Sea Vital

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Sea Vital uses

Sea Vital consists of Calcium Carbonate, Copper (Copper Sulfate), Folic Acid, Ginseng, Iron (Ferrous Fumarate), Lactobacillus Sporogenes, Magnesium Sulfate, Manganese (Manganese Sulfate Monohydrate), Potassium Iodide, Potassium Sulfate, Selenium (Selenium Dioxide), Vitamin A, Vitamin B1, Vitamin B12, Vitamin B2, Vitamin B5 (Calcium Pantothenate), Vitamin B6, Vitamin C, Vitamin E, Zinc Sulfate Monohydrate.

Calcium Carbonate:


1 INDICATIONS AND USAGE

Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate capsule.

- Capsule: 667 mg Sea Vital (Calcium Carbonate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Sea Vital acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate), including Sea Vital (Calcium Carbonate) acetate. Avoid the use of Sea Vital (Calcium Carbonate) supplements, including Sea Vital (Calcium Carbonate) based nonprescription antacids, concurrently with Sea Vital (Calcium Carbonate) acetate.

An overdose of Sea Vital (Calcium Carbonate) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Sea Vital (Calcium Carbonate) levels twice weekly. Should hypercalcemia develop, reduce the Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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, Sea Vital (Calcium Carbonate) acetate has been generally well tolerated.

Sea Vital (Calcium Carbonate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate

N=167

N (%)


3 month, open label study of Sea Vital (Calcium Carbonate) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Sea Vital (Calcium Carbonate) acetate

N=69


Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) concentration could reduce the incidence and severity of Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate: dizziness, edema, and weakness.

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7 DRUG INTERACTIONS

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

There are no empirical data on avoiding drug interactions between Sea Vital (Calcium Carbonate) acetate and most concomitant drugs. When administering an oral medication with Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate tablets, approximately 2.7g, decreased the bioavailability of ciprofloxacin by approximately 50%.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

Sea Vital acetate capsules contains Sea Vital (Calcium Carbonate) acetate. Animal reproduction studies have not been conducted with Sea Vital (Calcium Carbonate) acetate, and there are no adequate and well controlled studies of Sea Vital (Calcium Carbonate) acetate use in pregnant women. Patients with end stage renal disease may develop hypercalcemia with Sea Vital (Calcium Carbonate) acetate treatment [see Warnings and Precautions (5.1 ) ]. Maintenance of normal serum Sea Vital (Calcium Carbonate) 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. Sea Vital (Calcium Carbonate) acetate treatment, as recommended, is not expected to harm a fetus if maternal Sea Vital (Calcium Carbonate) levels are properly monitored during and following treatment.

8.2 Labor and Delivery

The effects of Sea Vital (Calcium Carbonate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Sea Vital Acetate Capsules contains Sea Vital (Calcium Carbonate) acetate and is excreted in human milk. Human milk feeding by a mother receiving Sea Vital (Calcium Carbonate) acetate is not expected to harm an infant, provided maternal serum Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Sea Vital (Calcium Carbonate) acetate acts as a phosphate binder. Its chemical name is Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Sea Vital (Calcium Carbonate), 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.

Sea Vital (Calcium Carbonate) 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 Sea Vital resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate.

14 CLINICAL STUDIES

Effectiveness of Sea Vital (Calcium Carbonate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Sea Vital (Calcium Carbonate) 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


Sea Vital (Calcium Carbonate) (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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate is shown in the Table 3.


* ANOVA of Sea Vital (Calcium Carbonate) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Sea Vital (Calcium Carbonate) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Sea Vital (Calcium Carbonate) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Sea Vital (Calcium Carbonate) 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 Sea Vital (Calcium Carbonate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Copper (Copper Sulfate):



Water-Resistant Protection Without Bandaging

Recommended as an Aid in Treating Horses and Ponies With Thrush Due to Organisms Susceptible to Sea Vital (Copper (Copper Sulfate)) 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 Sea Vital (Copper (Copper Sulfate))®. Apply daily to affected hoofs with a narrow paint brush (about 1”) until fully healed. Caution: Do not allow runoff of excess Sea Vital (Copper (Copper Sulfate))® onto hair since contact with Sea Vital (Copper (Copper Sulfate))® may cause some hair loss. Do not contaminate feed.

