Introduction
Calcitriol is the active form of vitamin D (1,25-dihydroxycholecalciferol) that plays a crucial role in calcium and phosphate homeostasis. As a potent vitamin D receptor agonist, it is used therapeutically to manage various disorders of calcium metabolism, particularly in patients with impaired renal function who cannot adequately convert vitamin D to its active form.
Mechanism of Action
Calcitriol binds to and activates the nuclear vitamin D receptor (VDR), which functions as a transcription factor. This activation promotes:
- Intestinal absorption of calcium and phosphorus
- Bone mineralization and resorption
- Renal tubular reabsorption of calcium
- Regulation of parathyroid hormone (PTH) secretion
Unlike nutritional vitamin D, calcitriol does not require hepatic or renal hydroxylation for activation, making it particularly useful in patients with renal impairment.
Indications
FDA-approved indications:- Management of hypocalcemia in patients with chronic kidney disease on dialysis
- Management of secondary hyperparathyroidism in patients with chronic kidney disease not on dialysis
- Treatment of hypocalcemia in patients with hypoparathyroidism
- Treatment of hypocalcemia in patients with pseudohypoparathyroidism
- Prevention and treatment of corticosteroid-induced osteoporosis
- Adjunctive therapy in psoriasis
- Renal osteodystrophy
- Nutritional rickets refractory to conventional vitamin D therapy
Dosage and Administration
Oral administration:- Hypocalcemia in dialysis patients: 0.25 mcg daily or every other day
- Secondary hyperparathyroidism in CKD: 0.25 mcg daily
- Hypoparathyroidism: 0.25 mcg daily, may increase by 0.25 mcg daily at 2-4 week intervals
- Initial dose: 0.5 mcg three times weekly
- Dose titration: Increase by 0.25-0.5 mcg at 2-4 week intervals
- Renal impairment: No dosage adjustment needed (drug of choice)
- Hepatic impairment: Use with caution; monitor closely
- Geriatric patients: Start at lower end of dosing range
- Pediatric patients: Safety and efficacy not established for all indications
Pharmacokinetics
Absorption: Rapidly absorbed from gastrointestinal tract (70-90% bioavailability) Distribution: Extensive tissue distribution; highly protein-bound (99.9%) to vitamin D-binding protein Metabolism: Undergoes enterohepatic recirculation; metabolized in liver via oxidation Elimination: Primarily excreted in feces (50%) with minor renal excretion (10%); elimination half-life: 3-6 hours Onset of action: 2-6 hours; maximal effect: 10-12 hoursContraindications
- Hypersensitivity to calcitriol or any component of the formulation
- Hypercalcemia or vitamin D toxicity
- Evidence of vitamin D overdose
Warnings and Precautions
Boxed Warning: Excessive administration may cause hypercalcemia, hypercalciuria, and hyperphosphatemia- Hypercalcemia: May occur at any time; monitor serum calcium frequently
- Digitalis toxicity: Hypercalcemia may precipitate cardiac arrhythmias in patients on digitalis
- Renal function: Monitor renal function periodically
- Adynamic bone disease: May develop with oversuppression of PTH
- Concomitant phosphate intake: May lead to soft tissue calcification
- Pregnancy: Category C - use only if potential benefit justifies potential risk
Drug Interactions
Major interactions:- Thiazide diuretics: Increased risk of hypercalcemia
- Digitalis glycosides: Increased risk of cardiac arrhythmias
- Cholestyramine, mineral oil: Reduced absorption of calcitriol
- Corticosteroids: May antagonize calcitriol effects
- Magnesium-containing antacids: Increased risk of hypermagnesemia
- CYP3A4 inducers: May reduce calcitriol effectiveness
Adverse Effects
Common (≥5%):- Hypercalcemia (15-30%)
- Hypercalciuria
- Elevated serum creatinine
- Headache
- Nausea/vomiting
- Severe hypercalcemia
- Nephrolithiasis
- Pancreatitis
- Cardiac arrhythmias
- Soft tissue calcification
- Allergic reactions
Monitoring Parameters
Baseline:- Serum calcium, phosphorus, magnesium
- Renal function (BUN, creatinine)
- Intact PTH level
- 24-hour urinary calcium (if indicated)
- Weekly: Serum calcium and phosphorus until stable
- Monthly: Serum calcium, phosphorus, creatinine
- Quarterly: Intact PTH levels
- Periodic assessment of 24-hour urinary calcium excretion
- Monitor for signs/symptoms of hypercalcemia
- Serum calcium: 8.4-9.5 mg/dL
- Calcium-phosphorus product: <55 mg²/dL²
- PTH: 150-300 pg/mL for CKD patients
Patient Education
- Take exactly as prescribed; do not exceed recommended dose
- Report signs of hypercalcemia: nausea, vomiting, constipation, weakness, confusion
- Maintain adequate fluid intake unless contraindicated
- Avoid concomitant use of magnesium-containing antacids
- Do not take additional calcium or vitamin D supplements unless prescribed
- Regular monitoring of blood tests is essential
- Inform all healthcare providers about calcitriol use
- Store at room temperature, away from light and moisture
References
1. 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. 2. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. 3. Calcitriol [package insert]. Lake Forest, IL: Hospira Inc; 2018. 4. Goodman WG, et al. Renal osteodystrophy in adults and children. In: Favus MJ, ed. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 6th ed. Washington, DC: American Society for Bone and Mineral Research; 2006:359-368. 5. FDA prescribing information: Calcitriol capsules and injection. 6. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319-329.