5.1 Hypercalcemia

Patients with kidney failure on dialysis may develop hypercalcemia when treated with calcium, including calcium acetate (PHOSLYRA). Avoid the concurrent use of calcium supplements, including calcium-based nonprescription antacids, with PHOSLYRA.

An overdose of PHOSLYRA may lead to progressive hypercalcemia , which may require emergency measures. Therefore, early in the treatment phase during the dosage adjustment period, monitor serum calcium levels twice weekly. Should hypercalcemia develop, reduce the PHOSLYRA 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 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.

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 clinical practice.

In clinical studies, calcium acetate has been generally well tolerated.

The solid dose formulation 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.

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.

Oral medications not listed in the Table

There are no empirical data on avoiding drug interactions between Phoslyra and most concomitant oral drugs. For oral medications where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, consider separation of the timing of the administration of the two drugs. The duration of separation depends upon the absorption characteristics of the medication concomitantly 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.

8.1 Pregnancy

8.2 Lactation

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.

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 concentrations.

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.

A randomized, 3-arm, open-label, cross-over study in healthy volunteers evaluated the bioavailability of PHOSLYRA compared to calcium acetate gelcaps. Each subject received ~1000 mg elemental calcium from each dose of the following study medications: 30 mL PHOSLYRA (test), 6 calcium acetate gelcaps (reference), or 5 calcium citrate caplets (positive control) in three periods. The study medications were administered 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

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity, mutagenicity, or fertility studies have been conducted with calcium acetate.

Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

The shelf life is 36 months.