Calcifediol

Calcifediol is used 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 less than 30 ng/mL.

• Calcifediol is available under the following different brand names: Rayaldee.

Dosage Forms and Strengths

Capsule, Extended-Release

• 30 mcg

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 less than 30 ng/mL
• Ensure serum calcium is less than 9.8 mg/dL before initiating calcifediol
• Initial: 30 mcg orally at night before bed
• The 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 less than 5.5 mg/dL

Dosage Modifications

Increase dose

• Increase the dose to 60 mcg orally at night before bed after approximately 3 months, if intact PTH remains above the desired therapeutic range
• Prior to raising the dose, ensure serum calcium is less than 9.8 mg/dL, serum phosphorus is below 5.5 mg/dL, and serum total 25-hydroxyvitamin D is less than 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 greater than 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 in pediatric patients

Safety and efficacy not established in pediatric patients.

Common side effects of calcifediol include:

• High blood phosphates (hyperphosphatemia), at least 1 episode greater than 4.5 mg/dL
• Anemia
• Runny or stuffy nose
• Increased blood creatinine
• Shortness of breath
• High blood calcium (hypercalcemia), at least 1 episode greater than 10.5 mg/dL
• Cough
• Congestive heart failure
• Constipation
• Bronchitis
• High blood potassium (hyperkalemia)
• Osteoarthritis
• High uric acid levels in the blood (hyperuricemia)
• Contusion
• Pneumonia
• Chronic obstructive pulmonary disease (COPD)

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Calcifediol has no listed severe interactions with other drugs.
• Serious interactions of calcifediol include:
  • apalutamide
  • ivosidenib
  • voxelotor
• Calcifediol has moderate interactions with at least 60 different drugs.
• Calcifediol has no listed mild interactions with other drugs.

Warnings

• This medication contains calcifediol. Do not take Rayaldee if you are allergic to calcifediol or any ingredients contained in this drug.

Contraindications

• None

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Calcifediol?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Calcifediol?"

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

Hypercalcemia

• Hypercalcemia may occur
• Acute hypercalcemia may increase the 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, 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 to 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 25¬hydroxyvitamin D, intact PTH, and serum calcium concentrations should be closely monitored when initiating or discontinuing a strong CYP3A4 inhibitor

Pregnancy and Lactation

• There are no human data with the use of calcifediol 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. Consult your doctor.
• There is no information available on the presence of calcifediol in human milk, the effects of calcifediol on breastfed infants, or milk production. Infants potentially exposed to calcifediol through breast milk should be monitored for signs and symptoms of hypercalcemia, including seizures, vomiting, constipation, and weight loss. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on a breastfed child from calcifediol or the underlying maternal condition.