Calcium Acetate for Kidney Failure

1. INDICATIONS & USAGE Calcium acetate capsules are a phosphate binder indicated to reduce serum phosphorus in patients with end stage renal disease (ESRD). • Calcium acetate capsules are a phosphate binder indicated for the reduction of serum phosphorus in patients with end stage renal disease. ( 1 )

DOSAGE AND ADMINISTRATION The recommended initial dose of calcium acetate capsules for the adult dialysis patient is 2 capsules with each meal. Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop. Most patients require 3 to 4 capsules with each meal. Starting dose is 2 capsules with each meal. ( 2 ) Titrate the dose every 2 to 3 weeks until acceptable serum phosphorus level is reached. Most patients require 3 to 4 capsules with each meal. ( 2 )

WARNINGS AND PRECAUTIONS Patients with end stage renal disease may develop hypercalcemia when treated with calcium, including calcium acetate. Avoid the use of calcium supplements, including calcium-based nonprescription antacids, concurrently with calcium acetate. An overdose of calcium acetate 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 calcium acetate 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 calcium acetate 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 calcium acetate 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 calcium acetate 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 solid dose formulation of calcium acetate; all cases resolved upon lowering the dose or discontinuing treatment. Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg 2 /dL 2 . Treat mild hypercalcemia by reducing or interrupting calcium acetate and Vitamin D. Severe hypercalcemia may require hemodialysis and discontinuation of calcium acetate. ( 5.1 ) Hypercalcemia may aggravate digitalis toxicity. ( 5.2 ) 5.1 Hypercalcemia Patients with end stage renal disease may develop hypercalcemia when treated with calcium, including calcium acetate. Avoid the use of calcium supplements, including calcium-based nonprescription antacids, concurrently with calcium acetate. An overdose of calcium acetate 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 calcium acetate 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 calcium acetate 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 calcium acetate 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 calcium acetate 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 solid dose formulation of calcium acetate; all cases resolved upon lowering the dose or discontinuing treatment. Maintain the serum calcium-phosphorus (Ca x P) product below 55 mg 2 /dL 2 . 5.2 Concomitant Use with Medications Hypercalcemia may aggravate digitalis toxicity.

7. DRUG INTERACTIONS The drug interaction of calcium acetate capsules is characterized by the potential of calcium to bind to drugs with anionic functions (e.g., carboxyl and hydroxyl groups). Calcium acetate capsules may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism. There are no empirical data on avoiding drug interactions between calcium acetate or calcium acetate capsules and most concomitant drugs. When administering an oral medication with calcium acetate capsules where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, administer the drug one hour before or three hours after calcium acetate capsules or calcium acetate. Monitor blood levels of the concomitant drugs that have a narrow therapeutic range. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials with all forms of calcium acetate. • Calcium acetate capsules may decrease the bioavailability of tetracyclines or fluoroquinolones. ( 7 ) • When clinically significant drug interactions are expected, administer the drug at least one hour before or at least three hours after calcium acetate capsules, or consider monitorinG blood levels of the drug. ( 7 ) 7.1 Ciprofloxacin 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%.

ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-362-3993 or drugsafety@avkare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The most common (>10%) adverse reactions are hypercalcemia, nausea, and vomiting. ( 6.1 ). In clinical studies, patients have occasionally experienced nausea during calcium acetate therapy. ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact AvKARE at 1-855-362-3993 or drugsafety@avkare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 practice. In clinical studies, calcium acetate has been generally well tolerated. 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 Preferred Term Total adverse reactions reported for calcium acetate 3 – mo , open-label study of calcium acetate n = 98 Double-blind , placebo-controlled , cross over study of calcium acetate n = 69 n = 167 n (%) n (%) 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) Mild hypercalcemia may be asymptomatic or manifest itself as constipation, anorexia, nausea, and vomiting. More severe hypercalcemia is associated with confusion, delirium, stupor, and coma. Decreasing dialysate calcium concentration could reduce the incidence and severity of calcium acetate-induced hypercalcemia. Isolated cases of pruritus have been reported, which may represent allergic reactions. 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.