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Calcifediol

Pronunciation

(kal si fe DYE ole)

Index Terms

  • 25-HCC
  • 25-Hydroxycholecalciferol
  • 25-Hydroxyvitamin D3
  • Calcidiol
  • Rayaldee

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Extended Release, Oral:

Rayaldee: 30 mcg [contains brilliant blue fcf (fd&c blue #1)]

Brand Names: U.S.

  • Rayaldee

Pharmacologic Category

  • Vitamin D Analog

Pharmacology

Calcifediol, a prohormone of the active form of vitamin D3, calcitriol (1,25 dihydroxyvitamin D3), is catalyzed to calcitriol by the 1-alpha-hydroxylase enzyme, CYP27B1, primarily in the kidney. Calcitriol binds to vitamin D receptors in target tissues activating vitamin D responsive pathways resulting in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis.

Distribution

Vd; Healthy adults: 8.8 L; Stage 3 and 4 CKD: 30.1 L

Metabolism

Primarily to calcitriol by CYP27B1 (1-alpha-hydroxylase enzyme) in the kidney

Excretion

Feces

Onset of Action

~2 weeks; maximum effect: ~3 months

Half-Life Elimination

Healthy adults: ~11 days; Stage 3 and 4 CKD: ~25 days

Protein Binding

>98%

Use: Labeled Indications

Secondary hyperparathyroidism: 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.

Limitations of use: Not indicated for the treatment of secondary hyperparathyroidism in patients with stage 5 chronic kidney disease or in patients with end-stage renal disease (ESRD) on dialysis.

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Dosing: Adult

Secondary hyperparathyroidism: Oral: Initial: 30 mcg once daily at bedtime; may increase to 60 mcg once daily at bedtime after 3 months if intact PTH remains above desired therapeutic range. Note: Ensure corrected serum total calcium is below 9.8 mg/dL prior to initiating therapy. Maintenance dose should target total 25-hydroxyvitamin D levels between 30 and 100 ng/mL, intact PTH levels within desired therapeutic range, serum calcium <9.8 mg/dL, and serum phosphorus ≤5.5 mg/dL.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.

Dosing: Adjustment for Toxicity

Hypercalcemia, low PTH, or serum total 25-hydroxyvitamin D >100 ng/mL: Temporarily discontinue therapy for persistently low intact PTH levels, or consistently elevated calcium or 25-hydroxyvitamin D levels (>100 ng/mL); resume therapy at a reduced dose after laboratory values have normalized.

Administration

Administer at bedtime. Swallow capsule whole.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

Aluminum Hydroxide: Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid combination

Bile Acid Sequestrants: May decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Monitor therapy

Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Calcifediol. Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Calcifediol. Monitor therapy

Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Mineral Oil: May decrease the serum concentration of Vitamin D Analogs. More specifically, mineral oil may interfere with the absorption of Vitamin D Analogs. Management: Avoid concomitant, oral administration of mineral oil and vitamin D analogs. Consider separating the administration of these agents by several hours to minimize the risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Orlistat: May decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Consider therapy modification

Sucralfate: Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combination

Adverse Reactions

>10%: Hematologic & oncologic: Abnormal phosphorus levels (increased: 45%; hyperphosphatemia: <1%)

1% to 10%:

Cardiovascular: Congestive heart failure (4%)

Endocrine & metabolic: Hypercalcemia (4%; patients requiring dose reduction for hypercalcemia: 2%), hyperkalemia (3%), hyperuricemia (2%)

Hematologic & oncologic: Anemia (5%), bruise (2%)

Neuromuscular & skeletal: Osteoarthritis (2%)

Renal: Increased serum creatinine (5%)

Respiratory: Nasopharyngitis (5%), cough (4%), dyspnea (4%), bronchitis (3%), chronic obstructive pulmonary disease (1%), pneumonia (1%)

Warnings/Precautions

Concerns related to adverse effects:

• Excessive vitamin D: Excessive vitamin D administration may lead to over suppression of PTH, progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia and adynamic bone disease.

• Hypercalcemia: Progressive and/or acute hypercalcemia may increase risk of cardiac arrhythmias and seizures; chronic hypercalcemia may lead to generalized vascular and other soft-tissue calcification. Risk of hypercalcemia may be increased by concomitant use of calcium-containing supplements, vitamin D containing compounds, and/or medications that increase serum calcium (eg, thiazide diuretics). Monitor calcium levels closely with initiation of therapy and with dose adjustments; discontinue use promptly in patients who develop hypercalcemia. Patients with a history of hypercalcemia prior to therapy should be monitored more frequently.

• Hyperphosphatemia: Should be corrected before initiating therapy; exacerbates secondary hyperparathyroidism, diminishing the effect of calcifediol.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Monitoring Parameters

Serum calcium, serum phosphorus, serum total 25-hydroxyvitamin D and intact PTH levels within 3 months after initiation of therapy or dose adjustment, and subsequently at least every 6 to 12 months; signs and symptoms of hypercalcemia.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Endogenous calcifediol crosses the placenta in concentrations generally lower than those in the maternal plasma; supplementation increases cord blood 25OHD concentrations (IOM 2011).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience pharyngitis or rhinitis. Have patient report immediately to prescriber signs of high calcium (weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain), abnormal heartbeat, seizures, lack of appetite, increased thirst, polyuria, weight loss, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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