Osteo-Force

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Osteo-Force uses

Osteo-Force consists of Calcium (Calcium Citrate), Calcium (Calcium HVP Chelate), Folic Acid, Magnesium (Magnesium Citrate), Magnesium (Magnesium HVP Chelate), Manganese (Manganese Citrate), Manganese (Manganese HVP Chelate), Potassium (Potassium Citrate), Potassium (Potassium HVP Chelate), Silicon Dioxide (Equisetum Arvense), Vitamin B1 (Thiamine Hydrochloride), Vitamin B12, Vitamin B2, Vitamin B3 (Nicotinamide), Vitamin B5 (D-Pantothenic Acid), Vitamin B6 (Pyridoxine Hydrochloride), Vitamin C, Vitamin D3, Zinc (Zinc HVP Chelate).

Calcium (Calcium Citrate):


1 INDICATIONS AND USAGE

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

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

2 DOSAGE AND ADMINISTRATION

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

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

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

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Osteo-Force (Calcium (Calcium Citrate)) acetate capsule.

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

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

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

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

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

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

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

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

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

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

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6 ADVERSE REACTIONS

Hypercalcemia is discussed elsewhere [see Warnings and Precautions ].

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

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

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

6.1 Clinical Trial Experience

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

In clinical studies, Osteo-Force (Calcium (Calcium Citrate)) acetate has been generally well tolerated.

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


Preferred Term


Total adverse reactions reported for Osteo-Force (Calcium (Calcium Citrate)) acetate

N=167

N (%)


3 month, open label study of Osteo-Force (Calcium (Calcium Citrate)) acetate

N=98

N (%)


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

N=69


Osteo-Force (Calcium (Calcium Citrate)) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


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

6.2 Postmarketing Experience

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

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

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7 DRUG INTERACTIONS

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

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

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

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

7.1 Ciprofloxacin

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Osteo-Force (Calcium (Calcium Citrate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

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

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10 OVERDOSAGE

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

11 DESCRIPTION

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


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

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

Chemical Structure

12 CLINICAL PHARMACOLOGY

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

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13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

14 CLINICAL STUDIES

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

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

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

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


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

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

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Osteo-Force (Calcium (Calcium Citrate)) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


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

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

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


* ANOVA of Osteo-Force (Calcium (Calcium Citrate)) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Osteo-Force (Calcium (Calcium Citrate)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Osteo-Force (Calcium (Calcium Citrate)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Osteo-Force (Calcium (Calcium Citrate)) Acetate Capsules

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

NDC 0615-2303-39: Blistercards of 30 Capsules

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

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

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

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

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium (Calcium HVP Chelate):


1 INDICATIONS AND USAGE

Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate capsule.

- Capsule: 667 mg Osteo-Force (Calcium (Calcium HVP Chelate)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

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

N=167

N (%)


3 month, open label study of Osteo-Force (Calcium (Calcium HVP Chelate)) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Osteo-Force (Calcium (Calcium HVP Chelate)) acetate

N=69


Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) concentration could reduce the incidence and severity of Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Osteo-Force (Calcium (Calcium HVP Chelate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

Osteo-Force (Calcium (Calcium HVP Chelate)) acetate acts as a phosphate binder. Its chemical name is Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate USP (anhydrous; Ca(CH3COO)2; MW=158.17 grams) equal to 169 mg (8.45 mEq) Osteo-Force (Calcium (Calcium HVP Chelate)), 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.

Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate.

14 CLINICAL STUDIES

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


Osteo-Force (Calcium (Calcium HVP Chelate)) (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 Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate is shown in the Table 3.


* ANOVA of Osteo-Force (Calcium (Calcium HVP Chelate)) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Osteo-Force (Calcium (Calcium HVP Chelate)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Osteo-Force (Calcium (Calcium HVP Chelate)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Osteo-Force (Calcium (Calcium HVP Chelate)) 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 Osteo-Force (Calcium (Calcium HVP Chelate)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Folic Acid:


INDICATIONS AND USAGE

Osteo-Force (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

Osteo-Force (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 Osteo-Force (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

Osteo-Force (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.

