Effervescent Ca / Mg plus K, Zn, Trace Minerals 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
• Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) reviews

1 INDICATIONS AND USAGE

Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate capsule.

- Capsule: 667 mg Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)), including Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate. Avoid the use of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) supplements, including Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) based nonprescription antacids, concurrently with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate.

An overdose of Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) levels twice weekly. Should hypercalcemia develop, reduce the Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate has been generally well tolerated.

Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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.

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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) concentration could reduce the incidence and severity of Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

The drug interaction of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) acetate is characterized by the potential of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) to bind to drugs with anionic functions (e.g., carboxyl, and hydroxyl groups). Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate and most concomitant drugs. When administering an oral medication with Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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:

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

8.2 Labor and Delivery

The effects of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) Acetate Capsules contains Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate and is excreted in human milk. Human milk feeding by a mother receiving Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate is not expected to harm an infant, provided maternal serum Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate acts as a phosphate binder. Its chemical name is Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate USP (anhydrous; Ca(CH₃COO)₂; MW=158.17 grams) equal to 169 mg (8.45 mEq) Effervescent Ca / Mg plus K, Zn, Trace Minerals 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.

Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate, when taken with meals, combines with dietary phosphate to form an insoluble Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate.

14 CLINICAL STUDIES

Effectiveness of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) levels are also presented.

There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate is shown in the Table 3.

Overall, 2 weeks of treatment with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate statistically significantly (p<0.01) decreased serum phosphorus by a mean of 19% and increased serum Effervescent Ca / Mg plus K, Zn, Trace Minerals 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

Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Effervescent Ca / Mg plus K, Zn, Trace Minerals 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 Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Calcium (Calcium Citrate)) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Magnesium (Magnesium Citrate):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• References
• Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) reviews

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate

Injection, USP

Ansyr Plastic Syringe

Rx only

Hospira Logo

DESCRIPTION

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

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

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate, USP heptahydrate is chemically designated MgSO₄ - 7H₂O with molecular weight of 246.48 and occurs as colorless crystals or white powder freely soluble in water.

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

CLINICAL PHARMACOLOGY

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) (Mg⁺⁺) is an important cofactor for enzymatic reactions and plays an important role in neurochemical transmission and muscular excitability.

As a nutritional adjunct in hyperalimentation, the precise mechanism of action for Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) is uncertain. Early symptoms of hypomagnesemia (less than 1.5 mEq/liter) may develop as early as three to four days or within weeks.

Predominant deficiency effects are neurological, e.g., muscle irritability, clonic twitching and tremors. Hypocalcemia and hypokalemia often follow low serum levels of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)). While there are large stores of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) present intracellularly and in the bones of adults, these stores often are not mobilized sufficiently to maintain plasma levels. Parenteral Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) therapy repairs the plasma deficit and causes deficiency symptoms and signs to cease.

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

As plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) rises above 4 mEq/liter, the deep tendon reflexes are first decreased and then disappear as the plasma level approaches 10 mEq/liter. At this level respiratory paralysis may occur. Heart block also may occur at this or lower plasma levels of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)). Serum Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) concentrations in excess of 12 mEq/L may be fatal.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) acts peripherally to produce vasodilation. With low doses only flushing and sweating occur, but larger doses cause lowering of blood pressure. The central and peripheral effects of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) poisoning are antagonized to some extent by intravenous administration of calcium.

Pharmacokinetics

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

INDICATIONS AND USAGE

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

In total parenteral nutrition (TPN), Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate may be added to the nutrient admixture to correct or prevent hypomagnesemia which can arise during the course of therapy.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is also indicated for the prevention and control of seizures (convulsions) in pre-eclampsia and eclampsia, respectively.

CONTRAINDICATIONS

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

WARNINGS

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

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

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

Parenteral use in the presence of renal insufficiency may lead to Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) intoxication. Intravenous use in the eclampsia should be reserved for immediate control of life-threatening convulsions.