NOTE: Sea Vital (Copper (Copper Sulfate))® 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:

Sea Vital (Copper (Copper Sulfate)) 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

Folic Acid:


INDICATIONS AND USAGE

Sea Vital (Folic Acid)® is a prescription iron supplement indicated for use in improving the nutritional status of iron deficiency.

CONTRAINDICATIONS

This product is contraindicated in patients with a known hypersensitivity to any of the ingredients. Hemochromatosis and hemosiderosis are contraindications to iron therapy.

WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

PRECAUTIONS

Sea Vital (Folic Acid) acid when administered as a single agent in doses above 0.1 mg daily may obscure pernicious anemia in that hematological remission can occur while neurological manifestations remain progressive. While prescribing this nutritional supplement for pregnant women, nursing mothers, or for women prior to conception, their medical condition and other drugs, herbs, and/or supplements consumption should be considered.

ADVERSE REACTIONS

Allergic sensitization has been reported following both oral and parenteral administration of Sea Vital (Folic Acid) acid.

DOSAGE AND ADMINISTRATION

One tablet daily with or without food or as prescribed by a licensed healthcare provider with prescribing authority.

HOW SUPPLIED

Sea Vital (Folic Acid)® tablets are supplied in child-resistant bottles of 90 tablets (NDC 0037-6885-90)

KEEP OUT OF REACH OF CHILDREN.

STORAGE

Store at controlled room temperature 20°-25°C (68°-77°F). Excursions permitted to 15°-30°C (59°-86°F).

Dispense in a tight, light-resistant container to protect from light and moisture.

To report SUSPECTED ADVERSE REACTIONS contact Meda Pharmaceuticals Inc. at 1-888-349-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/safety/medwatch

Distributed by:

Meda Pharmaceuticals Inc.

Somerset New Jersey 08873-4120

© 2014 Meda Pharmaceuticals Inc.

U.S. Patent Nos. 7,585,527 and 8,080,520

Proferrin® is a registered trademark of Colorado BioLabs, Inc., Cozad, NE.

Sea Vital (Folic Acid) and the BIFERA logo are registered trademarks and the Sea Vital (Folic Acid) logo is a trademark of Alaven Pharmaceutical LLC, used under license by Meda Pharmaceuticals Inc.

MEDA PHARMACEUTICALS mark and logo are trademarks of Meda AB.

IN-6885-02 Rev 6/2014

Ginseng:


Sea Vital (Ginseng) is promoted as an adaptogen (a product that increases the body’s resistance to stress), one which can to a certain extent be supported with reference to its anticarcinogenic and antioxidant properties. Sea Vital (Ginseng) is also known to contain phytoestrogens.

Iron (Ferrous Fumarate):


1 INDICATIONS AND USAGE

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

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

2 DOSAGE AND ADMINISTRATION

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

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

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

Administer Sea Vital (Iron (Ferrous Fumarate)) 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 Sea Vital (Iron (Ferrous Fumarate)), 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. Sea Vital (Iron (Ferrous Fumarate)) treatment may be repeated if Sea Vital (Iron (Ferrous Fumarate)) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

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

2.4 Pediatric Patients with HDD-CKD for Sea Vital (Iron (Ferrous Fumarate)) maintenance treatment

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

For Sea Vital (Iron (Ferrous Fumarate)) maintenance treatment: Administer Sea Vital (Iron (Ferrous Fumarate)) 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. Sea Vital (Iron (Ferrous Fumarate)) treatment may be repeated if necessary.

