Calcifediol

RAYALDEE is a vitamin D 3 analog indicated for the treatment of secondary hyperparathyroidism in adult patients with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Limitations of Use RAYALDEE is not indicated for the treatment of secondary hyperparathyroidism in patients with stage 5 chronic kidney disease or in patients with end-stage renal disease on dialysis. RAYALDEE is a vitamin D 3 analog indicated for the treatment of secondary hyperparathyroidism in adults with stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. Limitations of Use: RAYALDEE is not indicated in patients with stage 5 chronic kidney disease or end-stage renal disease on dialysis.

Calcifediol (25-hydroxyvitamin D 3 ) is a prohormone of the active form of vitamin D 3, calcitriol (1,25‑dihydroxyvitamin D 3 ). Calcifediol is converted to calcitriol by cytochrome P450 27B1 (CYP27B1), also called 1-alpha hydroxylase, primarily in the kidney. Calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis.

• The initial dose of RAYALDEE is 30 mcg administered orally once daily at bedtime. Serum calcium should be below 9.8 mg/dL before initiating treatment. • Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and intact parathyroid hormone (PTH) 3 months after starting therapy or changing dose. • Increase the dose to 60 mcg once daily after 3 months if intact PTH is above the treatment goal. Ensure serum calcium is below 9.8 mg/dL, phosphorus is below 5.5 mg/dL and 25-hydroxyvitamin D is below 100 ng/mL before increasing the dose. • Suspend dosing if intact PTH is persistently abnormally low, serum calcium is consistently above the normal range or serum 25-hydroxyvitamin D is consistently above 100 ng/mL.

None. None

• Hypercalcemia: Excessive administration of vitamin D compounds, including RAYALDEE, can cause hypercalcemia and hypercalciuria. Severe hypercalcemia due to substantial overdosage of vitamin D and its metabolites may require emergency attention. Patients should be informed about the symptoms of elevated calcium. • Digitalis toxicity: Potentiated by hypercalcemia of any cause. Monitor serum calcium and signs and symptoms of digitalis toxicity more frequently when initiating or adjusting the dose of RAYALDEE. • Adynamic Bone Disease: Monitor for abnormally low levels of intact PTH levels when using RAYALDEE, and adjust dose if needed.

The following important adverse reactions are discussed in greater detail in other sections of the label: • Hypercalcemia • Adynamic Bone Disease The most common adverse reactions (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation.

• Co-administration of cytochrome P450 inhibitors, such as ketoconazole, may alter serum levels of calcifediol. • Co-administration of thiazides may cause hypercalcemia. • Cholestyramine may impair the absorption of calcifediol. • The half-life of calcifediol is reduced by drugs stimulating microsomal hydroxylation, such as phenobarbital or other anticonvulsants.

Store at 20 to 25°C (68 to 77°F), excursions permitted to 15 to 30°C (59 to 86°F).