Intramuscular Vitamin D3 Dosing for Deficiency
For adults with documented vitamin D deficiency requiring intramuscular administration, a single injection of 300,000 IU cholecalciferol is effective and provides sustained elevation of serum 25(OH)D levels for at least 6 months, though oral high-dose regimens (50,000 IU weekly for 8–12 weeks) remain the preferred first-line approach unless malabsorption is documented. 1, 2
When to Use Intramuscular Vitamin D3
Intramuscular cholecalciferol is specifically indicated for patients with documented malabsorption syndromes who fail oral supplementation, including:
- Post-bariatric surgery patients (especially Roux-en-Y gastric bypass or biliopancreatic diversion) 1
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis) 1
- Short-bowel syndrome 1
- Pancreatic insufficiency 1
- Untreated celiac disease 1
- Patients requiring total parenteral nutrition 1
IM administration results in significantly higher 25(OH)D levels and lower rates of persistent deficiency compared to oral supplementation in these populations. 1
Adult IM Dosing Regimens
Single-Dose Protocol (Preferred for Malabsorption)
- Administer 300,000 IU cholecalciferol as a single intramuscular injection 1, 2
- This dose increases serum 25(OH)D by approximately 58–90 nmol/L (23–36 ng/mL) at 3 months 2
- Effects persist for at least 6 months, with sustained elevation of 25(OH)D levels 2
Alternative High-Dose IM Protocol
- 600,000 IU cholecalciferol as a single IM injection provides long-lasting increases in 25(OH)D, peaking at 4 weeks (mean 100–126 nmol/L or 40–50 ng/mL) and remaining elevated at 24 weeks 3
- This dose generally keeps levels below the 125 nmol/L (50 ng/mL) upper safety threshold 3
- Serum ionized calcium may transiently increase but remains within normal range 3
Monthly IM Maintenance (After Loading)
- 50,000 IU cholecalciferol IM monthly (equivalent to approximately 1,600 IU daily) can sustain adequate levels after initial repletion 1
Oral vs. Intramuscular: Evidence-Based Comparison
When both routes are feasible, oral cholecalciferol (50,000 IU weekly for 8–12 weeks) is preferred over IM injection because:
- Oral administration produces higher 25(OH)D levels at 3 months (90 nmol/L increase vs. 59 nmol/L with IM) 2
- By 6 months, both routes achieve similar efficacy (52 vs. 62 nmol/L increase) 2
- Oral dosing allows flexible scheduling (daily, weekly, or monthly equivalent doses) 1, 4
- IM preparations are not universally available and may be contraindicated in patients on anticoagulation or at infection risk 1
However, IM is superior when malabsorption is documented, as oral supplementation fails to achieve target levels in these patients despite high doses. 1
Pediatric IM Dosing (Limited Evidence)
IM vitamin D3 is rarely used in children; oral high-dose regimens are preferred. 5
- For children with severe deficiency and documented malabsorption, consider IM cholecalciferol 50,000 IU as a single dose, though pediatric-specific IM protocols are not well-established 5
- Smaller doses are required for infants <12 months (upper limit 1,000 IU/day for oral maintenance; IM dosing not recommended) 4, 5
- After any IM loading, transition to oral maintenance: 400 IU/day for infants, 600 IU/day for children 1–18 years 4, 5
Monitoring Protocol After IM Administration
- Recheck serum 25(OH)D at 3 months after IM injection to confirm adequate response 1, 2
- Target level: ≥30 ng/mL (75 nmol/L) for anti-fracture efficacy 1, 4
- Monitor serum calcium at 1,3, and 4 weeks after high-dose IM (≥300,000 IU) to detect transient hypercalcemia 3
- If using 600,000 IU IM, calcium may rise transiently but typically remains within normal range 3
- Once stable, recheck 25(OH)D annually 1
Contraindications and Safety
Absolute Contraindications to IM Vitamin D
- Active anticoagulation therapy (increased bleeding risk at injection site) 1
- Local or systemic infection risk 1
- Hypercalcemia (serum calcium >10.2 mg/dL or 2.54 mmol/L) 1
Safety Thresholds
- Upper safety limit for serum 25(OH)D: 100 ng/mL (250 nmol/L) 1
- Avoid single doses >300,000 IU unless using the 600,000 IU protocol with close calcium monitoring 1, 3
- Do NOT use active vitamin D analogs (calcitriol, alfacalcidol, doxercalciferol, paricalcitol) for nutritional deficiency—they bypass normal regulation and increase hypercalcemia risk 1, 4
Practical Algorithm for IM vs. Oral Decision
Step 1: Assess for Malabsorption
- If malabsorption documented (post-bariatric surgery, IBD, short bowel, pancreatic insufficiency, celiac disease): Use IM cholecalciferol 300,000 IU as single dose 1
- If no malabsorption: Use oral cholecalciferol 50,000 IU weekly × 8–12 weeks 1, 4
Step 2: Check for IM Contraindications
- If anticoagulation, infection risk, or IM unavailable: Use high-dose oral (4,000–5,000 IU daily × 2 months) or oral calcifediol (25(OH)D) if available 1
Step 3: Monitor Response
- Recheck 25(OH)D at 3 months 1, 2
- If <30 ng/mL despite IM: Increase to 50,000 IU IM monthly or switch to daily oral 4,000 IU 1
Step 4: Transition to Maintenance
Essential Co-Interventions
- Ensure calcium intake 1,000–1,500 mg daily (diet + supplements) 1, 4
- Divide calcium supplements into ≤600 mg doses for optimal absorption 1
- For children, provide 250–500 mg/day elemental calcium during treatment 5
Common Pitfalls to Avoid
- Do not use IM vitamin D as first-line unless malabsorption is documented—oral is equally effective and safer in most patients 1, 2
- Do not give single doses >600,000 IU—risk of transient hypercalcemia without added benefit 1, 3
- Do not use IM in patients on anticoagulation without assessing bleeding risk 1
- Do not substitute active vitamin D analogs (calcitriol, etc.) for nutritional deficiency—they do not correct 25(OH)D and increase hypercalcemia risk 1, 4
- Do not skip calcium monitoring after high-dose IM (≥300,000 IU)—transient hypercalcemia can occur 3
Special Populations
Chronic Kidney Disease (CKD Stages 3–4)
- Use standard nutritional vitamin D (cholecalciferol or ergocalciferol), not active analogs 1, 4
- IM dosing is the same as general population (300,000 IU single dose if malabsorption) 1
- Monitor calcium and phosphorus every 3 months during treatment 1