Seven Seas M Vit with Siberian Ginseng

Calcium:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Seven Seas M Vit with Siberian Ginseng (Calcium) reviews

1 INDICATIONS AND USAGE

Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate capsule.

- Capsule: 667 mg Seven Seas M Vit with Siberian Ginseng (Calcium) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Seven Seas M Vit with Siberian Ginseng acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium), including Seven Seas M Vit with Siberian Ginseng (Calcium) acetate. Avoid the use of Seven Seas M Vit with Siberian Ginseng (Calcium) supplements, including Seven Seas M Vit with Siberian Ginseng (Calcium) based nonprescription antacids, concurrently with Seven Seas M Vit with Siberian Ginseng (Calcium) acetate.

An overdose of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate may lead to progressive hypercalcemia, which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum Seven Seas M Vit with Siberian Ginseng (Calcium) levels twice weekly. Should hypercalcemia develop, reduce the Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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.

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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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, Seven Seas M Vit with Siberian Ginseng (Calcium) acetate has been generally well tolerated.

Seven Seas M Vit with Siberian Ginseng (Calcium) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate N=167 N (%)	3 month, open label study of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate N=98 N (%)	Double blind, placebo-controlled, cross-over study of liquid Seven Seas M Vit with Siberian Ginseng (Calcium) acetate N=69
			Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) concentration could reduce the incidence and severity of Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Seven Seas M Vit with Siberian Ginseng Acetate Capsules contains Seven Seas M Vit with Siberian Ginseng (Calcium) acetate and is excreted in human milk. Human milk feeding by a mother receiving Seven Seas M Vit with Siberian Ginseng (Calcium) acetate is not expected to harm an infant, provided maternal serum Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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.

10 OVERDOSAGE

Administration of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Seven Seas M Vit with Siberian Ginseng (Calcium) acetate acts as a phosphate binder. Its chemical name is Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Seven Seas M Vit with Siberian Ginseng (Calcium), 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.

Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Seven Seas M Vit with Siberian Ginseng (Calcium) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Seven Seas M Vit with Siberian Ginseng (Calcium) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Seven Seas M Vit with Siberian Ginseng (Calcium) 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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Seven Seas M Vit with Siberian Ginseng (Calcium) acetate.

14 CLINICAL STUDIES

Effectiveness of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Seven Seas M Vit with Siberian Ginseng (Calcium) 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
Seven Seas M Vit with Siberian Ginseng (Calcium) (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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate is shown in the Table 3.

* ANOVA of Seven Seas M Vit with Siberian Ginseng (Calcium) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM.
Parameter	Pre-Study	Post-Treatment		p-value*
		Seven Seas M Vit with Siberian Ginseng (Calcium) Acetate	Placebo
Phosphorus (mg/dL)†	7.3 ± 0.18	5.9 ± 0.24	7.8 ± 0.22	<0.01
Seven Seas M Vit with Siberian Ginseng (Calcium) (mg/dL)†	8.9 ± 0.11	9.5 ± 0.13	8.8 ± 0.12	<0.01

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Seven Seas M Vit with Siberian Ginseng (Calcium) 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 Seven Seas M Vit with Siberian Ginseng (Calcium) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Choline:

• Seven Seas M Vit with Siberian Ginseng (Choline) reviews

A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism.

Indication: For nutritional supplementation, also for treating dietary shortage or imbalance

This compound is needed for good nerve conduction throughout the CNS (central nervous system) as it is a precursor to acetylcholine (ACh). Seven Seas M Vit with Siberian Ginseng (Choline) is also needed for gallbladder regulation, liver function and lecithin (a key lipid) formation. Seven Seas M Vit with Siberian Ginseng (Choline) also aids in fat and cholesterol metabolism and prevents excessive fat build up in the liver. Seven Seas M Vit with Siberian Ginseng (Choline) has been used to mitigate the effects of Parkinsonism and tardive dyskinesia. Seven Seas M Vit with Siberian Ginseng (Choline) deficiencies may result in excessive build-up of fat in the liver, high blood pressure, gastric ulcers, kidney and liver dysfunction and stunted growth.

Cod Liver Oil:

• Directions for use
• Caution
• Contains
• Seven Seas M Vit with Siberian Ginseng (Cod Liver Oil) reviews

Seven Seas M Vit with Siberian Ginseng (Cod Liver Oil) was formulated to treat the raw, tender & cracked pads of hunting dogs. Also a terrific healing aid for all types of wounds, including fungal & bacterial infections of the feet, ears & elsewhere. Try Seven Seas M Vit with Siberian Ginseng (Cod Liver Oil) on cuts, abrasions, sores, burns, tender ears & hot spots (moist dermatitis). Promotes skin cell granulation & epithelial growth.

DIRECTIONS FOR USE

Shake well. Apply once or twice daily. Allow to dry before releasing dog. Use alcohol to remove stains from hands.

CAUTION

Not for use on animals intended for food.

CONTAINS

Active Ingredients

Seven Seas M Vit with Siberian Ginseng Oil, Gentian Violet, Brilliant Green.

Other Ingredients

Isopropyl Alcohol, Balsam Peru, Glycerine, Cade Oil, Tannic Acid, Turpentine.

SOLD BY:

Happy Jack, Inc.

POB 475

2122 Hwy. 258 S.

Snow Hill, NC 28580

1-252-747-2911

Made in the U.S.A.

Product No. 1054. Rev. 1212

www.happyjackinc.com

Since 1946

Happy Jack_®

Seven Seas M Vit with Siberian Ginseng (Cod Liver Oil)

Ask for

Happy Jack^®...

Your Dog

Would!

Aids Healing & Toughening of Raw,

Tender & Cracked Pads.

Also Promotes Healing of Fungal

& Bacterial Infections.

2 FL. OZ

(58mL)

Folic Acid:

• Indications and usage
• Contraindications
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Storage
• Seven Seas M Vit with Siberian Ginseng (Folic Acid) reviews

INDICATIONS AND USAGE

Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (Folic Acid) and the BIFERA logo are registered trademarks and the Seven Seas M Vit with Siberian Ginseng (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 Extract:

• Seven Seas M Vit with Siberian Ginseng (Ginseng Extract) reviews

Seven Seas M Vit with Siberian Ginseng (Ginseng Extract) 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. Seven Seas M Vit with Siberian Ginseng (Ginseng Extract) is also known to contain phytoestrogens.

Inositol:

• Seven Seas M Vit with Siberian Ginseng (Inositol) reviews

Niacin is used with a proper diet and exercise program to help lower "bad" cholesterol and fats ( LDL, triglycerides ) and raise "good" cholesterol (HDL) in the blood. It is generally used after non-drug treatments have not been fully successful at lowering cholesterol. Niacin is also known as vitamin B-3 ( nicotinic acid ), one of the B-complex vitamins. It may be used with or without other medications. Lowering "bad" cholesterol/triglycerides and raising "good" cholesterol helps prevent strokes and heart attacks. Lowering fats may also help reduce the risk of pancreas problems ( pancreatitis ) in people at risk. In addition to eating a proper diet (such as a low-cholesterol/low-fat diet), other lifestyle changes that may help this medication work better include exercising, losing weight if overweight, and stopping smoking. Consult your doctor for more details.

Iodine:

• Iodine tincture 7%
• Iodine tincture 7%
• Seven Seas M Vit with Siberian Ginseng (Iodine) reviews

Seven Seas M Vit with Siberian Ginseng Tincture 7%

Directions:

Topical Antiseptic

Use full Strength for superficial cuts, wounds, abrasions, insect bites and bruises on the skin of animals. Apply Seven Seas M Vit with Siberian Ginseng (Iodine) with a swab.

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

Apply Seven Seas M Vit with Siberian Ginseng (Iodine) Tincture 7% only once daily. Dilute product 3 to 1 if repeating application.

Do not apply under bandage.

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

Storage:

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

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

DANGER - Poison

Caution:

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

activated charcoal. A 5% solutions of sodium thiosulfate

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

rate of 10 ml per kilogram of body weight.

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

Avoid contamination of food.

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

Seven Seas M Vit with Siberian Ginseng Tincture 7%

image description

Iron:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Seven Seas M Vit with Siberian Ginseng (Iron) reviews

1 INDICATIONS AND USAGE

Seven Seas M Vit with Siberian Ginseng (Iron) is indicated for the treatment of Seven Seas M Vit with Siberian Ginseng (Iron) deficiency anemia in patients with chronic kidney disease (CKD).

Seven Seas M Vit with Siberian Ginseng (Iron) is an Seven Seas M Vit with Siberian Ginseng (Iron) replacement product indicated for the treatment of Seven Seas M Vit with Siberian Ginseng (Iron) deficiency anemia in patients with chronic kidney disease (CKD). (1)

2 DOSAGE AND ADMINISTRATION

Seven Seas M Vit with Siberian Ginseng must only be administered intravenously either by slow injection or by infusion. The dosage of Seven Seas M Vit with Siberian Ginseng (Iron) is expressed in mg of elemental Seven Seas M Vit with Siberian Ginseng (Iron). Each mL contains 20 mg of elemental Seven Seas M Vit with Siberian Ginseng (Iron).

Population		Dose
Adult patients	Hemodialysis Dependent-Chronic Kidney Disease (HDD-CKD) (2.1)	100 mg slow intravenous injection or infusion
	Non-Dialysis Dependent-Chronic Kidney Disease (NDD-CKD) (2.2)	200 mg slow intravenous injection or infusion
	Peritoneal Dialysis Dependent-Chronic Kidney Disease (PDD-CKD) (2.3)	300 mg or 400 mg intravenous infusion
Pediatric patients	HDD-CKD (2.4), PDD-CKD or NDD-CKD (2.5)	0.5 mg/kg slow intravenous injection or infusion

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

Administer Seven Seas M Vit with Siberian Ginseng (Iron) 100 mg undiluted as a slow intravenous injection over 2 to 5 minutes, or as an infusion of 100 mg diluted in a maximum of 100 mL of 0.9% NaCl over a period of at least 15 minutes, per consecutive hemodialysis session. Seven Seas M Vit with Siberian Ginseng (Iron) should be administered early during the dialysis session. The usual total treatment course of Seven Seas M Vit with Siberian Ginseng (Iron) is 1000 mg. Seven Seas M Vit with Siberian Ginseng (Iron) treatment may be repeated if Seven Seas M Vit with Siberian Ginseng (Iron) deficiency reoccurs.

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

Administer Seven Seas M Vit with Siberian Ginseng (Iron) 200 mg undiluted as a slow intravenous injection over 2 to 5 minutes or as an infusion of 200 mg in a maximum of 100 mL of 0.9% NaCl over a period of 15 minutes. Administer on 5 different occasions over a 14 day period. There is limited experience with administration of an infusion of 500 mg of Seven Seas M Vit with Siberian Ginseng (Iron), diluted in a maximum of 250 mL of 0.9% NaCl, over a period of 3.5 to 4 hours on Day 1 and Day 14. Seven Seas M Vit with Siberian Ginseng (Iron) treatment may be repeated if Seven Seas M Vit with Siberian Ginseng (Iron) deficiency reoccurs.

