DRUGS & SUPPLEMENTS

Senior Formula

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Senior Formula uses

Senior Formula consists of Beta-Carotene, Calcium (Calcium Phosphate Dibasic), Calcium (Calcium Phosphate Tribasic), Chlorine (Potassium Chloride), Chromium (Chromium Chloride), Copper (Copper Oxide), Folic Acid, Iodine (Potassium Iodide), Iron (Ferrous Fumarate), Magnesium (Magnesium Oxide), Manganese (Manganese Sulfate), Molybdenum (Sodium Molybdate), Nickel (Nickel Sulfate), Phosphorus (Calcium Phosphate Dibasic), Phosphorus (Calcium Phosphate Tribasic), Potassium (Potassium Chloride), Selenium (Sodium Selenate), Silicon (Sodium Metasilicate), Vanadium (Sodium Metavanadate), Vitamin A (Vitamin A Acetate), Vitamin B1 (Thiamine Mononitrate), Vitamin B12, Vitamin B2, Vitamin B3 (Nicotinamide), Vitamin B5 (Calcium D-Pantothenate), Vitamin B6 (Pyridoxine Hydrochloride), Vitamin C (Nia.

Calcium (Calcium Phosphate Dibasic):


1 INDICATIONS AND USAGE

Senior Formula (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 Senior Formula (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 Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate capsule.

- Capsule: 667 mg Senior Formula (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 Senior Formula ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Senior Formula (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 Senior Formula (Calcium (Calcium Phosphate Dibasic)), including Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate. Avoid the use of Senior Formula (Calcium (Calcium Phosphate Dibasic)) supplements, including Senior Formula (Calcium (Calcium Phosphate Dibasic)) based nonprescription antacids, concurrently with Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate.

An overdose of Senior Formula (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 Senior Formula (Calcium (Calcium Phosphate Dibasic)) levels twice weekly. Should hypercalcemia develop, reduce the Senior Formula (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 Senior Formula (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 Senior Formula (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 Senior Formula (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 Senior Formula (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.

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6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

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

- In clinical studies, patients have occasionally experienced nausea during Senior Formula (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, Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate has been generally well tolerated.

Senior Formula (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 Senior Formula (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.


Preferred Term


Total adverse reactions reported for Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate

N=167

N (%)


3 month, open label study of Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate

N=69


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

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7 DRUG INTERACTIONS

The drug interaction of Senior Formula ) acetate is characterized by the potential of Senior Formula (Calcium (Calcium Phosphate Dibasic)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Senior Formula (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 Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate and most concomitant drugs. When administering an oral medication with Senior Formula (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 Senior Formula (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 Senior Formula (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 Senior Formula (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 Senior Formula (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:

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

8.2 Labor and Delivery

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

8.3 Nursing Mothers

Senior Formula ) Acetate Capsules contains Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate is not expected to harm an infant, provided maternal serum Senior Formula (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 Senior Formula (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.

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10 OVERDOSAGE

Administration of Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

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

Senior Formula (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 Senior Formula ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Senior Formula (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.

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate.

14 CLINICAL STUDIES

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


Senior Formula (Calcium (Calcium Phosphate Dibasic)) (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 Senior Formula (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 Senior Formula (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 Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate is shown in the Table 3.


* ANOVA of Senior Formula (Calcium (Calcium Phosphate Dibasic)) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Senior Formula (Calcium (Calcium Phosphate Dibasic)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Senior Formula (Calcium (Calcium Phosphate Dibasic)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

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

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium (Calcium Phosphate Tribasic):


1 INDICATIONS AND USAGE

Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate capsule.

- Capsule: 667 mg Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

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

N=167

N (%)


3 month, open label study of Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate

N=69


Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) concentration could reduce the incidence and severity of Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate.

14 CLINICAL STUDIES

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


Senior Formula (Calcium (Calcium Phosphate Tribasic)) (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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate is shown in the Table 3.


* ANOVA of Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Senior Formula (Calcium (Calcium Phosphate Tribasic)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Senior Formula (Calcium (Calcium Phosphate Tribasic)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Senior Formula (Calcium (Calcium Phosphate Tribasic)) 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 Senior Formula (Calcium (Calcium Phosphate Tribasic)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Chlorine (Potassium Chloride):


Active ingredient

Active Senior Formula (Chlorine (Potassium Chloride)) Derived from Calcium Hypochlorite 3-4%

Available Senior Formula (Chlorine (Potassium Chloride)) 6-8%

Purpose

Topical Antisepsis

Keep Out of Reach of Children

Uses

Topical Antisepsis

Warnings

Caution

Never use Senior Formula (Chlorine (Potassium Chloride)) powder as is. This product is intended to be used only as a solution (in water). The powder can cause damage to human tissue, and particularly to infected areas or mucous membrane tissue.

