Milcal

Approved Indications:

• Prevention and treatment of calcium and Vitamin D deficiency
• Especially in elderly individuals, postmenopausal women, and patients with limited sun exposure.
• Adjunct in the management of osteoporosis and osteopenia
• For improving bone mineral density and reducing fracture risk.
• Supportive therapy in pregnancy and lactation
• To meet increased calcium and Vitamin D demands during these physiological states.
• Hypocalcemia
• Due to dietary deficiency or chronic illness (e.g., hypoparathyroidism, renal osteodystrophy).
• Rickets and osteomalacia
• As a supplement to treat or prevent bone softening in children and adults.
• Post-gastrectomy or malabsorption syndromes
• To prevent secondary nutritional deficiency.

Clinically Accepted Off-Label Uses:

• Support in periodontal therapy
• To enhance bone regeneration.
• Prevention of corticosteroid-induced bone loss
• Especially in long-term steroid users.

Route of Administration: Oral

Adults:

• Prevention of deficiency:
  1–2 tablets daily or as directed, typically providing calcium (500–1000 mg/day) + Vitamin D3 (400–800 IU/day).
• Treatment of deficiency/Osteoporosis adjunct:
  2–3 tablets daily in divided doses, with food to enhance absorption.

Pregnant or Lactating Women:

• Recommended dose: 1000–1200 mg elemental calcium + 600–1000 IU Vitamin D3 daily.
• Monitor total dietary intake to avoid hypercalcemia.

Pediatrics (over 6 years):

• Typical dose: 250–500 mg calcium + 200–400 IU Vitamin D3 once or twice daily (as directed by physician).

Elderly:

• No dose adjustment necessary. However, monitor renal function and calcium levels regularly.

Renal or Hepatic Impairment:

• Use with caution. Avoid in severe renal impairment (e.g., CrCl <30 mL/min) due to risk of hypercalcemia and calcium-phosphate deposition.

Calcium Phosphate serves as a source of elemental calcium, essential for various physiological functions including bone formation, nerve transmission, muscle contraction, and blood clotting. Vitamin D3 (Cholecalciferol) enhances the intestinal absorption of calcium and phosphate by promoting synthesis of calcium-binding proteins in the intestinal mucosa. Together, they maintain calcium-phosphate homeostasis, facilitate proper bone mineralization, and help prevent bone resorption.

Calcium Phosphate:

• Absorption: 20–30% absorbed in the small intestine; enhanced in presence of Vitamin D.
• Distribution: Mainly into bones and teeth.
• Metabolism: Not metabolized.
• Excretion: Primarily fecal (unabsorbed); small amounts via urine.

Vitamin D3:

• Absorption: Rapid and efficient absorption in the presence of dietary fats.
• Bioavailability: Enhanced with food.
• Distribution: Stored in adipose tissue and liver.
• Metabolism: Converted in the liver to 25-hydroxycholecalciferol and then in the kidneys to active 1,25-dihydroxycholecalciferol.
• Half-life: ~15 days (Vitamin D3); active form ~15 hours.
• Excretion: Primarily biliary and fecal.

• Pregnancy:
  Not assigned a specific FDA category under the new labeling rules. Considered safe at recommended dietary doses. Excessive calcium or Vitamin D can cause fetal hypercalcemia or suppression of parathyroid function.
• Lactation:
  Both calcium and Vitamin D3 are excreted in breast milk in low amounts. Safe for use at recommended doses. Monitor for signs of hypercalcemia in the infant if high doses are used.
• Caution:
  Avoid excess supplementation. Monitor serum calcium levels in pregnancy and lactation.

• Primary Class: Calcium Supplement with Vitamin D
• Subclass: Bone Health / Mineral & Electrolyte Supplement

• Known hypersensitivity to calcium, phosphate salts, or Vitamin D3
• Hypercalcemia or hypercalciuria
• Vitamin D toxicity
• Nephrolithiasis (calcium-containing kidney stones)
• Severe renal impairment or renal failure
• Sarcoidosis or other granulomatous diseases (risk of increased Vitamin D activation)

• Hypercalcemia Risk: Monitor serum calcium in prolonged therapy.
• Renal Impairment: Use cautiously; calcium-phosphate imbalance may worsen.
• Cardiac Patients: Avoid excessive calcium due to potential risk of arrhythmia.
• Vitamin D Toxicity: Signs include nausea, vomiting, weakness, and polyuria.
• Granulomatous Diseases: Increased endogenous conversion of Vitamin D may raise calcium levels.
• Pediatric Use: Use under medical supervision; avoid excessive supplementation.

Common (usually mild):

• Gastrointestinal: Nausea, constipation, flatulence, abdominal bloating
• Musculoskeletal: Muscle pain (rare), fatigue
• Renal: Increased risk of kidney stones with long-term high doses

Serious/Rare:

• Hypercalcemia: Confusion, arrhythmia, muscle weakness
• Hypervitaminosis D: Anorexia, polyuria, nephrocalcinosis
• Allergic reactions: Rash, itching, or anaphylaxis (very rare)

Onset: GI symptoms may appear within days; hypercalcemia over weeks of overdose
Severity: Mostly mild; serious effects are dose-dependent and preventable

• Thiazide Diuretics: Increase risk of hypercalcemia.
• Tetracyclines / Quinolones: Calcium reduces absorption—separate dosing by 2 hours.
• Bisphosphonates: Reduced absorption with calcium—administer separately.
• Corticosteroids: Reduce calcium absorption—may require dose adjustment.
• Antacids (containing aluminum/magnesium): Compete for absorption.
• Digoxin: Risk of cardiac arrhythmias if calcium is high.
• Enzyme Systems: Vitamin D is metabolized via CYP27B1 (renal enzyme), not primarily CYP450.

• Endocrine Society and NOF Guidelines: Continue to recommend calcium + Vitamin D supplementation for osteoporosis prevention and as adjunct to bisphosphonate therapy.
• EMA Notice (2024): Reiterated caution on long-term high-dose Vitamin D use due to hypercalcemia risk.
• WHO (2023): Updated recommendations for maternal calcium supplementation in high-risk populations to prevent preeclampsia.

• Storage Temperature: Store below 25°C (77°F)
• Humidity: Keep in a dry place
• Light Protection: Protect from direct sunlight
• Handling Instructions:
• Do not refrigerate or freeze
• Keep in original container with lid tightly closed
• Keep out of reach of children
• Shelf-Life: Refer to pack; generally stable for 2–3 years if unopened