DOXERCALCIFEROL
Clinical safety rating: safe
Animal studies have demonstrated safety
Doxercalciferol is a synthetic vitamin D2 analog that undergoes hepatic conversion to its active metabolite, 1α,25-dihydroxyvitamin D2, which binds to the vitamin D receptor (VDR) in the parathyroid glands, reducing parathyroid hormone (PTH) synthesis and secretion. It also increases intestinal calcium and phosphate absorption and promotes bone mineralization.
| Metabolism | Hepatic metabolism via 25-hydroxylation primarily by cytochrome P450 enzymes (CYP27A1, likely CYP2R1, and possibly CYP3A4) to form the active metabolite 1α,25-dihydroxyvitamin D2; further metabolism includes side-chain oxidation and glucuronidation; excreted primarily in feces. |
| Excretion | Primarily fecal (biliary) elimination; renal excretion accounts for <2% of unchanged drug in urine. |
| Half-life | Terminal elimination half-life is approximately 96 hours (range 48–168 hours) in patients with chronic kidney disease, reflecting slow release from adipose tissue and prolonged vitamin D receptor activation. |
| Protein binding | Approximately 99.9% bound to vitamin D-binding protein (DBP) and albumin. |
| Volume of Distribution | Volume of distribution is approximately 5–10 L/kg, indicating extensive tissue distribution, particularly into adipose tissue and bone. |
| Bioavailability | Not applicable for oral route (doxercalciferol is available as IV injection and oral capsules; oral bioavailability is approximately 25–30% due to first-pass metabolism in the liver). |
| Onset of Action | Intravenous administration: onset of increased serum calcium occurs within 2–4 weeks of regular dosing. |
| Duration of Action | Duration of therapeutic effect on calcium and parathyroid hormone levels lasts approximately 3–7 days after a single IV dose, but cumulative effects persist for weeks due to long half-life. |
| Molecular Weight | 412.65 |
0.5 mcg orally three times per week at each hemodialysis session; alternatively, 1 mcg orally three times per week. Intravenous: 0.5 mcg bolus three times per week at end of hemodialysis; titrate to target intact parathyroid hormone (iPTH) level.
| Dosage form | INJECTABLE |
| Renal impairment | Dosing is only for patients on hemodialysis. No adjustment needed for GFR as drug is not renally cleared; however, avoid use in patients with severe renal impairment not on dialysis. |
| Liver impairment | No specific dose adjustments for Child-Pugh class A, B, or C; use with caution in severe hepatic impairment due to limited data. |
| Pediatric use | Safety and efficacy not established; no FDA-approved pediatric dosing. |
| Geriatric use | No specific dose adjustment required; dosing same as adults. Monitor serum calcium, phosphorus, and iPTH closely due to potential for hypercalcemia and adynamic bone disease. |
| 1st trimester | Limited human data; animal studies show teratogenicity at high doses. Use only if benefit outweighs risk. |
| 2nd trimester | Same as T1; monitor for maternal hypercalcemia which may affect fetal calcium homeostasis. |
| 3rd trimester | Same as T1; potential for fetal hypercalcemia and suppression of parathyroid function. |
Clinical note
Cholestyramine may impair absorption Can cause hypercalcemia and hyperphosphatemia monitor serum levels.
| Placental transfer | Crosses placenta; extent unknown but expected due to lipophilic nature. |
| Breastfeeding | Excreted in human milk in small amounts; consider risk of infant hypercalcemia. Monitor infant serum calcium if used. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | Hypercalcemia |
| Serious Effects |
HypercalcemiaVitamin D toxicityKnown hypersensitivity to doxercalciferol or any of its components
| Precautions | Hypercalcemia: excessive suppression of PTH may lead to hypercalcemia, hyperphosphatemia, and adynamic bone disease; monitor serum calcium, phosphorus, and PTH levels regularly, Digitalis toxicity: hypercalcemia increases risk of cardiac arrhythmias in patients on digoxin, Aluminum overload: risk of aluminum-related bone disease with concomitant aluminum-containing phosphate binders, Oversedation with vitamin D toxicity: may cause hypercalciuria and nephrocalcinosis; risk in patients with impaired renal function |
| Food/Dietary | Avoid excessive intake of calcium-rich foods (e.g., dairy products) and vitamin D-fortified foods. High-phosphate foods (e.g., nuts, seeds, whole grains) may require restriction. Do not take phosphate binders within 2 hours of doxercalciferol. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | Doxercalciferol is a vitamin D analog. Data in pregnant women are limited. High doses of vitamin D have been associated with fetal anomalies (e.g., supravalvular aortic stenosis, elfin facies) due to hypercalcemia. Use only if clearly needed. For first trimester: potential risk of hypercalcemia-related teratogenicity; second and third trimesters: monitor maternal calcium to avoid fetal hypercalcemia and associated adverse outcomes. |
| Fetal Monitoring | Monitor serum calcium, phosphorus, and intact PTH regularly throughout pregnancy. Fetal monitoring may include ultrasound for signs of hypercalcemia-related effects (e.g., nephrocalcinosis, growth restriction). |
| Fertility Effects | No adequate data on effects on fertility. In animal studies, no adverse effects on fertility were reported at clinically relevant doses. |
| Clinical Pearls | Monitor serum calcium and phosphate levels closely; hypercalcemia risk increases with concurrent use of calcium-based phosphate binders. Doxercalciferol is a vitamin D analog requiring hepatic 25-hydroxylation; hepatic impairment may reduce efficacy. Initiate at 10 mcg three times weekly in hemodialysis patients, titrating based on intact PTH levels. Use with caution in patients with hypercalcemia or vitamin D toxicity. |
| Patient Advice | Take this medication exactly as prescribed, usually three times per week during dialysis. · Avoid taking additional calcium or vitamin D supplements unless directed by your doctor. · Report symptoms of high calcium levels: nausea, vomiting, constipation, confusion, or muscle weakness. · Do not change your dialysis schedule or diet without consulting your healthcare provider. · Regular blood tests are required to monitor calcium, phosphate, and PTH levels. |