Phoslyra (calcium acetate)

Phoslyra is a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD).

Management of elevated serum phosphorus levels usually includes all of the following:

• reduction in dietary intake of phosphate,
• removal of phosphate by dialysis, and
• inhibition of intestinal phosphate absorption with phosphate binders.

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.

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.

• 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.

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.

• Phoslyra contains calcium acetate.
• Animal reproduction studies have not been conducted with Phoslyra, and there are no adequate and well controlled studies of Phoslyra use in pregnant women.
• Patients with end stage renal disease may develop hypercalcemia with calcium acetate treatment.
• 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.
• Phoslyra treatment, as recommended, is not expected to harm a fetus if maternal calcium levels are properly monitored during and following treatment. Phoslyra contains calcium acetate and is excreted in human milk.
• Human milk feeding by a mother receiving Phoslyra is not expected to harm an infant, provided maternal serum calcium levels are appropriately monitored.