylene. Water permeates from inside the container at an extremely slow rate which will have an insignificant effect on solution concentration over the expected shelf life. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the syringe material.

CLINICAL PHARMACOLOGY

Multiminerals (Magnesium (Magnesium Oxide)) (Mg++) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for Multiminerals (Magnesium (Magnesium Oxide)) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of Multiminerals (Magnesium (Magnesium Oxide)). While there are large stores of Multiminerals (Magnesium (Magnesium Oxide)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Multiminerals (Magnesium (Magnesium Oxide)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Multiminerals (Magnesium (Magnesium Oxide)) prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Multiminerals (Magnesium (Magnesium Oxide)) is said to have a depressant effect on the central nervous system (CNS), but it does not adversely affect the woman, fetus or neonate when used as directed in eclampsia or pre-eclampsia. Normal plasma Multiminerals (Magnesium (Magnesium Oxide)) levels range from 1.5 to 2.5 mEq/liter.

As plasma Multiminerals (Magnesium (Magnesium Oxide)) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of Multiminerals (Magnesium (Magnesium Oxide)). Serum Multiminerals (Magnesium (Magnesium Oxide)) concentrations in excess of 12 mEq/L may be fatal.

Multiminerals (Magnesium (Magnesium Oxide)) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of Multiminerals (Magnesium (Magnesium Oxide)) poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

With intravenous administration the onset of anticonvulsant action is immediate and lasts about 30 minutes. Following intramuscular administration the onset of action occurs in about one hour and persists for three to four hours. Effective anticonvulsant serum levels range from 2.5 to 7.5 mEq/liter. Multiminerals (Magnesium (Magnesium Oxide)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is suitable for replacement therapy in Multiminerals (Magnesium (Magnesium Oxide)) deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum Multiminerals (Magnesium (Magnesium Oxide)) (Mg++) level is usually below the lower limit of normal (1.5 to 2.5 mEq/liter) and the serum calcium (Ca++) level is normal (4.3 to 5.3 mEq/liter) or elevated.

In total parenteral nutrition (TPN), Multiminerals (Magnesium (Magnesium Oxide)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

Parenteral administration of the drug is contraindicated in patients with heart block or myocardial damage.

WARNINGS

FETAL HARM: Continuous administration of Multiminerals (Magnesium (Magnesium Oxide)) sulfate beyond 5 to 7 days to pregnant women can lead to hypocalcemia and bone abnormalities in the developing fetus. These bone abnormalities include skeletal demineralization and osteopenia. In addition, cases of neonatal fracture have been reported. The shortest duration of treatment that can lead to fetal harm is not known. Multiminerals (Magnesium (Magnesium Oxide)) sulfate should be used during pregnancy only if clearly needed. If Multiminerals (Magnesium (Magnesium Oxide)) sulfate is given for treatment of preterm labor, the woman should be informed that the efficacy and safety of such use have not been established and that use of Multiminerals (Magnesium (Magnesium Oxide)) sulfate beyond 5 to 7 days may cause fetal abnormalities.

ALUMINUM TOXICITY: 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.

Parenteral use in the presence of renal insufficiency may lead to Multiminerals (Magnesium (Magnesium Oxide)) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with Multiminerals (Magnesium (Magnesium Oxide)), their dosage should be adjusted with caution because of additive CNS depressant effects of Multiminerals (Magnesium (Magnesium Oxide)).

Because Multiminerals (Magnesium (Magnesium Oxide)) is removed from the body solely by the kidneys, the drug should be used with caution in patients with renal impairment. Urine output should be maintained at a level of 100 mL or more during the four hours preceding each dose. Monitoring serum Multiminerals (Magnesium (Magnesium Oxide)) levels and the patient's clinical status is essential to avoid the consequences of overdosage in toxemia. Clinical indications of a safe dosage regimen include the presence of the patellar reflex (knee jerk) and absence of respiratory depression (approximately 16 breaths or more/minute). When repeated doses of the drug are given parenterally, knee jerk reflexes should be tested before each dose and if they are absent, no additional Multiminerals (Magnesium (Magnesium Oxide)) should be given until they return. Serum Multiminerals (Magnesium (Magnesium Oxide)) levels usually sufficient to control convulsions range from 3 to 6 mg/100 mL (2.5 to 5 mEq/liter). The strength of the deep tendon reflexes begins to diminish when Multiminerals (Magnesium (Magnesium Oxide)) levels exceed 4 mEq/liter. Reflexes may be absent at 10 mEq magnesium/liter, where respiratory paralysis is a potential hazard. An injectable calcium salt should be immediately available to counteract the potential hazards of Multiminerals (Magnesium (Magnesium Oxide)) intoxication in eclampsia.

50% Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

Multiminerals (Magnesium (Magnesium Oxide)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Multiminerals (Magnesium (Magnesium Oxide)) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with Multiminerals (Magnesium (Magnesium Oxide)), their dosage should be adjusted with caution because of additive CNS depressant effects of Multiminerals (Magnesium (Magnesium Oxide)). CNS depression and peripheral transmission defects produced by Multiminerals (Magnesium (Magnesium Oxide)) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Multiminerals (Magnesium (Magnesium Oxide)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Multiminerals (Magnesium (Magnesium Oxide)) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat Multiminerals (Magnesium (Magnesium Oxide)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Multiminerals (Magnesium (Magnesium Oxide)) sulfate can cause fetal abnormalities when administered beyond 5 to 7 days to pregnant women. There are retrospective epidemiological studies and case reports documenting fetal abnormalities such as hypocalcemia, skeletal demineralization, osteopenia and other skeletal abnormalities with continuous maternal administration of Multiminerals (Magnesium (Magnesium Oxide)) sulfate for more than 5 to 7 days.1-10 Multiminerals (Magnesium (Magnesium Oxide)) sulfate injection should be used during pregnancy only if clearly needed. If this drug is used during pregnancy, the woman should be apprised of the potential harm to the fetus.

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of Multiminerals (Magnesium (Magnesium Oxide)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Multiminerals (Magnesium (Magnesium Oxide)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Multiminerals (Magnesium (Magnesium Oxide)) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since Multiminerals (Magnesium (Magnesium Oxide)) is distributed into milk during parenteral Multiminerals (Magnesium (Magnesium Oxide)) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Multiminerals (Magnesium (Magnesium Oxide)) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Multiminerals (Magnesium (Magnesium Oxide)) usually are the result of Multiminerals (Magnesium (Magnesium Oxide)) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Multiminerals (Magnesium (Magnesium Oxide)) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Multiminerals (Magnesium (Magnesium Oxide)) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of Multiminerals (Magnesium (Magnesium Oxide)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Multiminerals (Magnesium (Magnesium Oxide)).

For Treatment of Overdose

Artificial respiration is often required. Intravenous calcium, 10 to 20 mL of a 5% solution (diluted if desirable with isotonic sodium chloride for injection) is used to counteract effects of hypermagnesemia. Subcutaneous physostigmine, 0.5 to 1 mg may be helpful.

Hypermagnesemia in the newborn may require resuscitation and assisted ventilation via endotracheal intubation or intermittent positive pressure ventilation as well as intravenous calcium.

DOSAGE AND ADMINISTRATION

Dosage of Multiminerals (Magnesium (Magnesium Oxide)) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

Both intravenous and intramuscular administration are appropriate. Intramuscular administration of the undiluted 50% solution results in therapeutic plasma levels in 60 minutes, whereas intravenous doses will provide a therapeutic level almost immediately. The rate of intravenous injection should generally not exceed 150 mg/minute (1.5 mL of a 10% concentration or its equivalent), except in severe eclampsia with seizures. Continuous maternal administration of Multiminerals (Magnesium (Magnesium Oxide)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Solutions for intravenous infusion must be diluted to a concentration of 20% or less prior to administration. The diluents commonly used are 5% Dextrose Injection, USP and 0.9% Sodium Chloride Injection, USP. Deep intramuscular injection of the undiluted (50%) solution is appropriate for adults, but the solution should be diluted to a 20% or less concentration prior to such injection in children.