Directions

Add the Senior Formula (Chlorine (Potassium Chloride)) powder to sterile or deionized water at room temperature (20-25° C.). The powder dissolves slowly in water. As a result even after 2-3 minutes of stirring or mixing some residue of incompletely dissolved product will remain. This residue consists of inactive ingredients and therefore there is no necessity to continue to stir or mix for a longer period of time. This residue can be removed by either filtering the solution through a coarse laboratory filter or allowing the solution to settle for about 5 minutes and then decanting the clear solution for use.

Storage

Senior Formula (Chlorine (Potassium Chloride)) solutions should preferably be used as soon as possible after preparation. If the solution must be stored, it can be kept refrigerated (4-8° C.) for up to 14 days in a capped or sealed plastic or glass container using a non-metallic cap. It can be stored at room temperature (20-25° C.) for up to 7 days after preparation.

Handling

As with any chlorinated product, Senior Formula (Chlorine (Potassium Chloride)) solution should be prepared in a ventilated area and inhalation of the vapors should be minimized. The solution can cause bleaching of fabrics or other materials if splashing or spilling occurs.

Inactive ingredients

sodium acid pyrophosphate, sodium hexametaphosphate, sodium dodecylbenzene sulfonate

PW018 - Revised September 20, 2010

NDC - 0327 -0001 - 10

The Ultimate Topical Bioticide

Clorpactin® wcs-90

Brand of Oxychlorosene, Sodium

  • Keep Under Refrigeration
  • Bactericide
  • Virucide
  • Fungicide
  • Sporicide

Active ingredient:

Active Senior Formula (Chlorine (Potassium Chloride)) derived from

Calcium hypochlorite 3-4%

Available Senior Formula (Chlorine (Potassium Chloride)) 6-8%

Contents: 5 - 2 gram bottles

Guardian Laboratories div. of United-Guardian, Inc. Hauppauge, NY 11788

Directions: Pour the contents of one bottle into a quart of cool or lukewarm water, in a glass or plastic container. Stir or shake for several minutes.

Use the freshly prepared solution for irrigating the infected area as a rinse, soak or spray.

Repeat applications with a fresh portion of the solution, or allow to soak for 20 to 30 minutes until symptoms disappear or are relieved.

See Enclosed Insert for Further Information

Made in U.S.A.

Copper (Copper Oxide):



Water-Resistant Protection Without Bandaging

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

For Animal Use Only.

INDICATIONS:

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

GENERAL DIRECTIONS:

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

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

CONTAINS FOIL SEAL – REMOVE BEFORE USE.

SHAKE WELL BEFORE USE.

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

ACTIVE INGREDIENT:

Senior Formula (Copper (Copper Oxide)) Naphthenate..........37.5% w/w

INACTIVE INGREDIENTS:

Inert Ingredients.........................62.5% w/w

Total......................................... 100.0%

CAUTION:

Do not use in horses intended for human consumption.

CAUTION: COMBUSTIBLE MIXTURE.

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

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

KEEP OUT OF REACH OF CHILDREN AND PETS.

STORAGE:

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

Manufactured for:

Aspen Veterinary Resources,® Ltd.

Liberty, MO 64068, USA

FC163FP 11/13

Manufactured by:

First Priority, Inc.

Elgin, IL 60123-1146, USA

NET CONTENTS:

16 OZ (473 mL)

ANADA 200-304, Approved by FDA

Image of 473 mL bottle/case label

Folic Acid:


INDICATIONS AND USAGE

Senior Formula (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

Senior Formula (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 Senior Formula (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

Senior Formula (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.

Senior Formula (Folic Acid) and the BIFERA logo are registered trademarks and the Senior Formula (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

Iodine (Potassium Iodide):


Senior Formula ) Tincture 7%

Directions:


Topical Antiseptic

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

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

Apply Senior Formula (Iodine (Potassium Iodide)) 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.