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

Administer Seven Seas M Vit with Siberian Ginseng (Iron) in 3 divided doses, given by slow intravenous infusion, within a 28 day period: 2 infusions each of 300 mg over 1.5 hours 14 days apart followed by one 400 mg infusion over 2.5 hours 14 days later. Dilute Seven Seas M Vit with Siberian Ginseng (Iron) in a maximum of 250 mL of 0.9% NaCl. Seven Seas M Vit with Siberian Ginseng (Iron) treatment may be repeated if Seven Seas M Vit with Siberian Ginseng (Iron) deficiency reoccurs.

2.4 Pediatric Patients with HDD-CKD for Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment

The dosing for Seven Seas M Vit with Siberian Ginseng (Iron) replacement treatment in pediatric patients with HDD-CKD has not been established.

For Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment: Administer Seven Seas M Vit with Siberian Ginseng (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every two weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Seven Seas M Vit with Siberian Ginseng (Iron) treatment may be repeated if necessary.

2.5 Pediatric Patients with NDD-CKD or PDD-CKD who are on erythropoietin therapy for Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment

The dosing for Seven Seas M Vit with Siberian Ginseng (Iron) replacement treatment in pediatric patients with NDD-CKD or PDD-CKD has not been established.

For Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment: Administer Seven Seas M Vit with Siberian Ginseng (Iron) at a dose of 0.5 mg/kg, not to exceed 100 mg per dose, every four weeks for 12 weeks given undiluted by slow intravenous injection over 5 minutes or diluted in 25 mL of 0.9% NaCl and administered over 5 to 60 minutes. Seven Seas M Vit with Siberian Ginseng (Iron) treatment may be repeated if necessary.

3 DOSAGE FORMS AND STRENGTHS

• 10 mL single-use vial / 200 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL)
• 5 mL single-use vial / 100 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL)
• 2.5 mL single-use vial / 50 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL)

• 10 mL single-use vial / 200 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL) (3)
• 5 mL single-use vial / 100 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL) (3)
• 2.5 mL single-use vial / 50 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL) (3)

4 CONTRAINDICATIONS

• Known hypersensitivity to Seven Seas M Vit with Siberian Ginseng (Iron)

• Known hypersensitivity to Seven Seas M Vit with Siberian Ginseng (Iron) (4)

5 WARNINGS AND PRECAUTIONS

• Hypersensitivity Reactions: Observe for signs and symptoms of hypersensitivity during and after Seven Seas M Vit with Siberian Ginseng administration for at least 30 minutes and until clinically stable following completion of each administration. Only administer Seven Seas M Vit with Siberian Ginseng (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. (5.1)
• Hypotension: Seven Seas M Vit with Siberian Ginseng (Iron) may cause hypotension. Monitor for signs and symptoms of hypotension during and following each administration of Seven Seas M Vit with Siberian Ginseng (Iron). (5.2)
• Seven Seas M Vit with Siberian Ginseng (Iron) Overload: Regularly monitor hematologic responses during Seven Seas M Vit with Siberian Ginseng (Iron) therapy. Do not administer Seven Seas M Vit with Siberian Ginseng (Iron) to patients with Seven Seas M Vit with Siberian Ginseng (Iron) overload. (5.3)

5.1 Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylactic-type reactions, some of which have been life-threatening and fatal, have been reported in patients receiving Seven Seas M Vit with Siberian Ginseng (Iron). Patients may present with shock, clinically significant hypotension, loss of consciousness, and/or collapse. If hypersensitivity reactions or signs of intolerance occur during administration, stop Seven Seas M Vit with Siberian Ginseng (Iron) immediately. Monitor patients for signs and symptoms of hypersensitivity during and after Seven Seas M Vit with Siberian Ginseng (Iron) administration for at least 30 minutes and until clinically stable following completion of the infusion. Only administer Seven Seas M Vit with Siberian Ginseng (Iron) when personnel and therapies are immediately available for the treatment of serious hypersensitivity reactions. Most reactions associated with intravenous Seven Seas M Vit with Siberian Ginseng (Iron) preparations occur within 30 minutes of the completion of the infusion .

5.2 Hypotension

Seven Seas M Vit with Siberian Ginseng may cause clinically significant hypotension. Monitor for signs and symptoms of hypotension following each administration of Seven Seas M Vit with Siberian Ginseng (Iron). Hypotension following administration of Seven Seas M Vit with Siberian Ginseng (Iron) may be related to the rate of administration and/or total dose administered .

5.3 Seven Seas M Vit with Siberian Ginseng (Iron) Overload

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

6 ADVERSE REACTIONS

The following serious adverse reactions associated with Seven Seas M Vit with Siberian Ginseng are described in other sections .

• The most common adverse reactions (≥2%) following the administration of Seven Seas M Vit with Siberian Ginseng (Iron) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact American Regent, Inc. at 1-800-734-9236 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1 Adverse Reactions in Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in practice.

Adverse Reactions in Adults Patients with CKD

Adverse Reactions in Adult Patients with CKD

The frequency of adverse reactions associated with the use of Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Iron) exceeds the rate for comparator are listed by indication in Table 1. Patients with HDD-CKD received 100 mg doses at 10 consecutive dialysis sessions until a cumulative dose of 1000 mg was administered. Patients with NDD-CKD received either 5 doses of 200 mg over 2 weeks or 2 doses of 500 mg separated by fourteen days, and patients with PDD-CKD received 2 doses of 300 mg followed by a dose of 400 mg over a period of 4 weeks.

* EPO=Erythropoietin
Adverse Reactions (Preferred Term)	HDD-CKD	NDD-CKD		PDD-CKD
	Seven Seas M Vit with Siberian Ginseng (Iron)	Seven Seas M Vit with Siberian Ginseng (Iron)	Oral Seven Seas M Vit with Siberian Ginseng (Iron)	Seven Seas M Vit with Siberian Ginseng (Iron)	EPO* Only
	(N=231)	(N=139)	(N=139)	(N=75)	(N=46)
	%	%	%	%	%
Subjects with any adverse reaction	78.8	76.3	73.4	72.0	65.2
Ear and Labyrinth Disorders
Ear Pain	0	2.2	0.7	0	0
Eye Disorders
Conjunctivitis	0.4	0	0	2.7	0
Gastrointestinal Disorders
Abdominal pain	3.5	1.4	2.9	4.0	6.5
Diarrhea	5.2	7.2	10.1	8.0	4.3
Dysgeusia	0.9	7.9	0	0	0
Nausea	14.7	8.6	12.2	5.3	4.3
Vomiting	9.1	5.0	8.6	8.0	2.2
General Disorders and
Administration Site Conditions
Asthenia	2.2	0.7	2.2	2.7	0
Chest pain	6.1	1.4	0	2.7	0
Feeling abnormal	3.0	0	0	0	0
Infusion site pain or burning	0	5.8	0	0	0
Injection site extravasation	0	2.2	0	0	0
Peripheral edema	2.6	7.2	5.0	5.3	10.9
Pyrexia	3.0	0.7	0.7	1.3	0
Infections and Infestations
Nasopharyngitis, Sinusitis, Upper respiratory tract infections, Pharyngitis	2.6	2.2	4.3	16.0	4.3
Injury, Poisoning and Procedural
Complications
Graft complication	9.5	1.4	0	0	0
Metabolism and Nutrition Disorders
Fluid overload	3.0	1.4	0.7	1.3	0
Gout	0	2.9	1.4	0	0
Hyperglycemia	0	2.9	0	0	2.2
Hypoglycemia	0.4	0.7	0.7	4.0	0
Musculoskeletal and Connective
Tissue Disorders
Arthralgia	3.5	1.4	2.2	4.0	4.3
Back pain	2.2	2.2	3.6	1.3	4.3
Muscle cramp	29.4	0.7	0.7	2.7	0
Myalgia	0	3.6	0	1.3	0
Pain in extremity	5.6	4.3	0	2.7	6.5
Nervous System Disorders
Dizziness	6.5	6.5	1.4	1.3	4.3
Headache	12.6	2.9	0.7	4.0	0
Respiratory, Thoracic and
Mediastinal Disorders
Cough	3.0	2.2	0.7	1.3	0
Dyspnea	3.5	5.8	1.4	1.3	2.2
Nasal congestion	0	1.4	2.2	1.3	0
Skin and Subcutaneous
Tissue Disorders
Pruritus	3.9	2.2	4.3	2.7	0
Vascular Disorders
Hypertension	6.5	6.5	4.3	8.0	6.5
Hypotension	39.4	2.2	0.7	2.7	2.2

One hundred thirty (11%) of the 1,151 patients evaluated in the 4 U.S. trials in HDD-CKD patients (studies A, B and the two post marketing studies) had prior other intravenous Seven Seas M Vit with Siberian Ginseng (Iron) therapy and were reported to be intolerant (defined as precluding further use of that Seven Seas M Vit with Siberian Ginseng (Iron) product). When these patients were treated with Seven Seas M Vit with Siberian Ginseng (Iron) there were no occurrences of adverse reactions that precluded further use of Seven Seas M Vit with Siberian Ginseng (Iron) .

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

Adverse Reactions in Pediatric Patients with CKD (ages 2 years and older)

In a randomized, open-label, dose-ranging trial for Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment with Seven Seas M Vit with Siberian Ginseng (Iron) in pediatric patients with CKD on stable erythropoietin therapy , at least one treatment-emergent adverse reaction was experienced by 57% (27/47) of the patients receiving Seven Seas M Vit with Siberian Ginseng (Iron) 0.5 mg/kg, 53% (25/47) of the patients receiving Seven Seas M Vit with Siberian Ginseng (Iron) 1.0 mg/kg, and 55% (26/47) of the patients receiving Seven Seas M Vit with Siberian Ginseng (Iron) 2.0 mg/kg.

A total of 5 (11%) subjects in the Seven Seas M Vit with Siberian Ginseng (Iron) 0.5 mg/kg group, 10 (21%) patients in the Seven Seas M Vit with Siberian Ginseng (Iron) 1.0 mg/kg group, and 10 (21%) patients in the Seven Seas M Vit with Siberian Ginseng (Iron) 2.0 mg/kg group experienced at least 1 serious adverse reaction during the study. The most common treatment-emergent adverse reactions (> 2% of patients) in all patients were headache (6%), respiratory tract viral infection (4%), peritonitis (4%), vomiting (4%), pyrexia (4%), dizziness (4%), cough (4%), renal transplant (4%), nausea (3%), arteriovenous fistula thrombosis (2%), hypotension (2%), and hypertension (2.1%).

6.2 Adverse Reactions from Post-Marketing Experience

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

In the post-marketing safety studies in 1,051 treated patients with HDD-CKD, the adverse reactions reported by > 1% were: cardiac failure congestive, sepsis and dysgeusia.

The following adverse reactions have been identified during post-approval use of Seven Seas M Vit with Siberian Ginseng (Iron). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Anaphylactic-type reactions, shock, loss of consciousness, collapse, bronchospasm, dyspnea, convulsions, light-headedness, confusion, angioedema, swelling of the joints, hyperhidrosis, back pain, bradycardia, and chromaturia.

