Cadolin

Approved Indications:

• Osteoporosis (prevention and treatment): Especially postmenopausal, senile, and glucocorticoid-induced osteoporosis.
• Calcium and Vitamin D deficiency: In individuals with dietary insufficiency, restricted sunlight exposure, or malabsorption.
• Osteomalacia and rickets: Supportive therapy in Vitamin D–dependent rickets and adult osteomalacia.
• Pregnancy and lactation: To meet increased maternal calcium and Vitamin D demands.
• Growth support in children: During rapid growth phases where bone development requires enhanced calcium/Vitamin D intake.
• Hypocalcemia: As adjunct treatment in mild chronic hypocalcemia.
• Supportive therapy in chronic renal failure: For correction of secondary hyperparathyroidism due to hypocalcemia.

Off-label/Clinically Accepted Uses:

• Post-thyroidectomy hypocalcemia
• Peri- and postmenopausal support to reduce bone loss
• Adjunct in anticonvulsant therapy, where Vitamin D metabolism is affected

Adults (including elderly):

• Typical dose: 1–2 tablets per day (commonly 500 mg elemental calcium + 400–800 IU Vitamin D3 per tablet), taken with meals.
• Osteoporosis prevention/treatment: 1000–1200 mg elemental calcium + 800–1000 IU Vitamin D3 daily.

Children (above 1 year):

• Supplementation: 250–500 mg calcium + 200–400 IU Vitamin D3 daily depending on age and dietary intake.

Pregnancy/Lactation:

• Usual recommendation: 1000–1300 mg calcium + 600–2000 IU Vitamin D3 daily, based on nutritional status and physician assessment.

Renal Impairment:

• Mild-to-moderate: Use cautiously; monitor serum calcium and phosphate levels.
• Severe: Avoid use or switch to active forms of Vitamin D (e.g., calcitriol) due to impaired conversion.

Hepatic Impairment:

• No dose adjustment typically required.

Administration:

• Oral. Preferably taken with food to enhance absorption.
• Chewable or effervescent forms must be fully dissolved before ingestion.

Calcium plays a central role in bone mineralization, neuromuscular function, and enzymatic activities. Vitamin D3 (cholecalciferol) is converted in the liver to 25-hydroxycholecalciferol and then in the kidneys to its active form, calcitriol. Calcitriol enhances calcium and phosphate absorption from the intestine, facilitates calcium reabsorption in the kidneys, and promotes bone mineralization by activating osteoblasts. Together, calcium and Vitamin D3 maintain calcium-phosphorus balance and bone integrity.

Calcium:

• Absorption: ~25–30% absorbed in the small intestine; enhanced by active Vitamin D.
• Distribution: Stored in bones and teeth (~99%), remainder in plasma and soft tissues.
• Metabolism: Not metabolized; exists in ionized or protein-bound form.
• Elimination: Primarily via feces (unabsorbed portion); renal excretion of absorbed calcium.

Vitamin D3:

• Absorption: Well-absorbed orally with dietary fat.
• Distribution: Stored in adipose tissue and liver.
• Metabolism: Hepatic 25-hydroxylation, followed by renal 1-α hydroxylation to active form.
• Elimination half-life: ~15–25 days.
• Excretion: Bile and feces.

• Pregnancy: Generally considered safe (Category C for high-dose Vitamin D) when used within recommended dietary limits. Excessive dosing may cause fetal hypercalcemia and complications.
• Lactation: Safe at physiological doses. Both calcium and Vitamin D3 pass into breast milk, but not in harmful quantities. High doses may alter serum calcium in infants.

• Primary class: Nutritional supplement
• Subclass: Bone health supplement / Calcium-regulating agent
• Pharmacologic group: Mineral + Fat-soluble vitamin combination

• Hypersensitivity to calcium salts, Vitamin D3, or formulation excipients
• Hypercalcemia or conditions causing it (e.g., hyperparathyroidism, malignancy)
• Hypervitaminosis D
• Nephrolithiasis (calcium-containing kidney stones)
• Severe renal impairment or renal failure (risk of calcium-phosphate imbalance)
• Sarcoidosis or other granulomatous diseases (may increase endogenous Vitamin D activation)

• Use cautiously in renal impairment, with regular monitoring of calcium, phosphate, and Vitamin D levels.
• Prolonged high doses may lead to hypercalcemia, nephrocalcinosis, or cardiovascular calcification.
• Thiazide diuretics, which reduce urinary calcium excretion, may increase hypercalcemia risk.
• Monitor patients with malabsorption syndromes or granulomatous disease closely.
• Avoid co-administration with high-oxalate foods or iron/zinc supplements, which may reduce calcium absorption.

Common:

• Gastrointestinal: Constipation, bloating, flatulence, nausea
• Musculoskeletal: Mild hypercalcemia (fatigue, muscle weakness)

Serious/Rare:

• Severe hypercalcemia: Confusion, arrhythmia, polyuria, dehydration
• Nephrolithiasis or renal impairment (from calcium overload)
• Hypersensitivity reactions: Rash, pruritus, swelling (rare)

Timing/Severity:

• GI symptoms often appear within the first few days of high-dose use
• Hypercalcemia is dose-dependent and may develop with prolonged high intake

• Thiazide diuretics: Risk of hypercalcemia due to decreased urinary calcium excretion
• Tetracyclines, fluoroquinolones, bisphosphonates: Calcium can reduce absorption; separate dosing by at least 2 hours
• Anticonvulsants (phenytoin, carbamazepine): May reduce Vitamin D levels via enzyme induction
• Glucocorticoids: Reduce calcium absorption and Vitamin D efficacy
• Digitalis glycosides: Risk of arrhythmia in hypercalcemia

Enzyme interactions:
Vitamin D3 is metabolized via CYP27A1 and CYP24A1; however, typical doses do not cause significant hepatic enzyme interactions.

• Updated guidelines from international osteoporosis societies (e.g., IOF, NOF) recommend ensuring adequate calcium and Vitamin D intake in elderly and postmenopausal individuals as baseline management for bone health.
• EMA and FDA emphasize caution with excessive over-the-counter supplementation, advising monitoring of total daily intake from all sources.
• Ongoing clinical evaluations are reassessing the cardiovascular safety of calcium supplementation in certain populations, but no formal restrictions exist.

• Temperature: Store below 25°C in a cool, dry place
• Humidity: Protect from moisture
• Light: Store in original container to protect from light
• Handling: Keep container tightly closed; avoid excessive heat
• Reconstitution/Refrigeration: Not required (unless in liquid form—refrigeration may be advised after opening)