In Multiminerals (Magnesium (Magnesium Oxide)) Deficiency

In the treatment of mild Multiminerals (Magnesium (Magnesium Oxide)) deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of Multiminerals (Magnesium (Magnesium Oxide)) (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of Multiminerals (Magnesium (Magnesium Oxide)) per 24 hours). For severe hypomagnesemia, as much as 250 mg (approximately 2 mEq) per kg of body weight (0.5 mL of the 50% solution) may be given intramuscularly within a period of four hours if necessary. Alternatively, 5 grams, (approximately 40 mEq) can be added to one liter of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP for slow intravenous infusion over a three-hour period. In the treatment of deficiency states, caution must be observed to prevent exceeding the renal excretory capacity.

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for Multiminerals (Magnesium (Magnesium Oxide)) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

In severe pre-eclampsia or eclampsia, the total initial dose is 10 grams to 14 grams of Multiminerals (Magnesium (Magnesium Oxide)) sulfate. Intravenously, a dose of 4 grams to 5 grams in 250 mL of 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP may be infused. Simultaneously, intramuscular doses of up to 10 grams (5 grams or 10 mL of the undiluted 50% solution in each buttock) are given. Alternatively, the initial intravenous dose of 4 grams may be given by diluting the 50% solution to a 10 or 20% concentration; the diluted fluid (40 mL of a 10% solution or 20 mL of a 20% solution) may then be injected intravenously over a period of three to four minutes. Subsequently, 4 grams to 5 grams (8 to 10 mL of the 50% solution) are injected intramuscularly into alternate buttocks every four hours as needed, depending on the continuing presence of the patellar reflex and adequate respiratory function. Alternatively, after the initial intravenous dose, some clinicians administer 1 gram to 2 grams/hour by constant intravenous infusion. Therapy should continue until paroxysms cease. A serum Multiminerals (Magnesium (Magnesium Oxide)) level of 6 mg/100 mL is considered optimal for control of seizures. A total daily (24 hr) dose of 30 grams to 40 grams should not be exceeded. In the presence of severe renal insufficiency, the maximum dosage of Multiminerals (Magnesium (Magnesium Oxide)) sulfate is 20 grams/48 hours and frequent serum Multiminerals (Magnesium (Magnesium Oxide)) concentrations must be obtained. Continuous use of Multiminerals (Magnesium (Magnesium Oxide)) sulfate in pregnancy beyond 5 to 7 days can cause fetal abnormalities.

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Multiminerals (Magnesium (Magnesium Oxide)) sulfate is 1 gram to 2 grams given intravenously.

For controlling seizures associated with epilepsy, glomerulonephritis or hypothyroidism, the usual adult dose is 1 gram administered intramuscularly or intravenously.

In paroxysmal atrial tachycardia, Multiminerals (Magnesium (Magnesium Oxide)) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

For reduction of cerebral edema, 2.5 grams (25 mL of a 10% solution) is given intravenously.

Incompatibilities

Multiminerals (Magnesium (Magnesium Oxide)) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

The potential incompatibility will often be influenced by the changes in the concentration of reactants and the pH of the solutions.

It has been reported that Multiminerals (Magnesium (Magnesium Oxide)) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

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

HOW SUPPLIED

Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is supplied in single-dose containers as follows:


NDC No.


Container


Total

Amount


Concentration


mEq

Mg++/mL


0409-1754-10


Ansyr

Plastic Syringe


5 g/10 mL


50%


4 mEq/mL


Do not administer unless solution is clear and container is undamaged. Discard unused portion.

Store at 20 to 25°C (68 to 77°F).