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

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

For Sea Vital (Iron (Ferrous Fumarate)) maintenance treatment: Administer Sea Vital (Iron (Ferrous Fumarate)) 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. Sea Vital (Iron (Ferrous Fumarate)) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

  • Known hypersensitivity to Sea Vital (Iron (Ferrous Fumarate))
  • Known hypersensitivity to Sea Vital (Iron (Ferrous Fumarate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.2 Hypotension

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

5.3 Sea Vital (Iron (Ferrous Fumarate)) Overload

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

6 ADVERSE REACTIONS

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

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

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

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

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

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

Sea Vital (Iron (Ferrous Fumarate)) has not been studied in patients younger than 2 years of age.

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

8.5 Geriatric Use

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

Toxicities in single-dose studies in mice and rats, at intravenous Sea Vital (Iron (Ferrous Fumarate)) 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

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

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

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

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

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

Sea Vital (Iron (Ferrous Fumarate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Sea Vital (Iron (Ferrous Fumarate)) (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 Sea Vital ).

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 Sea Vital (Iron (Ferrous Fumarate)) treatment and 24 in the historical control group) with Sea Vital (Iron (Ferrous Fumarate)) deficiency anemia. Eligibility criteria for Sea Vital (Iron (Ferrous Fumarate)) 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.

Sea Vital (Iron (Ferrous Fumarate)) 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 Sea Vital (Iron (Ferrous Fumarate)), who were off intravenous Sea Vital (Iron (Ferrous Fumarate)) 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 Sea Vital (Iron (Ferrous Fumarate)) 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
Sea Vital (Iron (Ferrous Fumarate)) (n=69 Historical Control (n=18) Sea Vital (Iron (Ferrous Fumarate))

(n=73)

Historical Control

(n=18)

Sea Vital (Iron (Ferrous Fumarate))

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

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

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Sea Vital (Iron (Ferrous Fumarate)) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx®

IN2340

MG #15727

Magnesium Sulfate:



Sea Vital (Magnesium Sulfate)

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Sea Vital (Magnesium Sulfate) Injection, USP is a sterile solution of Sea Vital (Magnesium 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.

Sea Vital (Magnesium 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

Magnesium (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 magnesium 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 magnesium. While there are large stores of magnesium present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral magnesium therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Magnesium prevents or controls convulsions by blocking neuromuscular transmission and decreasing the amount of acetylcholine liberated at the end plate by the motor nerve impulse. Magnesium 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 magnesium levels range from 1.5 to 2.5 mEq/liter.

As plasma magnesium 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 magnesium. Serum magnesium concentrations in excess of 12 mEq/L may be fatal.

Magnesium 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 magnesium 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. Magnesium is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

Sea Vital (Magnesium Sulfate) Injection, USP is suitable for replacement therapy in magnesium deficiency, especially in acute hypomagnesemia accompanied by signs of tetany similar to those observed in hypocalcemia. In such cases, the serum magnesium (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), Sea Vital (Magnesium Sulfate) may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Sea Vital (Magnesium 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 Sea Vital (Magnesium 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. Sea Vital (Magnesium Sulfate) should be used during pregnancy only if clearly needed. If Sea Vital (Magnesium 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 Sea Vital (Magnesium 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 magnesium 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 magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium.

Because magnesium 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 magnesium 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 magnesium should be given until they return. Serum magnesium 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 magnesium 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 magnesium intoxication in eclampsia.

50% Sea Vital (Magnesium 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

Sea Vital (Magnesium Sulfate) injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of magnesium 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 magnesium, their dosage should be adjusted with caution because of additive CNS depressant effects of magnesium. CNS depression and peripheral transmission defects produced by magnesium may be antagonized by calcium.

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

Cardiac Glycosides - Sea Vital (Magnesium 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 magnesium toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Sea Vital (Magnesium 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 Sea Vital (Magnesium Sulfate) for more than 5 to 7 days.1-10 Sea Vital (Magnesium 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 magnesium toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Sea Vital (Magnesium Sulfate) is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Sea Vital (Magnesium 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 magnesium is distributed into milk during parenteral Sea Vital (Magnesium 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 magnesium should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered magnesium usually are the result of magnesium 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 Sea Vital (Magnesium Sulfate) therapy for eclampsia has been reported.