PRECAUTIONS

General

Administer with caution if flushing and sweating occurs. When barbiturates, narcotics or other hypnotics (or systemic anesthetics) are to be given in conjunction with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)).

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

50% Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate Injection, USP must be diluted to a concentration of 20% or less prior to intravenous infusion. Rate of administration should be slow and cautious, to avoid producing hypermagnesemia. The 50% solution also should be diluted to 20% or less for intramuscular injection in infants and children.

Laboratory Tests

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate injection should not be given unless hypomagnesemia has been confirmed and the serum concentration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) is monitored. The normal serum level is 1.5 to 2.5 mEq/L.

Drug Interactions

CNS Depressants - When barbiturates, narcotics or other hypnotics (or systemic anesthetics), or other CNS depressants are to be given in conjunction with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)), their dosage should be adjusted with caution because of additive CNS depressant effects of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)). CNS depression and peripheral transmission defects produced by Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) may be antagonized by calcium.

Neuromuscular Blocking Agents - Excessive neuromuscular block has occurred in patients receiving parenteral Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate and a neuromuscular blocking agent; these drugs should be administered concomitantly with caution.

Cardiac Glycosides - Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate should be administered with extreme caution in digitalized patients, because serious changes in cardiac conduction which can result in heart block may occur if administration of calcium is required to treat Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) toxicity.

Pregnancy

Teratogenic Effects

Pregnancy Category D (See WARNINGS and PRECAUTIONS )

See WARNINGS and PRECAUTIONS .

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

Nonteratogenic Effects

When administered by continuous intravenous infusion (especially for more than 24 hours preceding delivery) to control convulsions in a toxemic woman, the newborn may show signs of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) toxicity, including neuromuscular or respiratory depression (See OVERDOSAGE ).

Labor and Delivery

Continuous administration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate is an unapproved treatment for preterm labor. The safety and efficacy of such use have not been established. The administration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate outside of its approved indication in pregnant women should be by trained obstetrical personnel in a hospital setting with appropriate obstetrical care facilities.

Nursing Mothers

Since Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) is distributed into milk during parenteral Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate administration, the drug should be used with caution in nursing women.

Geriatrics

Geriatric patients often require reduced dosage because of impaired renal function. In patients with severe impairment, dosage should not exceed 20 grams in 48 hours. Serum Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) should be monitored in such patients.

ADVERSE REACTIONS

The adverse effects of parenterally administered Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) usually are the result of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) intoxication. These include flushing, sweating, hypotension, depressed reflexes, flaccid paralysis, hypothermia, circulatory collapse, cardiac and central nervous system depression proceeding to respiratory paralysis. Hypocalcemia with signs of tetany secondary to Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate therapy for eclampsia has been reported.

OVERDOSAGE

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) intoxication is manifested by a sharp drop in blood pressure and respiratory paralysis. Disappearance of the patellar reflex is a useful clinical sign to detect the onset of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) intoxication. In the event of overdosage, artificial ventilation must be provided until a calcium salt can be injected intravenously to antagonize the effects of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)).

For Treatment of Overdose

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

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

DOSAGE AND ADMINISTRATION

Dosage of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate must be carefully adjusted according to individual requirements and response, and administration of the drug should be discontinued as soon as the desired effect is obtained.

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

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

In Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Deficiency

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

In Hyperalimentation

In total parenteral nutrition, maintenance requirements for Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) are not precisely known. The maintenance dose used in adults ranges from 8 to 24 mEq (1 gram to 3 grams) daily; for infants, the range is 2 to 10 mEq (0.25 gram to 1.25 grams) daily.

In Pre-eclampsia or Eclampsia

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

Other Uses

In counteracting the muscle-stimulating effects of barium poisoning, the usual dose of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate is 1 gram to 2 grams given intravenously.

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

In paroxysmal atrial tachycardia, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) should be used only if simpler measures have failed and there is no evidence of myocardial damage. The usual dose is 3 grams to 4 grams (30 to 40 mL of a 10% solution) administered intravenously over 30 seconds with extreme caution.

