Medically Reviewed on 2/14/2023

Generic Name: calcifediol

Brand Name: Rayaldee

Drug Class: Vitamin D Analogs

What is calcifediol, and what is it used for?

Calcifediol is a medication used to treat secondary hyperparathyroidism caused by vitamin D deficiency in patients with stage 3 or 4 chronic kidney disease (CKD).

Impaired kidney function causes defective activation of vitamin D3 which results in low calcium in blood (hypocalcemia), high phosphorous levels (hyperphosphatemia), and consequently, overactive parathyroid glands (hyperparathyroidism), which produce excessive parathyroid hormone (PTH).

Vitamin D3 is a fat-soluble vitamin essential for the absorption of calcium and phosphorous in the gastrointestinal (GI) tract, reabsorption in the kidneys, and mineralization of bone. When calcium levels fall due to vitamin D deficiency, parathyroid glands secrete PTH in order to maintain a stable balance (homeostasis) of calcium and phosphorous in the blood. PTH increases calcium absorption and phosphorous excretion in the kidneys, and also mobilizes calcium from the bones, which results in soft and brittle bone conditions such as rickets and osteomalacia.

Calcifediol is a synthetically manufactured drug with a chemical structure similar to vitamin D3 and is used to supplement vitamin D deficiency caused by chronic kidney disease. Calcifediol is a prohormone of calcitriol, the active form of vitamin D3, also known as 25-hydroxyvitamin D3. Calcifediol is converted to calcitriol in the kidneys by the enzyme cytochrome P450 27B1 (CYP27B1). Calcitriol activates the vitamin D3 pathways and increases intestinal absorption of calcium and phosphorus, which results in reduced parathyroid activity.


  • Calcifediol treatment can result in excessive calcium levels in blood (hypercalcemia) which can cause irregular heart rhythms, seizures, and calcification of blood vessels and soft tissues. Monitor the patient’s calcium levels regularly, apprise them of hypercalcemia symptoms, and advise them to report immediately, should such symptoms arise. Severe hypercalcemia may require emergency attention.
  • Hypercalcemia can increase the effects and toxicity of digitalis, a drug used to treat irregular heart rhythms and congestive heart failure. If calcifediol and digitalis are used concurrently, monitor the patient’s serum calcium levels and for signs of digitalis toxicity, especially during dose initiation and titration.
  • Excessive vitamin D supplementation can suppress the parathyroid hormone to abnormally low levels, resulting in progressive or acute hypercalcemia, hypercalciuria, hyperphosphatemia, adynamic bone disease, and an increased risk of fractures. Monitor PTH levels in patients and adjust calcifediol dosage as required.


Kidney Stones: Symptoms, Causes, and Treatment See Slideshow

What are the side effects of calcifediol?

Common side effects of calcifediol include:

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

What are the dosages of calcifediol?

Capsule, extended-release

30 mcg



  • 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 below 30 ng/mL
  • Ensure serum calcium is below 9.8 mg/dL before initiating calcifediol
  • Initial: 30 mcg orally every night
  • 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 below 5.5 mg/dL

Dosage Modifications

Increase dose

  • Increase the dose to 60 mcg orally every night after 3 months, if intact PTH remains above the desired therapeutic range
  • Prior to raising the dose, ensure serum calcium is below 9.8 mg/dL, serum phosphorus is below 5.5 mg/dL, and serum total 25-hydroxyvitamin D is below 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 above 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


Safety and efficacy not established


  • Overdose of calcifediol can lead to electrolyte imbalances including high blood levels of calcium (hypercalcemia) and phosphate (hyperphosphatemia), excessive excretion of calcium in the urine (hypercalciuria), and excessive suppression of parathyroid hormone (PTH).
  • Overdose symptoms include constipation, reduced appetite, vomiting, dehydration, fatigue, weakness, and irritability.
  • Calcifediol overdose is treated with induced vomiting and gastric lavage to eliminate any undigested drug in the gastrointestinal tract, and general supportive and symptomatic care. Blood and urine calcium levels are monitored and the patient is evaluated for heart rhythm abnormalities from hypercalcemia.

What drugs interact with calcifediol?

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

  • Calcifediol has no listed severe interactions with other drugs.
  • Serious interactions of calcifediol include:
    • abametapir
    • apalutamide
    • fexinidazole
    • ivosidenib
    • lonafarnib
    • tucatinib
    • voxelotor
  • Calcifediol has moderate interactions with at least 67 different drugs.
  • Mild interactions of calcifediol include:

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

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Pregnancy and breastfeeding

  • There are no adequate and well-controlled studies on the safety of calcifediol use in pregnant women, however, animal reproductive studies show it can cause fetal harm. Use calcifediol with caution during pregnancy only if potential benefits justify the potential risks to the fetus.
  • Natural vitamin D3 is poorly excreted in breastmilk, however, supplementation may increase its concentration. Use with caution in nursing mothers and monitor the breastfed infant for calcium levels and hypercalcemia symptoms such as vomiting, constipation, weight loss, and seizure.

What else should I know about calcifediol?

  • Take calcifediol exactly as prescribed, at bedtime. Swallow the capsule whole.
  • Inform your physician immediately if you experience symptoms of hypercalcemia, which may include, nausea, vomiting, constipation, loss of appetite, weight loss, increased thirst, increased urination, tiredness, and inability to think clearly.
  • You will need periodic lab tests during calcifediol therapy, follow up with your physician, and do not miss your appointments.
  • Store calcifediol safely out of reach of children.
  • In case of overdose, seek immediate medical help or contact Poison Control.


Calcifediol is a medication used to treat secondary hyperparathyroidism caused by vitamin D deficiency in patients with stage 3 or 4 chronic kidney disease (CKD). Common side effects of calcifediol include high calcium in the blood (hypercalcemia), high phosphorous in the blood (hyperphosphatemia), high potassium in the blood (hyperkalemia), high level of uric acid in the blood (hyperuricemia), increase in serum creatinine, low red blood cell count (anemia), contusion, inflammation of the nose and throat (nasopharyngitis), bronchial inflammation (bronchitis), cough, shortness of breath (dyspnea), chronic obstructive pulmonary disease (COPD), pneumonia, heart failure, degeneration and inflammation of joints (osteoarthritis), adynamic bone disease, and constipation. Consult your doctor if pregnant or breastfeeding.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 2/14/2023