Symptoms associated with Seven Seas M Vit with Siberian Ginseng (Iron) total dosage or infusing too rapidly included hypotension, dyspnea, headache, vomiting, nausea, dizziness, joint aches, paresthesia, abdominal and muscle pain, edema, and cardiovascular collapse. These adverse reactions have occurred up to 30 minutes after the administration of Seven Seas M Vit with Siberian Ginseng (Iron) injection. Reactions have occurred following the first dose or subsequent doses of Seven Seas M Vit with Siberian Ginseng (Iron). Symptoms may respond to intravenous fluids, hydrocortisone, and/or antihistamines. Slowing the infusion rate may alleviate symptoms.

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

7 DRUG INTERACTIONS

Drug interactions involving Seven Seas M Vit with Siberian Ginseng (Iron) have not been studied. However, Seven Seas M Vit with Siberian Ginseng (Iron) may reduce the absorption of concomitantly administered oral Seven Seas M Vit with Siberian Ginseng (Iron) preparations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Pregnancy Category B

There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, Seven Seas M Vit with Siberian Ginseng sucrose was administered intravenously to rats and rabbits during the period of organogenesis at doses up to 13 mg/kg/day of elemental Seven Seas M Vit with Siberian Ginseng (Iron) (half or equivalent to the maximum recommended human dose based on body surface area, respectively) and revealed no evidence of harm to the fetus due to Seven Seas M Vit with Siberian Ginseng (Iron) sucrose. Because animal reproductive studies are not always predictive of human response, Seven Seas M Vit with Siberian Ginseng (Iron) should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether Seven Seas M Vit with Siberian Ginseng (Iron) sucrose is excreted in human milk. Seven Seas M Vit with Siberian Ginseng (Iron) sucrose is secreted into the milk of lactating rats. Because many drugs are excreted in human milk, caution should be exercised when Seven Seas M Vit with Siberian Ginseng (Iron) is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness of Seven Seas M Vit with Siberian Ginseng for Seven Seas M Vit with Siberian Ginseng (Iron) replacement treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD have not been established.

Safety and effectiveness of Seven Seas M Vit with Siberian Ginseng (Iron) for Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment in pediatric patients 2 years of age and older with dialysis-dependent or non-dialysis-dependent CKD receiving erythropoietin therapy were studied. Seven Seas M Vit with Siberian Ginseng (Iron) at doses of 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg was administered. All three doses maintained hemoglobin between 10.5 g/dL and 14.0 g/dL in about 50% of subjects over the 12-week treatment period with stable EPO dosing. [See Clinical Studies (14.6)]

Seven Seas M Vit with Siberian Ginseng (Iron) has not been studied in patients younger than 2 years of age.

In a country where Seven Seas M Vit with Siberian Ginseng (Iron) is available for use in children, at a single site, five premature infants (weight less than 1,250 g) developed necrotizing enterocolitis and two of the five died during or following a period when they received Seven Seas M Vit with Siberian Ginseng (Iron), several other medications and erythropoietin. Necrotizing enterocolitis may be a complication of prematurity in very low birth weight infants. No causal relationship to Seven Seas M Vit with Siberian Ginseng (Iron) or any other drugs could be established.

8.5 Geriatric Use

Clinical studies of Seven Seas M Vit with Siberian Ginseng (Iron) did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the 1,051 patients in two post-marketing safety studies of Seven Seas M Vit with Siberian Ginseng (Iron), 40% were 65 years and older. No overall differences in safety were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. In general, dose administration to an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

No data are available regarding overdosage of Seven Seas M Vit with Siberian Ginseng (Iron) in humans. Excessive dosages of Seven Seas M Vit with Siberian Ginseng (Iron) may lead to accumulation of Seven Seas M Vit with Siberian Ginseng (Iron) in storage sites potentially leading to hemosiderosis. Do not administer Seven Seas M Vit with Siberian Ginseng (Iron) to patients with Seven Seas M Vit with Siberian Ginseng (Iron) overload.

Toxicities in single-dose studies in mice and rats, at intravenous Seven Seas M Vit with Siberian Ginseng (Iron) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

11 DESCRIPTION

Seven Seas M Vit with Siberian Ginseng (Iron) (iron sucrose injection, USP), an Seven Seas M Vit with Siberian Ginseng (Iron) replacement product, is a brown, sterile, aqueous, complex of polynuclear Seven Seas M Vit with Siberian Ginseng (Iron) (III)-hydroxide in sucrose for intravenous use. Seven Seas M Vit with Siberian Ginseng (Iron) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:

[Na₂Fe₅O₈(OH) ·3(H₂O)]_n ·m(C₁₂H₂₂O₁₁)

where: n is the degree of Seven Seas M Vit with Siberian Ginseng (Iron) polymerization and m is the number of sucrose molecules associated with the Seven Seas M Vit with Siberian Ginseng (Iron) (III)-hydroxide.

Each mL contains 20 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) as Seven Seas M Vit with Siberian Ginseng (Iron) sucrose in water for injection. Seven Seas M Vit with Siberian Ginseng (Iron) is available in 10 mL single-use vials (200 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) per 10 mL), 5 mL single-use vials (100 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) per 5 mL), and 2.5 mL single-use vials (50 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) per 2.5 mL). The drug product contains approximately 30% sucrose w/v (300 mg/mL) and has a pH of 10.5 to 11.1. The product contains no preservatives. The osmolarity of the injection is 1,250 mOsmol/L.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

In healthy adults administered intravenous doses of Seven Seas M Vit with Siberian Ginseng, its Seven Seas M Vit with Siberian Ginseng (Iron) component exhibited first order kinetics with an elimination half-life of 6 h, total clearance of 1.2 L/h, and steady state apparent volume of distribution of 7.9 L. The Seven Seas M Vit with Siberian Ginseng (Iron) component appeared to distribute mainly in blood and to some extent in extravascular fluid. A study evaluating Seven Seas M Vit with Siberian Ginseng (Iron) containing 100 mg of Seven Seas M Vit with Siberian Ginseng (Iron) labeled with ⁵²Fe/⁵⁹Fe in patients with Seven Seas M Vit with Siberian Ginseng (Iron) deficiency showed that a significant amount of the administered Seven Seas M Vit with Siberian Ginseng (Iron) is distributed to the liver, spleen and bone marrow and that the bone marrow is an irreversible Seven Seas M Vit with Siberian Ginseng (Iron) trapping compartment.

Following intravenous administration of Seven Seas M Vit with Siberian Ginseng (Iron), Seven Seas M Vit with Siberian Ginseng (Iron) sucrose is dissociated into Seven Seas M Vit with Siberian Ginseng (Iron) and sucrose. The sucrose component is eliminated mainly by urinary excretion. In a study evaluating a single intravenous dose of Seven Seas M Vit with Siberian Ginseng (Iron) containing 1,510 mg of sucrose and 100 mg of Seven Seas M Vit with Siberian Ginseng (Iron) in 12 healthy adults (9 female, 3 male: age range 32 to 52), 68.3% of the sucrose was eliminated in urine in 4 h and 75.4% in 24 h. Some Seven Seas M Vit with Siberian Ginseng (Iron) was also eliminated in the urine. Neither transferrin nor transferrin receptor levels changed immediately after the dose administration. In this study and another study evaluating a single intravenous dose of Seven Seas M Vit with Siberian Ginseng (Iron) sucrose containing 500 to 700 mg of Seven Seas M Vit with Siberian Ginseng (Iron) in 26 patients with anemia on erythropoietin therapy (23 female, 3 male; age range 16 to 60), approximately 5% of the Seven Seas M Vit with Siberian Ginseng (Iron) was eliminated in urine in 24 h at each dose level. The effects of age and gender on the pharmacokinetics of Seven Seas M Vit with Siberian Ginseng (Iron) have not been studied.

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

In a single-dose PK study of Seven Seas M Vit with Siberian Ginseng (Iron), patients with NDD-CDK ages 12 to 16 (N=11) received intravenous bolus doses of Seven Seas M Vit with Siberian Ginseng (Iron) at 7 mg/kg (maximum 200 mg) administered over 5 minutes. Following single dose Seven Seas M Vit with Siberian Ginseng (Iron), the half-life of total serum Seven Seas M Vit with Siberian Ginseng (Iron) was 8 hours. The mean Cmax and AUC values were 8545 μg/dl and 31305 hr-μg/dL, respectively, which were 1.42- and 1.67-fold higher than dose adjusted adult Cmax and AUC values.

Seven Seas M Vit with Siberian Ginseng (Iron) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Seven Seas M Vit with Siberian Ginseng (Iron) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with Seven Seas M Vit with Siberian Ginseng (Iron) sucrose.

Seven Seas M Vit with Siberian Ginseng (Iron) sucrose was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Seven Seas M Vit with Siberian Ginseng (Iron) sucrose was not clastogenic in the in vitro chromosome aberration assay using human lymphocytes or in the in vivo mouse micronucleus assay.

Seven Seas M Vit with Siberian Ginseng (Iron) sucrose at intravenous doses up to 15 mg/kg/day of elemental Seven Seas M Vit with Siberian Ginseng (Iron) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

14 CLINICAL STUDIES

Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Seven Seas M Vit with Siberian Ginseng.

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 Seven Seas M Vit with Siberian Ginseng (Iron) treatment and 24 in the historical control group) with Seven Seas M Vit with Siberian Ginseng (Iron) deficiency anemia. Eligibility criteria for Seven Seas M Vit with Siberian Ginseng (Iron) treatment included patients undergoing chronic hemodialysis, receiving erythropoietin, hemoglobin level between 8.0 and 11.0 g/dL, transferrin saturation < 20%, and serum ferritin < 300 ng/mL. The mean age of the patients was 65 years with the age range of 31 to 85 years. Of the 77 patients, 44 (57%) were male and 33 (43%) were female.

Seven Seas M Vit with Siberian Ginseng (Iron) 100 mg was administered at 10 consecutive dialysis sessions either as slow injection or a slow infusion. The historical control population consisted of 24 patients with similar ferritin levels as patients treated with Seven Seas M Vit with Siberian Ginseng (Iron), who were off intravenous Seven Seas M Vit with Siberian Ginseng (Iron) for at least 2 weeks and who had received erythropoietin therapy with hematocrit averaging 31 to 36 for at least two months prior to study entry. The mean age of patients in the historical control group was 56 years, with an age range of 29 to 80 years. Patient age and serum ferritin level were similar between treatment and historical control patients.

Patients in the Seven Seas M Vit with Siberian Ginseng (Iron) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.

**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates.
Efficacy parameters	End of treatment		2 week follow-up		5 week follow-up
	Seven Seas M Vit with Siberian Ginseng (Iron) (n=69	Historical Control (n=18)	Seven Seas M Vit with Siberian Ginseng (Iron) (n=73)	Historical Control (n=18)	Seven Seas M Vit with Siberian Ginseng (Iron) (n=71)	Historical Control (n=15)
Hemoglobin (g/dL)	1.0 ± 0.12**	0.0 ± 0.21	1.3 ± 0.14**	-0.6 ± 0.24	1.2 ± 0.17*	-0.1 ± 0.23
Hematocrit (%)	3.1 ± 0.37**	-0.3 ± 0.65	3.6 ± 0.44**	-1.2 ± 0.76	3.3 ± 0.54	0.2 ± 0.86

Serum ferritin increased at endpoint of study from baseline in the Venofer-treated population (165.3 ± 24.2 ng/mL) compared to the historical control population (-27.6 ± 9.5 ng/mL). Transferrin saturation also increased at endpoint of study from baseline in the Venofer-treated population (8.8 ± 1.6%) compared to this historical control population (-5.1 ± 4.3%).