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

Incompatibilities

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) sulfate in solution may result in a precipitate formation when mixed with solutions containing:

Alcohol (in high Heavy Metals

concentrations) Hydrocortisone sodium

Alkali carbonates and succinate

bicarbonates Phosphates

Alkali hydroxides Polymixin B sulfate

Arsenates Procaine hydrochloride

Barium Salicylates

Calcium Strontium

Clindamycin phosphate Tartrates

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

It has been reported that Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) may reduce the antibiotic activity of streptomycin, tetracycline and tobramycin when given together.

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

HOW SUPPLIED

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate Injection, USP is supplied in single-dose containers as follows:

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

Hospira, Inc., Lake Forest, IL 60045 USA

LAB-1024-1.0

April 2017

Hospira Logo

50% Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate 5 g/10 mL (500 mg/mL)

Rx only

NDC 0409-1754-10

10 mL Single-dose syringe

50% Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Magnesium (Magnesium Citrate)) Sulfate Injection, USP

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

MUST BE DILUTED FOR INTRAVENOUS USE.

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

Contains no more than 75 mcg/L of aluminum.

Hospira, Inc., Lake Forest, IL 60045 USA

Hospira

RL-6891

Potassium (Potassium Citrate):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) reviews

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) CHLORIDE EXTENDED RELEASE TABLETS USP 20 mEq K

Rx Only

DESCRIPTION

The Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq product is an immediately dispersing extended release oral dosage form of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride containing 1500 mg of microencapsulated Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride, USP equivalent to 20 mEq of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) in a tablet.

These formulations are intended to slow the release of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) so that the likelihood of a high localized concentration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride within the gastrointestinal tract is reduced.

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

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

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

CLINICAL PHARMACOLOGY

The Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) ion is the principal intracellular cation of most body tissues. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) ions participate in a number of essential physiological processes including the maintenance of intracellular tonicity; the transmission of nerve impulses; the contraction of cardiac, skeletal, and smooth muscle; and the maintenance of normal renal function.

The intracellular concentration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) is approximately 150 to 160 mEq per liter. The normal adult plasma concentration is 3.5 to 5 mEq per liter. An active ion transport system maintains this gradient across the plasma membrane.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) is a normal dietary constituent and under steady-state conditions the amount of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) absorbed from the gastrointestinal tract is equal to the amount excreted in the urine. The usual dietary intake of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) is 50 to 100 mEq per day.

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

If Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) depletion associated with metabolic alkalosis cannot be managed by correcting the fundamental cause of the deficiency, eg, where the patient requires long-term diuretic therapy, supplemental Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) in the form of high Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) food or Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride may be able to restore normal Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) levels.

In rare circumstances (eg, patients with renal tubular acidosis) Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) depletion may be associated with metabolic acidosis and hyperchloremia. In such patients Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) replacement should be accomplished with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) salts other than the chloride, such as Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) bicarbonate, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) citrate, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) acetate, or Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) gluconate.

INDICATIONS AND USAGE

BECAUSE OF REPORTS OF INTESTINAL AND GASTRIC ULCERATION AND BLEEDING WITH CONTROLLED-RELEASE Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) CHLORIDE PREPARATIONS, THESE DRUGS SHOULD BE RESERVED FOR THOSE PATIENTS WHO CANNOT TOLERATE OR REFUSE TO TAKE LIQUID OR EFFERVESCENT Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) PREPARATIONS OR FOR PATIENTS IN WHOM THERE IS A PROBLEM OF COMPLIANCE WITH THESE PREPARATIONS.

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

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

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

CONTRAINDICATIONS

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

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

All solid oral dosage forms of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride are contraindicated in any patient in whom there is structural, pathological (eg, diabetic gastroparesis), or pharmacologic (use of anticholinergic agents or other agents with anticholinergic properties at sufficient doses to exert anticholinergic effects) cause for arrest or delay in tablet passage through the gastrointestinal tract.