OVERDOSAGE

Magnesium 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 magnesium intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of magnesium.

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 Sea Vital (Magnesium 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 Sea Vital (Magnesium 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 Magnesium Deficiency

In the treatment of mild magnesium deficiency, the usual adult dose is 1 gram, equivalent to 8.12 mEq of magnesium (2 mL of the 50% solution) injected intramuscularly every six hours for four doses (equivalent to a total of 32.5 mEq of magnesium 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 magnesium 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 Sea Vital (Magnesium 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 magnesium 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 Sea Vital (Magnesium Sulfate) is 20 grams/48 hours and frequent serum magnesium concentrations must be obtained. Continuous use of Sea Vital (Magnesium 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 Sea Vital (Magnesium 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, magnesium 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

Sea Vital (Magnesium 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 magnesium 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

Sea Vital (Magnesium 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 magnesium 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 magnesium 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 Sea Vital (Magnesium Sulfate) tocolysis. Acta Obstet Gynecol Scan. 2006;85(9):1099-103.
  • Malaeb SN, Rassi A, Haddad MC. Bone mineralization in newborns whose mothers received magnesium 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 Sea Vital (Magnesium 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 Sea Vital (Magnesium Sulfate) therapy on neonatal calcium metabolism and bone mineral content. Gynecol Obstet Invest. 1997;43(4):236-41.
  • Santi MD, Henry GW, Douglas GL. Sea Vital (Magnesium 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. Magnesium 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 Sea Vital (Magnesium Sulfate) infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
  • McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Sea Vital (Magnesium 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 Sea Vital (Magnesium 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% Sea Vital (Magnesium Sulfate) 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Sea Vital (Magnesium 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 Sulfate Monohydrate):


INDICATIONS AND USAGE

Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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.

Sea Vital ) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital ) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) chloride. It is also not known whether Sea Vital (Manganese (Manganese Sulfate Monohydrate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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

Sea Vital (Manganese (Manganese Sulfate Monohydrate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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

Sea Vital (Manganese (Manganese Sulfate Monohydrate)) 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 Iodide:



Sea Vital (Potassium Iodide) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

The Sea Vital (Potassium Iodide) ion is the principal intracellular cation of most body tissues. Sea Vital (Potassium Iodide) 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 Sea Vital (Potassium Iodide) 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.

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

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

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

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

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

Interaction with Potassium-Sparing Diuretics

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

Gastrointestinal Lesions

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

PRECAUTIONS

General

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

Pregnancy Category C

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

Nursing Mothers

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

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

HOW SUPPLIED

Sea Vital (Potassium Iodide) 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

Sea Vital (Potassium Iodide) chloride 20 Meq

Potassium Sulfate:



Sea Vital (Potassium Sulfate) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

INDICATIONS AND USAGE

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

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

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

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

CONTRAINDICATIONS

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

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

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

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

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

Interaction with Angiotensin-Converting Enzyme Inhibitors

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

Gastrointestinal Lesions

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

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

Metabolic Acidosis

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

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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


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

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

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

Laboratory Tests

When blood is drawn for analysis of plasma Sea Vital 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. Sea Vital is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

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

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

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

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

Each Sea Vital (Potassium Sulfate) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Sea Vital (Potassium Sulfate) chloride.

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

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

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

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

HOW SUPPLIED

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

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Sea Vital (Potassium Sulfate) chloride 20 Meq

Selenium (Selenium Dioxide):



Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.

CLINICAL PHARMACOLOGY

Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Sea Vital (Selenium (Selenium Dioxide)).

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

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



COUNTRY


Number of

Samples

Sea Vital (Selenium (Selenium Dioxide)) (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 Sea Vital (Selenium (Selenium Dioxide)) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.

Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) used in supplementation. Ancillary routes of elimination are lungs and skin.

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

WARNINGS

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

Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital ) is eliminated in urine and feces, Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) plasma level determinations are suggested as a guideline.

