Calcium Acetate Oral Solution

Administration of PHOSLYRA in excess of the appropriate daily dosage may result in hypercalcemia [see WARNINGS AND PRECAUTIONS].

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.

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.

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 non-fasting 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 Cmax) 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.

Pharmcokinetics

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%.

Clinical Studies

Effectiveness of calcium acetate in decreasing serum phosphorus has been demonstrated in two studies of the solid 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 Phosphorus and Calcium Levels at Pre-Study, Interim, and Study Completion Time points

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

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%.

No clinical trials have been performed with PHOSLYRA in the intended population. Because the dose and active ingredients of PHOSLYRA are equivalent to that of the calcium acetate gelcaps or tablets, the scope of the adverse reactions is anticipated to be similar.

Hypercalcemia is discussed elsewhere [see WARNINGS AND PRECAUTIONS].

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 a 3-month, open-label, non-randomized study of 98 enrolled ESRD hemodialysis patients and 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.

Table 1: Adverse Reactions in Patients with End-Stage Renal Disease Undergoing Hemodialysis

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.

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.

Read the entire FDA prescribing information for Phoslyra (Calcium Acetate Oral Solution)

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take calcium acetate oral solution or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to calcium acetate oral solution. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017