Prescription Drug Information: Phoslyra

PHOSLYRA — calcium acetate solution
Fresenius Medical Care North America

1 INDICATIONS AND USAGE

PHOSLYRA ® is indicated as an adjunct to reduction in dietary intake of phosphate and dialysis to reduce serum phosphorus in patients with kidney failure on dialysis.

2 DOSAGE AND ADMINISTRATION

The recommended initial dose of PHOSLYRA for the adult dialysis patient is 10 mL with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Titrate the dose every 2 to 3 weeks until an acceptable serum phosphorus level is reached. Most patients require 15–20 mL with each meal.

3 DOSAGE FORMS AND STRENGTHS

Oral Solution: 667 mg calcium acetate per 5 mL.

4 CONTRAINDICATIONS

Patients with hypercalcemia.

5 WARNINGS AND PRECAUTIONS

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 ADVERSE REACTIONS

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 ( 5.1)] .

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.

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.

7 DRUG INTERACTIONS

Oral drugs that have to be separated from Phoslyra
Dosing Recommendations
Flouroquinolones Take at least 2 hours before or 6 hours after Phoslyra
Tetracyclines Take at least 1 hour before Phoslyra
Levothyroxine Take at least 4 hours before or 4 hours after Phoslyra

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 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Administration of the recommended dose of PHOSLYRA is not expected to cause major birth defects, miscarriage, or adverse maternal or fetal outcomes. Patients with kidney failure on dialysis may develop hypercalcemia with calcium acetate treatment [see Contraindications ( 4)] and [Warnings and Precautions ( 5.1)]. Maintenance of normal serum calcium levels is important for maternal and fetal wellbeing. There are adverse effects on maternal and fetal outcomes associated with kidney failure on dialysis in pregnancy (see Clinical Considerations). Animal reproduction studies have not been conducted with PHOSLYRA.

Clinical Consideration

Disease-Associated Maternal and/or Embryo/Fetal Risk

Pregnancies that occur in women with kidney failure on dialysis are associated with a high rate of complications, including increased maternal mortality, hypertension, preeclampsia, anemia, intrauterine growth restriction, preterm delivery, and still 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.

10 OVERDOSAGE

Administration of PHOSLYRA in excess of the appropriate daily dosage may result in hypercalcemia [see Warnings and Precautions ( 5.1)] .

11 DESCRIPTION

PHOSLYRA acts as a phosphate binder. Its chemical name is calcium acetate. Its molecular formula is C 4 H 6 CaO 4 , and its molecular weight is 158.17. Its structural formula is:

Structural Formula

PHOSLYRA for oral administration is provided as pale to light greenish-yellow clear liquid. Each 5 mL of PHOSLYRA contains 667 mg calcium acetate, USP equal to 169 mg (8.45 mEq) calcium. PHOSLYRA also contains the following inactive ingredients: maltitol NF, glycerin USP, Magnasweet 110, propylene glycol USP, povidone K25 USP, sucralose NF, methylparaben NF, artificial black cherry flavor, menthol flavor, purified water USP.

Page 1 of 2 1 2

RxDrugLabels.com provides trustworthy package insert and label information about marketed prescription drugs as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by RxDrugLabels.com. Every individual prescription drug label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

As a leading independent provider of trustworthy medication information, we source our database directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. RxDrugLabels.com provides the full prescription-only subset of the FDA's repository. Medication information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2022. All Rights Reserved.