Calcium Acetate (Page 2 of 3)

8.1 Pregnancy

Pregnancy Category C:

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

8.2 Labor and Delivery

The effects of calcium acetate on labor and delivery are unknown.

8.3 Nursing Mothers

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

11 DESCRIPTION

Calcium acetate acts as a phosphate binder. Its chemical name is calcium acetate. Its molecular formula is C4 H6 CaO4 , and its molecular weight is 158.17. Its structural formula is:

chem.jpg
(click image for full-size original)

Each white opaque/blue opaque capsule contains 667 mg of calcium acetate, USP (anhydrous; Ca(CH3 COO)2 ; MW=158.17 grams) equal to 169 mg (8.45 mEq) calcium, 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.

Calcium Acetate Capsules, USP are administered orally for the control of hyperphosphatemia in end-stage renal failure.

12 CLINICAL PHARMACOLOGY

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

12.1 Mechanism of Action

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

12.2 Pharmacodynamics

Orally administered calcium 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 calcium acetate.

14 CLINICAL STUDIES

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

Table 2: Average Serum Phosphorous and Calcium Levels at Pre-Study, Interim, and Study Completion Time Points
*
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

Calcium (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 calcium 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 calcium 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 calcium acetate is shown in the Table 3.

Table 3: Serum Phosphorous and Calcium Levels at Study Initiation and After Completion of Each Treatment Arm
*
ANOVA of calcium acetate vs. placebo after 2 weeks of treatment.
Values expressed as mean ± SEM.

Parameter

Pre-Study

Post-Treatment

p-value *

Calcium Acetate

Placebo

Phosphorus (mg/dL)

7.3 ± 0.18

5.9 ± 0.24

7.8 ± 0.22

<0.01

Calcium (mg/dL)

8.9 ± 0.11

9.5 ± 0.13

8.8 ± 0.12

<0.01

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

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