WARNINGS

Hyperkalemia (see OVERDOSAGE )

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

Interaction with Potassium-Sparing Diuretics

Hypokalemia should not be treated by the concomitant administration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) salts and a potassium-sparing diuretic (eg, spironolactone, triamterene, or amiloride) since the simultaneous administration of these agents can produce severe hyperkalemia.

Interaction with Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE) inhibitors (eg, captopril, enalapril) will produce some Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) retention by inhibiting aldosterone production. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) supplements should be given to patients receiving ACE inhibitors only with close monitoring.

Gastrointestinal Lesions

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

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

Metabolic Acidosis

Hypokalemia in patients with metabolic acidosis should be treated with an alkalinizing Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) salt such as Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) bicarbonate, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) citrate, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) acetate, or Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) gluconate.

PRECAUTIONS

General

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

Information for Patients

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

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

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

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

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

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

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

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

Aqueous suspension of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

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

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

Laboratory Tests

When blood is drawn for analysis of plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals 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. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) is a normal dietary constituent.

Pregnancy Category C

Animal reproduction studies have not been conducted with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq. It is unlikely that Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) supplementation that does not lead to hyperkalemia would have an adverse effect on the fetus or would affect reproductive capacity.

Nursing Mothers

The normal Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) ion content of human milk is about 13 mEq per liter. Since oral Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) becomes part of the body Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) pool, so long as body Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) is not excessive, the contribution of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride supplementation should have little or no effect on the level in human milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

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

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

ADVERSE REACTIONS

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

OVERDOSAGE

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

Treatment measures for hyperkalemia include the following:

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

In treating hyperkalemia, it should be recalled that in patients who have been stabilized on digitalis, too rapid a lowering of the serum Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) concentration can produce digitalis toxicity.

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

Consider standard measures to remove any unabsorbed drug.

DOSAGE AND ADMINISTRATION

The usual dietary intake of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) by the average adult is 50 to 100 mEq per day. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) depletion sufficient to cause hypokalemia usually requires the loss of 200 or more mEq of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) from the total body store.

Dosage must be adjusted to the individual needs of each patient. The dose for the prevention of hypokalemia is typically in the range of 20 mEq per day. Doses of 40-100 mEq per day or more are used for the treatment of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) depletion. Dosage should be divided if more than 20 mEq per day is given such that no more than 20 mEq is given in a single dose.

Each Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablet USP, 20 mEq provides 20 mEq of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq should be taken with meals and with a glass of water or other liquid. This product should not be taken on an empty stomach because of its potential for gastric irritation (see WARNINGS ).

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

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

Aqueous suspension of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride that is not taken immediately should be discarded. The use of other liquids for suspending Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq is not recommended.

HOW SUPPLIED

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) Chloride Extended Release Tablets USP, 20 mEq are available in bottles of 100 (NDC 62037-999-01), bottles of 500 (NDC 62037-999-05), and bottles of 1000 (NDC 62037-999-10). Potassium Chloride Extended Release Tablets USP, 20 mEq are capsule shaped, white to off-white tablets, with “ABRS-123” imprinted on one side and scored on the other side for flexibility of dosing.

Storage Conditions

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

Manufactured by:

Eurand, Inc.

Vandalia, OH 45377 USA

Distributed by:

Watson Pharma, Inc.

Rev. Date (01/09) 173714

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Potassium (Potassium Citrate)) chloride 20 Meq

Selenium (Selenium HVP Chelate):

• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Overdosage
• Dosage and administration
• How supplied
• Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) reviews

Rx Only

TRACE ELEMENT ADDITIVE FOR IV USE AFTER DILUTION

DESCRIPTION

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection is a sterile, nonpyrogenic solution for use as an additive to solutions for Total Parenteral Nutrition (TPN).

Each mL contains Selenious Acid 65.4 mcg (equivalent to elemental Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) 40 mcg/mL) and Water for Injection q.s. pH may be adjusted with nitric acid to 1.8 to 2.4.

CLINICAL PHARMACOLOGY

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) is part of glutathione peroxidase which protects cell components from oxidative damage due to peroxides produced in cellular metabolism.

