Calcifediol: uses, dosing, side effects & brands

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…

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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.