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Calcifediol

Medically reviewed by Drugs.com. Last updated on May 27, 2020.

Pronunciation

(kal si fe DYE ole)

Index Terms

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

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.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

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

Oral: Administer at bedtime. Swallow capsule whole.

Bariatric surgery: Capsule, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Cannot open capsule. No IR formulation available. Switch to calcitriol.

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 (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Burosumab: Vitamin D Analogs may enhance the adverse/toxic effect of Burosumab. Avoid combination

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

Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Consider therapy modification

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. Monitor therapy

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

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

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

1% to 10%:

Cardiovascular: Cardiac 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, exacerbate nephrolithiasis, and has been associated with increased mortality in adults with chronic kidney disease (CKD) (KDIGO 2017). 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.

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.

KDIGO guidelines:

Serum calcium, phosphorus, and parathyroid hormone (PTH): Frequency of measurement may be dependent upon the presence and magnitude of abnormalities, the rate of progression of chronic kidney disease (CKD), and the use of treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD) (KDIGO 2017):

CKD stage G3a-G3b: Serum calcium and phosphate: Every 6 to 12 months; PTH: Frequency based on baseline level and progression of CKD

CKD stage G4: Serum calcium and phosphate: Every 3 to 6 months; PTH: Every 6 to 12 months

CKD stage G5 and G5D: Serum calcium and phosphate: Every 1 to 3 months; PTH: Every 3 to 6 months

Pregnancy Considerations

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

What is this drug used for?

• It is used to treat high parathyroid hormone levels in certain patients.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Sore throat

• Stuffy nose

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• High calcium like weakness, confusion, fatigue, headache, nausea and vomiting, constipation, or bone pain

• Abnormal heartbeat

• Seizures

• Lack of appetite

• Increased thirst

• Passing a lot of urine

• Weight loss

• Bone pain

• Severe loss of strength and energy

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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