Osteo-Force (Folic Acid) and the BIFERA logo are registered trademarks and the Osteo-Force (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

Magnesium (Magnesium Citrate):



Osteo-Force (Magnesium (Magnesium Citrate)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Osteo-Force (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is a sterile solution of Osteo-Force (Magnesium (Magnesium Citrate)) 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.

Osteo-Force (Magnesium (Magnesium Citrate)) 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

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

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

As plasma Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)). Serum Osteo-Force (Magnesium (Magnesium Citrate)) concentrations in excess of 12 mEq/L may be fatal.

Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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. Osteo-Force (Magnesium (Magnesium Citrate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

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

Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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. Osteo-Force (Magnesium (Magnesium Citrate)) sulfate should be used during pregnancy only if clearly needed. If Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Osteo-Force (Magnesium (Magnesium Citrate)).

Because Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) should be given until they return. Serum Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) intoxication in eclampsia.

50% Osteo-Force (Magnesium (Magnesium Citrate)) 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

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

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

Cardiac Glycosides - Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) sulfate for more than 5 to 7 days.1-10 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Osteo-Force (Magnesium (Magnesium Citrate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) is distributed into milk during parenteral Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Osteo-Force (Magnesium (Magnesium Citrate)) usually are the result of Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Osteo-Force (Magnesium (Magnesium Citrate)).

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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) Deficiency

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

Osteo-Force (Magnesium (Magnesium Citrate)) 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 Osteo-Force (Magnesium (Magnesium Citrate)) 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

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

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Osteo-Force (Magnesium (Magnesium Citrate)) 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

Magnesium (Magnesium HVP Chelate):



Osteo-Force (Magnesium (Magnesium HVP Chelate)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

Osteo-Force (Magnesium (Magnesium HVP Chelate)) Sulfate Injection, USP is a sterile solution of Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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.

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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

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

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

As plasma Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)). Serum Osteo-Force (Magnesium (Magnesium HVP Chelate)) concentrations in excess of 12 mEq/L may be fatal.

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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. Osteo-Force (Magnesium (Magnesium HVP Chelate)) is excreted solely by the kidneys at a rate proportional to the plasma concentration and glomerular filtration.

INDICATIONS AND USAGE

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

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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. Osteo-Force (Magnesium (Magnesium HVP Chelate)) sulfate should be used during pregnancy only if clearly needed. If Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Osteo-Force (Magnesium (Magnesium HVP Chelate)).

Because Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) should be given until they return. Serum Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) intoxication in eclampsia.

50% Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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

Osteo-Force (Magnesium (Magnesium HVP Chelate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Osteo-Force (Magnesium (Magnesium HVP Chelate)). CNS depression and peripheral transmission defects produced by Osteo-Force (Magnesium (Magnesium HVP Chelate)) may be antagonized by calcium.

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

Cardiac Glycosides - Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) sulfate for more than 5 to 7 days.1-10 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Osteo-Force (Magnesium (Magnesium HVP Chelate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) is distributed into milk during parenteral Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Osteo-Force (Magnesium (Magnesium HVP Chelate)) usually are the result of Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Osteo-Force (Magnesium (Magnesium HVP Chelate)).

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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) Deficiency

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

Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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

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

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Osteo-Force (Magnesium (Magnesium HVP Chelate)) 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 Citrate):


INDICATIONS AND USAGE

Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force (Manganese (Manganese Citrate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force (Manganese (Manganese Citrate)) 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.

