mitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.

emia can be treated by acute hemodialysis and discontinuing phoslyra 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 phoslyra 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 phoslyra 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 a solid dose formulation of calcium acetate; all cases resolved upon lowering the dose or discontinuing treatment. 5.2 concomitant use with medications hypercalcemia may aggravate digitalis toxicity. phoslyra contains maltitol (1 g per 5 ml) and may induce a laxative effect, especially if taken with other products containing maltitol.

tion of calcium acetate was studied in two clinical trials: a 3-month, openlabel, non-randomized study with 98 kidney failure patients on hemodialysis (hd); and in a 2week, double-blind, placebo-controlled, cross-over clinical trial with 69 kidney failure patients on hd. table 1: adverse reactions in kidney failure patients on hemodialysis preferred term total adverse reactions reported for calcium acetate n=167 n (%) 3-mo, openlabel study of calcium acetate n=98 n (%) double-blind, placebo-controlled, cross-over study of calcium acetate n=69 calcium acetate n (%) placebo n (%) nausea 6 (3.6) 6 (6.1) 0 (0.0) 0 (0.0) vomiting 4 (2.4) 4 (4.1) 0 (0.0) 0 (0.0) hypercalcemia 21 (12.6) 16 (16.3) 5 (7.2) 0 (0.0) calcium acetate oral solution was studied in a randomized, controlled, 3-arm, open label, crossover, single-dose study comparing calcium acetate oral solution to a solid formulation in healthy volunteers on a controlled diet. of the observed drug-related adverse reactions, diarrhea (5/38, 13.2%) was more common with the oral solution. 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 calcium acetate: dizziness, edema, and weakness.

mitantly administered, such as the time to reach peak systemic levels and whether the drug is an immediate release or an extended release product. consider monitoring clinical responses or blood levels of concomitant medications that have a narrow therapeutic range.

ll birth. maternal and fetal/neonatal adverse reactions hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. monitor maternal serum calcium levels to maintain normal serum calcium. 8.2 lactation risk summary calcium and acetate are excreted in human milk. there are no data on the effects of calcium acetate on the concentration of calcium or acetate in milk, the effect on the breastfed child, or the effects on milk production. 8.4 pediatric use safety and effectiveness of phoslyra 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 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.

eonatal adverse reactions hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism. monitor maternal serum calcium levels to maintain normal serum calcium.

stered three times per day with meals from day 0 through day 2 and one morning dose on day 3 of each period. treatment (baseline-subtracted) related changes (auc and c max ) in serum calcium and phosphorus assessed over the 6 hours following dosing were similar for phoslyra and calcium acetate gelcaps. urinary excretion of calcium and phosphorus were not significantly increased with phoslyra compared to calcium acetate gelcaps. 12.3 pharmcokinetics drug interactions in vivo in a study of 15 healthy subjects, a co-administered single dose of 4 calcium acetate tablets (approximately 2.7 g) decreased the bioavailability of ciprofloxacin by approximately 50%.

ects on serum calcium levels are also presented. table 2: average serum phosphorus and calcium levels at pre-study, interim, and study completion time points a values expressed as mean ± se. b ninety-one patients completed at least 6 weeks of the study. c anova of difference in values at pre-study and study completion. parameter pre-study week 4 b week 8 week 12 p-value c phosphorus (mg/dl) a 7.4 ± 0.17 5.9 ± 0.16 5.6 ± 0.17 5.2 ± 0.17 ≤0.01 calcium (mg/dl) a 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 table 3 . table 3: serum phosphorus and calcium levels at study initiation and after completion of each treatment arm a values expressed as mean ± sem b anova of calcium acetate vs. placebo after 2 weeks of treatment. parameter pre-study post-treatment p-value b calcium acetate placebo phosphorus (mg/dl) a 7.3 ± 0.18 5.9 ± 0.24 7.8 ± 0.22 <0.01 calcium (mg/dl) a 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%.