Vitamin D analogue (25-hydroxy metabolite)
ATC code: A11CC06 (Calcifediol (25-OH-D))
Brand names
Rayaldee
25-hydroxycholecalciferol – an intermediate vitamin D metabolite formed in the liver from cholecalciferol. Drives 1,25-dihydroxyvitamin D synthesis in the kidneys and regulates intestinal calcium and phosphorus absorption and bone mineralization. Compared with cholecalciferol (D3), it bypasses hepatic 25-hydroxylation – faster increases in serum 25(OH)D (hours to days versus weeks). Particularly useful with hepatic dysfunction, malabsorption, or very low baseline 25(OH)D. In Spain it is the dominant form of vitamin D under the brand Hidroferol, unlike most countries where cholecalciferol prevails.
Adjunct
Adjunct to bisphosphonates, denosumab, and zoledronate in osteoporosis to ensure adequate vitamin D status before and during antiresorptive therapy. In patients with low baseline 25(OH)D, calcifediol restores levels faster, reducing hypocalcemia risk on bisphosphonates. AACE/ACE 2020 and SEIOMM 2024 set 25(OH)D target above 30 ng/mL before antiresorptive therapy.
First line
Used in confirmed vitamin D deficiency (25(OH)D under 20 ng/mL) when fast target response is needed, with hepatic dysfunction or malabsorption. SEEN 2021 and SEEDO 2024 place calcifediol in first-line therapy in Spain. Standard dose 0.266 mg (266 mcg) orally once or twice monthly, or 0.1 mg (100 mcg) weekly depending on baseline. Target 25(OH)D 30–50 ng/mL. In most patients without specific causes, cholecalciferol 800–2000 IU/day suffices; routine calcifediol use without documented deficiency is not indicated.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Calcifediol (25-hydroxyvitamin D) is an intermediate metabolite of vitamin D that raises blood 25(OH)D faster than cholecalciferol. It is prescribed for vitamin D deficiency, especially with malabsorption (AEMPS Ficha Técnica). Healthy adults take calcifediol in drops and capsules for an anti-aging level of vitamin D. With normal 25(OH)D (above 20 ng/mL per most international guidelines), no clinical studies of prophylactic use exist. Vitamin D overdose causes hypercalcemia (nausea, vomiting, weakness, kidney dysfunction, arrhythmias). If calcifediol is being taken without confirmed 25(OH)D deficiency on blood test, consider seeking a second opinion and getting tested.
Opens the checker prefilled with this drug. Pick the second one from your regimen.
With confirmed vitamin D deficiency in pregnancy, use is acceptable at doses that restore 25(OH)D without exceeding normal range. Calcium and 25(OH)D monitoring is mandatory. Overdose is hazardous due to maternal and fetal hypercalcemia.
Compatible with breastfeeding at standard doses. Monitor calcium in mother and infant with high doses.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Calcifediol (25-hydroxyvitamin D) is evaluated for the following indications with varying evidence strength: Vitamin D deficiency (evidence tier B), Postmenopausal osteoporosis (evidence tier B), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Calcifediol (25-hydroxyvitamin D) (≥ 1 in 100): Nausea, Constipation, Dry mouth, Metallic taste. See the Safety section for uncommon and serious reactions.
FDA category C. With confirmed vitamin D deficiency in pregnancy, use is acceptable at doses that restore 25(OH)D without exceeding normal range. Calcium and 25(OH)D monitoring is mandatory. Overdose is hazardous due to maternal and fetal hypercalcemia.
Compatible with breastfeeding at standard doses. Monitor calcium in mother and infant with high doses.
Calcifediol (25-hydroxyvitamin D) is contraindicated in: Calcifediol or excipient hypersensitivity; Hypercalcemia; Hypervitaminosis D; Active calcium-containing urolithiasis; Severe hypercalciuria. Full list in the Safety section.