Injectable Vitamin D3 (Cholecalciferol Injection)

What It Is

Injectable Vitamin D3 is cholecalciferol (the native form of vitamin D) formulated as a sterile oil-based solution for intramuscular (IM) administration. It bypasses the gastrointestinal tract entirely and forms a depot in muscle tissue, from which it is slowly released into circulation.

Goodman & Gilman confirms: "Cholecalciferol (vitamin D3) and calcitriol are available for oral administration or injection."
Common formulations: 100,000 IU/mL or 300,000 IU/mL ampoules (1 mL), prepared in oil vehicles (e.g., grapeseed oil or arachis oil).

Indications

Indication	Notes
Severe vitamin D deficiency	When rapid repletion is needed
Malabsorption syndromes	Celiac disease, Crohn's, short bowel syndrome - oral absorption is unreliable
Non-adherence to oral therapy	Depot injection ensures compliance
Post-bariatric surgery	Reduced GI absorption
Secondary hyperparathyroidism (CKD/dialysis)	Injectable activated vitamin D associated with improved hemodialysis survival
Rickets / osteomalacia	When oral therapy has failed or is impractical
Hypoparathyroidism	As part of calcium-vitamin D replacement

Dosing ("Stoss Therapy")

The single high-dose IM injection approach is called Stoss therapy:

Scenario	Dose
Standard deficiency correction	200,000 - 300,000 IU IM as a single dose
Repeat dosing (maintenance)	300,000 IU every 3 months, based on serum 25(OH)D levels
Severe deficiency (alternate)	100,000 IU IM (depot lasts 2-3 months)
Psychiatric research protocols	150,000-300,000 IU single dose IM (used in depression studies)

A Korean study (200,000 IU IM with 3-month follow-up intervals) demonstrated significant and sustained increases in serum 25(OH)D for 12 months with no serious adverse events.

Pharmacokinetics

Route: Deep intramuscular (gluteal muscle)
Onset: Serum 25(OH)D rises within days; peak levels achieved faster than oral dosing
Duration: A single depot injection can maintain adequate circulating vitamin D for 2-3 months
Activation: Requires two hydroxylation steps - first in the liver (→ 25-hydroxyvitamin D3) then in the kidney (→ 1,25-dihydroxyvitamin D3 = calcitriol, the active form)
Advantage: More predictable bioavailability than oral dosing in malabsorption states

Monitoring

After injection, monitor:

Serum 25(OH)D (target: 30-50 ng/mL)
Serum calcium (risk of hypercalcemia)
Serum phosphate
PTH (especially in CKD/hyperparathyroidism)
Urinary calcium (if repeated high doses)

Adverse Effects / Toxicity

Primary concern is hypervitaminosis D, which causes:

Hypercalcemia - nausea, vomiting, weakness, polyuria, polydipsia
Nephrocalcinosis / renal dysfunction
Vascular calcification (with chronic excess)
Cardiac arrhythmias (severe cases)

From Goodman & Gilman: "Hypervitaminosis D is treated by immediate withdrawal of the vitamin, a low-calcium diet, administration of glucocorticoids, and vigorous fluid support; forced saline diuresis with loop diuretics is also useful."

Contraindications

Hypercalcemia (any cause)
Hypervitaminosis D
Idiopathic infantile hypercalcemia
Sarcoidosis or other granulomatous disease (endogenous overactivation of vitamin D)
Hypersensitivity to cholecalciferol or the oil vehicle

Special Populations

CKD/Dialysis: Activated injectable vitamin D (calcitriol/paricalcitol) is associated with improved survival in hemodialysis patients. Plain cholecalciferol injection is used cautiously due to impaired renal activation.
Pregnancy: Preferred daily or weekly oral regimens; single high-dose IM injections (300,000 IU) reserved for severe malabsorption emergencies only.
Pediatrics: Dosing is weight-adjusted; high-dose Stoss therapy is used for severe rickets in some protocols.

Key Distinction: Cholecalciferol vs. Calcitriol Injection

Property	Cholecalciferol (D3) injection	Calcitriol injection
Form	Native vitamin D (prodrug)	Active form (1,25-dihydroxy D3)
Requires activation	Yes (liver + kidney)	No
Use in CKD	Cautious - requires intact kidneys	Preferred in CKD (bypasses renal step)
Duration	Depot effect, weeks-months	Short acting
Toxicity risk	Lower with single dose	Higher (immediate effect on calcium)

Sources:

Goodman & Gilman's Pharmacological Basis of Therapeutics, Available Vitamin D Analogues section
Park's Textbook of Preventive and Social Medicine, Section 30: Vitamins and Minerals
Frontiers in Nutrition 2025 - Cholecalciferol efficacy, safety, and dosing
Brenner & Rector's The Kidney (injectable vitamin D and hemodialysis survival)

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