14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease

Study B was a multicenter, open label study of Seven Seas M Vit with Siberian Ginseng (Iron) in 23 patients with Seven Seas M Vit with Siberian Ginseng (Iron) deficiency and HDD-CKD who had been discontinued from Seven Seas M Vit with Siberian Ginseng (Iron) dextran due to intolerance. Eligibility criteria were otherwise identical to Study A. The mean age of the patients in this study was 53 years, with ages ranging from 21 to 79 years. Of the 23 patients enrolled in the study, 10 (44%) were male and 13 (56%) were female.

All 23 enrolled patients were evaluated for efficacy. Increases in mean hemoglobin (1.1 ± 0.2 g/dL), hematocrit (3.6 ± 0.6%), serum ferritin (266.3 ± 30.3 ng/mL) and transferrin saturation (8.7 ± 2.0%) were observed from baseline to end of treatment.

14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease

Study C was a multicenter, open-label study in patients with HDD-CKD. This study enrolled patients with a hemoglobin ≤ 10 g/dL, a serum transferrin saturation ≤ 20%, and a serum ferritin ≤ 200 ng/mL, who were undergoing maintenance hemodialysis 2 to 3 times weekly. The mean age of the patients enrolled in this study was 41 years, with ages ranging from 16 to 70 years. Of 130 patients evaluated for efficacy in this study, 68 (52%) were male and 62 (48%) were female. Forty-eight percent of the patients had previously been treated with oral Seven Seas M Vit with Siberian Ginseng (Iron). Exclusion criteria were similar to those in studies A and B. Seven Seas M Vit with Siberian Ginseng (Iron) was administered in doses of 100 mg during sequential dialysis sessions until a pre-determined (calculated) total dose of Seven Seas M Vit with Siberian Ginseng (Iron) was administered. A 50 mg dose (2.5 mL) was given to patients within two weeks of study entry as a test dose. Twenty-seven patients (20%) were receiving erythropoietin treatment at study entry and they continued to receive the same erythropoietin dose for the duration of the study.

The modified intention-to-treat (mITT) population consisted of 131 patients. Increases from baseline in mean hemoglobin (1.7 g/dL), hematocrit (5%), serum ferritin (434.6 ng/mL), and serum transferrin saturation (14%) were observed at week 2 of the observation period and these values remained increased at week 4 of the observation period.

14.4 Study D: Non-Dialysis Dependent-Chronic Kidney Disease

Study D was a randomized, open-label, multicenter, active-controlled study of the safety and efficacy of oral Seven Seas M Vit with Siberian Ginseng (Iron) versus Seven Seas M Vit with Siberian Ginseng (Iron) in patients with NDD-CKD with or without erythropoietin therapy. Erythropoietin therapy was stable for 8 weeks prior to randomization. In the study 188 patients with NDD-CKD, hemoglobin of ≤ 11.0 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL were randomized to receive oral Seven Seas M Vit with Siberian Ginseng (Iron) (325 mg ferrous sulfate three times daily for 56 days); or Seven Seas M Vit with Siberian Ginseng (Iron) (either 200 mg over 2 to 5 minutes 5 times within 14 days or two 500 mg infusions on Day 1 and Day 14, administered over 3.5 to 4 hours). The mean age of the 91 treated patients in the Seven Seas M Vit with Siberian Ginseng (Iron) group was 61.6 years (range 25 to 86 years) and 64 years (range 21 to 86 years) for the 91 patients in the oral Seven Seas M Vit with Siberian Ginseng (Iron) group.

A statistically significantly greater proportion of Seven Seas M Vit with Siberian Ginseng (Iron) subjects (35/79; 44.3%) compared to oral Seven Seas M Vit with Siberian Ginseng (Iron) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).

14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease

Study E was a randomized, open-label, multicenter study comparing patients with PDD-CKD receiving an erythropoietin and intravenous Seven Seas M Vit with Siberian Ginseng (Iron) to patients with PDD-CKD receiving an erythropoietin alone without Seven Seas M Vit with Siberian Ginseng (Iron) supplementation. Patients with PDD-CKD, stable erythropoietin for 8 weeks, hemoglobin of ≤ 11.5 g/dL, TSAT ≤ 25%, ferritin ≤ 500 ng/mL were randomized to receive either no Seven Seas M Vit with Siberian Ginseng (Iron) or Seven Seas M Vit with Siberian Ginseng (Iron) (300 mg in 250 mL 0.9% NaCl over 1.5 hours on Day 1 and 15 and 400 mg in 250 mL 0.9% NaCl over 2.5 hours on Day 29). The mean age of the 75 treated patients in the Seven Seas M Vit with Siberian Ginseng (Iron) / erythropoietin group was 51.9 years (range 21 to 81 years) vs. 52.8 years (range 23 to 77 years) for 46 patients in the erythropoietin alone group.

Patients in the Seven Seas M Vit with Siberian Ginseng (Iron) / erythropoietin group had statistically significantly greater mean change from baseline to the highest hemoglobin value (1.3 g/dL), compared to subjects who received erythropoietin alone (0.6 g/dL) (p < 0.01). A greater proportion of subjects treated with Seven Seas M Vit with Siberian Ginseng (Iron) / erythropoietin (59.1 %) had an increase in hemoglobin of ≥ 1 g/dL at any time during the study compared to the subjects who received erythropoietin only (33.3%).

14.6 Study F: Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Iron) maintenance treatment in pediatric patients with dialysis-dependent or non-dialysis-dependent CKD on stable erythropoietin therapy. The study randomized patients to one of three doses of Seven Seas M Vit with Siberian Ginseng (Iron) (0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg). The mean age was 13 years (range 2 to 20 years). Over 70% of patients were 12 years or older in all three groups. There were 84 males and 61 females. About 60% of patients underwent hemodialysis and 25% underwent peritoneal dialysis in all three dose groups. At baseline, the mean hemoglobin was 12 g/dL, the mean TSAT was 33% and the mean ferritin was 300 ng/mL. Patients with HDD-CKD received Seven Seas M Vit with Siberian Ginseng (Iron) once every other week for 6 doses. Patients with PDD-CKD or NDD-CKD received Seven Seas M Vit with Siberian Ginseng (Iron) once every 4 weeks for 3 doses. Among 131 evaluable patients with stable erythropoietin dosing, the proportion of patients who maintained hemoglobin between 10.5 g/dL and 14.0 g/dL during the 12-week treatment period was 58.7%, 46.7%, and 45.0% in the Seven Seas M Vit with Siberian Ginseng (Iron) 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg groups, respectively. A dose-response relationship was not demonstrated.

16 HOW SUPPLIED/storage and handling

16.1 How Supplied

Seven Seas M Vit with Siberian Ginseng is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron), each 5 mL vial contains 100 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron), and each 2.5 mL vial contains 50 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) (20 mg/mL).

NDC-0517-2310-05	200 mg/10 mL Single-Use Vial	Packages of 5
NDC-0517-2310-10	200 mg/10 mL Single-Use Vial	Packages of 10
NDC-0517-2340-01	100 mg/5 mL Single-Use Vial	Individually Boxed
NDC-0517-2340-10	100 mg/5 mL Single-Use Vial	Packages of 10
NDC-0517-2340-25	100 mg/5 mL Single-Use Vial	Packages of 25
NDC-0517-2340-99	100 mg/5 mL Single-Use Vial	Packages of 10
NDC-0517-2325-10	50 mg/2.5 mL Single-Use Vial	Packages of 10
NDC-0517-2325-25	50 mg/2.5 mL Single-Use Vial	Packages of 25

16.2 Stability and Storage

Contains no preservatives. Store in original carton at 20°C to 25°C (68° F to 77° F); excursions permitted to 15° to 30°C (59° to 86°F).. Do not freeze.

Syringe Stability: Seven Seas M Vit with Siberian Ginseng (Iron), when diluted with 0.9% NaCl at concentrations ranging from 2 mg to 10 mg of elemental Seven Seas M Vit with Siberian Ginseng (Iron) per mL, or undiluted (20 mg elemental Seven Seas M Vit with Siberian Ginseng (Iron) per mL) and stored in a plastic syringe, was found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C) and under refrigeration (4°C ± 2°C).

Intravenous Admixture Stability: Seven Seas M Vit with Siberian Ginseng (Iron), when added to intravenous infusion bags (PVC or non-PVC) containing 0.9% NaCl at concentrations ranging from 1 mg to 2 mg of elemental Seven Seas M Vit with Siberian Ginseng (Iron) per mL, has been found to be physically and chemically stable for 7 days at controlled room temperature (25°C ± 2°C).

Do not dilute to concentrations below 1 mg/mL.

Do not mix Seven Seas M Vit with Siberian Ginseng (Iron) with other medications or add to parenteral nutrition solutions for intravenous infusion.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to infusion.

17 PATIENT COUNSELING INFORMATION

Prior to Seven Seas M Vit with Siberian Ginseng (Iron) administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

Seven Seas M Vit with Siberian Ginseng (Iron) is manufactured under license from Vifor (International) Inc., Switzerland.

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

PREMIERProRx^®

IN2340

MG #15727

Magnesium:

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Seven Seas M Vit with Siberian Ginseng (Magnesium) reviews

Seven Seas M Vit with Siberian Ginseng (Magnesium) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Seven Seas M Vit with Siberian Ginseng (Magnesium) Sulfate Injection, USP is a sterile solution of Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium). While there are large stores of Seven Seas M Vit with Siberian Ginseng (Magnesium) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Seven Seas M Vit with Siberian Ginseng (Magnesium) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) levels range from 1.5 to 2.5 mEq/liter.

As plasma Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium). Serum Seven Seas M Vit with Siberian Ginseng (Magnesium) concentrations in excess of 12 mEq/L may be fatal.

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (Magnesium) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

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

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate should be used during pregnancy only if clearly needed. If Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of Seven Seas M Vit with Siberian Ginseng (Magnesium).

Because Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) should be given until they return. Serum Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) intoxication in eclampsia.

50% Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium), their dosage should be adjusted with caution because of additive CNS depressant effects of Seven Seas M Vit with Siberian Ginseng (Magnesium). CNS depression and peripheral transmission defects produced by Seven Seas M Vit with Siberian Ginseng (Magnesium) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate for more than 5 to 7 days.^1-10 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) is distributed into milk during parenteral Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Seven Seas M Vit with Siberian Ginseng (Magnesium) usually are the result of Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) Deficiency

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

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Magnesium) sulfate infusion for tocolysis. J Pediatr. 1988; 113(6):1078-82.
• McGuinness GA, Weinstein MM, Cruikshank DP, et al. Effects of Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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% Seven Seas M Vit with Siberian Ginseng (Magnesium) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Seven Seas M Vit with Siberian Ginseng (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:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Rl-0104
• Seven Seas M Vit with Siberian Ginseng (Manganese) reviews

INDICATIONS AND USAGE

Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng (Manganese) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng (Manganese) 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.

Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng (Manganese) chloride. It is also not known whether Seven Seas M Vit with Siberian Ginseng (Manganese) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Seven Seas M Vit with Siberian Ginseng (Manganese) 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

Seven Seas M Vit with Siberian Ginseng (Manganese) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng (Manganese) 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 Seven Seas M Vit with Siberian Ginseng (Manganese) 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

Seven Seas M Vit with Siberian Ginseng (Manganese) 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

Soybean Oil:

• Warnings
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdose section
• Dosage and administration
• How supplied
• Storage and handling
• Limited warranty
• References
• Seven Seas M Vit with Siberian Ginseng (Soybean Oil) reviews

WARNINGS

This product is intended for use only by licensed medical personnel experienced in administering allergenic extracts and trained to provide immediate emergency treatment in the event of a life-threatening reaction. Allergenic extracts may potentially elicit a severe life-threatening systemic reaction, rarely resulting in death.1

Therefore, emergency measures and personnel trained in their use must be available immediately in the event of such a reaction.

Patients should be instructed to recognize adverse reaction symptoms, be observed in the office for at least 30 minutes after skin testing or treatment, and be cautioned to contact the physician's office if symptoms occur. See ADVERSE REACTION section of this package insert regarding adverse event reporting.

Standardized glycerinated extracts may be more potent than regular extracts and therefore are not directly interchangeable with non-standardized extracts, or other manufacturers' products.

Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1

Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat allergic reactions. 2

This product should never be injected intravenously.

Refer to the WARNINGS, PRECAUTIONS, ADVERSE REACTIONS and OVERDOSE Sections for further discussion.

DESCRIPTION

The allergenic extract in this vial is referred to as a "bulk" extract or stock concentrate since it is designed primarily for the physician equipped to prepare dilutions and mixtures as required. The extract is sterile and intended for subcutaneous injection for immunotherapy and scratch, prick or puncture for diagnosis. Unless specified otherwise, the concentration of extract supplied will in most cases be expressed in weight to volume (e.g., 1:10 or 1:20 w/v) and will be the strongest available. Where mixtures of pollens and non-pollens have been ordered, the mixed extract will be treated as a pollen mixture. To insure maximum potency for the entire dating period, all bulk concentrates will contain 50% volume to volume (v/v) glycerin unless otherwise requested. Dilutions will also be prepared with 50% (v/v) glycerin unless another diluent is specified.

Source materials utilized in allergenic extract products include pollens, molds, animal epidermals, insects, foods and environmental materials.

Pollens are collected using techniques such as waterset or vacuuming, cleaned and purified to greater than 99% single specie pollen (less than 1% foreign particle presence).

Molds are typically grown on synthetic nutrient medias and are derived from the surface growth (mycelia).

Animal source materials are collected from animals deemed to be healthy at the time of collection by a veterinarian or individual trained and certified by a veterinarian. Epidermals include feathers, hair and dander, or the whole epidermal (pelt) as described on product labeling.

Regular process epidermals are extractions of the source material without additional processing, except that certain materials are defatted. AP (acetone precipitated) epidermal source materials are derived from the precipitate formed when acetone is added to an aqueous extract. The resulting precipitate is dried, and becomes the source material for the AP product.

Insects are collected in whole body form. Extractions take place as whole body or ground insects.

Information on Foods and other Environmental source materials can be obtained by contacting our Customer Service Department.

The following is a brief summary of the six methods of describing allergenic product concentration.

1. Weight to volume (w/v). Weight to volume (w/v) describes the weight of allergenic source material added to a given volume of extracting fluid. A 1:10 w/v extract, e.g., indicates that the solution contains the extractable material from one gram of raw material added to each 10 mL Glycero-Coca's or 10 mL Coca's extracting fluid. The amount and composition of extracted materials will vary with the type of antigen, the extracting fluid, duration of extraction, pH, temperature, and other variables. Pollens are typically extracted at a 1:20 w/v ratio in Glycero-Coca's while Coca's extracts are 1:10 w/v. Epidermal, environmental, regular molds and insect products are typically extracted at 1:10 w/v. AP (acetone precipitated) epidermal products are prepared at a 1:50 w/v concentration (i.e., 1 gram of dried precipitate in 50 mL of reconstitution fluid). AP Dog Hair-Dander is prepared at 1:100 w/v concentration. (i.e., 1 gram of dried precipitate in 100 mL of reconstitution fluid.)

2. Protein Nitrogen Units per mL (PNU/mL). One protein nitrogen unit represents 0.00001 mg phosphotungstic acid precipitable protein nitrogen dissolved in one mL of antigen extract. The PNU content of extracts of the same antigen may vary according to the method of measuring the PNU. Thus, the PNU content of extracts from different manufacturers is not comparable unless the PNU method is known to be the same and is reproducible from lot to lot. The amount of protein nitrogen extracted from the source material is influenced by such factors as the type of antigen, the extracting fluid, duration of extraction, pH, temperature and other variables. Allergenic materials make up a variable proportion of the total protein of an extract. Most allergenic extracts are assayed for PNU. Specific PNU information is available upon request.

3. Amb a 1. Of the many allergens from Short Ragweed which have been purified and characterized [Amb a 1 3 (also known as Antigen E), Amb a 2 3 (also known as Antigen K), Ra3 4, Ra4 (BPA-R) 5, Ra5 6, Ra6, Ra7, Ra87, and cytochrome C 8], Amb a 1 is considered the most important and has been selected as the basis for standardization. Extracts of Short Ragweed containing Amb a 1 are diffused in agar against standard anti-serum to Amb a 1, and compared to the diffusion of standard Amb a 1 solutions. The amount of Amb a 1 is expressed as units of Amb a 1 per mL of extract. A Short Ragweed pollen extracted at 1:20 (w/v) usually assays within a range of 50,000 to 70,000 PNU/mL and 100 to 300 units of Amb a 1 per mL.

The Amb a 1 concentration of any Short Ragweed extract which is diluted with a diluent or other allergenic extracts is determined by calculation. The resulting Amb a 1 value does not reflect the total potency of the product if Short Ragweed extract is mixed with another allergenic extract.

4. Allergy Units per mL (AU/mL). The potency of extracts labeled in Allergy Units (AU)/mL is determined by in vitro comparison to a reference standard established by the Center for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA).

5. Bioequivalent Allergy Units per mL (BAU/mL). Other standardized allergenic extracts are labeled in Bioequivalent Allergy Units/mL (BAU/mL) based on their comparison (by in vitro assay or major allergen content) to CBER, FDA Reference Preparations. The FDA reference extracts have been assigned Bioequivalent Allergy Units based on the CBER ID₅₀EAL method.9 Briefly, highly sensitive patients are skin tested to the reference preparation using an intradermal technique employing 3-fold extract dilutions. Depending on the dilution which elicits a summation of erythema diameter of 50, Bioequivalent Allergy Units are assigned as follows:

BAU/mL	D50 Range
100,000	13.9 - 15.9
10,000	10.9 - 12.9
1,000	8.8 - 10.8
100	6.7 - 8.7

References labeled 10,000 BAU/mL can be diluted one to a half million fold, and references labeled 100,000 BAU/mL can be diluted one to 5 million fold and produce a sum of erythema diameter of 50 mm when Intradermal testing highly reactive subjects.

6. Concentrate. Concentrate label terminology applies to allergenic extract mixtures, where the individual allergens being combined vary in strength or the designation of strength.

e.g. Concentrate

50% Short Ragweed 1:20 w/v

25% Std. Cat Pelt 10,000 BAU/mL

25% Mite D. farinae 10,000 AU/mL

Should the physician choose to calculate the actual strength of each component in the "Concentrate" mixture, the following formulation may be used:

Actual Allergen Strength in Concentrate	=	Allergen Manufacturing Strength	X	% Allergen in Formulation (by volume or parts)

Ingredients: Active ingredients are the allergen(s) noted on the vial label. Preservative is 50% (v/v) glycerin, or 0.4% phenol, as indicated on the vial label. Additional ingredients are 0.5% sodium chloride, and 0.275% sodium bicarbonate.

CLINICAL PHARMACOLOGY

The mechanism by which hyposensitization is achieved is not known completely. It has been shown that repeated injections of appropriate allergenic extracts will ameliorate the intensity of allergic symptoms upon contact with the allergen.11, 12, 13, 14 Clinical studies which address the efficacy of immunotherapy are available. The allergens which have been studied are cat, mite, and some pollen extracts.10, 15, 16, 17, 18, 19

IgE antibodies bound to receptors on mast cell membranes are required for the allergic reaction, and their level is probably related to serum IgE concentrations. Immunotherapy has been associated with decreased levels of IgE, and also with increases in allergen specific IgG "blocking" antibody.

The histamine release response of circulating basophils to a specific allergen is reduced in some patients by immunotherapy, but the mechanism of this change is not clear.

Further study and clarification of the relationships among changes in blocking antibody, reaginic antibody, and mediator-releasing cells, and between these three factors and successful immunotherapy, is needed.

INDICATIONS AND USAGE

20,21,22,23

Allergenic extracts are indicated for use in diagnosis and immunotherapy of patients presenting symptoms of allergy (hay fever, rhinitis, etc.) to specific environmental allergens. The selection of allergenic extracts to be used should be based on a thorough and carefully taken history of hypersensitivity, and confirmed by skin testing.

The use of mixed or unrelated antigens for skin testing is not recommended since, in the case of a positive reaction, it does not indicate which component of the mix is responsible for the reaction, while, in the case of a negative reaction, it fails to indicate whether the individual antigens at full concentration would give a positive reaction. Utilization of such mixes for compounding a treatment may result, in the former case, in administering unnecessary antigens and, in the latter case, in the omission of a needed antigen.

Avoidance of allergens is to be advocated if possible, but cannot always be attained, e.g., allergy to dog dander in kennel owners and employees, dog breeders, research workers, veterinarians, etc.

Allergens to which a patient is extremely sensitive should not be included in treatment mixes with allergens to which there is much less sensitivity, but should be administered separately. This allows individualized and better control of dosage increases, including adjustments in dosage becoming necessary after severe reactions which may occur with the highly reactive allergen.

CONTRAINDICATIONS

There are no known absolute contraindications to immunotherapy. See PRECAUTIONS and WARNINGS.

Patients with cardiovascular diseases and/or pulmonary diseases such as symptomatic unstable, steroid-dependent asthma, and/or those who are receiving cardiovascular drugs such as beta blockers, may be at higher risk for severe adverse reactions. These patients may also be more refractory to the normal allergy treatment regimen. Patients should be treated only if the benefit of treatment outweighs the risks.1

Treat patients only with allergens to which they are allergic by skin test reaction, have a history of symptoms on exposure, and are likely to be exposed to again.

Any injections, including immunotherapy, should be avoided in patients with a bleeding tendency. Patients on beta blockers may be more reactive to allergens given for testing or treatment and may be unresponsive to the usual doses of epinephrine used to treat systemic reactions.2

Since there are differences of opinion concerning the possibility of routine immunizations exacerbating autoimmune diseases, immunotherapy should be given cautiously to patients with other immunologic diseases and only if the risk from exposure is greater than the risk of exacerbating the underlying disorder.