REFERENCES

  • Yokoyama K, Takahashi N, Yada Y. Prolonged maternal Multiminerals (Magnesium (Magnesium Oxide)) administration and bone metabolism in neonates. Early Hum Dev. 2010;86(3):187-91. Epub 2010 Mar 12.
  • Wedig KE, Kogan J, Schorry EK et al. Skeletal demineralization and fractures caused by fetal Multiminerals (Magnesium (Magnesium Oxide)) toxicity. J. Perinatol. 2006; 26(6):371-4.
  • Nassar AH, Sakhel K, Maarouf H, et al. Adverse maternal and neonatal outcome of prolonged course of Multiminerals (Magnesium (Magnesium Oxide)) sulfate tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received Multiminerals (Magnesium (Magnesium Oxide)) sulphate for tocolysis of premature labor. Pediatr Radiol. 2004;34(5):384-6. Epub 2004 Feb 18.
  • Matsuda Y, Maeda Y, Ito M, et al. Effect of Multiminerals (Magnesium (Magnesium Oxide)) sulfate treatment on neonatal bone abnormalities. Gynecol Obstet Invest. 1997;44(2):82-8.
  • Schanler RJ, Smith LG, Burns PA. Effects of long-term maternal intravenous Multiminerals (Magnesium (Magnesium Oxide)) sulfate therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Multiminerals (Magnesium (Magnesium Oxide)) sulfate treatment of preterm labor as a cause of abnormal neonatal bone mineralization. J Pediatr Orthrop. 1994;14(2):249-53.
  • Holcomb WL, Shackelford GD, Petrie RH. Multiminerals (Magnesium (Magnesium Oxide)) tocolysis and neonatal bone abnormalities; a controlled study. Obstet Gynecol. 1991; 78(4):611-4.
  • Cumming WA, Thomas VJ. Hypermagnesemia: a cause of abnormal metaphyses in the neonate. Am J Roentgenol. 1989; 152(5):1071-2.
  • Lamm CL, Norton KL, Murphy RJ. Congenital rickets associated with Multiminerals (Magnesium (Magnesium Oxide)) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Multiminerals (Magnesium (Magnesium Oxide)) sulfate treatment on perinatal calcium metabolism. II. Neonatal responses. Obstet Gynecol. 1980; 56(5): 595-600.
  • Riaz M, Porat R, Brodsky NL, et al. The effects of maternal Multiminerals (Magnesium (Magnesium Oxide)) sulfate treatment on newborns: a prospective controlled study. J. Perinatol. 1998;18(6 pt 1):449-54.

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Multiminerals (Magnesium (Magnesium Oxide)) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Multiminerals (Magnesium (Magnesium Oxide)) Sulfate Injection, USP

5 g/10 mL (500 mg/mL) (4 mEq Mg++/mL)

MUST BE DILUTED FOR INTRAVENOUS USE.

For Intravenous or Intramuscular Use. Sterile. 4.06 mOsmol/mL (calc.).

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Manganese (Manganese HVP Chelate):


INDICATIONS AND USAGE

Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals (Manganese (Manganese HVP Chelate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals (Manganese (Manganese HVP Chelate)) 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.

Multiminerals ) 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 Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals ) 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 Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals (Manganese (Manganese HVP Chelate)) chloride. It is also not known whether Multiminerals (Manganese (Manganese HVP Chelate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Multiminerals (Manganese (Manganese HVP Chelate)) 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

Multiminerals (Manganese (Manganese HVP Chelate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals (Manganese (Manganese HVP Chelate)) 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 Multiminerals (Manganese (Manganese HVP Chelate)) 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

Multiminerals (Manganese (Manganese HVP Chelate)) 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 (Potassium HVP Chelate):



Multiminerals (Potassium (Potassium HVP Chelate)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

These formulations are intended to slow the release of Multiminerals (Potassium (Potassium HVP Chelate)) so that the likelihood of a high localized concentration of Multiminerals (Potassium (Potassium HVP Chelate)) chloride within the gastrointestinal tract is reduced.

Multiminerals (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablets USP, 20 mEq is an electrolyte replenisher. The chemical name of the active ingredient is Multiminerals (Potassium (Potassium HVP Chelate)) chloride, and the structural formula is KCl. Multiminerals (Potassium (Potassium HVP Chelate)) 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.

Multiminerals (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulation (not enteric coated or wax matrix) containing individually microencapsulated Multiminerals (Potassium (Potassium HVP Chelate)) chloride crystals which disperse upon tablet disintegration. In simulated gastric fluid at 37°C and in the absence of outside agitation, Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) chloride.

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

CLINICAL PHARMACOLOGY

The Multiminerals (Potassium (Potassium HVP Chelate)) ion is the principal intracellular cation of most body tissues. Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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.