Senior Formula ) Tincture 7%

image description

Iron (Ferrous Fumarate):


1 INDICATIONS AND USAGE

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

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

2 DOSAGE AND ADMINISTRATION

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

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

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

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

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

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

2.3 Adult Patients with Peritoneal Dialysis Dependent-Chronic Kidney Disease

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

2.4 Pediatric Patients with HDD-CKD for Senior Formula (Iron (Ferrous Fumarate)) maintenance treatment

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

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

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

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

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

3 DOSAGE FORMS AND STRENGTHS

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

4 CONTRAINDICATIONS

  • Known hypersensitivity to Senior Formula (Iron (Ferrous Fumarate))
  • Known hypersensitivity to Senior Formula (Iron (Ferrous Fumarate)) (4)

5 WARNINGS AND PRECAUTIONS

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

5.1 Hypersensitivity Reactions

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

5.2 Hypotension

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

5.3 Senior Formula (Iron (Ferrous Fumarate)) Overload

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

6 ADVERSE REACTIONS

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

  • The most common adverse reactions (≥2%) following the administration of Senior Formula (Iron (Ferrous Fumarate)) are diarrhea, nausea, vomiting, headache, dizziness, hypotension, pruritus, pain in extremity, arthralgia, back pain, muscle cramp, injection site reactions, chest pain, and peripheral edema. (6.1)

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

6.1 Adverse Reactions in Clinical Trials

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

Adverse Reactions in Adults Patients with CKD

Adverse Reactions in Adult Patients with CKD

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


* EPO=Erythropoietin

Adverse Reactions

(Preferred Term)

HDD-CKD NDD-CKD PDD-CKD
Senior Formula (Iron (Ferrous Fumarate)) Senior Formula (Iron (Ferrous Fumarate)) Oral Senior Formula (Iron (Ferrous Fumarate)) Senior Formula (Iron (Ferrous Fumarate)) EPO* Only
(N=231) (N=139) (N=139) (N=75) (N=46)
% % % % %
Subjects with any adverse reaction 78.8 76.3 73.4 72.0 65.2
Ear and Labyrinth Disorders
Ear Pain 0 2.2 0.7 0 0
Eye Disorders
Conjunctivitis 0.4 0 0 2.7 0
Gastrointestinal Disorders
Abdominal pain 3.5 1.4 2.9 4.0 6.5
Diarrhea 5.2 7.2 10.1 8.0 4.3
Dysgeusia 0.9 7.9 0 0 0
Nausea 14.7 8.6 12.2 5.3 4.3
Vomiting 9.1 5.0 8.6 8.0 2.2
General Disorders and
Administration Site Conditions
Asthenia 2.2 0.7 2.2 2.7 0
Chest pain 6.1 1.4 0 2.7 0
Feeling abnormal 3.0 0 0 0 0
Infusion site pain or burning 0 5.8 0 0 0
Injection site extravasation 0 2.2 0 0 0
Peripheral edema 2.6 7.2 5.0 5.3 10.9
Pyrexia 3.0 0.7 0.7 1.3 0
Infections and Infestations
Nasopharyngitis, Sinusitis, Upper

respiratory tract infections, Pharyngitis

2.6 2.2 4.3 16.0 4.3
Injury, Poisoning and Procedural
Complications
Graft complication 9.5 1.4 0 0 0
Metabolism and Nutrition Disorders
Fluid overload 3.0 1.4 0.7 1.3 0
Gout 0 2.9 1.4 0 0
Hyperglycemia 0 2.9 0 0 2.2
Hypoglycemia 0.4 0.7 0.7 4.0 0
Musculoskeletal and Connective
Tissue Disorders
Arthralgia 3.5 1.4 2.2 4.0 4.3
Back pain 2.2 2.2 3.6 1.3 4.3
Muscle cramp 29.4 0.7 0.7 2.7 0
Myalgia 0 3.6 0 1.3 0
Pain in extremity 5.6 4.3 0 2.7 6.5
Nervous System Disorders
Dizziness 6.5 6.5 1.4 1.3 4.3
Headache 12.6 2.9 0.7 4.0 0
Respiratory, Thoracic and
Mediastinal Disorders
Cough 3.0 2.2 0.7 1.3 0
Dyspnea 3.5 5.8 1.4 1.3 2.2
Nasal congestion 0 1.4 2.2 1.3 0
Skin and Subcutaneous
Tissue Disorders
Pruritus 3.9 2.2 4.3 2.7 0
Vascular Disorders
Hypertension 6.5 6.5 4.3 8.0 6.5
Hypotension 39.4 2.2 0.7 2.7 2.2

