1. Clinical Overview
Vitamin D3 (Cholecalciferol) 600,000 IU is a high-dose, single-administration oral or intramuscular formulation used for the rapid correction of severe vitamin D deficiency. It is a fat-soluble vitamin that functions as a prohormone, essential for calcium and phosphate homeostasis, bone mineralization, and various non-skeletal functions including immune modulation and neuromuscular function.
| Onset | Duration | Bioavailability |
|---|---|---|
| Serum 25-hydroxyvitamin D (25(OH)D) levels begin to rise within 24-48 hours of administration. Peak serum concentrations of 25(OH)D are typically achieved 7-14 days post-dose. | The therapeutic effect on serum 25(OH)D levels can last for 8 to 12 weeks, depending on baseline status, body fat, and subsequent maintenance therapy. | Approximately 55-70% after oral administration with a fatty meal. Intramuscular bioavailability is considered 100% but is subject to depot release kinetics. |
2. Mechanism of Action
Vitamin D3 is a prohormone. After metabolic activation to calcitriol, it binds to the Vitamin D Receptor (VDR), a nuclear receptor. The VDR-ligand complex heterodimerizes with the Retinoid X Receptor (RXR) and binds to Vitamin D Response Elements (VDREs) in the promoter regions of target genes, regulating their transcription. This genomic action leads to increased intestinal absorption of calcium and phosphate, mobilization of calcium from bone, and renal reabsorption of calcium.
3. Indications & Uses
- Severe Vitamin D Deficiency (Serum 25(OH)D < 10 ng/mL or < 25 nmol/L)
- Vitamin D Deficiency with symptomatic osteomalacia (bone pain, proximal muscle weakness)
- Rapid correction prior to initiating potent antiresorptive therapy (e.g., Zoledronic acid) for osteoporosis
4. Dosage & Administration
Adult Dosage: A single oral or intramuscular dose of 600,000 IU for rapid repletion. Often administered as 60,000 IU per day for 10 days, or 60,000 IU per week for 10 weeks, but the 6Lac single dose is a common stoss regimen. MUST be followed by maintenance therapy (e.g., 60,000 IU monthly or 1500-2000 IU daily).
Administration: Oral: Administer after a main meal containing fats (e.g., lunch/dinner) to enhance absorption. The softgel/liquid can be swallowed whole. Intramuscular: Administered as a deep IM injection in the gluteal or deltoid muscle by a healthcare professional.
5. Side Effects
Common side effects may include:
- Nausea
- Constipation
- Dry mouth
- Metallic taste
- Headache
6. Drug Interactions
| Drug | Effect | Severity |
|---|---|---|
| Thiazide Diuretics (e.g., Hydrochlorothiazide) | Increased risk of hypercalcemia due to reduced renal calcium excretion. | Major |
| Cardiac Glycosides (Digoxin) | Hypercalcemia potentiates digitalis toxicity, increasing risk of cardiac arrhythmias. | Major |
| Anticonvulsants (Phenytoin, Phenobarbital, Carbamazepine) | Induce hepatic CYP450 enzymes, increasing metabolism of vitamin D to inactive compounds, reducing efficacy. | Moderate |
| Systemic Corticosteroids (e.g., Prednisolone) | Antagonize vitamin D action, reduce calcium absorption, may increase requirement. | Moderate |
| Orlistat, Bile Acid Sequestrants (Cholestyramine) | Reduce absorption of fat-soluble vitamin D. Administer at least 4 hours apart. | Moderate |
| CYP3A4 Inducers (Rifampicin, St. John's Wort) | May increase vitamin D metabolism, reducing levels. | Moderate |
7. Patient Counselling
- DO take the oral dose immediately after your largest meal of the day (lunch or dinner).
- DO follow up with your doctor for maintenance therapy (daily/weekly/monthly doses).
- DO get your blood test (25-hydroxyvitamin D, calcium) repeated as advised (usually 8-12 weeks after loading dose).
- DONT take additional over-the-counter vitamin D supplements without consulting your doctor.
- DONT take the loading dose more frequently than prescribed.
8. Toxicology & Storage
Overdose: Manifests as hypervitaminosis D, leading to hypercalcemia. Symptoms: anorexia, nausea, vomiting, constipation, weakness, fatigue, headache, metallic taste, polyuria, polydipsia, confusion, cardiac arrhythmias, renal impairment, nephrocalcinosis.
Storage: Store below 30°C. Protect from light and moisture. Keep the oral softgel/liquid in the original blister/container. Keep out of reach of children. Do not freeze.