E Plus

Calcium (Calcium Phosphate Dibasic):

• 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
• E Plus (Calcium (Calcium Phosphate Dibasic)) reviews

1 INDICATIONS AND USAGE

E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate capsule.

- Capsule: 667 mg E Plus (Calcium (Calcium Phosphate Dibasic)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

E Plus (Calcium (Calcium Phosphate Dibasic)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of E Plus (Calcium (Calcium Phosphate Dibasic)) 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.

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 E Plus (Calcium (Calcium Phosphate Dibasic)) concentration could reduce the incidence and severity of E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of E Plus (Calcium (Calcium Phosphate Dibasic)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate.

14 CLINICAL STUDIES

Effectiveness of E Plus (Calcium (Calcium Phosphate Dibasic)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum E Plus (Calcium (Calcium Phosphate Dibasic)) levels are also presented.

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 E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate is shown in the Table 3.

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

16 HOW SUPPLIED/STORAGE AND HANDLING

E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of E Plus (Calcium (Calcium Phosphate Dibasic)) 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 E Plus (Calcium (Calcium Phosphate Dibasic)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Selenium (Sodium Selenite):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• E Plus (Selenium (Sodium Selenite)) reviews

Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

E Plus (Selenium (Sodium Selenite)) Injection is a sterile, nonpyrogenic solution for use as an additive to solutions for Total Parenteral Nutrition (TPN).

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

CLINICAL PHARMACOLOGY

E Plus (Selenium (Sodium Selenite)) is part of glutathione peroxidase which protects cell components from oxidative damage due to peroxides produced in cellular metabolism.

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

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

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

Plasma E Plus (Selenium (Sodium Selenite)) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.

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

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

WARNINGS

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

E Plus (Selenium (Sodium Selenite)) Injection is a hypotonic solution and should be administered in admixtures only.

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

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

PRECAUTIONS

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

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

Pregnancy

Teratogenic Effects

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

Presence of E Plus (Selenium (Sodium Selenite)) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

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

OVERDOSAGE

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

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

DOSAGE AND ADMINISTRATION

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

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

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

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

HOW SUPPLIED

E Plus (Selenium (Sodium Selenite)) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental E Plus (Selenium (Sodium Selenite)) 40 mcg/mL).

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN6510

Rev. 11/15

PRINCIPAL DISPLAY PANEL - Container

NDC 0517-6510-25

E Plus (Selenium (Sodium Selenite)) INJECTION

E Plus (Selenium (Sodium Selenite)) 400 mcg/10 mL

(40 mcg/mL)

10 mL

SINGLE DOSE VIAL

Trace Element Additive

FOR IV USE AFTER DILUTION

PRESERVATIVE FREE

Rx Only

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

PRINCIPAL DISPLAY PANEL - Carton

E Plus (Selenium (Sodium Selenite)) INJECTION

E Plus (Selenium (Sodium Selenite)) 400 mcg/10 mL

(40 mcg/mL)

Trace Element Additive

NDC 0517-6510-25

25 x 10 mL

SINGLE DOSE VIALS

FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only

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

pH adjusted with Nitric Acid. Sterile, nonpyrogenic.

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

permitted to 15°-30°C (59°-86°F).

Directions for Use: See Package Insert.

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

Container Carton

Vitamin E:

• E Plus (Vitamin E) reviews

Indication: E Plus (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.

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