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

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

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

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

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

6.2 Adverse Reactions from Post-Marketing Experience

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

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

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

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

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

7 DRUG INTERACTIONS

Drug interactions involving Senior Formula (Iron (Ferrous Fumarate)) have not been studied. However, Senior Formula (Iron (Ferrous Fumarate)) may reduce the absorption of concomitantly administered oral Senior Formula (Iron (Ferrous Fumarate)) preparations.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category B

Pregnancy Category B

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

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

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

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

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

8.5 Geriatric Use

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

10 OVERDOSAGE

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

Toxicities in single-dose studies in mice and rats, at intravenous Senior Formula (Iron (Ferrous Fumarate)) sucrose doses up to 8 times the maximum recommended human dose based on body surface area, included sedation, hypoactivity, pale eyes, bleeding in the gastrointestinal tract and lungs, and mortality.

11 DESCRIPTION

Senior Formula (Iron (Ferrous Fumarate)) (iron sucrose injection, USP), an Senior Formula (Iron (Ferrous Fumarate)) replacement product, is a brown, sterile, aqueous, complex of polynuclear Senior Formula (Iron (Ferrous Fumarate)) (III)-hydroxide in sucrose for intravenous use. Senior Formula (Iron (Ferrous Fumarate)) sucrose injection has a molecular weight of approximately 34,000 to 60,000 daltons and a proposed structural formula:

[Na2Fe5O8(OH) ·3(H2O)]n ·m(C12H22O11)

where: n is the degree of Senior Formula (Iron (Ferrous Fumarate)) polymerization and m is the number of sucrose molecules associated with the Senior Formula (Iron (Ferrous Fumarate)) (III)-hydroxide.

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

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

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

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

Pharmacokinetics in Pediatric Patients

Pharmacokinetics in Pediatric Patients

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

Senior Formula (Iron (Ferrous Fumarate)) is not dialyzable through CA210 (Baxter) High Efficiency or Fresenius F80A High Flux dialysis membranes. In in vitro studies, the amount of Senior Formula (Iron (Ferrous Fumarate)) sucrose in the dialysate fluid was below the levels of detection of the assay (less than 2 parts per million).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been performed with Senior Formula (Iron (Ferrous Fumarate)) sucrose.

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

Senior Formula (Iron (Ferrous Fumarate)) sucrose at intravenous doses up to 15 mg/kg/day of elemental Senior Formula (Iron (Ferrous Fumarate)) (1.2 times the maximum recommended human dose based on body surface area) had no effect on fertility and reproductive function of male and female rats.

14 CLINICAL STUDIES

Five clinical trials involving 647 adult patients and one clinical trial involving 131 pediatric patients were conducted to assess the safety and efficacy of Senior Formula ).

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

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

Patients in the Senior Formula (Iron (Ferrous Fumarate)) treated population showed a greater increase in hemoglobin and hematocrit than did patients in the historical control population. See Table 2.


**p < 0.01 and *p < 0.05 compared to historical control from ANCOVA analysis with baseline hemoglobin, serum ferritin and erythropoietin dose as covariates.


Efficacy

parameters

End of treatment 2 week follow-up 5 week follow-up
Senior Formula (Iron (Ferrous Fumarate)) (n=69 Historical Control (n=18) Senior Formula (Iron (Ferrous Fumarate))

(n=73)

Historical Control

(n=18)

Senior Formula (Iron (Ferrous Fumarate))

(n=71)

Historical

Control

(n=15)

Hemoglobin (g/dL) 1.0 ± 0.12** 0.0 ± 0.21 1.3 ± 0.14** -0.6 ± 0.24 1.2 ± 0.17* -0.1 ± 0.23
Hematocrit (%) 3.1 ± 0.37** -0.3 ± 0.65 3.6 ± 0.44** -1.2 ± 0.76 3.3 ± 0.54 0.2 ± 0.86

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

14.2 Study B: Hemodialysis Dependent-Chronic Kidney Disease

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

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

14.3 Study C: Hemodialysis Dependent-Chronic Kidney Disease

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

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

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

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

A statistically significantly greater proportion of Senior Formula (Iron (Ferrous Fumarate)) subjects (35/79; 44.3%) compared to oral Senior Formula (Iron (Ferrous Fumarate)) subjects (23/82; 28%) had an increase in hemoglobin ≥ 1 g/dL at anytime during the study (p = 0.03).