Prolonged TPN support in humans has resulted in Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) deficiency symptoms which include muscle pain and tenderness. The symptoms have been reported to respond to supplementation of TPN solutions with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)).

Pediatric conditions, Keshan disease, and Kwashiorkor, have been associated with low dietary intake of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)). The conditions are endemic to geographical areas with low Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) soil content. Dietary supplementation with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) salts has been reported to reduce the incidence of the conditions among affected children.

Normal blood levels of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) in different human populations have been found to vary and depend on the Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) content of the food consumed. Results of surveys carried out in some countries are tabulated below:

Plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) levels of 0.3 and 0.9 mcg/100 mL have been reported to produce deficiency symptoms in humans.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) is eliminated primarily in urine. However, significant endogenous losses through feces also occur. The rate of excretion and the relative importance of two routes varies with the chemical form of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) used in supplementation. Ancillary routes of elimination are lungs and skin.

INDICATIONS AND USAGE

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection is indicated for use as a supplement to intravenous solutions given for total parenteral nutrition (TPN). Administration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) in TPN solutions helps to maintain plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

CONTRAINDICATIONS

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection should not be given undiluted by direct injection into a peripheral vein because of the potential for infusion phlebitis.

WARNINGS

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection can be toxic if given in excessive amounts. Supplementation of TPN solution with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) should be immediately discontinued if toxicity symptoms are observed. Frequent determination of plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) levels during TPN support and close medical supervision is recommended.

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection is a hypotonic solution and should be administered in admixtures only.

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

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

PRECAUTIONS

As Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) is eliminated in urine and feces, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) supplements may be adjusted, reduced or omitted in renal dysfunction and/or gastrointestinal malfunction. In patients receiving blood transfusions, contribution from such transfusions should also be considered. Frequent Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) plasma level determinations are suggested as a guideline.

In animals, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) has been reported to enhance the action of Vitamin E and decrease the toxicity of mercury, cadmium and arsenic.

Pregnancy

Teratogenic Effects

Pregnancy Category C: Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) at high dose levels (15-30 mcg/egg) has been reported to have adverse embryological effects among chickens. There are however, no adequate and wellcontrolled studies in pregnant women. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection should be used during pregnancy only if potential benefit justifies the potential risk to the fetus.

Presence of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) in placenta and umbilical cord blood has been reported in humans.

ADVERSE REACTIONS

The amount of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) present in Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection is small. Symptoms of toxicity from Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) are unlikely to occur at the recommended dosage level.

OVERDOSAGE

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

No effective antidote to Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) poisoning in humans is known. Animal studies have shown casein and linseed oil in feeds, reduced glutathione, arsenic, magnesium sulfate, and bromobenzene to afford limited protection.

DOSAGE AND ADMINISTRATION

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection provides 40 mcg selenium/mL. For metabolically stable adults receiving TPN, the suggested additive dosage level is 20 to 40 mcg selenium/day. For pediatric patients, the suggested additive dosage level is 3 mcg/kg/day.

In adults, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) deficiency states resulting from long-term TPN support, Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) as selenomethionine or selenious acid, administered intravenously at 100 mcg/day for a period of 24 and 31 days, respectively, has been reported to reverse deficiency symptoms without toxicity.

Aseptic addition of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection to the TPN solution under laminar flow hood is recommended. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) is physically compatible with the electrolytes and other trace elements usually present in amino-acid/dextrose solution used for TPN. Frequent monitoring of plasma Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) levels is suggested as a guideline for subsequent administration. The normal whole blood range for Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) is approximately 10 to 37 mcg/100 mL.

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

HOW SUPPLIED

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) Injection containing selenious acid 65.4 mcg/mL (equivalent to elemental Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) 40 mcg/mL).

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

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

AMERICAN

REGENT, INC.

