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. …

• 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
• Important Dosage and Administration Information • Ensure serum calcium is below 9.8 mg/dL before initiating treatment [ see Warnings and Precautions ]. • Instruct patients to swallow RAYALDEE capsules whole. • Instruct patients to skip a missed dose and to resume taking the medicine at the next regularly scheduled time
• Do not administer an extra dose
• Starting Dose and Dose Titration • The initial dose of RAYALDEE is 30 mcg administered orally once daily at bedtime. • The maintenance dose of RAYALDEE should target serum total 25-hydroxyvitamin D levels between 30 and 100 ng/mL, intact parathyroid hormone (PTH) levels within the desired therapeutic range, serum calcium (corrected for low albumin) within the normal range and serum phosphorus below 5.5 mg/dL. …

Extended-release capsules, 30 mcg available as: • blue oval soft capsules imprinted with “O” in white ink • White two-piece banded hard capsules imprinted with ”O” and “30” in blue ink Extended-release capsules: 30 mcg ( 3 )

• The safety and efficacy of RAYALDEE have not been established
• In pediatric patients

Of the total number of subjects in phase 3 placebo-controlled clinical studies of RAYALDEE, 63% were ≥65 years of age and 22% were ≥75 years of age. No overall differences in the safety or efficacy of RAYALDEE were observed between subjects older than 65 years and younger subjects.

• Inform patients to take RAYALDEE at bedtime and to swallow the capsules whole. • Inform patients if they miss a dose, to take RAYALDEE at the next scheduled time
• Do not take an extra dose to make up for the missed dose. • Inform patients that they will need routine monitoring of laboratory parameters such as calcium, iPTH and total 25-hydroxyvitamin D while taking RAYALDEE. • Advise patients to contact a health care provider if they develop symptoms of elevated calcium (e.g., feeling tired, having difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination or weight loss). …

• None
• None

• Co-administration of cytochrome P450 inhibitors, such as ketoconazole, may alter serum levels of calcifediol. ( 7.1 ) • Co-administration of thiazides may cause hypercalcemia. ( 7.2 ) • Cholestyramine may impair the absorption of calcifediol. ( 7.3 ) • The half-life of calcifediol is reduced by drugs stimulating microsomal hydroxylation, such as phenobarbital or other anticonvulsants. …

• 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. ( 5.1 ) • 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. ( 5.2 ) • 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 [ see Warnings and Precautions ( 5.1 ) ] • Adynamic Bone Disease [ see Warnings and Precautions ( 5.3 ) ] The most common adverse reactions (≥3% and more frequent than placebo) were anemia, nasopharyngitis, increased blood creatinine, dyspnea, cough, congestive heart failure and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact OPKO Pharmaceuticals, LLC at 1-844-729-2539 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary There are no human data with calcifediol use in pregnant women to identify a drug-associated risk for major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with chronic kidney disease in pregnancy (see Clinical Considerations ) . …

Excessive administration of RAYALDEE can cause hypercalciuria, hypercalcemia, hyperphosphatemia, or oversuppression of intact PTH. Common symptoms of vitamin D overdosage may include constipation, decreased appetite, dehydration, fatigue, irritability, muscle weakness, or vomiting. Treatment of acute accidental overdosage with RAYALDEE should consist of general supportive measures. If the overdosage is discovered within a short time, induce emesis or perform gastric lavage to prevent further absorption. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.