14.5 Study E: Peritoneal Dialysis Dependent-Chronic Kidney Disease

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

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

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

16 HOW SUPPLIED/storage and handling

16.1 How Supplied

Senior Formula ) is supplied sterile in 10 mL, 5 mL, and 2.5 mL single-use vials. Each 10 mL vial contains 200 mg elemental Senior Formula (Iron (Ferrous Fumarate)), each 5 mL vial contains 100 mg elemental Senior Formula (Iron (Ferrous Fumarate)), and each 2.5 mL vial contains 50 mg elemental Senior Formula (Iron (Ferrous Fumarate)) (20 mg/mL).

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

16.2 Stability and Storage

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

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

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

Do not dilute to concentrations below 1 mg/mL.

Do not mix Senior Formula (Iron (Ferrous Fumarate)) with other medications or add to parenteral nutrition solutions for intravenous infusion.

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

17 PATIENT COUNSELING INFORMATION

Prior to Senior Formula (Iron (Ferrous Fumarate)) administration:

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

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

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

PREMIERProRx®

IN2340

MG #15727

Magnesium (Magnesium Oxide):



Senior Formula (Magnesium (Magnesium Oxide)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

Pharmacokinetics

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

INDICATIONS AND USAGE

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

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

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

CONTRAINDICATIONS

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

WARNINGS

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

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

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

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

PRECAUTIONS

General

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

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

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

Laboratory Tests

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

Drug Interactions

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

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

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

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

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

Nonteratogenic Effects

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

Labor and Delivery

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

Nursing Mothers

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

Geriatrics

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

For Treatment of Overdose

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

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

DOSAGE AND ADMINISTRATION

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

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

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

In Senior Formula (Magnesium (Magnesium Oxide)) Deficiency

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

In Hyperalimentation

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

In Pre-eclampsia or Eclampsia

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

Other Uses

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

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

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

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

Incompatibilities

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

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

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

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

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

HOW SUPPLIED

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


NDC No.


Container


Total

Amount


Concentration


mEq

Mg++/mL


0409-1754-10


Ansyr

Plastic Syringe


5 g/10 mL


50%


4 mEq/mL


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

Store at 20 to 25°C (68 to 77°F).

REFERENCES

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

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

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

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Senior Formula (Magnesium (Magnesium Oxide)) Sulfate Injection, USP

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

MUST BE DILUTED FOR INTRAVENOUS USE.

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

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Manganese (Manganese Sulfate):


INDICATIONS AND USAGE

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

Administration helps to maintain Senior Formula (Manganese (Manganese Sulfate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

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

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

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

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

PRECAUTIONS

General

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

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

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Senior Formula ) 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 Senior Formula (Manganese (Manganese Sulfate)) 0.1 mg/mL (Manganese Chloride Injection, USP) additive is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C.

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

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Senior Formula (Manganese (Manganese Sulfate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

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

Periodic monitoring of Senior Formula (Manganese (Manganese Sulfate)) plasma levels is suggested as a guideline for subsequent administration.

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

HOW SUPPLIED

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

Store at 20 to 25°C (68 to 77°F)

Revised: November, 2009

Printed in USA EN-2320

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0104


Potassium (Potassium Chloride):



Senior Formula (Potassium (Potassium Chloride)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

INDICATIONS AND USAGE

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

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

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

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

CONTRAINDICATIONS

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

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

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

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

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

Interaction with Angiotensin-Converting Enzyme Inhibitors

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

Gastrointestinal Lesions

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

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

Metabolic Acidosis

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

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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


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

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

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

Laboratory Tests

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

Drug Interactions

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity, mutagenicity, and fertility studies in animals have not been performed. Senior Formula ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

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

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

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

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

Each Senior Formula (Potassium (Potassium Chloride)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Senior Formula (Potassium (Potassium Chloride)) chloride.

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

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

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

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

HOW SUPPLIED

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

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Senior Formula (Potassium (Potassium Chloride)) chloride 20 Meq

Selenium (Sodium Selenate):



Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

Senior Formula (Selenium (Sodium Selenate)) 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 Senior Formula (Selenium (Sodium Selenate)) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.

