DRUGS & SUPPLEMENTS

Calcigran

advertisement
When are you taking this medicine?

Calcigran uses

Calcigran consists of Calcium (Calcium Phosphate Dibasic), Calcium Carbonate, Vitamin C (Ascorbic Acid), Vitamin D2 (Ergocalciferol).

Calcium (Calcium Phosphate Dibasic):


1 INDICATIONS AND USAGE

Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

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

2 DOSAGE AND ADMINISTRATION

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

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

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

3 DOSAGE FORMS AND STRENGTHS

Capsule: 667 mg Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate capsule.

- Capsule: 667 mg Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

- Treat mild hypercalcemia by reducing or interrupting Calcigran ) acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate. (5.1)

- Hypercalcemia may aggravate digitalis toxicity. (5.2)

5.1 Hypercalcemia

Patients with end stage renal disease may develop hypercalcemia when treated with Calcigran (Calcium (Calcium Phosphate Dibasic)), including Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate. Avoid the use of Calcigran (Calcium (Calcium Phosphate Dibasic)) supplements, including Calcigran (Calcium (Calcium Phosphate Dibasic)) based nonprescription antacids, concurrently with Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate.

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

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

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

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

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

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

5.2 Concomitant Use with Medications

Hypercalcemia may aggravate digitalis toxicity.

advertisement

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 Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate therapy. (6)

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

6.1 Clinical Trial Experience

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

In clinical studies, Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate has been generally well tolerated.

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


Preferred Term


Total adverse reactions reported for Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate

N=167

N (%)


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

N=98

N (%)


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

N=69


Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


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

6.2 Postmarketing Experience

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

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

advertisement

7 DRUG INTERACTIONS

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

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

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

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

7.1 Ciprofloxacin

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

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

8.3 Nursing Mothers

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

8.4 Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

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

advertisement

10 OVERDOSAGE

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

11 DESCRIPTION

Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate acts as a phosphate binder. Its chemical name is Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate. Its molecular formula is C4H6CaO4, and its molecular weight is 158.17. Its structural formula is:


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

Calcigran (Calcium (Calcium Phosphate Dibasic)) Acetate Capsules are administered orally for the control of hyperphosphatemia in end-stage renal failure.

Chemical Structure

12 CLINICAL PHARMACOLOGY

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

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

advertisement

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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

14 CLINICAL STUDIES

Effectiveness of Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate solid oral dosage form.

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

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

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


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

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

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Calcigran (Calcium (Calcium Phosphate Dibasic)) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


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

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

The phosphate binding effect of Calcigran (Calcium (Calcium Phosphate Dibasic)) acetate is shown in the Table 3.


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

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Calcigran (Calcium (Calcium Phosphate Dibasic)) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Calcigran (Calcium (Calcium Phosphate Dibasic)) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

Calcigran (Calcium (Calcium Phosphate Dibasic)) Acetate Capsules

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

NDC 0615-2303-39: Blistercards of 30 Capsules

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

STORAGE

Store at 20° to 25°C (68° to 77°F).

17 PATIENT COUNSELING INFORMATION

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

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

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Calcium Carbonate:


1 INDICATIONS AND USAGE

Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) acetate capsule.

- Capsule: 667 mg Calcigran (Calcium Carbonate) acetate capsule. (3)

4 CONTRAINDICATIONS

Patients with hypercalcemia.

- Hypercalcemia. (4)

5 WARNINGS AND PRECAUTIONS

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

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

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


Preferred Term


Total adverse reactions reported for Calcigran (Calcium Carbonate) acetate

N=167

N (%)


3 month, open label study of Calcigran (Calcium Carbonate) acetate

N=98

N (%)


Double blind, placebo-controlled, cross-over study of liquid Calcigran (Calcium Carbonate) acetate

N=69


Calcigran (Calcium Carbonate) acetate

N (%)


Placebo

N (%)


Nausea


6 (3.6)


6 (6.1)


0 (0)


0 (0)


Vomiting


4 (2.4)


4 (4.1)


0 (0)


0 (0)


Hypercalcemia


21 (12.6)


16 (16.3)


5 (7.2)


0 (0)


Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate Calcigran (Calcium Carbonate) concentration could reduce the incidence and severity of Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) acetate: dizziness, edema, and weakness.

7 DRUG INTERACTIONS

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

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

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of Calcigran (Calcium Carbonate) acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

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

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) acetate.

14 CLINICAL STUDIES

Effectiveness of Calcigran (Calcium Carbonate) acetate in decreasing serum phosphorus has been demonstrated in two studies of the Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) acetate in the treatment of hyperphosphatemia in end-stage renal disease patients. The effects on serum Calcigran (Calcium Carbonate) levels are also presented.


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

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

‡ Values expressed as mean ± SE.


Parameter


Pre-Study


Week 4*


Week 8


Week 12


p-value†


Phosphorus (mg/dL)‡


7.4 ± 0.17


5.9 ± 0.16


5.6 ± 0.17


5.2 ± 0.17


≤0.01


Calcigran (Calcium Carbonate) (mg/dL)‡


8.9 ± 0.09


9.5 ± 0.10


9.7 ± 0.10


9.7 ± 0.10


≤0.01


There was a 30% decrease in serum phosphorus levels during the 12 week study period (p<0.01). Two-thirds of the decline occurred in the first month of the study. Serum Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) 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 Calcigran (Calcium Carbonate) acetate is shown in the Table 3.


* ANOVA of Calcigran (Calcium Carbonate) acetate vs. placebo after 2 weeks of treatment.

Values expressed as mean ± SEM.


