General Information

Rayaldee (calcifediol) is a vitamin D3 analog.

Rayaldee is specifically 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.

Rayaldee is supplied as an extended release capsule for oral administration. The initial recommended 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

Mechanism of Action

Calcifediol (25-hydroxyvitamin D3) is a prohormone of the active form of vitamin D3, calcitriol (1,25-dihydroxyvitamin D3). 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.

Side Effects

Adverse effects associated with the use of Rayaldee may include, but are not limited to, the following:

• anemia
• nasopharyngitis
• increased blood creatinine
• dyspnea
• congestive heart failure
• constipation

Clinical Trial Results

The FDA approval of Rayaldee was based on two identical multicenter, randomized, placebo-controlled, double-blind trials in patients with secondary hyperparathyroidism, stage 3 or 4 chronic kidney disease and serum total 25-hydroxyvitamin D levels between 10 and 30 ng/mL. Subjects were stratified by chronic kidney disease stage and randomized in a 2:1 ratio to receive Rayaldee or a matching placebo at bedtime over 26 weeks. The dose of Rayaldee was 30 mcg once daily for the first 12 weeks and either 30 or 60 mcg once daily for the last 14 weeks. The dose was increased to 60 mcg at the start of week 13 if the plasma intact PTH level was greater than 70 pg/mL, the serum 25-hydroxyvitamin D level was less than 65 ng/mL and the serum calcium level was less than 9.8 mg/dL. A total of 213 subjects were randomized in one trial and 216 subjects were randomized in the second trial. The primary analysis compared the proportion of individuals who experienced an at least 30% reduction in plasma intact PTH from baseline to end of trial (average of weeks 20, 22, 24 and 26). A larger proportion of patients randomized to Rayaldee experienced an at least 30% reduction in plasma intact PTH from baseline compared to placebo in both trials [33% versus 8% in the first trial (P<0.001) and 34% versus 7% in the second trial (P<0.001)]. Serum total 25-hydroxyvitamin D levels increased to at least 30 ng/mL in 80% and 83% of subjects treated with RAYALDEE vs. 3% and 7% of subjects treated with placebo (P<0.001) in the two studies, respectively. Average steady state 25-hydroxyvitamin D levels were 50 and 56 ng/mL for subjects receiving 30 mcg daily, and 69 and 67 ng/mL for subjects receiving 60 mcg daily, in the first and second studies, respectively.