Introduction
Calcifediol (25-hydroxyvitamin D3) is a vitamin D analog that serves as the major circulating metabolite of vitamin D3 (cholecalciferol). It is a prohormone that requires further hydroxylation in the kidneys to become the active form of vitamin D (calcitriol). Calcifediol is primarily used for the treatment of vitamin D deficiency and metabolic bone diseases in patients with chronic kidney disease who have impaired renal hydroxylation of vitamin D.
Mechanism of Action
Calcifediol undergoes 1α-hydroxylation in the kidneys to form the active metabolite calcitriol (1,25-dihydroxyvitamin D3). Calcitriol binds to vitamin D receptors in target tissues, promoting intestinal absorption of calcium and phosphate, renal tubular reabsorption of calcium, and mobilization of calcium from bone. This helps maintain normal serum calcium levels and promotes bone mineralization.
Indications
- Treatment of vitamin D deficiency in patients with chronic kidney disease stages 3 and 4
- Management of secondary hyperparathyroidism in patients with chronic kidney disease
- Treatment of metabolic bone disease in patients with hypoparathyroidism
- Adjunct therapy in nutritional rickets and osteomalacia
Dosage and Administration
Initial dosing: 30 mcg orally once daily or 60 mcg orally twice weekly Maintenance dosing: Individualized based on serum calcium, phosphorus, and parathyroid hormone levels Renal impairment: Dosage adjustment required based on CKD stage Hepatic impairment: No specific dosage adjustment recommended Administration: May be taken with or without foodPharmacokinetics
Absorption: Well absorbed from the gastrointestinal tract (approximately 75% bioavailability) Distribution: Highly protein-bound to vitamin D-binding protein Metabolism: Hydroxylated in the kidneys to active form (calcitriol) Elimination: Primarily excreted in bile and feces; elimination half-life approximately 15-20 days Onset of action: 2-4 weeks for full therapeutic effectContraindications
- Hypercalcemia or vitamin D toxicity
- Known hypersensitivity to calcifediol or any component of the formulation
- Patients with evidence of vitamin D toxicity
- Concurrent use with other vitamin D analogs
Warnings and Precautions
- Hypercalcemia: Monitor serum calcium closely; may occur during treatment
- Hyperphosphatemia: May exacerbate in patients with renal impairment
- Renal function: Use with caution in patients with severe renal impairment
- Adynamic bone disease: May develop with oversuppression of PTH
- Cardiovascular risk: Hypercalcemia may predispose to cardiac arrhythmias
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Drug Interactions
- Thiazide diuretics: Increased risk of hypercalcemia
- Calcium supplements: Enhanced hypercalcemic effect
- Magnesium-containing antacids: Increased risk of hypermagnesemia
- Cholestyramine: May reduce absorption of calcifediol
- Phenytoin, phenobarbital: May enhance metabolism of vitamin D analogs
- Digitalis glycosides: Hypercalcemia may precipitate cardiac arrhythmias
Adverse Effects
Common (>10%):- Hypercalcemia
- Hyperphosphatemia
- Gastrointestinal discomfort
- Headache
- Dizziness
- Weakness
- Pruritus
- Nausea
- Allergic reactions
- Pancreatitis
- Nephrolithiasis
- Cardiac arrhythmias
Monitoring Parameters
- Serum calcium levels (weekly initially, then monthly)
- Serum phosphorus levels
- Intact parathyroid hormone (iPTH) levels
- 25-hydroxyvitamin D levels
- Renal function (BUN, creatinine)
- Urine calcium excretion
- Bone mineral density (annually)
- Signs and symptoms of hypercalcemia
Patient Education
- Take medication exactly as prescribed
- Do not take additional calcium or vitamin D supplements unless advised by healthcare provider
- Report symptoms of hypercalcemia: nausea, vomiting, constipation, weakness, confusion
- Maintain adequate fluid intake
- Regular follow-up appointments for laboratory monitoring
- Dietary considerations: maintain consistent calcium intake
- Inform all healthcare providers about calcifediol use
References
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. 2. National Kidney Foundation. KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1-S201. 3. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011. 4. Calcifediol prescribing information. FDA-approved labeling. 5. Bover J, et al. Vitamin D and renal disease. Kidney Int Suppl. 2010;(117):S50-S57. 6. Moe SM, et al. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl. 2009;(113):S1-S130.