D-Star

Approved Indications:

• Vitamin D Deficiency (Prevention and Treatment): For individuals with inadequate sun exposure, dietary insufficiency, or malabsorption syndromes.
• Hypoparathyroidism: To manage hypocalcemia resulting from reduced parathyroid hormone secretion.
• Rickets and Osteomalacia: For nutritional or renal causes leading to defective bone mineralization.
• Chronic Kidney Disease (CKD): To manage secondary hyperparathyroidism in CKD patients.
• Osteoporosis (Adjunctive Therapy): Used alongside calcium supplements to reduce the risk of fractures, especially in postmenopausal women and elderly patients.

Off-Label/Clinically Accepted Uses:

• Immune Support: Adjunctive use in autoimmune diseases like multiple sclerosis and rheumatoid arthritis, though evidence is evolving.
• Psoriasis and Atopic Dermatitis (Topical Form): Used in calcitriol form for plaque-type psoriasis.
• Prevention of Falls in Elderly: May reduce fall risk due to improved musculoskeletal function.
• Polycystic Ovary Syndrome (PCOS): Used adjunctively in vitamin D-deficient patients for improving metabolic parameters.
• Diabetes Mellitus: Investigated for glycemic control support in deficient individuals.

Adults:

• Prevention of Deficiency: 400–1,000 IU once daily orally.
• Mild to Moderate Deficiency: 1,000–2,000 IU daily for 8–12 weeks, then maintenance dose.
• Severe Deficiency: 50,000 IU weekly for 6–8 weeks or 6,000 IU/day, then 1,500–2,000 IU/day as maintenance.
• CKD-Associated Hypocalcemia: Dosing individualized; typically 0.25–1 mcg/day of active form (calcitriol).

Pediatrics:

• Prevention (0–12 months): 400 IU daily.
• Children (>1 year): 600–1,000 IU/day; up to 2,000 IU/day if deficient.

Elderly:

• 800–2,000 IU/day depending on serum 25(OH)D levels and fall risk.

Special Populations:

• Renal Impairment: Use calcitriol or alfacalcidol as cholecalciferol activation may be impaired.
• Hepatic Impairment: No adjustment generally needed; monitor levels if cholestasis is present.

Administration:

• Oral route preferred. Best absorbed with meals containing fat.
• IM form available for patients with malabsorption or compliance issues.
• Avoid exceeding 4,000 IU/day unless medically justified.

Cholecalciferol (Vitamin D3) is biologically inactive and undergoes hepatic hydroxylation to form 25-hydroxyvitamin D, then renal hydroxylation to the active metabolite 1,25-dihydroxyvitamin D (calcitriol). Calcitriol binds to vitamin D receptors (VDR) in target tissues (intestine, bone, kidney), modulating gene transcription. It increases intestinal absorption of calcium and phosphate, promotes bone mineralization, suppresses parathyroid hormone secretion, and regulates immune and inflammatory responses. These combined actions help maintain calcium-phosphate homeostasis and skeletal integrity.

• Absorption: Oral bioavailability 50–80%, enhanced by dietary fat.
• Distribution: Widely distributed; stored in adipose and muscle tissues; 85–90% protein-bound.
• Metabolism: Hepatically converted to 25-hydroxyvitamin D (calcidiol), then in kidneys to 1,25-dihydroxyvitamin D (calcitriol); CYP27A1 and CYP27B1 are key enzymes.
• Elimination: Mainly via bile and feces; minimal renal excretion.
• Half-life: 25(OH)D ~15 days to 3 weeks; longer in obese patients.
• Onset: Gradual; clinical response typically in weeks.

• Pregnancy: Generally considered safe in recommended doses. High doses may lead to fetal hypercalcemia or developmental toxicity. No formal FDA pregnancy category assigned under the revised labeling.
• Lactation: Cholecalciferol is excreted into breast milk in small amounts. Supplementation of lactating mothers can improve infant vitamin D status, but direct supplementation for the infant is still recommended. No adverse effects noted in breastfed infants when maternal intake is appropriate.
• Caution: Avoid high doses. Monitor maternal and neonatal calcium levels in long-term use.

• Primary Class: Vitamin D Analog / Nutritional Supplement.
• Subclass: Fat-soluble secosteroid; Prohormone of active vitamin D (calcitriol).

• Known hypersensitivity to cholecalciferol or any formulation component
• Hypercalcemia or hypervitaminosis D
• Malabsorption syndromes (unless administered parenterally)
• Severe renal impairment with hyperphosphatemia (relative)
• Williams syndrome or other conditions predisposing to hypercalcemia

• Hypercalcemia risk: Monitor serum calcium, phosphate, and 25(OH)D during prolonged or high-dose therapy.
• Renal impairment: Use active forms if conversion is impaired; monitor for hyperphosphatemia and soft tissue calcification.
• Obese patients and malabsorption: May require higher doses; monitor serum levels.
• Granulomatous diseases (e.g., sarcoidosis): Enhanced vitamin D activation can lead to hypercalcemia.
• Long-term high-dose use: Risk of vascular and soft tissue calcification.

Common:

• Gastrointestinal: Nausea, constipation, abdominal pain
• Musculoskeletal: Bone or muscle pain (paradoxical)
• CNS: Fatigue, headache

Serious:

• Hypercalcemia: Polyuria, polydipsia, weakness, confusion, arrhythmias
• Hypercalciuria
• Renal stones
• Pancreatitis (rare)

Rare:

• Anaphylaxis (extremely rare)
• Hypersensitivity reactions (rash, itching)

Onset of adverse effects is typically delayed and correlates with cumulative dosing and serum 25(OH)D levels.

• CYP450 System: Limited direct metabolism via CYP enzymes, but may alter CYP3A4 activity at high levels.
• Drugs Increasing Toxicity: Thiazide diuretics (↑ hypercalcemia risk), digoxin (↑ arrhythmogenic potential with hypercalcemia)
• Drugs Reducing Efficacy: Rifampin, phenytoin, and carbamazepine (↑ vitamin D metabolism)
• Chelating Agents: Orlistat, cholestyramine reduce absorption
• Magnesium-containing antacids: ↑ risk of hypermagnesemia in renal impairment

Alcohol and high-fat meals may enhance absorption, though caution is needed in liver disease.

• Endocrine Society (2023): Reiterated that a serum 25(OH)D level ≥30 ng/mL is sufficient for most individuals; supplementation tailored based on risk.
• KDIGO Guidelines (2024): Recommend active vitamin D analogs (e.g., calcitriol) in advanced CKD stages only when PTH is persistently elevated.
• EMA and FDA (2023–2024): Emphasize caution with high-dose bolus vitamin D regimens due to potential fall/fracture risk in elderly.

• Temperature: Store at 20°C to 25°C; excursions permitted to 15°C–30°C.
• Light: Protect from direct sunlight.
• Humidity: Store in a dry place; keep tightly closed.
• Handling: Shake oral suspensions well before use.
• Parenteral Form: Protect ampoules from light; do not freeze.
• Stability: Observe expiry; discard any discolored or precipitated solution.