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

Multiminerals (Potassium (Potassium HVP Chelate)) depletion will occur whenever the rate of Multiminerals (Potassium (Potassium HVP Chelate)) loss through renal excretion and/or loss from the gastrointestinal tract exceeds the rate of Multiminerals (Potassium (Potassium HVP Chelate)) intake. Such depletion usually develops as a consequence of therapy with diuretics, primary or secondary hyperaldosteronism, diabetic ketoacidosis, or inadequate replacement of Multiminerals (Potassium (Potassium HVP Chelate)) in patients on prolonged parenteral nutrition. Depletion can develop rapidly with severe diarrhea, especially if associated with vomiting. Multiminerals (Potassium (Potassium HVP Chelate)) depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis. Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) in the form of high Multiminerals (Potassium (Potassium HVP Chelate)) food or Multiminerals (Potassium (Potassium HVP Chelate)) chloride may be able to restore normal Multiminerals (Potassium (Potassium HVP Chelate)) levels.

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

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Multiminerals (Potassium (Potassium HVP Chelate)) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) salts may be indicated.

CONTRAINDICATIONS

Multiminerals (Potassium (Potassium HVP Chelate)) supplements are contraindicated in patients with hyperkalemia since a further increase in serum Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) chloride have produced esophageal ulceration in certain cardiac patients with esophageal compression due to enlarged left atrium. Multiminerals (Potassium (Potassium HVP Chelate)) supplementation, when indicated in such patients, should be given as a liquid preparation or as an aqueous (water) suspension of Multiminerals (Potassium (Potassium HVP Chelate)) Chloride (see PRECAUTIONS: Information for Patients , and DOSAGE AND ADMINISTRATION sections).

All solid oral dosage forms of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)), the administration of Multiminerals (Potassium (Potassium HVP Chelate)) salts can produce hyperkalemia and cardiac arrest. This occurs most commonly in patients given Multiminerals (Potassium (Potassium HVP Chelate)) by the intravenous route but may also occur in patients given Multiminerals (Potassium (Potassium HVP Chelate)) orally. Potentially fatal hyperkalemia can develop rapidly and be asymptomatic. The use of Multiminerals (Potassium (Potassium HVP Chelate)) salts in patients with chronic renal disease, or any other condition which impairs Multiminerals (Potassium (Potassium HVP Chelate)) excretion, requires particularly careful monitoring of the serum Multiminerals (Potassium (Potassium HVP Chelate)) concentration and appropriate dosage adjustment.

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) retention by inhibiting aldosterone production. Multiminerals (Potassium (Potassium HVP Chelate)) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

Solid oral dosage forms of Multiminerals (Potassium (Potassium HVP Chelate)) chloride can produce ulcerative and/or stenotic lesions of the gastrointestinal tract. Based on spontaneous adverse reaction reports, enteric-coated preparations of Multiminerals (Potassium (Potassium HVP Chelate)) 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. Multiminerals (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablets USP, 20 mEq is a tablet formulated to provide a controlled rate of release of microencapsulated Multiminerals (Potassium (Potassium HVP Chelate)) chloride and thus to minimize the possibility of a high local concentration of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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. Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) salt such as Multiminerals (Potassium (Potassium HVP Chelate)) bicarbonate, Multiminerals (Potassium (Potassium HVP Chelate)) citrate, Multiminerals (Potassium (Potassium HVP Chelate)) acetate, or Multiminerals (Potassium (Potassium HVP Chelate)) gluconate.

PRECAUTIONS

General

The diagnosis of Multiminerals ) depletion is ordinarily made by demonstrating hypokalemia in a patient with a clinical history suggesting some cause for Multiminerals (Potassium (Potassium HVP Chelate)) depletion. In interpreting the serum Multiminerals (Potassium (Potassium HVP Chelate)) level, the physician should bear in mind that acute alkalosis per se can produce hypokalemia in the absence of a deficit in total body Multiminerals (Potassium (Potassium HVP Chelate)) while acute acidosis per se can increase the serum Multiminerals (Potassium (Potassium HVP Chelate)) concentration into the normal range even in the presence of a reduced total body Multiminerals (Potassium (Potassium HVP Chelate)). The treatment of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals ) 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. Multiminerals ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

