calcifediol + doxercalciferol

**Calcifediol + doxercalciferol** is a combination of two vitamin D analogs used or proposed for the management of secondary hyperparathyroidism associated with chronic kidney disease (CKD). Both agents act as vitamin D receptor agonists but differ in activation pathways—calcifediol (25-hydroxyvitamin D3) is a prohormone converted in the kidney to the active form, while doxercalciferol (1-hydroxyvitamin D2) is a synthetic analog that is metabolized in the liver to its active form and does not require renal activation. Each lowers serum parathyroid hormone (PTH) levels by binding to the vitamin D receptor in target tissues, exerting negative feedback on PTH synthesis and secretion, regulating calcium and phosphate metabolism, and improving bone mineralization in CKD. The rationale for combined use, although not standard, would be to address vitamin D deficiency (by replenishment with calcifediol) alongside direct PTH suppression with the activated analog (doxercalciferol), especially in CKD patients with impaired renal conversion of vitamin D or combined deficiency and PTH-driven bone disease[2][3][4][5].