WARNINGS

Allergenic extracts must be temporarily withheld from patients or the dose adjusted downward if any of the following conditions exist: (1) severe symptoms of rhinitis and/or asthma; (2) infection or flu accompanied by fever; (3) any evidence of an excessively large local or any generalized reaction during the initial stages of immunotherapy or during maintenance therapy, and/or (4) exposure to excessive amounts of clinically relevant allergen prior to a scheduled injection. Do not administer immunotherapy during a period of symptoms due to exposure. Since the individual components of the extract are those to which the patient is allergic, and to which s/he will be exposed, typical allergic symptoms may follow shortly after the injection, particularly when the antigen load from exposure plus the injected antigen exceeds the patient's antigen tolerance.

THE CONCENTRATE MUST NOT BE INJECTED AT ANY TIME UNLESS TOLERANCE HAS BEEN ESTABLISHED. DILUTE CONCENTRATED EXTRACTS WITH STERILE DILUENT FOR SKIN TESTING AND IMMUNOTHERAPY.

INJECTIONS MUST NEVER BE GIVEN INTRAVENOUSLY. Subcutaneous injection is recommended. Intracutaneous or intramuscular injection may produce large local reactions or be excessively painful.

AFTER INSERTING NEEDLE SUBCUTANEOUSLY, BUT BEFORE INJECTING, ALWAYS WITHDRAW THE PLUNGER SLIGHTLY. IF BLOOD APPEARS IN THE SYRINGE, CHANGE NEEDLE AND GIVE THE INJECTION IN ANOTHER SITE.

IF CHANGING TO A DIFFERENT LOT OF EXTRACT: All extracts lose potency over time, and a fresh extract could have an effective potency that is substantially greater than that of the old extract. Even though it is the same formula and concentration, the first dose from the new vial should not exceed 50% of the previous dose.

IF THE EXTRACT PREVIOUSLY USED WAS FROM ANOTHER MANUFACTURER: Since manufacturing processes and sources of raw materials differ among manufacturers, the interchangeability of extracts from different manufacturers cannot be insured. The starting dose of the extract therefore should be greatly decreased even though the extract is the same formula and dilution. In general, a dose reduction to 50% of the previous product dose should be adequate, but each situation must be evaluated separately considering the patient's history of sensitivity, tolerance of previous injections, and other factors. If the patient tolerates a 50% decrease, the next dose could be raised to the previous dose amount. If the decrease is greater than 50%, the next dose would need to be determined by the allergist, depending on the situation. Dose intervals should not exceed one week when rebuilding dose. See DOSAGE AND ADMINISTRATION.

IF A PROLONGED PERIOD OF TIME HAS ELAPSED SINCE THE LAST INJECTION: Patients may lose tolerance for allergen injections during prolonged periods between doses. The duration of tolerance is an individual characteristic and varies from patient to patient. In general, the longer the lapse in the injection schedule, the greater dose reduction required. If the interval since last dose is over four weeks, perform skin tests to determine starting dose. See DOSAGE AND ADMINISTRATION.

IF THE PREVIOUS EXTRACT WAS OUTDATED: The dating period for allergenic extracts indicates the time that they can be expected to remain potent under refrigerated storage conditions (2° - 8°C). During the storage of extracts, even under ideal conditions, some loss of potency occurs. For this reason, extracts should not be used beyond their expiration date. If a patient has been receiving injections of an outdated extract, s/he may experience excessive local or systemic reactions when changed to a new and possibly more potent extract. In general, the longer the material has been outdated, the greater the dose reduction necessary for the fresh extract.

IF CHANGING FROM ALUM-ADSORBED TO AQUEOUS OR GLYCERINATED EXTRACTS: When the patient was previously receiving alum-adsorbed or alum-precipitated extract, the safest course is to start over as though the patient had not been receiving immunotherapy. See DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS.

IF ANY OTHER CHANGES HAVE BEEN MADE IN THE EXTRACT CONCENTRATE FORMULA: Changes other than those listed above may include situations such as a redistribution of component parts or percentages, a difference in extracting fluid (i.e., change from non-glycerin extracts to 50% glycerin extracts), combining two or more stock concentrates, or any other change. It should be recognized that any change in formula can affect a patient's tolerance of the treatment. The usual 1/2 of the previous dose for a new extract may produce an adverse reaction; extra dilutions are recommended whenever starting a revised formula. The greater the change, the greater the number of dilutions required.

Proper selection of the dose and careful injection should prevent most systemic reactions. It must be remembered that allergenic extracts are highly potent in sensitive individuals, and that systemic reactions of varying degrees of severity may occur, including urticaria, rhinitis, conjunctivitis, wheezing, coughing, angioedema, hypotension, bradycardia, pallor, laryngeal edema, fainting, or even anaphylactic shock and death, as described under ADVERSE REACTIONS. Patients should be informed of this, and the precautions should be discussed prior to immunotherapy. Severe systemic reactions should be treated as indicated in ADVERSE REACTIONS. Refer to WARNINGS box.

PRECAUTIONS

1. General

The presence of asthmatic signs and symptoms appear to be an indicator for severe reactions following allergy injections. An assessment of airway obstruction either by measurement of peak flow or an alternate procedure may provide a useful indicator as to the advisability of administering an allergy injection.1, 24, 25, 26, 27

Concentrated extracts must not be injected unless tolerance has been established. Concentrated extracts must be diluted prior to use: See DOSAGE and ADMINISTRATION for detailed instructions on the dilution of allergenic extracts.

Any evidence of a local or generalized reaction requires a reduction in dosage during the initial stages of immunotherapy, as well as during maintenance therapy.

Allergenic extracts diluted with sterile Albumin Saline with Phenol may be more potent than extracts diluted with diluents which do not contain stabilizers. When switching from non-stabilized to stabilized diluent, consider weaker initial dilutions for both intradermal testing and immunotherapy.

Sterile solutions, vials, syringes, etc. should be used and aseptic precautions observed in making dilutions.

To avoid cross-contamination, do not use the same needle to withdraw materials from vials of more than one extract, or extract followed by diluent.

A sterile tuberculin syringe graduated in 0.01 mL units and with a needle at least 5/8" long should be used to measure each dose from the appropriate dilution.

Aseptic techniques should always be employed when injections of allergenic extracts are being administered. A separate sterile syringe should be used for each patient to prevent transmission of hepatitis and other infectious agents from one person to another.

Patient reactions to previous injections should be reviewed before each new injection, so that dosage can be adjusted accordingly. See ADVERSE REACTIONS and WARNINGS.

Rarely, a patient is encountered who develops systemic reactions to minute doses of allergen and does not demonstrate increasing tolerance to injections after several months of treatment. If systemic reactions or excessive local responses occur persistently at very small doses, efforts at immunotherapy should be stopped.

PATIENTS SHOULD BE OBSERVED IN THE OFFICE FOR AT LEAST 30 MINUTES AFTER SKIN TESTING AND EACH TREATMENT INJECTION. Most severe reactions will occur within this time period, and rapid treatment measures should be instituted. See ADVERSE REACTIONS for such treatment measures.

In order to avoid darkening and possible precipitation, do not dilute the following extracts with solutions containing phenol: Privet pollen and food extracts of White Potato, Corn, Oat, Rye, and Wheat. Injections of such extracts discolored by reaction with phenol may produce a lasting tattoo-like discoloration of the skin.

2. Information for Patients

Patients should be instructed in the recognition of adverse reactions to immunotherapy, and in particular, to the symptoms of shock. Patients should be made to understand the importance of a 30 minute observation period, and be cautioned to return to the office promptly if symptoms occur after leaving. Patients should be instructed to report any symptoms of exposure to the allergen, so the physician can adjust the dosage appropriately.

3. Drug Interactions

Patientswith cardiovascular diseases and/or pulmonary diseases such assymptomatic unstable, steroid-dependent asthma, and/or those who arereceiving cardiovascular drugs such as beta blockers, may be at higherrisk for severe adverse reactions. These patients may also be morerefractory to the normal allergy treatment regimen. Patients should betreated only if the benefit of treatment outweighs the risks.1

Patientson beta blockers may be more reactive to allergens given for testing ortreatment and may be unresponsive to the usual doses of epinephrineused to treat allergic reactions.2. Certain medications may lessen the skin test wheal anderythema responses elicited by allergens and histamine for varying timeperiods. Conventional antihistamines should be discontinued at least 5days before skin testing. Long acting antihistamines should bediscontinued for at least 3 weeks prior to skin testing. 28 Topical steroids should be discontinued at the skin test site for at least 2-3 weeks before skin testing.28, 29

Tricyclic antidepressants such as Doxepin should be withheld for at least 7 days before skin testing. 30 Topical local anesthetics may suppress the flare responses and should be avoided in skin test sites.31

4. Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been conducted with allergenic extracts to determine their potential for carcinogenicity, mutagenicity or impairment of fertility.

5. Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with allergenic extracts. It is also not known whether allergenic extracts can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Allergenic extracts should be given to a pregnant woman only if clearly needed. The physician must carefully consider the benefit-to-risk ratio to both patient and fetus, of performing skin testing or continuing immunotherapy during pregnancy. The recommended precautions for preventing adverse reactions are especially important in the pregnant patient. Based on the physician's discretion, immunotherapy maintenance doses may be continued during pregnancy if the patient has not experienced adverse side effects. Immunotherapy is generally not initiated during pregnancy due to the risks associated with systemic reactions and their treatment. 33

6. Nursing Mothers

There are no current studies on the secretion of allergenic extract components in human milk or their effect on the nursing infant. Because many drugs are excreted in human milk, caution should be exercised when allergenic extracts are administered to a nursing woman.

7. Pediatric Use

Since dosage for the pediatric population is the same as for adults 34, 35 larger volumes of solution may produce excessive discomfort. Therefore, in order to achieve the total dose required, the volume of the dose may need to be divided into more than one injection per visit.

8. Geriatric Use

The reactions from immunotherapy can be expected to be the same in elderly patients as in younger ones. Elderly patients may be more likely to be on medication that could block the effect of epinephrine which could be used to treat serious reactions, or they could be more sensitive to the cardiovascular side effect of epinephrine because of pre-existing cardiovascular disease. 36

ADVERSE REACTIONS

Physicians administering allergenic extract testing or treatment materials should be experienced in the treatment of severe systemic reactions. See WARNINGS box at the beginning of this package insert.

1. Local Reactions

Some erythema, swelling or pruritus at the site of injection are common, the extent varying with the patient. Such reactions should not be considered significant unless they persist for at least 24 hours. Local reactions (erythema or swelling) which exceed 4-5 cm in diameter are not only uncomfortable, but also indicate the possibility of a systemic reaction if dosage is increased. In such cases the dosage should be reduced to the last level not causing the reaction and maintained at this level for two or three treatments before cautiously increasing again. Large persistent local reactions may be treated by local cold, wet dressings and/or the use of oral antihistamines. They should be considered a warning of possible severe systemic reactions and an indication of the need for temporarily reduced dosages. A mild burning immediately after the injection is to be expected. This usually subsides in 10 to 20 seconds.

2. Systemic Reactions

With careful attention to dosage and administration, systemic reactions occur infrequently, but it cannot be overemphasized that in sensitive individuals, any injection could result in anaphylactic shock. Therefore, it is imperative that physicians administering allergenic extracts understand and be prepared for the treatment of severe reactions.

Most severe systemic reactions will begin within a 30 minute time period, but systemic reactions may occur at any time after skin tests or immunotherapy. Symptoms may range from mild to life-threatening (due to anaphylaxis)as described below.