Parameter


Pre-Study


Post-Treatment


p-value*


Calcigran (Calcium Carbonate) Acetate


Placebo


Phosphorus (mg/dL)


7.3 ± 0.18


5.9 ± 0.24


7.8 ± 0.22


<0.01


Calcigran (Calcium Carbonate) (mg/dL)


8.9 ± 0.11


9.5 ± 0.13


8.8 ± 0.12


<0.01


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

16 HOW SUPPLIED/STORAGE AND HANDLING

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

Distr. by: West-Ward

Pharmaceuticals Corp.

Eatontown, NJ 07724

10003705/05

Revised April 2016

Vitamin C (Ascorbic Acid):


Pharmacological action

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

With intravaginal application of Calcigran (Vitamin C (Ascorbic Acid)) lowers the vaginal pH, inhibiting the growth of bacteria and helps to restore and maintain normal pH and vaginal flora (Lactobacillus acidophilus, Lactobacillus gasseri).

Pharmacokinetics

After oral administration Calcigran (Vitamin C (Ascorbic Acid)) is completely absorbed from the gastrointestinal tract. Widely distributed in body tissues.

The concentration of Calcigran (Vitamin C (Ascorbic Acid)) in blood plasma in normal amounts to approximately 10-20 mg / ml.

The concentration of Calcigran (Vitamin C (Ascorbic Acid)) in white blood cells and platelets is higher than in erythrocytes and plasma. When deficient state of concentration in leucocytes is reduced later and more slowly and is regarded as the best criterion for evaluating the deficit than the concentration in plasma.

Plasma protein binding is about 25%.

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

Calcigran (Vitamin C (Ascorbic Acid)) taken in excessive quantities is rapidly excreted unchanged in urine, it usually happens when exceeding a daily dose is 200 mg.

Why is Calcigran ) prescribed?

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

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

Dosage and administration

This medication administered orally, IM, IV, intravaginally.

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

For intravaginal used Calcigran (Vitamin C (Ascorbic Acid)) drugs in appropriate dosage forms.

Calcigran (Vitamin C (Ascorbic Acid)) side effects, adverse reactions

CNS: headache, fatigue, insomnia.

Digestive system: stomach cramps, nausea and vomiting.

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

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

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

Calcigran ) contraindications

Increased sensitivity to Calcigran (Vitamin C (Ascorbic Acid)).

Using during pregnancy and breastfeeding

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

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

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

Special instructions

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

Patients with high content body iron should apply Calcigran (Vitamin C (Ascorbic Acid)) in minimal doses.

Calcigran (Vitamin C (Ascorbic Acid)) is used with caution in patients with deficiency of glucose-6-phosphate dehydrogenase.

The use of Calcigran (Vitamin C (Ascorbic Acid)) in high doses can cause exacerbation of sickle cell anemia.

Data on the diabetogenic action of Calcigran (Vitamin C (Ascorbic Acid)) are contradictory. However, prolonged use of Calcigran (Vitamin C (Ascorbic Acid)) should periodically monitor your blood glucose levels.

It is believed that the use of Calcigran (Vitamin C (Ascorbic Acid)) in patients with rapidly proliferating and widely disseminated tumors may worsen during the process. It should therefore be used with caution in Calcigran (Vitamin C (Ascorbic Acid)) in patients with advanced cancer.

Absorption of Calcigran (Vitamin C (Ascorbic Acid)) decreased while use of fresh fruit or vegetable juices, alkaline drinking.

Calcigran ) drug interactions

In an application with barbiturates, primidone increases the excretion of Calcigran (Vitamin C (Ascorbic Acid)) in the urine.

With the simultaneous use of oral contraceptives reduces the concentration of Calcigran (Vitamin C (Ascorbic Acid)) in blood plasma.

In an application of Calcigran (Vitamin C (Ascorbic Acid)) with iron preparations Calcigran (Vitamin C (Ascorbic Acid)), due to its regenerative properties, transforms ferric iron in the bivalent, which improves its absorption.

Calcigran (Vitamin C (Ascorbic Acid)) in high doses can decrease urine pH that while the application reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With the simultaneous use of aspirin reduces the absorption of Calcigran (Vitamin C (Ascorbic Acid)) by about a third.

Calcigran (Vitamin C (Ascorbic Acid)) in an application with warfarin may decrease effects of warfarin.

With the simultaneous application of Calcigran (Vitamin C (Ascorbic Acid)) increases the excretion of iron in patients receiving deferoxamine. In the application of Calcigran (Vitamin C (Ascorbic Acid)) at a dose of 500 mg / day possibly left ventricular dysfunction.

In an application with tetracycline is increased excretion of Calcigran (Vitamin C (Ascorbic Acid)) in the urine.

There is a described case of reducing the concentration of fluphenazine in plasma in patients treated with Calcigran (Vitamin C (Ascorbic Acid)) 500 mg 2 times / day.

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

Calcigran ) in case of emergency / overdose

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

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

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

Vitamin D2 (Ergocalciferol):


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

Calcigran pharmaceutical active ingredients containing related brand and generic drugs:

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


Calcigran available forms, composition, doses:

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


Calcigran destination | category:

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


Calcigran Anatomical Therapeutic Chemical codes:

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


Calcigran pharmaceutical companies:

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


advertisement

References

  1. Dailymed."D-CAL (CALCIUM CARBONATE) TABLET, CHEWABLE [A&Z PHARMACEUTICAL INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."CALCIUM CARBONATE; FAMOTIDINE; MAGNESIUM HYDROXIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. Dailymed."CALCIUM: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Calcigran?

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

Is Calcigran addictive or habit forming?

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

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

advertisement

Review

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

Visitor reports

Visitor reviews


There are no reviews yet. Be the first to write one!


Your name: 
Email: 
Spam protection:  < Type 28 here

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

© 2002 - 2020 "sDrugs.com". All Rights Reserved