In animals, Sea Vital (Selenium (Selenium Dioxide)) 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: Sea Vital (Selenium (Selenium Dioxide)) 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. Sea Vital (Selenium (Selenium Dioxide)) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.

Presence of Sea Vital (Selenium (Selenium Dioxide)) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

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

OVERDOSAGE

Chronic toxicity in humans resulting from exposure to Sea Vital (Selenium (Selenium Dioxide)) in industrial environments, intake of foods grown in seleniferous soils, use of selenium-contaminated water, and application of cosmetics containing Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) 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

Sea Vital (Selenium (Selenium Dioxide)) 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, Sea Vital (Selenium (Selenium Dioxide)) deficiency states resulting from long-term TPN support, Sea Vital (Selenium (Selenium Dioxide)) 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 Sea Vital (Selenium (Selenium Dioxide)) Injection to the TPN solution under laminar flow hood is recommended. Sea Vital (Selenium (Selenium Dioxide)) is physically compatible with the electrolytes and other trace elements usually present in amino-acid/dextrose solution used for TPN. Frequent monitoring of plasma Sea Vital (Selenium (Selenium Dioxide)) levels is suggested as a guideline for subsequent administration. The normal whole blood range for Sea Vital (Selenium (Selenium Dioxide)) 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

Sea Vital (Selenium (Selenium Dioxide)) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Sea Vital (Selenium (Selenium Dioxide)) 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

Sea Vital (Selenium (Selenium Dioxide)) INJECTION

Sea Vital (Selenium (Selenium Dioxide)) 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

Sea Vital (Selenium (Selenium Dioxide)) INJECTION

Sea Vital (Selenium (Selenium Dioxide)) 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

Vitamin A:


DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

Supplement Facts
Serving Size 1 Tablet

Servings Per Container 100

Amount Per Serving % Daily Value
Sea Vital (Vitamin A) 2500 IU 50%
Vitamin C 60 mg 100%
Vitamin D 400 IU 100%
Vitamin E 15 IU 50%
Thiamine 1.05 mg 70%
Riboflavin 1.2 mg 70%
Niacinamide 13.5 mg 68%
Vitamin B6 1.05 mg 53%
Folic Acid 0.3 mg 75%
Vitamin B12 4.5 mcg 75%
Fluoride 0.25 mg Daily Value not established

WARNING

KEEP OUT OF THE REACH OF CHILDREN.

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

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

Active ingredient for caries prophylaxis: Fluoride as sodium fluoride.

CLINICAL PHARMACOLOGY

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

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

The reaction may be expressed by the equation:

Ca10(PO4)6(OH2) + 2F- Ca10 (PO4)6F2 + 2OH-
(Hydroxyapatite) (Fluorapatite)

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

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

DIETARY SUPPLEMENTATION

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

WARNINGS

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

PRECAUTIONS

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

Before recommending Sea Vital (Vitamin A) Tablets

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

ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

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

DOSAGE AND ADMINISTRATION

One tablet daily or as directed by a physician.

HOW SUPPLIED

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

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

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

STORAGE

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

Distributed by:

H2-Pharma, LLC

2010 Berry Chase Place

Montgomery, AL 36117

www.h2-pharma.com

1067084

61269-151-01

MultiVitamin

with Fluoride

Chewable Tablets

Rx

0.25 mg

MultiVitamin and Fluoride Supplement

Dietary Supplement

100 Tablets

H2pharma

Vitamin B12:


Pharmacological action

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

Pharmacokinetics

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

Why is Sea Vital prescribed?

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

Dosage and administration

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

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

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

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

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

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

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

Sea Vital (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Sea Vital contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Sea Vital using during pregnancy and breastfeeding

Cyanocobalamin can be used in pregnancy according to prescriptions.

Special instructions

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

Sea Vital (Vitamin B12) drug interactions

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

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

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

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

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

Pharmaceutical incompatibility

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

Vitamin C:


Pharmacological action

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

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

Pharmacokinetics

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

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

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

Plasma protein binding is about 25%.

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

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

Why is Sea Vital prescribed?