CLINICAL PHARMACOLOGY

Senior Formula (Selenium (Sodium Selenate)) 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 Senior Formula (Selenium (Sodium Selenate)) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Senior Formula (Selenium (Sodium Selenate)).

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

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



COUNTRY


Number of

Samples

Senior Formula (Selenium (Sodium Selenate)) (mcg/100 mL) (a)

Whole Blood


Blood Cells

Plasma/

Serum

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

Southern USA

10 Adults

9 Children (c)

19-28 (22)

(23 ± 5)

--

(36 ± 12)

--

(15 ± 5)

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

9 Children (e)

14.4-20.2

(12.0 ± 3.6) (f)

17.8-35.8

(19.5 ± 8.2)

8.1-12.5

(8.3 ± 2.2)

USA 210 Adults 15.7-25.6

(20.6)

-- --

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

Senior Formula (Selenium (Sodium Selenate)) 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 Senior Formula (Selenium (Sodium Selenate)) used in supplementation. Ancillary routes of elimination are lungs and skin.

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

WARNINGS

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

Senior Formula (Selenium (Sodium Selenate)) 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 Senior Formula ) is eliminated in urine and feces, Senior Formula (Selenium (Sodium Selenate)) 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 Senior Formula (Selenium (Sodium Selenate)) plasma level determinations are suggested as a guideline.

In animals, Senior Formula (Selenium (Sodium Selenate)) 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: Senior Formula (Selenium (Sodium Selenate)) 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. Senior Formula (Selenium (Sodium Selenate)) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.

Presence of Senior Formula (Selenium (Sodium Selenate)) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

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

OVERDOSAGE

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

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

Senior Formula (Selenium (Sodium Selenate)) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Senior Formula (Selenium (Sodium Selenate)) 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

Senior Formula (Selenium (Sodium Selenate)) INJECTION

Senior Formula (Selenium (Sodium Selenate)) 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

Senior Formula (Selenium (Sodium Selenate)) INJECTION

Senior Formula (Selenium (Sodium Selenate)) 400 mcg/10 mL

(40 mcg/mL)

Trace Element Additive

NDC 0517-6510-25

25 x 10 mL

SINGLE DOSE VIALS

FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only

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

pH adjusted with Nitric Acid. Sterile, nonpyrogenic.

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

permitted to 15°-30°C (59°-86°F).

Directions for Use: See Package Insert.

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

Container Carton

Vitamin A (Vitamin A Acetate):


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
Senior Formula (Vitamin A (Vitamin A Acetate)) 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, Senior Formula (Vitamin A (Vitamin A Acetate)) 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.

Senior Formula (Vitamin A (Vitamin A Acetate)) 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 Senior Formula (Vitamin A (Vitamin A Acetate)) Tablets should not be exceeded, since dental fluorosis may result from continued ingestion of large amounts of fluoride.

Before recommending Senior Formula (Vitamin A (Vitamin A Acetate)) 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

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

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

Senior Formula (Vitamin A (Vitamin A Acetate)) 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

Senior Formula refers to a group of water-soluble vitamins. It has high biological activity. Senior Formula (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 Senior Formula (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 Senior Formula 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 Senior Formula (Vitamin B12) (including the application of biguanide, PASA, vitamin C in high doses); radiation sickness.

Dosage and administration

Senior Formula is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Senior Formula (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 Senior Formula (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 Senior Formula (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.

Senior Formula (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Senior Formula contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Senior Formula 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 Senior Formula 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.

Senior Formula (Vitamin B12) drug interactions

In an application of Senior Formula (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 Senior Formula (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.

Senior Formula pharmaceutical active ingredients containing related brand and generic drugs:

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


Senior Formula available forms, composition, doses:

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


Senior Formula destination | category:

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


Senior Formula Anatomical Therapeutic Chemical codes:

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


Senior Formula pharmaceutical companies:

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


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References

  1. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."ASCORBIC ACID; BIOTIN; CYANOCOBALAMIN; DEXPANTHENOL; ERGOCALCIFEROL; FOLIC ACID; NIACINAMIDE; PHYTONADIONE; PYRIDOXINE HYDROCHLORIDE; RIBOFLAVIN 5'-PHOSPHATE SODIUM; THIAMINE HYDROCHLORIDE; VITAMIN A; VITAMIN E: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."COPPER: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Senior Formula?

Depending on the reaction of the Senior Formula after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Senior Formula not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Senior Formula addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Senior Formula, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Senior Formula consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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