Other possible systemic reactions which may occur in varying degrees of severity are laryngeal edema, fainting, pallor, bradycardia, hypotension, angioedema, cough, wheezing, conjunctivitis, rhinitis, and urticaria. Adverse reaction frequency data for allergenic extract administration for testing and treatment show that risk is low. 1, 37

If a systemic or anaphylactic reaction does occur, apply a tourniquet above the site of injection and inject 1:1,000 epinephrine-hydrochloride intramuscularly or subcutaneously into the opposite arm. Loosen the tourniquet at least every 10 minutes. Do not obstruct arterial blood flow with the tourniquet.

EPINEPHRINE

Dosage:

ADULT: 0.3 to 0.5 mL should be injected. Repeat in 5 to 10 minutes if necessary.

PEDIATRIC: The usual initial dose is 0.01 mg (mL) per kg body weight or 0.3 mg (mL) per square meter of body surface area. Suggested dosage for infants to 2 years of age is 0.05 mL to 0.1 mL; for children 2 to 6 years, 0.15 mL; and children 6 to 12 years, 0.2 mL. Single pediatric doses should not exceed 0.3 mg (mL). Doses may be repeated as frequently as every 20 minutes, depending on the severity of the condition and the response of the patient. After administration of epinephrine, profound shock or vasomotor collapse should be treated with intravenous fluids, and possibly vasoactive drugs. Airway patency should be insured. Oxygen should be given by mask. Intravenous antihistamine, inhaled bronchodilators, theophylline and/or adrenal corticosteroids may be used if necessary after adequate epinephrine and circulatory support has been given. Emergency resuscitation measures and personnel trained in their use must be available immediately in the event of a serious systemic or anaphylactic reaction not responsive to the above measures [Ref. J. Allergy and Clinical Immunology, 77(2):p. 271-273, 1986].

Rarely are all of the above measures necessary; the tourniquet and epinephrine usually produce prompt responses. However, the physician should be prepared in advance for all contingencies. Promptness in beginning emergency treatment measures is of utmost importance.

Severe systemic reactions mandate a decrease of at least 50% in the next dose, followed by cautious increases. Repeated systemic reactions, even of a mild nature, are sufficient reason for the cessation of further attempts to increase the reaction-causing dose.

3. Adverse Event Reporting

Report all adverse events to Jubilant HollisterStier LLC, Customer Technical Services Department at 1 (800) 992-1120. A voluntary adverse event reporting system for health professionals is available through the FDA MEDWATCH program. Preprinted forms (FDA Form 3500) are available from the FDA by calling 1 (800) FDA-1088. Completed forms should be mailed to MEDWATCH, 5600 Fisher Lane, Rockville, MD 20852-9787 or Fax to: 1 (800) FDA-0178.

OVERDOSE SECTION

See ADVERSE REACTIONS.

DOSAGE AND ADMINISTRATION

1. General

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

Dosage of allergenic extracts is a highly individualized matter and varies according to the degree of sensitivity of the patient, his clinical response, and tolerance to the extract administered during the early phases of an injection regimen.

Allergen extracts should be administered using a sterile syringe with 0.01 mL gradations and a 25-27 gauge x 1/2" to 5/8" needle. The injections are given subcutaneously. The most common sites of injection are the lateral aspect of the upper arm or thigh. Intracutaneous or intramuscular injections may produce large local reactions and may be very painful.

Sterile aqueous diluent containing human serum albumin [Albumin Saline with Phenol ] or diluent of 50% glycerin may be used when preparing dilutions of the concentrate for immunotherapy. Dilutions should be made accurately and aseptically, using sterile diluent, vials, syringes, etc. Mix thoroughly and gently by rocking or swirling. Maintain stock solutions and dilutions constantly at 2° - 8°C. To prepare dilutions for intradermal and therapeutic use, make a 1:10 dilution by adding 1.0 mL of the Concentrate to 9.0 mL of sterile aqueous diluent. Subsequent serial dilutions are made in a similar manner.

Following is a suggested schedule for average patients and will be satisfactory in most cases. However, the degree of sensitivity varies in many patients. The size of the dose should be adjusted according to the patient's tolerance and reaction. Decrease the size of the dose if the previous injection resulted in marked local or the slightest general reaction. Another dose should never be given until all reactions resulting from the previous dose have disappeared.

The starting dose should be based on skin tests of the extract to be used for immunotherapy. To determine the starting dose, begin intradermal testing with the most dilute extract preparation. Inject 0.02 mL and read the reaction after 15 minutes. Intradermal testing is continued with increasing concentrations of the extract until a reaction of 10-20 mm erythema ( ∑ E 0-40 mm) and/or a 5 mm wheal occurs. This concentration at a dose of 0.03 mL then can serve as a starting dose for immunotherapy. Subsequent doses can be increased by 0.03 mL to as high as 0.12 mL increments each time until 0.3 mL is reached, at which time a dilution 10 times as strong can be used, starting with 0.03 mL. Proceed in this way until a tolerance dose is reached or symptoms are controlled. Suggested maintenance dose for a pollen extract is 0.2 mL of the Concentrate, while for a non-pollen extract the maximum suggested dose is 0.5 mL of the Concentrate. Occasionally, higher doses are necessary to relieve symptoms. Special caution is required in administering doses greater than 0.2 mL. The interval between doses is normally 3 to 7 days during dose building regimen.

Normally immunotherapy can be started with a 1:100,000 dilution of extracts labeled in weight/volume. Certain therapeutic mixtures are labeled as Concentrate, (v/v) dilutions of Concentrate, Amb a 1, Allergy units/mL or Bioequivalent Allergy Units/mL. (See DESCRIPTION.) Strength of each antigen in the mixture is indicated in the product labeling. For beginning treatment, use at least a 1,000-fold dilution of the Concentrate extract for non-pollens, and at least a 10,000-fold dilution of the Concentrate extract for pollens.

In some patients, the dosage may be increased more rapidly than recommended above. In seasonal allergies, treatment should be started and the interval between doses regulated so that at least the first twenty doses will have been administered by the time symptoms are expected. Thus, the shorter the interval between the start of immunotherapy and the expected onset of symptoms, the shorter the interval between each dose. Some patients may even tolerate daily doses.

Should symptoms develop before the next injection is scheduled, the interval between doses should be decreased. Should allergic symptoms or local reactions develop shortly after the dose is administered, the size of the dose should be decreased. In seasonal allergies, it is often advisable to decrease the dose to one-half or one-quarter of the maximum dose previously attained if the patient has any seasonal symptoms.

A maintenance dose, the largest dose tolerated by the patient that relieves symptoms without producing undesirable local or general reactions, is recommended for most patients. The upper limits of dosage have not been established; however, doses larger than 0.2 mL of extract may be painful if glycerin is present. The dosage of allergenic extract does not vary significantly with the respiratory allergic disease under treatment. The size of this dose and the interval between doses will vary and can be adjusted as necessary.

The interval between maintenance doses can be increased gradually from one week to 10 days, to two weeks, to three weeks, or even to four weeks, if tolerated. Repeat the doses at a given interval three or four times to check for untoward reactions before further increasing the interval. Protection is lost rapidly if the interval between doses is more than four weeks. (See WARNINGS.)

The usual duration of treatment has not been established. A period of two or three years of injection therapy constitutes an average minimum course of treatment.

2. Pediatric Use

The dose for the pediatric population is the same as for adults.

3. Geriatric Use

The dose for elderly patients is the same as for adult patients under 65.36

HOW SUPPLIED

In 10 mL, 30 mL and 50 mL vials at the w/v, Concentrate, v/v dilution of Concentrate, AU/mL (Standardized Mite Extracts: D. farinae, D. pteronyssinus 10,000 and 30,000 AU/mL; Mite Mixtures: 5,000 AU/mL each species, or 15,000 AU/mL each species), BAU/mL (Standardized Cat Hair and Cat Pelt extracts: 10,000 BAU/mL; Standardized Grass extracts: 10,000 and 100,000 BAU/mL); Amb a 1 units/mL; or PNU/mL ordered by the physician. Please see the current Allergy Product Catalog.

STORAGE AND HANDLING

The expiration date is listed on the container label. To ensure the maximum potency, the extract and its dilutions should be stored at 2° - 8°C, and kept in this temperature range at all times, even during use. Dilutions are less stable than concentrates. If loss of potency is suspected, dilutions should be checked by skin testing with equal v/v dilutions of a freshly prepared dilution on individuals known to be allergic to the specific allergen.

LIMITED WARRANTY

A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration and biological differences in individual patients. Because of these factors, it is important that this product be stored properly and that the directions be followed carefully during use. No warranty, express or implied, including any warranty of merchantability or fitness, is made. Representatives of the Company are not authorized to vary the terms or the contents of any printed labeling, including the package insert, for this product except by printed notice from the Company's headquarters. The prescriber and user of this product must accept the terms hereof.

REFERENCES

1. Lockey, R.F., L.M. Benedict, P.C. Turkletaub, S.C. Bukantz. Fatalities from immunotherapy (IT) and skin testing (ST). J. Allergy Clin. Immunol., 79 (4): 660-677, 1987.

2. Jacobs, R.L., G.W. Rake, Jr., et al. Potentiated anaphylaxis in patients with drug-induced beta-adrenergic blockade. J. Allergy Clin. Immunol., 68 (2): 125-127, August 1981.

3. Griffith, I.J., J. Pollock, D.G. Klapper, B.L. Rogers and A.K. Nault. Sequence Polymorphism of Amb a I and Amb a II, the Major Allergens in Ambrosia artemisiifolia (Short Ragweed). Int. Arch. Allergy Apply. Immunol., 96: 296-304, 1991.

4. Underdown, B. J. and L. Goodfriend. Isolation and characterization of an allergen from short ragweed pollen. Biochem. 8 (3): 980-989, 1969.

5. Griffiths, B. W and R. Brunet. Isolation of a basic protein antigen of low ragweed pollen. Can. J. Biochem. 49 (3): 396-400, 1971.

6. Lapkoff, C. B. and L. Goodfriend. Isolation of a low molecular weight ragweed allergen: Ra5. Int. Arch. Allergy Appl. Immunol. 46 (2): 215-229, 1974.

7. Hussain, R. and D. G. March. Characterization and allergenic activity of ragweed allergens Ra6, Ra7, Ra8. J. Allergy Clin. Immunol. 65 (3): 230, abstr. 218, 1980

8. Goodfriend, L., A. M. Choudhury, J. Del Carpio and T. P. King. Cytochrome C: New ragweed pollen allergen. Fed. Proc. 38 (3, part II): 1415, abstr. 6261, 1979.

9. Turkeltaub, P.C., MD, and S.C. Rastogi, PhD. Quantitative intradermal test procedure for evaluation of subject sensitivity to standardized allergenic extracts and for assignment of bioequivalent allergy units to reference preparations using the ID₅₀EAL method. Allergenics Products Testing Laboratory, Center for Biologics Evaluation and Research (CBER), FDA. Revised: November, 1994.

10. Norman, P. S. Postgraduate Course Presentation. An overview of immunotherapy, implications for the future. J. Allergy Clin. Immunol., 65 (2): 87-96, 1980.

