Calcitriol

Approved Indications:

• Chronic Renal Failure (CKD-associated secondary hyperparathyroidism): Management of hypocalcemia and prevention/treatment of secondary hyperparathyroidism in patients with stages 3–5 CKD.
• Hypocalcemia: Treatment of hypocalcemia in patients undergoing chronic renal dialysis.
• Hypoparathyroidism & Pseudohypoparathyroidism: Management of calcium metabolism disorders in postsurgical, idiopathic, and pseudohypoparathyroidism.
• Rickets & Osteomalacia: For vitamin D-resistant or hypophosphatemic rickets and familial or nutritional osteomalacia.
• Postmenopausal Osteoporosis (off-label): Occasionally used in conjunction with calcium supplements to reduce bone loss.

Route of Administration: Oral and intravenous (IV)

Adults:

• Chronic renal dialysis patients (oral): Start with 0.25 mcg/day; adjust in 2–4 week intervals based on serum calcium and PTH levels. Maintenance: 0.5–1 mcg/day.
• Hypoparathyroidism or pseudohypoparathyroidism: Initial dose: 0.25 mcg/day; adjust every 2–4 weeks. Maintenance: 0.5–2 mcg/day depending on severity.
• Vitamin D-resistant rickets/osteomalacia: 0.25–1 mcg/day initially; can be increased based on clinical and lab response.

Pediatrics:

• Infants: 0.04–0.08 mcg/kg/day orally.
• Children 1–5 years: 0.25–0.75 mcg/day.
• Children 6–12 years: 0.25–1 mcg/day.

Elderly: No specific dose adjustment required, but monitor calcium levels carefully.

Renal or Hepatic Impairment: No dose adjustment provided in labeling, but increased monitoring is essential due to altered vitamin D metabolism.

IV Administration (dialysis patients):

• Initial: 0.5 mcg to 1 mcg three times per week, given during dialysis; titrate every 2–4 weeks.

Important: Serum calcium, phosphate, and PTH should be monitored biweekly during titration.

Calcitriol is the hormonally active form of vitamin D₃. It binds to the intracellular vitamin D receptor (VDR), forming a complex that regulates gene transcription involved in calcium and phosphate homeostasis. Calcitriol increases intestinal absorption of calcium and phosphate, promotes renal reabsorption of calcium, and suppresses parathyroid hormone (PTH) secretion. These effects together normalize serum calcium levels, prevent bone demineralization, and correct secondary hyperparathyroidism.

• Absorption: Rapidly absorbed from the GI tract with oral bioavailability of ~90%.
• Distribution: Widely distributed; 99.9% protein-bound (mainly to vitamin D-binding protein).
• Metabolism: Metabolized in the liver and other tissues to inactive forms (calcitroic acid).
• Half-life: Approximately 5–8 hours.
• Onset of Action: Within 2–6 hours for increasing serum calcium levels.
• Elimination: Primarily via the biliary route in feces; some renal excretion of metabolites.

• Pregnancy: Category C (USA); use only if potential benefit justifies the potential risk. High doses may cause fetal hypercalcemia.
• Lactation: Calcitriol is excreted in breast milk. Monitor infant for signs of hypercalcemia (e.g., vomiting, poor feeding, irritability). Use with caution in breastfeeding mothers.
• Note: Limited human data; close monitoring of maternal and infant calcium levels is essential.

• Primary Class: Vitamin D Analog
• Subclass: Active form of vitamin D₃ (Calcitriol); hormone replacement

• Hypersensitivity to calcitriol or any component of the formulation
• Hypercalcemia
• Vitamin D toxicity
• Severe renal dysfunction not under dialysis without monitoring

• Hypercalcemia Risk: Monitor serum calcium frequently; symptoms may include weakness, headache, nausea, or arrhythmia.
• Hyperphosphatemia: Monitor and manage dietary phosphate; may require phosphate binders.
• Cardiac Arrhythmias: Especially in patients with digitalis toxicity—calcitriol can exacerbate digitalis toxicity.
• Renal Stones: Avoid in patients with a history of renal calculi unless strictly necessary.
• Monitoring: Frequent monitoring of serum calcium, phosphorus, alkaline phosphatase, and PTH is essential during therapy.

Common:

• Hypercalcemia (fatigue, muscle weakness, nausea, constipation)
• Hyperphosphatemia
• Pruritus

Less Common:

• Abdominal pain
• Vomiting
• Headache

Serious:

• Cardiac arrhythmias (especially with digitalis co-administration)
• Seizures (in rare severe hypercalcemia)
• Acute pancreatitis (very rare)
• Nephrolithiasis or nephrocalcinosis with prolonged high calcium

• Thiazide diuretics: May enhance risk of hypercalcemia.
• Magnesium-containing antacids: Risk of hypermagnesemia in renal patients.
• Phenytoin/Phenobarbital: May reduce calcitriol efficacy by increasing catabolism.
• Digitalis glycosides (e.g., digoxin): Increased risk of arrhythmias in hypercalcemia.
• Cholestyramine: May impair absorption of calcitriol.

Enzyme Involvement:

• CYP24A1 deactivates calcitriol; medications affecting this enzyme may alter drug levels.

• KDIGO 2024 update emphasizes individualized use of calcitriol in CKD, discouraging routine use in non-dialysis CKD unless PTH is significantly elevated.
• EMA/FDA Label Revisions: Emphasis on tighter monitoring for hypercalcemia; recommended integration of PTH and phosphate targets when adjusting dose.

• Temperature: Store below 25°C (77°F)
• Protection: Protect from light and moisture
• Handling: Do not freeze; keep in original packaging
• Oral solution/capsules: Shake solution well before use. Use within the recommended period after opening.