rayaldee

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. ( 2 ) • Monitor serum calcium, phosphorus, 25-hydroxyvitamin D and intact parathyroid hormone (PTH) 3 months after starting therapy or changing dose. ( 2.2 , 5.3 ) • 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. ( 2.2 ) • 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. ( 2.2 ) 2.1 Important Dosage and Administration Information • Ensure serum calcium is below 9.8 mg/dL before initiating treatment [ see Warnings and Precautions ( 5.1 ) ]. • 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. 2.2 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 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. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. The data in Table 1 are derived from two pivotal studies described below [ see Clinical Studies ( 14 ) ]. These data reflect exposure of 285 subjects to RAYALDEE 30 or 60 mcg daily for up to 6 months (mean 24 weeks, range 1 to 31 weeks). The mean age of the study population was 66 years old (range 25-85 years). Half of the subjects were male, 65% were White, and 32% were African-American or Black. At baseline, subjects had secondary hyperparathyroidism, stage 3 (52%) or 4 (48%) chronic kidney disease without macroalbuminuria and serum total 25-hydroxyvitamin D levels less than 30…

None. None ( 4 )

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. Obtain serial serum and urine calcium measurements, and assess any electrocardiographic abnormalities due to hypercalcemia. Discontinue supplemental calcium. Treat with standard medical care if persistent and markedly elevated serum calcium levels occur. Calcifediol is not significantly removed by dialysis.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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. ( 7.4 ) 7.1 CYP3A Inhibitors Cytochrome P450 inhibitors, such as ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin or voriconazole, may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1), and may alter serum levels of calcifediol. Dose adjustment of RAYALDEE may be required, and serum 25-hydroxyvitamin D, intact PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with a strong CYP3A4 inhibitor. 7.2 Thiazides Thiazides are known to induce hypercalcemia by reducing excretion of calcium in the urine. Concomitant administration of thiazides with RAYALDEE may cause hypercalcemia. Patients may require more frequent serum calcium monitoring in this setting [ see Warnings and Precautions ( 5.1 ) ]. 7.3 Cholestyramine Cholestyramine has been reported to reduce intestinal absorption of fat-soluble vitamins and may impair the absorption of calcifediol, the active ingredient in RAYALDEE. Dose adjustment of RAYALDEE may be required, and serum total 25-hydroxyvitamin D, intact PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with cholestyramine. 7.4 Other Agents Phenobarbital or other anticonvulsants or other compounds that stimulate microsomal hydroxylation reduce the half-life of calcifediol, the active ingredient in RAYALDEE. Dose adjustment of RAYALDEE may be required, and serum total 25-hydroxyvitamin D, intact PTH and serum calcium concentrations should be closely monitored if a patient initiates or discontinues therapy with phenobarbital or other anticonvulsants.