The normal Multiminerals ) ion content of human milk is about 13 mEq per liter. Since oral Multiminerals (Potassium (Potassium HVP Chelate)) becomes part of the body Multiminerals (Potassium (Potassium HVP Chelate)) pool, so long as body Multiminerals (Potassium (Potassium HVP Chelate)) is not excessive, the contribution of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) salts to persons with normal excretory mechanisms for Multiminerals (Potassium (Potassium HVP Chelate)) rarely causes serious hyperkalemia. However, if excretory mechanisms are impaired or if Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) by the average adult is 50 to 100 mEq per day. Multiminerals (Potassium (Potassium HVP Chelate)) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Multiminerals (Potassium (Potassium HVP Chelate)) chloride.

Multiminerals (Potassium (Potassium HVP Chelate)) 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 Multiminerals (Potassium (Potassium HVP Chelate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Multiminerals (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Multiminerals (Potassium (Potassium HVP Chelate)) 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

Multiminerals (Potassium (Potassium HVP Chelate)) chloride 20 Meq

Selenium (Yeast):



Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

Multiminerals (Selenium (Yeast)) Injection is a sterile, nonpyrogenic solution for use as an additive to solutions for Total Parenteral Nutrition (TPN).

Each mL contains Selenious Acid 65.4 mcg (equivalent to elemental Multiminerals (Selenium (Yeast)) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.

CLINICAL PHARMACOLOGY

Multiminerals (Selenium (Yeast)) is part of glutathione peroxidase which protects cell components from oxidative damage due to peroxides produced in cellular metabolism.

Prolonged TPN support in humans has resulted in Multiminerals (Selenium (Yeast)) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Multiminerals (Selenium (Yeast)).

Pediatric conditions, Keshan disease, and Kwashiorkor, have been associated with low dietary intake of Multiminerals (Selenium (Yeast)). The conditions are endemic to geographical areas with low Multiminerals (Selenium (Yeast)) soil content. Dietary supplementation with Multiminerals (Selenium (Yeast)) salts has been reported to reduce the incidence of the conditions among affected children.

Normal blood levels of Multiminerals (Selenium (Yeast)) in different human populations have been found to vary and depend on the Multiminerals (Selenium (Yeast)) content of the food consumed. Results of surveys carried out in some countries are tabulated below:



COUNTRY


Number of

Samples

Multiminerals (Selenium (Yeast)) (mcg/100 mL) (a)

Whole Blood


Blood Cells

Plasma/

Serum

(a) Mean values with or without standard deviation in parentheses, all other ranges.
(b) Age group unknown.
(c) Three children recovered from Kwashiorkor and the other six under treatment for other diseases.
(d) Low selenium-content soil area.
(e) Well nourished children, three recovered from Kwashiorkor and the other six under treatment for other diseases.
(f) Mean values from seven subjects.
Canada 254 Adults (37.9 ± 7.8) (23.6 ± 6.0) (14.4 ± 2.9)
England 8 (b) 26-37 (32) -- --
Guatemala &

Southern USA

10 Adults

9 Children (c)

19-28 (22)

(23 ± 5)

--

(36 ± 12)

--

(15 ± 5)

New Zealand (d) 113 Adults (5.4 ± 0.1) (6.6 ± 0.3) (4.3 ± 0.1)
Thailand 3 Adults

9 Children (e)

14.4-20.2

(12.0 ± 3.6) (f)

17.8-35.8

(19.5 ± 8.2)

8.1-12.5

(8.3 ± 2.2)

USA 210 Adults 15.7-25.6

(20.6)

-- --

Plasma Multiminerals (Selenium (Yeast)) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.

Multiminerals (Selenium (Yeast)) is eliminated primarily in urine. However, significant endogenous losses through feces also occur. The rate of excretion and the relative importance of two routes varies with the chemical form of Multiminerals (Selenium (Yeast)) used in supplementation. Ancillary routes of elimination are lungs and skin.

INDICATIONS AND USAGE

Multiminerals (Selenium (Yeast)) Injection is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN). Administration of Multiminerals (Selenium (Yeast)) in TPN solutions helps to maintain plasma Multiminerals (Selenium (Yeast)) levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

Multiminerals (Selenium (Yeast)) Injection should not be given undiluted by direct injection into a peripheral vein because of the potential for infusion phlebitis.

