calcifediol (Rx)

Brand and Other Names:Rayaldee
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule, extended-release

  • 30mcg

Hyperparathyroidism

Indicated for secondary hyperparathyroidism associated with vitamin D insufficiency in patients with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels <30 ng/mL

Ensure serum calcium in <9.8 mg/dL before initiating calcifediol

Initial: 30 mcg PO qHS

Maintenance dose should target serum total 25-hydroxyvitamin D levels to 30-100 mg/mL, intact parathyroid hormone (PTH) levels within the desired therapeutic range, serum calcium (corrected for low albumin) within the normal range, and serum phosphorus <5.5 mg/dL

Also see Administration

Dosage Modifications

Increase dose

  • Increase the dose to 60 mcg PO qHS after ~3 months, if intact PTH remains above the desired therapeutic range
  • Prior to raising the dose, ensure serum calcium is <9.8 mg/dL, serum phosphorus is below 5.5 mg/dL, and serum total 25-hydroxyvitamin D is <100 ng/mL

Suspend dosing

  • Suspend dosing if intact PTH is persistently and abnormally low to reduce the risk of adynamic bone disease, if serum calcium is consistently above the normal range to reduce the risk of hypercalcemia, or if serum total 25-hydroxyvitamin D is consistently >100 ng/mL
  • Restart at a reduced dose after these laboratory values have normalized

Dosing Considerations

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 then at least every 6-12 months

Patients with a history of hypercalcemia prior to initiating therapy should be monitored more frequently for possible hypercalcemia during therapy

Limitations of use

  • Not indicated for secondary hyperparathyroidism in patients with stage 5 CKD or end-stage renal disease on dialysis

Safety and efficacy not established

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Interactions

Interaction Checker

and calcifediol

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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Hyperphosphatemia, at least 1 episode >4.5 mg/dL (45%)

            1-10%

            Anemia (4.9%)

            Nasopharyngitis (4.9%)

            Increased blood creatinine (4.9%)

            Dyspnea (4.2%)

            Hypercalcemia, at least 1 episode >10.5 mg/dL (4.2%)

            Cough (3.5%)

            Congestive heart failure (3.5%)

            Constipation (3.2%)

            Bronchitis (2.8%)

            Hyperkalemia (2.5%)

            Osteoarthritis (2.1%)

            Hyperuricemia (1.8%)

            Contusion (1.8%)

            Pneumonia (1.4%)

            COPD (1.5%)

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            Warnings

            Contraindications

            None

            Cautions

            Adynamic bone disease with subsequent increased risk of fractures may develop if intact PTH levels are suppressed by calcifediol to abnormally low levels; monitor intact PTH levels and adjust calcifediol dose accordingly (see Dosage Modifications)

            Hypercalcemia

            • Hypercalcemia may occur
            • Acute hypercalcemia may increase risk of cardiac arrhythmias, and seizures and may potentiate the effect of digitalis on the heart
            • 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
            • Careful and regular monitoring of serum calcium levels is necessary
            • Inform patients about the symptoms of hypercalcemia and to contact their physician if they develop; symptoms include feeling tired, difficulty thinking clearly, loss of appetite, nausea, vomiting, constipation, increased thirst, increased urination, and weight loss

            Interaction overview

            • Calcifediol may cause hypercalcemia, which would increase the risk of digitalis toxicity; monitor both serum calcium levels and for signs and symptoms of digitalis toxicity
            • Coadministration of calcifediol and thiazide diuretics may cause hypercalcemia
            • Cholestyramine may impair the absorption of calcifediol
            • Phenobarbital or other anticonvulsants or other compounds that stimulate microsomal hydroxylation reduce the half-life of calcifediol
            • CYP3A inhibitors
              • CYP450 inhibitors may inhibit enzymes involved in vitamin D metabolism (CYP24A1 and CYP27B1)
              • This may alter serum levels of calcifediol and decrease the conversion of calcifediol to calcitriol
              • Dose adjustment of calcifediol may be required, and serum 25­hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor
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            Pregnancy

            Pregnancy

            There are no adequate and well-controlled studies in pregnant women

            Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus

            Animal studies

            • Calcifediol has been shown to be teratogenic in rabbits when given in doses 8-16 times the human dose of 60 mcg/day, based on body surface area

            Lactation

            Limited data suggest calcifediol is poorly excreted in human milk; caution if administered to a breastfeeding female

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Extended-release formulation of calcifediol (25-hydroxyvitamin D3), a prohormone of the active form of vitamin D3

            Calcifediol is converted to calcitriol by 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

            Absorption

            Steady-state: Levels of serum total 25-hydroxyvitamin D are reached after ~3 months

            Distribution

            Protein bound: >98%

            Vd, steady-state: 8.8 L (healthy volunteers); 30.1 L (stage 4 CKD)

            Metabolism

            Production of calcitriol from calcifediol is catalyzed by the 1-alpha-hydroxylase enzyme, CYP27B1, located in the kidney and other tissues

            CYP24A1, located in all vitamin D responsive tissues, catabolizes both calcifediol and calcitriol to inactive metabolites

            Elimination

            Excretion: Primarily through biliary fecal route

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            Administration

            Oral Administration

            Swallow capsule whole

            Missed dose

            • Instruct patients to skip a missed dose and resume taking at the next regularly scheduled time
            • Do not administer an extra dose

            Storage

            Store at controlled room temperature (20-25°C [68-77°F]); excursions permitted to 15-30°C (59-86°F)

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            Formulary

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.