Calcium Citrate + Calcitriol

Approved Indications:

• Osteoporosis (postmenopausal, senile, and glucocorticoid-induced): As part of calcium and vitamin D supplementation in patients with low bone mineral density.
• Osteomalacia and Rickets: Treatment and prevention of calcium and vitamin D deficiency-related bone softening.
• Hypocalcemia: Especially in chronic kidney disease and hypoparathyroidism where active vitamin D is required.
• Chronic Renal Osteodystrophy: Correction of secondary hyperparathyroidism in CKD patients on dialysis or not on dialysis.
• Calcium and Vitamin D3 Deficiency: In elderly, pregnancy, lactation, or malabsorption syndromes.

Clinically Accepted (Off-label) Uses:

• Adjunct in Bone Healing: Post-fracture or post-orthopedic surgery support.
• Support in Anticonvulsant Therapy: To prevent bone demineralization due to long-term antiepileptic drug use.

Adults:

• Typical Dose: Calcium Citrate (500–1000 mg elemental calcium) + Calcitriol 0.25–0.5 mcg once or twice daily, with or without food.
• Osteoporosis: Usually 1 tablet (e.g., 500 mg calcium + 0.25 mcg calcitriol) twice daily.
• Hypocalcemia (CKD-related): Start with 0.25 mcg calcitriol daily with 500–1000 mg calcium; titrate based on serum calcium and PTH levels.

Pediatrics:

• Rickets/Osteomalacia: Dose individualized based on weight, calcium levels, and severity; usually under specialist supervision.

Elderly:

• No routine dose adjustment required unless renal impairment is present; monitor calcium levels regularly.

Renal Impairment:

• Caution in mild-to-moderate impairment; avoid use in severe renal dysfunction due to hypercalcemia risk.

Administration Route:

• Oral only. Tablets should be swallowed whole or chewed if chewable; take with water.

Monitoring:

• Regular monitoring of serum calcium, phosphate, and PTH is essential during therapy.

Calcium Citrate serves as a bioavailable source of elemental calcium, essential for neuromuscular function, muscle contraction, blood clotting, and bone mineralization. Calcitriol, the active form of vitamin D3 (1,25-dihydroxycholecalciferol), binds to vitamin D receptors in the intestine, kidney, and bone, promoting active calcium absorption in the gut, renal tubular reabsorption, and suppression of PTH. Together, they enhance calcium homeostasis and correct hypocalcemia.

Calcium Citrate:

• Absorption: About 30–40% of elemental calcium is absorbed in the small intestine; does not require gastric acid for absorption.
• Distribution: Enters extracellular fluid and is incorporated into bone.
• Elimination: Primarily excreted in feces (unabsorbed); minimal renal excretion.

Calcitriol:

• Absorption: Rapid oral absorption; peak plasma levels in 3–6 hours.
• Bioavailability: ~90% orally.
• Distribution: Binds to plasma vitamin D-binding proteins.
• Metabolism: Metabolized in the liver to inactive forms.
• Half-life: 5–8 hours.
• Excretion: Primarily via bile and feces.

• Pregnancy: Calcitriol is categorized as Pregnancy Category C. Use only if clearly needed. Calcium at recommended doses is generally considered safe.
• Lactation: Both calcium and calcitriol are excreted into breast milk. Monitor infant calcium status if used in nursing mothers. Use with caution.

• Primary Class: Bone Mineral Regulator
• Subclass: Calcium-Vitamin D3 Combination
• Calcitriol Class: Active Vitamin D3 Analog

• Known hypersensitivity to calcium salts, calcitriol, or any excipients.
• Hypercalcemia or hypervitaminosis D.
• Severe renal impairment or renal calculi.
• Sarcoidosis or other granulomatous diseases (risk of increased endogenous calcitriol).
• Malabsorption syndrome if unresponsive to oral therapy.

• Hypercalcemia Risk: Monitor calcium and phosphate levels regularly, especially in renal impairment.
• Renal Calculi: Avoid in patients with nephrolithiasis history.
• Cardiac Disease: Use with caution in digitalis-treated patients—hypercalcemia may precipitate arrhythmias.
• Immobilized Patients: At increased risk of hypercalcemia.
• Monitor PTH and Vitamin D levels in CKD and elderly populations.

Common (≥1%):

• Gastrointestinal: Constipation, flatulence, abdominal pain, nausea.
• Musculoskeletal: Muscle weakness, bone pain (in overdose).
• Renal: Polyuria, thirst (due to hypercalcemia).

Less Common:

• CNS: Headache, drowsiness, fatigue.
• Dermatologic: Pruritus, rash.

Serious/Rare:

• Hypercalcemia symptoms: Vomiting, confusion, arrhythmia, renal impairment.
• Hyperphosphatemia, nephrocalcinosis (long-term high-dose use).

• Thiazide Diuretics: ↑ risk of hypercalcemia.
• Digitalis Glycosides (e.g., digoxin): ↑ risk of arrhythmia with elevated calcium.
• Antacids (aluminum/magnesium): ↑ aluminum absorption—avoid in CKD.
• Corticosteroids: ↓ calcium absorption.
• Cholestyramine, Orlistat: May impair calcitriol absorption.
• CYP3A4 Inducers (e.g., rifampin, phenytoin): May ↓ calcitriol levels.

• KDIGO 2023 update: Recommends careful calcitriol use only in advanced CKD with secondary hyperparathyroidism.
• Revised labeling: Now advises individualized dosing based on calcium and PTH targets rather than fixed supplementation, particularly in CKD.
• EMA/FDA advisories: Emphasis on hypercalcemia monitoring in long-term use.

• Temperature: Store below 25°C (77°F).
• Light: Protect from direct sunlight.
• Humidity: Store in a dry place, tightly closed.
• Handling: Do not freeze. Keep out of reach of children.
• Special note: Chewable tablets should be kept in original container to avoid moisture exposure.