WARNINGS

Multiminerals (Selenium (Yeast)) Injection can be toxic if given in excessive amounts. Supplementation of TPN solution with Multiminerals (Selenium (Yeast)) should be immediately discontinued if toxicity symptoms are observed. Frequent determination of plasma Multiminerals (Selenium (Yeast)) levels during TPN support and close medical supervision is recommended.

Multiminerals (Selenium (Yeast)) Injection is a hypotonic solution and should be administered in admixtures only.

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

As Multiminerals ) is eliminated in urine and feces, Multiminerals (Selenium (Yeast)) supplements may be adjusted, reduced or omitted in renal dysfunction and/or gastrointestinal malfunction. In patients receiving blood transfusions, contribution from such transfusions should also be considered. Frequent Multiminerals (Selenium (Yeast)) plasma level determinations are suggested as a guideline.

In animals, Multiminerals (Selenium (Yeast)) has been reported to enhance the action of Vitamin E and decrease the toxicity of mercury, cadmium and arsenic.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Multiminerals (Selenium (Yeast)) at high dose levels (15-30 mcg/egg) has been reported to have adverse embryological effects among chickens. There are however, no adequate and wellcontrolled studies in pregnant women. Multiminerals (Selenium (Yeast)) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.

Presence of Multiminerals (Selenium (Yeast)) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

The amount of Multiminerals (Selenium (Yeast)) present in Multiminerals (Selenium (Yeast)) Injection is small. Symptoms of toxicity from Multiminerals (Selenium (Yeast)) are unlikely to occur at the recommended dosage level.

OVERDOSAGE

Chronic toxicity in humans resulting from exposure to Multiminerals (Selenium (Yeast)) in industrial environments, intake of foods grown in seleniferous soils, use of selenium-contaminated water, and application of cosmetics containing Multiminerals (Selenium (Yeast)) has been reported in literature. Toxicity symptoms include hair loss, weakened nails, dermatitis, dental defects, gastrointestinal disorders, nervousness, mental depression, metallic taste, vomiting, and garlic odor of breath and sweat. Acute poisoning due to ingestion of large amounts of Multiminerals (Selenium (Yeast)) compounds has resulted in death with histopathological changes including fulminating peripheral vascular collapse, internal vascular congestion, diffusely hemorrhagic, congested and edematus lungs, brick-red color gastric mucosa. The death was preceded by coma.

No effective antidote to Multiminerals (Selenium (Yeast)) poisoning in humans is known. Animal studies have shown casein and linseed oil in feeds, reduced glutathione, arsenic, magnesium sulfate, and bromobenzene to afford limited protection.

DOSAGE AND ADMINISTRATION

Multiminerals (Selenium (Yeast)) Injection provides 40 mcg selenium/mL. For metabolically stable adults receiving TPN, the suggested additive dosage level is 20 to 40 mcg selenium/day. For pediatric patients, the suggested additive dosage level is 3 mcg/kg/day.

In adults, Multiminerals (Selenium (Yeast)) deficiency states resulting from long-term TPN support, Multiminerals (Selenium (Yeast)) as selenomethionine or selenious acid, administered intravenously at 100 mcg/day for a period of 24 and 31 days, respectively, has been reported to reverse deficiency symptoms without toxicity.

Aseptic addition of Multiminerals (Selenium (Yeast)) Injection to the TPN solution under laminar flow hood is recommended. Multiminerals (Selenium (Yeast)) is physically compatible with the electrolytes and other trace elements usually present in amino-acid/dextrose solution used for TPN. Frequent monitoring of plasma Multiminerals (Selenium (Yeast)) levels is suggested as a guideline for subsequent administration. The normal whole blood range for Multiminerals (Selenium (Yeast)) is approximately 10 to 37 mcg/100 mL.

Parenteral drug products should be inspected visually for particulate matter and discoloration, whenever solution and container permit.

HOW SUPPLIED

Multiminerals (Selenium (Yeast)) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Multiminerals (Selenium (Yeast)) 40 mcg/mL).

NDC 0517-6510-25 10 mL Single Dose Vial Packaged in boxes of 25

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F).

