How should Vigantol (cholecalciferol) be dosed to correct vitamin D deficiency in a patient on lifelong hydrocortisone 20 mg daily therapy?

Vitamin D Supplementation in Patients on Chronic Glucocorticoid Therapy

For a patient on lifelong hydrocortisone 20 mg daily with vitamin D deficiency, start with cholecalciferol (Vigantol) 50,000 IU once weekly for 12 weeks, then transition to a maintenance dose of 2,000 IU daily, ensuring concurrent calcium intake of 1,000–1,200 mg daily. 1, 2

Understanding the Glucocorticoid-Vitamin D Interaction

Chronic glucocorticoid therapy creates a dose-dependent impairment of intestinal calcium absorption and accelerates vitamin D metabolism, leading to increased vitamin D requirements. 3 Hydrocortisone 20 mg daily (equivalent to approximately 5 mg prednisone) falls into the range where vitamin D metabolism is affected, though less severely than with higher doses. 3 The American College of Rheumatology guidelines specifically address this population, recommending that patients on chronic glucocorticoids receive adequate vitamin D and calcium supplementation as foundational therapy for glucocorticoid-induced osteoporosis prevention. 1

The key mechanism: Glucocorticoids reduce serum 25-hydroxyvitamin D levels and impair calcium absorption through effects on vitamin D metabolism, not through direct intestinal blockade. 3 This means standard nutritional vitamin D (cholecalciferol) is appropriate—you should never use active vitamin D analogs like calcitriol for nutritional deficiency in this setting. 2

Loading Phase Protocol

Initial 12-Week Repletion

• Dose: Cholecalciferol 50,000 IU once weekly for 12 weeks 2
• Rationale: This cumulative dose of 600,000 IU over 12 weeks reliably raises 25(OH)D levels from deficiency (<20 ng/mL) to target (≥30 ng/mL) 2
• Timing: Take with the largest, fattiest meal of the day to maximize absorption 4

Why 12 Weeks Instead of 8 Weeks?

For patients on chronic glucocorticoids, the 12-week protocol is preferred over the standard 8-week regimen because glucocorticoids accelerate vitamin D metabolism, requiring a longer loading period to achieve stable target levels. 3 The dose-response relationship shows that lower baseline 25(OH)D levels respond better to supplementation, but glucocorticoid use may blunt this response. 5

Maintenance Phase (After Week 12)

Standard Maintenance Dosing

• Dose: 2,000 IU cholecalciferol daily 2, 6
• Target serum 25(OH)D: ≥30 ng/mL for anti-fracture efficacy 2
• Duration: Lifelong, as long as glucocorticoid therapy continues 1

Why 2,000 IU Instead of 800 IU?

Patients on chronic glucocorticoids require higher maintenance doses than the general population (600–800 IU) because: 6

1. Glucocorticoids accelerate vitamin D catabolism 3
2. They impair intestinal calcium absorption even with adequate vitamin D 3
3. The 2,000 IU dose is well within the safe upper limit (4,000 IU daily) and is specifically recommended for at-risk populations 2, 6

Alternative maintenance regimen: 50,000 IU once monthly (equivalent to approximately 1,600 IU daily) is acceptable if weekly dosing improves compliance. 2

Essential Calcium Co-Supplementation

Calcium intake of 1,000–1,200 mg daily from diet plus supplements is mandatory. 1, 2 Vitamin D cannot protect bone health without adequate calcium substrate. 2

Practical calcium dosing:

• Divide calcium supplements into doses ≤600 mg for optimal absorption 2
• Take calcium supplements separately from the weekly vitamin D dose by at least 2 hours 2
• Separate calcium from iron-containing supplements by 2 hours 2

Monitoring Protocol

Initial Monitoring (First Year)

1. Baseline: Measure serum 25(OH)D, calcium, and phosphorus before starting 2
2. At 3 months (after loading phase): Recheck 25(OH)D to confirm achievement of ≥30 ng/mL 2
3. Every 3 months during first year: Monitor serum calcium to detect hypercalcemia 2

Long-Term Monitoring

• 25(OH)D: Annually once stable 2
• Serum calcium: Every 3 months if on maintenance therapy 2
• Hold all vitamin D immediately if serum calcium exceeds 10.2 mg/dL (2.54 mmol/L) 2

Critical Pitfalls to Avoid

Do NOT Use Active Vitamin D Analogs

Never prescribe calcitriol, alfacalcidol, doxercalciferol, or paricalcitol for nutritional vitamin D deficiency in glucocorticoid-treated patients. 2 These bypass normal regulatory mechanisms and dramatically increase hypercalcemia risk. 2 They are reserved only for advanced chronic kidney disease with impaired 1α-hydroxylase activity. 2

Do NOT Use Single Mega-Doses

Avoid single doses ≥300,000 IU, as they are inefficient and may paradoxically increase fall and fracture risk. 2, 6 The weekly 50,000 IU regimen is safe because it spreads the dose over time. 2

Do NOT Rely on Lower Maintenance Doses

The standard 600–800 IU daily recommended for the general population is insufficient for patients on chronic glucocorticoids. 6 These patients require 2,000–4,000 IU daily for maintenance. 6

Do NOT Forget Calcium

Vitamin D supplementation without adequate calcium intake will not prevent glucocorticoid-induced bone loss. 1, 2 The two must be given together. 2

Special Considerations for Hydrocortisone 20 mg Daily

At this dose (equivalent to ~5 mg prednisone), the patient is at moderate risk for glucocorticoid-induced osteoporosis. 1 While lower than the high-dose regimens studied (≥15 mg prednisone), lifelong exposure still warrants aggressive vitamin D and calcium supplementation. 1

If Malabsorption is Present

If the patient has concurrent malabsorption (inflammatory bowel disease, celiac disease, post-bariatric surgery), consider: 2

• Escalating oral dose to 50,000 IU 2–3 times weekly 2
• Or intramuscular cholecalciferol 50,000 IU if oral therapy fails 2

If Chronic Kidney Disease is Present

For patients with eGFR 20–60 mL/min/1.73m², use the same cholecalciferol regimen—do not switch to active vitamin D analogs unless PTH >300 pg/mL despite vitamin D repletion. 2

Expected Outcomes

• Serum 25(OH)D increase: Approximately 10 ng/mL per 1,000 IU daily intake 2, 6
• Fracture risk reduction: Achieving ≥30 ng/mL reduces non-vertebral fractures by 20% and hip fractures by 18% 2
• Fall risk reduction: Levels ≥24 ng/mL reduce falls by 19% in elderly patients 2

Safety Parameters

• Daily doses up to 4,000 IU are completely safe for long-term use 2, 6
• Upper safety limit for serum 25(OH)D: 100 ng/mL 2, 6
• Toxicity threshold: Typically requires daily intake >10,000 IU or serum levels >100 ng/mL 2, 6
• Hypercalcemia risk: Monitor calcium every 3 months; discontinue vitamin D if calcium >10.2 mg/dL 2