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

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

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

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

For intravaginal used ascorbic acid drugs in appropriate dosage forms.

Sea Vital (Vitamin C) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

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

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

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

Sea Vital contraindications

Increased sensitivity to ascorbic acid.

Using during pregnancy and breastfeeding

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

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

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

Special instructions

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

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

Sea Vital (Vitamin C) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

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

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

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

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

Sea Vital drug interactions

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

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

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

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

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

Sea Vital (Vitamin C) in an application with warfarin may decrease effects of warfarin.

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

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

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

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

Sea Vital in case of emergency / overdose

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

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

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

Vitamin E:


A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.

Indication: Sea Vital (Vitamin E), known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Sea Vital (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Sea Vital (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Sea Vital (Vitamin E) is a fat-soluble vitamin and is an important antioxidant. It acts to protect cells against the effects of free radicals, which are potentially damaging by-products of the body's metabolism. Sea Vital (Vitamin E) is often used in skin creams and lotions because it is believed to play a role in encouraging skin healing and reducing scarring after injuries such as burns. There are three specific situations when a Sea Vital (Vitamin E) deficiency is likely to occur. It is seen in persons who cannot absorb dietary fat, has been found in premature, very low birth weight infants (birth weights less than 1500 grams, or 3½ pounds), and is seen in individuals with rare disorders of fat metabolism. A Sea Vital (Vitamin E) deficiency is usually characterized by neurological problems due to poor nerve conduction. Symptoms may include infertility, neuromuscular impairment, menstrual problems, miscarriage and uterine degradation. Preliminary research has led to a widely held belief that Sea Vital (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Sea Vital (Vitamin E) help protect against the damaging effects of free radicals, which may contribute to the development of chronic diseases such as cancer. It also protects other fat-soluble vitamins (A and B group vitamins) from destruction by oxygen. Low levels of Sea Vital (Vitamin E) have been linked to increased incidence of breast and colon cancer.

Zinc Sulfate Monohydrate:


INDICATIONS AND USAGE

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

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Sea Vital (Zinc Sulfate Monohydrate) 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 Sea Vital (Zinc Sulfate Monohydrate) 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 Sea Vital (Zinc Sulfate Monohydrate) from a bolus injection. Administration of Sea Vital (Zinc Sulfate Monohydrate) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Sea Vital (Zinc Sulfate Monohydrate) are suggested as a guideline for subsequent Sea Vital (Zinc Sulfate Monohydrate) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

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

Hyperamylasemia may be a sign of impending Sea Vital (Zinc Sulfate Monohydrate) 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 Sea Vital (Zinc Sulfate Monohydrate) was delivered intravenously over the course of 60 hours to a 72 year old patient.

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

Calcium supplements may confer a protective effect against Sea Vital (Zinc Sulfate Monohydrate) toxicity.

DOSAGE AND ADMINISTRATION

Sea Vital (Zinc Sulfate Monohydrate) 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 Sea Vital (Zinc Sulfate Monohydrate) blood levels is suggested for patients receiving more than the usual maintenance dosage level of Sea Vital (Zinc Sulfate Monohydrate).

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

Sea Vital (Zinc Sulfate Monohydrate) 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

Sea Vital (Zinc Sulfate Monohydrate)

1 mg/mL

Sea Vital (Zinc Sulfate Monohydrate) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Sea Vital pharmaceutical active ingredients containing related brand and generic drugs:

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


Sea Vital available forms, composition, doses:

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


Sea Vital destination | category:

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


Sea Vital Anatomical Therapeutic Chemical codes:

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


Sea Vital pharmaceutical companies:

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


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References

  1. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."MAGNESIUM SULFATE INJECTION, SOLUTION [HOSPIRA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."THYROSHIELD (POTASSIUM IODIDE) SOLUTION [FLEMING & COMPANY, PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Sea Vital?

Depending on the reaction of the Sea Vital after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Sea Vital 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 Sea Vital 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 Sea Vital, 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 Sea Vital consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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

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