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN6510

Rev. 11/15

PRINCIPAL DISPLAY PANEL - Container

NDC 0517-6510-25

Multiminerals (Selenium (Yeast)) INJECTION

Multiminerals (Selenium (Yeast)) 400 mcg/10 mL

(40 mcg/mL)

10 mL

SINGLE DOSE VIAL

Trace Element Additive

FOR IV USE AFTER DILUTION

PRESERVATIVE FREE

Rx Only

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

PRINCIPAL DISPLAY PANEL - Carton

Multiminerals (Selenium (Yeast)) INJECTION

Multiminerals (Selenium (Yeast)) 400 mcg/10 mL

(40 mcg/mL)

Trace Element Additive

NDC 0517-6510-25

25 x 10 mL

SINGLE DOSE VIALS

FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only

Each mL contains: Selenious Acid 65.4 mcg, Water for Injection q.s.

pH adjusted with Nitric Acid. Sterile, nonpyrogenic.

WARNING: DISCARD UNUSED PORTION. Store at 20°-25°C (68°-77°F); excursions

permitted to 15°-30°C (59°-86°F).

Directions for Use: See Package Insert.

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

Container Carton

Zinc (Zinc HVP Chelate):


INDICATIONS AND USAGE

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

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) from a bolus injection. Administration of Multiminerals (Zinc (Zinc HVP Chelate)) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Multiminerals (Zinc (Zinc HVP Chelate)) are suggested as a guideline for subsequent Multiminerals (Zinc (Zinc HVP Chelate)) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Multiminerals ) 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 Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals ) chloride. It is also not known whether Multiminerals (Zinc (Zinc HVP Chelate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) concentration of 207 mcg/dl. Symptoms abated within three hours.

Hyperamylasemia may be a sign of impending Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) was delivered intravenously over the course of 60 hours to a 72 year old patient.

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

Calcium supplements may confer a protective effect against Multiminerals (Zinc (Zinc HVP Chelate)) toxicity.

DOSAGE AND ADMINISTRATION

Multiminerals (Zinc (Zinc HVP Chelate)) 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 Multiminerals (Zinc (Zinc HVP Chelate)) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Multiminerals (Zinc (Zinc HVP Chelate)).

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

Multiminerals (Zinc (Zinc HVP Chelate)) 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

Multiminerals (Zinc (Zinc HVP Chelate))

1 mg/mL

Multiminerals (Zinc (Zinc HVP Chelate)) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Multiminerals pharmaceutical active ingredients containing related brand and generic drugs:


Multiminerals available forms, composition, doses:


Multiminerals destination | category:


Multiminerals Anatomical Therapeutic Chemical codes:


Multiminerals pharmaceutical companies:


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References

  1. Dailymed."COPPER: 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).
  2. Dailymed."CALCIUM: 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. "Iodine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Multiminerals?

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

Visitor reports

Visitor reported useful

No survey data has been collected yet

One visitor reported side effects

Did you get side effects while taking the Multiminerals drug, or were there no side effects?
According to the survey conducted by website sdrugs.com users, the below-mentioned percentages indicate the number of people experiencing the side effects and the number of people not experiencing the side effects when taking Multiminerals medicine. Every drug produces minimal side effects, and they are negligible most times, when compared to the desired effect [use] of the medicine. Side effects depend on the dose you are taking, any drug interactions that happen when you are on other medications, if the patient is sensitive, and other associated conditions. If you cannot tolerate the side effects, consult your doctor immediately, so he can either adjust the dose or change the medication.
Visitors%
No side effects1
100.0%

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

One visitor reported doses

What is the dose of Multiminerals drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 1-5mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
1-5mg1
100.0%

One visitor reported time for results

What is the time duration Multiminerals drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 2 weeks to notice the result from using Multiminerals drug. The time needed to show improvement in health condition after using the medicine Multiminerals need not be same for all the users. It varies based on other factors.
Visitors%
2 weeks1
100.0%

Visitor reported administration

No survey data has been collected yet

Six visitors reported age

Visitors%
> 602
33.3%
46-602
33.3%
6-152
33.3%

Visitor reviews


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

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