SHIRLEY, NY 11967

IN6510

Rev. 11/15

PRINCIPAL DISPLAY PANEL - Container

NDC 0517-6510-25

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) INJECTION

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) 400 mcg/10 mL

(40 mcg/mL)

10 mL

SINGLE DOSE VIAL

Trace Element Additive

FOR IV USE AFTER DILUTION

PRESERVATIVE FREE

Rx Only

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

PRINCIPAL DISPLAY PANEL - Carton

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) INJECTION

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Selenium (Selenium HVP Chelate)) 400 mcg/10 mL

(40 mcg/mL)

Trace Element Additive

NDC 0517-6510-25

25 x 10 mL

SINGLE DOSE VIALS

FOR INTRAVENOUS USE AFTER DILUTION PRESERVATIVE FREE Rx Only

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

pH adjusted with Nitric Acid. Sterile, nonpyrogenic.

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

permitted to 15°-30°C (59°-86°F).

Directions for Use: See Package Insert.

AMERICAN REGENT, INC.

SHIRLEY, NY 11967

Rev. 11/05

Container Carton

Zinc (Zinc Citrate):

• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) reviews

INDICATIONS AND USAGE

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) 1 mg/mL (Zinc Chloride Injection, USP) is indicated for use as a supplement to intravenous solutions given for TPN. Administration helps to maintain Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) serum levels and to prevent depletion of endogenous stores, and subsequent deficiency symptoms.

CONTRAINDICATIONS

None known.

WARNINGS

Direct intramuscular or intravenous injection of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) 1 mg/mL (Zinc Chloride Injection, USP) is contraindicated as the acidic pH of the solution (2) may cause considerable tissue irritation.

Severe kidney disease may make it necessary to reduce or omit chromium and Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) doses because these elements are primarily eliminated in the urine.

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

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

PRECAUTIONS

General

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

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

Zinc should not be given undiluted by direct injection into a peripheral vein because of the likelihood of infusion phlebitis and the potential for increased excretory loss of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) from a bolus injection. Administration of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) in the absence of copper may cause a decrease in serum copper levels.

Laboratory Tests

Periodic determinations of serum copper as well as Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) are suggested as a guideline for subsequent Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) administration.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies to evaluate the carcinogenic potential of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) 1 mg/mL (Zinc Chloride Injection, USP) have not been performed, nor have studies been done to assess mutagenesis or impairment of fertility.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) 1 mg/mL (Zinc Chloride Injection, USP) is administered to a nursing woman.

Pediatric Use

Pregnancy Category C. Animal reproduction studies have not been conducted with Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D ) chloride. It is also not known whether Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) chloride can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) chloride should be given to a pregnant woman only if clearly needed.

Geriatric Use

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

ADVERSE REACTIONS

None known.

DRUG ABUSE AND DEPENDENCE

None known.

OVERDOSAGE

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

Hyperamylasemia may be a sign of impending Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) overdosage; patients receiving an inadvertent overdose (25 mg zinc/liter of TPN solution, equivalent to 50 to 70 mg zinc/day) developed hyperamylasemia (557 to 1850 Klein units; normal: 130 to 310).

Death resulted from an overdosage in which 1683 mg Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) was delivered intravenously over the course of 60 hours to a 72 year old patient.

Symptoms of Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) toxicity included hypotension (80/40 mm Hg), pulmonary edema, diarrhea, vomiting, jaundice, and oliguria, with a serum Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) level of 4184 mcg/dl.

Calcium supplements may confer a protective effect against Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) toxicity.

DOSAGE AND ADMINISTRATION

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

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

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

HOW SUPPLIED

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) 1 mg/mL (Zinc Chloride Injection, USP) is supplied in 10 mL Plastic Vials (List No. 4090).

Store at 20 to 25°C (68 to 77°F).

Revised: October, 2004

© Hospira 2004 EN-0488 Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA

10 mL Vial

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate))

1 mg/mL

Effervescent Ca / Mg plus K, Zn, Trace Minerals and Vitamin D (Zinc (Zinc Citrate)) Chloride Inj., USP

Rx only

FOR I.V. USE ONLY AFTER DILUTION.

HOSPIRA, INC., LAKE FOREST, IL 60045 USA