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)]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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.
Dosage and Administration
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: 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 (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. 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: 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.
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.
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
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
- 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 sore throat or stuffy nose. 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, passing a lot of urine, weight loss, bone pain, 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.
