Doxerol

Approved Indications:

• Secondary Hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stages 3 and 4.
• Secondary Hyperparathyroidism in Dialysis Patients: For the treatment of SHPT in adult patients undergoing chronic dialysis.

Off-label / Clinically Accepted Uses:

• Management of vitamin D–resistant rickets or osteomalacia in select populations.
• Prevention of renal osteodystrophy in CKD when other forms of vitamin D are ineffective or not tolerated.

Route: Oral capsules and Intravenous injection.

Adults:

• CKD stages 3 & 4 (Oral):
• Initial: 1 mcg once daily or three times per week (e.g., Monday/Wednesday/Friday).
• Titrate every 2–4 weeks based on serum iPTH, calcium, and phosphorus levels.
• Usual maintenance dose: 1–3.5 mcg/day.
• CKD on Dialysis (IV):
• Initial: 4 mcg three times weekly at the end of dialysis.
• Titrate in 2 mcg increments at 2-week intervals.
• Maximum dose: Usually not to exceed 18 mcg/week.

Pediatrics:

• Safety and efficacy not established.

Elderly:

• Start at the lower end of the dosing range due to increased sensitivity.

Renal Impairment:

• No initial dose adjustment required beyond CKD-specific guidelines.
• Close monitoring of calcium, phosphorus, and iPTH is essential.

Hepatic Impairment:

• Use with caution; Doxercalciferol is hepatically activated.

Doxercalciferol is a synthetic analog of vitamin D₂ that undergoes hepatic 25-hydroxylation to form the active hormone 1α,25-dihydroxyvitamin D₂. This active metabolite binds to the vitamin D receptor (VDR) in target tissues, including the parathyroid gland, intestines, and bone. Activation of VDR suppresses parathyroid hormone (PTH) gene transcription and synthesis, decreases PTH-mediated bone resorption, and increases calcium and phosphorus absorption in the gut, thus managing secondary hyperparathyroidism associated with CKD.

• Absorption: Well absorbed orally; bioavailability is enhanced with a low-fat meal.
• Distribution: Highly protein bound (>98%).
• Metabolism: Hepatically converted to 1α,25-(OH)₂D₂ via 25-hydroxylation.
• Half-life: ~32–48 hours.
• Elimination: Primarily fecal via biliary excretion; minor urinary excretion.

• Pregnancy: FDA Category C
• Animal studies showed adverse fetal outcomes; no well-controlled human studies.
• Use only if benefits outweigh risks.
• Lactation:
• Unknown whether excreted in breast milk.
• Potential risk of hypercalcemia in infants; caution advised.

• Primary Class: Vitamin D Analog
• Subclass: Synthetic Vitamin D₂ prohormone

• Known hypersensitivity to doxercalciferol or any of its components.
• Hypercalcemia.
• Vitamin D toxicity.
• Evidence of elevated serum phosphorus not adequately controlled.

• Hypercalcemia and hyperphosphatemia: Risk increases with excessive doses or inadequate monitoring.
• Adynamic bone disease: May occur if PTH is excessively suppressed.
• Hepatic dysfunction: Use with caution due to hepatic activation requirement.
• Electrolyte abnormalities: Frequent monitoring of calcium, phosphorus, and iPTH is required.
• Vitamin D toxicity: Risk with prolonged high doses; monitor for anorexia, nausea, vomiting, polyuria, and weakness.

Common:

• Hypercalcemia
• Hyperphosphatemia
• Nausea
• Edema
• Fatigue

Less Common:

• Pruritus
• Headache
• Dizziness
• Muscle cramps

Serious / Rare:

• Severe hypercalcemia with cardiac arrhythmias
• Soft tissue calcification
• Suppressed parathyroid hormone leading to adynamic bone disease

• Aluminum-containing antacids: Increased risk of aluminum toxicity in renal failure.
• Thiazide diuretics: Additive hypercalcemia.
• Digitalis glycosides (e.g., digoxin): Increased risk of arrhythmias with hypercalcemia.
• Magnesium-containing products: Risk of hypermagnesemia in dialysis patients.
• Cholestyramine: May reduce absorption of doxercalciferol.

• KDIGO and other nephrology guidelines recommend active vitamin D analogs like doxercalciferol for SHPT management in later-stage CKD and dialysis patients.
• Emphasis on balancing PTH control with avoidance of hypercalcemia and hyperphosphatemia.
• Emerging preference for selective VDR activators due to reduced hypercalcemic effects.

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture.
• Do not freeze.
• Keep in a tightly closed container.
• Keep out of reach of children.