Rayaldee
(calcifediol)Dosage & Administration
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Rayaldee Prescribing Information
RAYALDEE is a vitamin D3 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.
Important Dosage and Administration Information
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- Ensure serum calcium is below 9.8 mg/dL before initiating treatment [see Warnings and Precautions ].
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- Instruct patients to swallow RAYALDEE capsules whole.
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- 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
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- The initial dose of RAYALDEE is 30 mcg administered orally once daily at bedtime.
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- 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.
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- Monitor serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D and intact PTH levels at a minimum of 3 months after initiation of therapy or dose adjustment, and subsequently at least every 6 to 12 months.
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- Increase the dose to 60 mcg orally once daily at bedtime after approximately 3 months, if intact PTH remains above the desired therapeutic range. Prior to raising the dose, ensure serum calcium is below 9.8 mg/dL, serum phosphorus is below 5.5 mg/dL and serum total 25-hydroxyvitamin D is below 100 ng/mL.
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- Suspend dosing if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease [see Warnings and Precautions ], if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia [see Warnings and Precautions ], or if serum total 25-hydroxyvitamin D is consistently above 100 ng/mL. Restart at a reduced dose after these laboratory values have normalized.
Extended-release capsules, 30 mcg available as:
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- blue oval soft capsules imprinted with “O” in white ink
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- White two-piece banded hard capsules imprinted with ”O” and “30” in blue ink
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). In animal reproduction studies, calcifediol increased skeletal and soft tissue malformation when rabbits were given once daily oral doses representing ≥8 times the human dose of 60 mcg/day, based on body surface area (mg/m2), during the period of organogenesis. No adverse developmental effects were observed in rats given up to 10 times the human dose, based on body surface area (mg/m2), during organogenesis.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.
Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Chronic kidney disease in pregnancy increases the maternal risk for hypertension, miscarriage, preterm labor, and preeclampsia. Chronic kidney disease increases the fetal risk for intrauterine growth restriction (IUGR), prematurity, polyhydramnios, still birth, and low birth weight.
Data
Animal Data
Calcifediol was given orally to pregnant rats and rabbits during the period of organogenesis (in rats, from gestation day [GD] 6 to 15; in rabbits, from GD 6 to 18). Rats were given 0, 12, 40, 60 mcg/kg/day; and rabbits were given 0, 5, 25, 50 mcg/kg/day, representing up to 10 and 16 times, respectively, a human dose of 60 mcg/day, based on body surface area (mg/m2).
In rats, no adverse developmental effects were observed at calcifediol doses up to 60 mcg/kg/day. In rabbits, increased incidences of domed skull, enlarged atrium of the heart, and dilatation of pulmonary artery, were observed at doses of 25 and 50 mcg/kg/day (representing 8 and 16 times the human dose of 60 mcg/day, respectively, based on body surface area (mg/m2). Rats were given calcifediol during the pre/postnatal period (GD 15 to weaning). No adverse effects on gestation, parturition, lactation or survival of offspring were observed at calcifediol doses up to 60 mcg/kg/day.
Lactation
Risk Summary
There is no information available on the presence of calcifediol in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Infants potentially exposed to calcifediol through breast milk should be monitored for signs and symptoms of hypercalcemia (see Clinical Considerations). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RAYALDEE and any potential adverse effects on the breastfed child from RAYALDEE or from the underlying maternal condition.
Clinical Considerations
Monitor infants exposed to calcifediol through breast milk for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation and weight loss. Consider monitoring of serum calcium in the infant.
Pediatric Use
The safety and efficacy of RAYALDEE have not been established in pediatric patients.
Geriatric Use
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.
Renal Impairment
No difference in efficacy was observed between patients with stage 3 chronic kidney disease or those with stage 4 disease in subgroup analysis. Safety outcomes were similar in these subgroups. The safety and efficacy of RAYALDEE in the treatment of secondary hyperparathyroidism in patients with stage 2 or stage 5 chronic kidney disease and patients with end-stage renal disease on dialysis have not been established [see Indications and Usage ].
None.
Hypercalcemia
Hypercalcemia may occur during RAYALDEE treatment [see Adverse Reactions ]. Acute hypercalcemia may increase the risk of cardiac arrhythmias and seizures and may potentiate the effect of digitalis on the heart [see Warnings and Precautions ]. Chronic hypercalcemia can lead to generalized vascular calcification and other soft-tissue calcification. Severe hypercalcemia may require emergency attention.
Hypercalcemia may be exacerbated by concomitant administration of high doses of calcium containing preparations, thiazide diuretics, or other vitamin D compounds. In addition, high intake of calcium and phosphate concomitantly with vitamin D compounds may lead to hypercalciuria and hyperphosphatemia. In these circumstances, frequent serum calcium monitoring and RAYALDEE dose adjustments may be required. Patients with a history of hypercalcemia prior to initiating therapy with RAYALDEE should be monitored more frequently for possible hypercalcemia during therapy.
Patients should be informed about the symptoms of elevated serum calcium, which include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss.
Digitalis Toxicity
Hypercalcemia of any cause, including RAYALDEE [see Warnings and Precautions ], increases the risk of digitalis toxicity. In patients using RAYALDEE concomitantly with digitalis compounds, monitor both serum calcium and patients for signs and symptoms of digitalis toxicity and increase the frequency of monitoring when initiating or adjusting the dose of RAYALDEE [see Dosage and Administration ].
Adynamic Bone Disease
Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by RAYALDEE to abnormally low levels. Monitor intact PTH levels and adjust RAYALDEE dose, if needed [see Dosage and Administration ].