11. Lowell, F. C. and W. Franklin. A "double-blind" study of treatment with aqueous allergenic extracts in cases of allergic rhinitis. J. Allergy, 34 (2):165-182, 1963.

12. Lowell, F. C. and W. Franklin. A double-blind study of the effectiveness and specificity of injection therapy in ragweed hay fever. N. Eng. J. Med. 273 (13): 675-679, 1965.

13. Zavazal, V. and A. Stajner. Immunologic changes during specific treatment of the atopic state. II. Acta. Allergol. 25 (1): 11-17, 1970.

14. Reisman, R. E., J. I. Wypych, and E. E. Arbesman. Relationship of immunotherapy, seasonal pollen exposure and clinical response to serum concentrations of total IgE and ragweed-specific IgE. Int. Arch. Allergy Appl. Immunol. 48 (6): 721-730, 1975.

15. Taylor, W. W., J. L. Ohman, F. C. Lowell. Immunotherapy in cat-induced asthma; double-blind trial with evaluation of bronchial responses to cat allergen and histamine. J. Allergy Clin. Immunol., 61 (5): 283-287, 1978.

16. Smith, A. P. Hyposensitization with Dermatophagoides pteronyssinus antigen: Trial in asthma induced by house dust. Br. Med. J., 4: 204-206, 1971.

17. Chapman, M. D., T. A. E. Platts-Mills, M. Gabriel, H. K. Ng, W. G. L. Allen, L. E.Hill, A. J. Nunn. Antibody response following prolonged hyposensitization with Dermatophagoides pteronyssinus extract. Int. Arch. Allergy Appl. Immunol., 61:431-440, 1980.

18. Norman, P. S., W. L. Winkenwerder. Maintenance immunotherapy in ragweed hay fever. J. Allergy, 74: 273-282, 1971.

19. Norman, P. S., W. L. Winkenwerder, L. M. Lichtenstein. Immunotherapy of hay fever with ragweed Antigen E; comparisons with whole pollen extract and placebos. J. Allergy, 42: 93-108, 1968.

20. Middleton, E., C. E. Reed and E. F. Ellis, editors. Allergy Principles and Practice. C. V. Mosby Co., St. Louis, 1978, pp. 877-898.

21. Sheldon, J. M., R. G. Lovell and K. P. Mathews. A Manual of Clinical Allergy, Second Edition. W. B. Saunders. Philadelphia, 1967, pp. 107-112.

22. Sherman, W. B. Hypersensitivity Mechanisms and Management. W. B. Saunders. Philadelphia, 1968, pp. 169-172.

23. Swineford, O. Asthma and Hay Fever. Charles C. Thomas. Springfield, IL, 1971, pp. 148-155.

24. Reid, M.J., R.F. Lockey, P.C. Turkletaub, T.A.E., Platts-Mills. Survey of fatalities from skin testing and immunotherapy. J. 0 Clin. Immunol. 92 (1): 6-15, July 1993.

25. Reid, M.J., G. Gurka. Deaths associated with skin testing and immunotherapy. J. Allergy Clin. Immunol. 97(1) Part 3:231, Abstract 195, January 1996.

26. Thompson, R.A., et al, report of a WHO/IUIS working group. The current status of allergen immunotherapy (hyposensitization). Allergy. 44: 369-379, 1989.

27. Malling, H.J., B. Weeke, et al, The European Academy of Allergology and Clinical Immunology. Position Papers. Allergy. 48 (Supplement 14): 9-82, 1993.

28. Pipkorn, U. Pharmacological influence of anti-allergic medication on In Vivo allergen testing. Allergy. 43: 81-86,1988.

29. Andersson, M. and U. Pipkorn. Inhibition of the dermal immediate allergic reaction through prolonged treatment with topical glucocorticosteroids. J. Allergy Clin. Immunol. 79 (2): 345-349, February 1987.

30. Rao, K.S., et al. Duration of suppressive effect of tricyclic anti-depressants on histamine induced wheal and flare reactions on human skin. J. Allergy Clin. Immunol. 82: 752-757, November 1988.

31. Pipkorn, U., and M. Andersson. Topical dermal anesthesia inhibits the flare but not the wheal response to allergen and histamine in the skin prick test. Clinical Allergy. 17: 307-311, 1987.

32. DuBuske, L.M., C.J. Ling and A.L. Sheffer. Special problems regarding allergen immunotherapy. Immunol. Allergy Clin. North Am. (USA). 12(1): 145-175, 1992.

33. Li, J.T., R.F. Lockey, I.L. Bernstein, J.M. Ortnoy, R.A. Nicklas. Allergen Immunotherapy: A Practice Parameter. Ann. Allergy, Asthma and Immunotherapy 90 (1): 26, 2003.

34. Patterson, R., et al. Allergy Principles and Practice, 2nd ed. E. Middleton, Jr., C. E. Reed, E. F. Ellis, Ed., C. V. Mosby Co., 1983, St. Louis, MO, 1983, Chapter 52

35. Levy, D. A., L. M. Lichtenstein, E. O. Goldstein, and K. Ishizaka. Immunologic and cellular changes accompanying the therapy of pollen allergy. J. Clinical Investigation, 50:360, 1971.

36. Peebles, R.S., Jr., B. Bochner, Howard J. Zeitz, ed. Anaphylaxis in the elderly. Immunology and Allergy Clinics of North America. 13 (3): 627-646, August 1993.

37. Turkeltaub, P.C., MD, and P.J. Gergen, MD. The risk of adverse reactions from percutaneous prick-puncture allergen skin testing, venipuncture, and body measurements: Data from the second National Health and Nutrition Examination Survey 1976-80 (NHANES II). J. Allergy Clin. Immunol. 84(6): 886-890, Dec. 1989.

Vitamin A:

• Dosage and administration
• Warning
• Clinical pharmacology
• Dietary supplementation
• Warnings
• Precautions
• Adverse reactions
• Dosage and administration
• How supplied
• Seven Seas M Vit with Siberian Ginseng (Vitamin A) reviews

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
Seven Seas M Vit with Siberian Ginseng (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, Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Vitamin A) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Seven Seas M Vit with Siberian Ginseng (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

Seven Seas M Vit with Siberian Ginseng Tablets 0.25 mg are available as orange, red and purple chewable tablets imprinted with "151" in 100 tablet bottles.

Seven Seas M Vit with Siberian Ginseng (Vitamin A) Tablets 0.5 mg are available as orange, red and purple chewable tablets imprinted with "152" in 100 tablet bottles.

Seven Seas M Vit with Siberian Ginseng (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
• Pharmacokinetics
• Why is Seven Seas M Vit with Siberian Ginseng prescribed?
• Dosage and administration
• Seven Seas M Vit with Siberian Ginseng (Vitamin B12) side effects, adverse reactions
• Seven Seas M Vit with Siberian Ginseng contraindications
• Seven Seas M Vit with Siberian Ginseng using during pregnancy and breastfeeding
• Special instructions
• Seven Seas M Vit with Siberian Ginseng (Vitamin B12) drug interactions
• Seven Seas M Vit with Siberian Ginseng (Vitamin B12) reviews

Pharmacological action

Seven Seas M Vit with Siberian Ginseng refers to a group of water-soluble vitamins. It has high biological activity. Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Seven Seas M Vit with Siberian Ginseng is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Seven Seas M Vit with Siberian Ginseng contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng 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.

Seven Seas M Vit with Siberian Ginseng (Vitamin B12) drug interactions

In an application of Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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
• Pharmacokinetics
• Why is Seven Seas M Vit with Siberian Ginseng prescribed?
• Dosage and administration
• Seven Seas M Vit with Siberian Ginseng (Vitamin C) side effects, adverse reactions
• Seven Seas M Vit with Siberian Ginseng contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Seven Seas M Vit with Siberian Ginseng drug interactions
• Seven Seas M Vit with Siberian Ginseng in case of emergency / overdose
• Seven Seas M Vit with Siberian Ginseng (Vitamin C) reviews

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. Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng prescribed?

For systemic use of Seven Seas M Vit with Siberian Ginseng (Vitamin C) Kimia Farma: prevention and treatment of hypo- and avitaminosis of Seven Seas M Vit with Siberian Ginseng (Vitamin C); providing increased need for Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng 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.

Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng 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

Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng 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 D2:

• Seven Seas M Vit with Siberian Ginseng (Vitamin D2) reviews

Vitamin D (ergocalciferol-D2, cholecalciferol-D3, alfacalcidol) is a fat-soluble vitamin that helps your body absorb calcium and phosphorus. Having the right amount of vitamin D, calcium, and phosphorus is important for building and keeping strong bones. Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun. Vitamin D with calcium is used to treat or prevent bone loss ( osteoporosis ). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia ). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth. Vitamin D drops (or other supplements ) are given to breast -fed infants because breast milk usually has low levels of vitamin D.

Vitamin E:

• Seven Seas M Vit with Siberian Ginseng (Vitamin E) reviews

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: Seven Seas M Vit with Siberian Ginseng (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.

Seven Seas M Vit with Siberian Ginseng (Vitamin E) has antioxidant activity. It may also have anti-atherogenic, antithrombotic, anticoagulant, neuroprotective, antiviral, immunomodulatory, cell membrane-stabilizing and antiproliferative actions. Seven Seas M Vit with Siberian Ginseng (Vitamin E) is a collective term used to describe eight separate forms, the best-known form being alpha-tocopherol. Seven Seas M Vit with Siberian Ginseng (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. Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Vitamin E) may help prevent or delay coronary heart disease. Antioxidants such as Seven Seas M Vit with Siberian Ginseng (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 Seven Seas M Vit with Siberian Ginseng (Vitamin E) have been linked to increased incidence of breast and colon cancer.

Zinc:

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Seven Seas M Vit with Siberian Ginseng (Zinc) reviews

INDICATIONS AND USAGE

Seven Seas M Vit with Siberian Ginseng (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Seven Seas M Vit with Siberian Ginseng (Zinc) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Seven Seas M Vit with Siberian Ginseng (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Seven Seas M Vit with Siberian Ginseng (Zinc) doses because these elements are primarily eliminated in the urine.

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

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

PRECAUTIONS

General

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

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

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Seven Seas M Vit with Siberian Ginseng (Zinc) from a bolus injection. Administration of Seven Seas M Vit with Siberian Ginseng (Zinc) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Seven Seas M Vit with Siberian Ginseng (Zinc) are suggested as a guideline for subsequent Seven Seas M Vit with Siberian Ginseng (Zinc) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Seven Seas M Vit with Siberian Ginseng 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 Seven Seas M Vit with Siberian Ginseng (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

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

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

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

Hyperamylasemia may be a sign of impending Seven Seas M Vit with Siberian Ginseng (Zinc) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Seven Seas M Vit with Siberian Ginseng (Zinc) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Seven Seas M Vit with Siberian Ginseng (Zinc) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Seven Seas M Vit with Siberian Ginseng (Zinc) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Seven Seas M Vit with Siberian Ginseng (Zinc) toxicity.

DOSAGE AND ADMINISTRATION

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

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

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

HOW SUPPLIED

Seven Seas M Vit with Siberian Ginseng (Zinc) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Seven Seas M Vit with Siberian Ginseng (Zinc)

1 mg/mL

Seven Seas M Vit with Siberian Ginseng (Zinc) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA