Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D

Calcium (Calcium Citrate):

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) reviews

1 INDICATIONS AND USAGE

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate capsule.

- Capsule: 667 mg Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

An overdose of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) levels twice weekly. Should hypercalcemia develop, reduce the Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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.

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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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, Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate has been generally well tolerated.

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate N=167 N (%)	3 month, open label study of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate N=98 N (%)	Double blind, placebo-controlled, cross-over study of liquid Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate N=69
			Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) concentration could reduce the incidence and severity of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) acetate is characterized by the potential of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate and most concomitant drugs. When administering an oral medication with Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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:

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

8.2 Labor and Delivery

The effects of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) Acetate Capsules contains Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate is not expected to harm an infant, provided maternal serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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.

10 OVERDOSAGE

Administration of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions (5.1)].

11 DESCRIPTION

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate acts as a phosphate binder. Its chemical name is Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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.

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate.

14 CLINICAL STUDIES

Effectiveness of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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
Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate is shown in the Table 3.

* ANOVA of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM.
Parameter	Pre-Study	Post-Treatment		p-value*
		Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) Acetate	Placebo
Phosphorus (mg/dL)†	7.3 ± 0.18	5.9 ± 0.24	7.8 ± 0.22	<0.01
Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Citrate)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium (Calcium Malate):

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) reviews

1 INDICATIONS AND USAGE

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate capsule.

- Capsule: 667 mg Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate N=167 N (%)	3 month, open label study of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate N=98 N (%)	Double blind, placebo-controlled, cross-over study of liquid Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate N=69
			Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) concentration could reduce the incidence and severity of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate acts as a phosphate binder. Its chemical name is Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)), 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.

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) resulting in ectopic calcification. Hyperphosphatemia also plays a role in the development of secondary hyperparathyroidism in patients with ESRD.

12.1 Mechanism of Action

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) phosphate complex, which is excreted in the feces, resulting in decreased serum phosphorus concentration.

12.2 Pharmacodynamics

Orally administered Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate.

14 CLINICAL STUDIES

Effectiveness of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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
Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) (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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate is shown in the Table 3.

* ANOVA of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate vs. placebo after 2 weeks of treatment. † Values expressed as mean ± SEM.
Parameter	Pre-Study	Post-Treatment		p-value*
		Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) Acetate	Placebo
Phosphorus (mg/dL)†	7.3 ± 0.18	5.9 ± 0.24	7.8 ± 0.22	<0.01
Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) (mg/dL)†	8.9 ± 0.11	9.5 ± 0.13	8.8 ± 0.12	<0.01

Overall, 2 weeks of treatment with Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) by a statistically significant (p<0.01) but clinically unimportant mean of 7%.

16 HOW SUPPLIED/STORAGE AND HANDLING

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) 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 Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Calcium (Calcium Malate)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Magnesium (Magnesium Oxide):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) reviews

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

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

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

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

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

CLINICAL PHARMACOLOGY

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) (Mg⁺⁺) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

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

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

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

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

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

Pharmacokinetics

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

INDICATIONS AND USAGE

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

In total parenteral nutrition (TPN), Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

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

WARNINGS

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

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

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

Parenteral use in the presence of renal insufficiency may lead to Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

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

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

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

Laboratory Tests

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

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

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

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

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

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

Nonteratogenic Effects

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

Labor and Delivery

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

Nursing Mothers

Since Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) is distributed into milk during parenteral Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) should be monitored in such patients.

ADVERSE REACTIONS

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

OVERDOSAGE

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

For Treatment of Overdose

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

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

DOSAGE AND ADMINISTRATION

Dosage of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

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

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

In Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Deficiency

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

In Hyperalimentation

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

In Pre-eclampsia or Eclampsia

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

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate is 1 gram to 2 grams given intravenously.

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

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

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

Incompatibilities

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

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

It has been reported that Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

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

HOW SUPPLIED

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Sulfate Injection, USP is supplied in single-dose containers as follows:

NDC No.	Container	Total Amount	Concentration	mEq Mg++/mL
0409-1754-10	Ansyr Plastic Syringe	5 g/10 mL	50%	4 mEq/mL

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

Store at 20 to 25°C (68 to 77°F).

REFERENCES

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

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Magnesium (Magnesium Oxide)) Sulfate Injection, USP

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

MUST BE DILUTED FOR INTRAVENOUS USE.

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

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Potassium (Potassium Chloride):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) reviews

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) chloride containing 1500 mg of microencapsulated Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) chloride, USP equivalent to 20 mEq of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) in a tablet.

These formulations are intended to slow the release of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) so that the likelihood of a high localized concentration of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) chloride within the gastrointestinal tract is reduced.

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

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

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

CLINICAL PHARMACOLOGY

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

The intracellular concentration of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

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

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

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

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

INDICATIONS AND USAGE

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

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

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

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

CONTRAINDICATIONS

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

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

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

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

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

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) retention by inhibiting aldosterone production. Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

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

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

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) salt such as Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) bicarbonate, Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) citrate, Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) acetate, or Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) gluconate.

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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

Aqueous suspension of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

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

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

Laboratory Tests

When blood is drawn for analysis of plasma Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) 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. Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D ) is a normal dietary constituent.

Pregnancy Category C

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

Nursing Mothers

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

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) concentration can produce digitalis toxicity.

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) by the average adult is 50 to 100 mEq per day. Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) from the total body store.

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

Each Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) chloride.

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

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

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

Aqueous suspension of Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

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

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Potassium (Potassium Chloride)) chloride 20 Meq

Vitamin D2 (Ergocalciferol):

• Calcimate Plus Calcium, Potassium, Magnesium and Vitamin D (Vitamin D2 (Ergocalciferol)) reviews

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