Osteo-Force ) 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 Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force ) 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 Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force (Manganese (Manganese Citrate)) chloride. It is also not known whether Osteo-Force (Manganese (Manganese Citrate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Osteo-Force (Manganese (Manganese Citrate)) 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

Osteo-Force (Manganese (Manganese Citrate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force (Manganese (Manganese Citrate)) 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 Osteo-Force (Manganese (Manganese Citrate)) 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

Osteo-Force (Manganese (Manganese Citrate)) 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


Manganese (Manganese HVP Chelate):


INDICATIONS AND USAGE

Osteo-Force (Manganese (Manganese HVP Chelate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN).

Administration helps to maintain Osteo-Force (Manganese (Manganese HVP Chelate)) serum levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Osteo-Force (Manganese (Manganese HVP Chelate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is contraindicated as the acidic pH of the solution (pH 2.0) may cause considerable tissue irritation.

Liver and/or biliary tract dysfunction may require omission or reduction of copper and Osteo-Force (Manganese (Manganese HVP Chelate)) doses because these elements are primarily eliminated in the bile.

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

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

PRECAUTIONS

General

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

Osteo-Force ) 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 Osteo-Force (Manganese (Manganese HVP Chelate)) levels can be measured periodically at the discretion of the investigator. Because of the low serum concentration normally present, samples will usually be analyzed by a reference laboratory.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Pregnancy Category C.

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

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

Osteo-Force (Manganese (Manganese HVP Chelate)) toxicity in TPN patients has not been reported.

DOSAGE AND ADMINISTRATION

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

Periodic monitoring of Osteo-Force (Manganese (Manganese HVP Chelate)) plasma levels is suggested as a guideline for subsequent administration.

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

HOW SUPPLIED

Osteo-Force (Manganese (Manganese HVP Chelate)) 0.1 mg/mL (Manganese Chloride Injection, USP) is supplied in 10 mL Plastic Vials (NDC No. 0409-4091-01).

Store at 20 to 25°C (68 to 77°F)

Revised: November, 2009

Printed in USA EN-2320

Hospira, Inc., Lake Forest, IL 60045 USA

RL-0104


Potassium (Potassium Citrate):



Osteo-Force (Potassium (Potassium Citrate)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

These formulations are intended to slow the release of Osteo-Force (Potassium (Potassium Citrate)) so that the likelihood of a high localized concentration of Osteo-Force (Potassium (Potassium Citrate)) chloride within the gastrointestinal tract is reduced.

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

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

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

CLINICAL PHARMACOLOGY

The Osteo-Force (Potassium (Potassium Citrate)) ion is the principal intracellular cation of most body tissues. Osteo-Force (Potassium (Potassium Citrate)) 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 Osteo-Force (Potassium (Potassium Citrate)) 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.

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

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

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

INDICATIONS AND USAGE

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

CONTRAINDICATIONS

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

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

Interaction with Potassium-Sparing Diuretics

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

Gastrointestinal Lesions

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

PRECAUTIONS

General

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

Pregnancy Category C

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

Nursing Mothers

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

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

HOW SUPPLIED

Osteo-Force (Potassium (Potassium Citrate)) 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

Osteo-Force (Potassium (Potassium Citrate)) chloride 20 Meq

Potassium (Potassium HVP Chelate):



Osteo-Force (Potassium (Potassium HVP Chelate)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

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

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

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

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

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

CLINICAL PHARMACOLOGY

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

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

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

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

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

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

INDICATIONS AND USAGE

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

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

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

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

CONTRAINDICATIONS

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

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

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

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

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

Interaction with Angiotensin-Converting Enzyme Inhibitors

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

Gastrointestinal Lesions

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

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

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Osteo-Force (Potassium (Potassium HVP Chelate)) salt such as Osteo-Force (Potassium (Potassium HVP Chelate)) bicarbonate, Osteo-Force (Potassium (Potassium HVP Chelate)) citrate, Osteo-Force (Potassium (Potassium HVP Chelate)) acetate, or Osteo-Force (Potassium (Potassium HVP Chelate)) gluconate.

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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


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

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

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

Laboratory Tests

When blood is drawn for analysis of plasma Osteo-Force ) 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. Osteo-Force ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

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

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

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

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

Each Osteo-Force (Potassium (Potassium HVP Chelate)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Osteo-Force (Potassium (Potassium HVP Chelate)) chloride.

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

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

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

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

HOW SUPPLIED

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

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Osteo-Force (Potassium (Potassium HVP Chelate)) chloride 20 Meq

Vitamin B12:


Pharmacological action

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

Dosage and administration

Osteo-Force is used as injections SC, IV, IM, intralumbar, and also oral. With anemia associated with Osteo-Force (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 Osteo-Force (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 Osteo-Force (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.

Osteo-Force (Vitamin B12) side effects, adverse reactions

CNS: rarely - a state of arousal.

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

Allergic reactions: rarely - urticaria.

Osteo-Force contraindications

Thromboembolism, erythremia, erythrocytosis, increased sensitivity to cyanocobalamin.

Osteo-Force 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 Osteo-Force 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.

Osteo-Force (Vitamin B12) drug interactions

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

Cyanocobalamin may exacerbate allergic reactions caused by thiamine.

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

Pharmaceutical incompatibility

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

Vitamin C:


Pharmacological action

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

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

Pharmacokinetics

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

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

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

Plasma protein binding is about 25%.

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

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

Why is Osteo-Force prescribed?

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

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

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

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

For intravaginal used ascorbic acid drugs in appropriate dosage forms.

Osteo-Force (Vitamin C) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

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

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

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

Osteo-Force contraindications

Increased sensitivity to ascorbic acid.

Using during pregnancy and breastfeeding

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

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

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

Special instructions

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

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

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

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

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

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

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

Osteo-Force drug interactions

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

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

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

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

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

Osteo-Force (Vitamin C) in an application with warfarin may decrease effects of warfarin.

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

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

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

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

Osteo-Force in case of emergency / overdose

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

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

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

Zinc (Zinc HVP Chelate):


INDICATIONS AND USAGE

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

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Osteo-Force (Zinc (Zinc HVP Chelate)) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Osteo-Force (Zinc (Zinc HVP Chelate)) doses because these elements are primarily eliminated in the urine.

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

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

PRECAUTIONS

General

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

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

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Osteo-Force (Zinc (Zinc HVP Chelate)) from a bolus injection. Administration of Osteo-Force (Zinc (Zinc HVP Chelate)) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

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

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Osteo-Force ) 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Osteo-Force (Zinc (Zinc HVP Chelate)) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Osteo-Force ) chloride. It is also not known whether Osteo-Force (Zinc (Zinc HVP Chelate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Osteo-Force (Zinc (Zinc HVP Chelate)) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

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

Hyperamylasemia may be a sign of impending Osteo-Force (Zinc (Zinc HVP Chelate)) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Osteo-Force (Zinc (Zinc HVP Chelate)) was delivered intravenously over the course of 60 hours to a 72 year old patient.

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

Calcium supplements may confer a protective effect against Osteo-Force (Zinc (Zinc HVP Chelate)) toxicity.

DOSAGE AND ADMINISTRATION

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

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

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

HOW SUPPLIED

Osteo-Force (Zinc (Zinc HVP Chelate)) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004


© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Osteo-Force (Zinc (Zinc HVP Chelate))

1 mg/mL

Osteo-Force (Zinc (Zinc HVP Chelate)) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

Osteo-Force pharmaceutical active ingredients containing related brand and generic drugs:

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


Osteo-Force available forms, composition, doses:

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


Osteo-Force destination | category:

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


Osteo-Force Anatomical Therapeutic Chemical codes:

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


Osteo-Force pharmaceutical companies:

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


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References

  1. Dailymed."FOLIC ACID INJECTION, SOLUTION [FRESENIUS KABI USA, LLC]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."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."CHOLECALCIFEROL: 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 Osteo-Force?

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

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

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