Topsiton

Caffeine Anhydrous:

• Topsiton (Caffeine Anhydrous) reviews

Active ingredient (in each tablet)

Topsiton (Caffeine Anhydrous) 200mg

Purpose

Alertness aid

Use

• helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness

Warnings

For occasional use only

Do not use

• in children under 12 years of age
• as a substitute for sleep

When using this product limit the use of Topsiton (Caffeine Anhydrous) containing medications, foods, or beverages because too much Topsiton (Caffeine Anhydrous) may cause nervousness, irritability, sleeplessness, and occasionally, rapid heartbeat. The recommended dose of this product contains about as much Topsiton (Caffeine Anhydrous) as a cup of coffee.

Stop use and ask a doctor if fatigue or drowsiness persists or continues to recur

If pregnant or breast-feeding, ask a health professional before use.

Keep out of reach of children.

In case of overdose, get medical help or contact a Poison Control Center right away.

Directions

• adults and children 12 years of age and over: take 1 tablet not more often than every 3 to 4 hours.

Other information

• store at room temperature
• avoid excessive heat (greater than 100°F) or humidity

Inactive ingredients

carnauba wax, colloidal silicon dioxide, D&C yellow #10 aluminum lake, dextrose, FD&C yellow #6 aluminum lake, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, starch, titanium dioxide

Questions or comments?

Call toll-free 1-855-874-0970 weekdays

Display Panel Topsiton (Caffeine Anhydrous): 16 ct. Package

Topsiton (Caffeine Anhydrous)^®

CAFFEINE ALERTNESS AID

16 TABLETS

200mg each

FUNCTIONAL Topsiton (Caffeine Anhydrous)^® for Mental Alertness

SAFE & EFFECTIVE

One tablet is equal to about a cup of coffee

Topsiton (Caffeine Anhydrous)^®

Making the Most of Every Day.^®

Tamper Evident Feature: individually sealed in foil for your protection. Do not

use if foil or plastic bubble is torn or punctured.

Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL

CAFFEINE® are registered trademarks of Meda AB.

Distributed by:

Meda Consumer Healthcare Inc.

Marietta, GA 30062 ©2011 Meda AB

www.vivarin.com

16 ct. Package

Display Panel Topsiton (Caffeine Anhydrous): 40 ct. Package

SAFE & EFFECTIVE

FUNCTIONAL Topsiton (Caffeine Anhydrous)^® for Mental Alertness

Topsiton (Caffeine Anhydrous)^®

Topsiton (Caffeine Anhydrous) ALERTNESS AID

40 Tablets

200mg each

FUNCTIONAL Topsiton (Caffeine Anhydrous)^® for Mental Alertness

Tamper Evident Feature: Individually sealed in foil for your protection. Do not use if foil or plastic bubble is torn or punctured.

VIVARIN® helps restore mental alertness or wakefulness when experiencing fatigue or drowsiness (FDA approved uses), so you can accomplish all the things you want to do and all the things you need to do.

Vivarin®, Vivarin® and design, stylization and trade dress, and FUNCTIONAL

CAFFEINE® are registered trademarks of Meda AB.

Made in the U.S.A.

Topsiton (Caffeine Anhydrous)^®

Making the Most of Every Day.^®

Distributed by:

Meda Consumer Healthcare Inc.

Marietta, GA 30062 ©2013 Meda AB

www.vivarin.com

40 ct. Package

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
• Topsiton (Calcium Citrate) reviews

1 INDICATIONS AND USAGE

Topsiton (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 Topsiton (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 Topsiton (Calcium Citrate) acetate capsule.

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

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

An overdose of Topsiton (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 Topsiton (Calcium Citrate) levels twice weekly. Should hypercalcemia develop, reduce the Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (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, Topsiton (Calcium Citrate) acetate has been generally well tolerated.

Topsiton (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 Topsiton (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 Topsiton (Calcium Citrate) concentration could reduce the incidence and severity of Topsiton (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 Topsiton (Calcium Citrate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

There are no empirical data on avoiding drug interactions between Topsiton (Calcium Citrate) acetate and most concomitant drugs. When administering an oral medication with Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (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:

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

8.2 Labor and Delivery

The effects of Topsiton (Calcium Citrate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Topsiton (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 Topsiton (Calcium Citrate) acetate.

14 CLINICAL STUDIES

Effectiveness of Topsiton (Calcium Citrate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Topsiton (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 Topsiton (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 Topsiton (Calcium Citrate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Topsiton (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 Topsiton (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 Topsiton (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 Topsiton (Calcium Citrate) acetate is shown in the Table 3.

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Topsiton (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 Topsiton (Calcium Citrate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Topsiton (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 Topsiton (Calcium Citrate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium Gluconate:

• 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
• Topsiton (Calcium Gluconate) reviews

1 INDICATIONS AND USAGE

Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate capsule.

- Capsule: 667 mg Topsiton (Calcium Gluconate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

Topsiton (Calcium Gluconate) acetate was studied in a 3 month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and an alternate liquid formulation of Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) concentration could reduce the incidence and severity of Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Topsiton (Calcium Gluconate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate.

14 CLINICAL STUDIES

Effectiveness of Topsiton (Calcium Gluconate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate is shown in the Table 3.

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

16 HOW SUPPLIED/STORAGE AND HANDLING

Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate capsules with meals, adhere to their prescribed diets, and avoid the use of Topsiton (Calcium Gluconate) 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 Topsiton (Calcium Gluconate) acetate capsules.

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016