ERGOCALCIFEROL

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Ergocalciferol is a fat-soluble vitamin that increases intestinal absorption of calcium and phosphate. It binds to vitamin D receptors (VDR), which regulate gene expression of proteins involved in calcium homeostasis, including calbindin-D9k, calcium channels, and the calcium pump. It also promotes renal tubular reabsorption of calcium and phosphate and mobilizes calcium from bone.

What the body does with it

Metabolism	Ergocalciferol is hydroxylated in the liver to 25-hydroxyergocalciferol, then in the kidney to the active form 1,25-dihydroxyergocalciferol. Metabolized via cytochrome P450 enzymes (CYP27A1, CYP2R1, CYP24A1). Inactive metabolites are excreted in bile and feces.
Excretion	Primarily excreted in bile and feces as metabolites; less than 5% excreted unchanged in urine. Renal excretion of metabolites accounts for approximately 2-4% of the dose.
Half-life	Terminal half-life is approximately 19 to 48 hours in healthy adults following oral administration. Due to extensive tissue storage, the functional half-life may be prolonged to weeks to months in cases of toxicity.
Protein binding	Approximately 50-80% bound to vitamin D-binding protein (DBP, also known as GC-globulin), with minor binding to albumin. Binding is saturable.
Volume of Distribution	Apparent volume of distribution is approximately 0.3-0.6 L/kg. High Vd indicates extensive distribution into tissues, particularly fat and muscle.
Bioavailability	Well absorbed from the gastrointestinal tract; absolute oral bioavailability is estimated at 60-90% when taken with fatty meals. Bioavailability decreases with cholestasis or malabsorption syndromes.
Onset of Action	Oral: Onset of action for increasing serum calcium levels occurs within 12 to 24 hours, with maximal effect on intestinal calcium absorption seen after 4 to 10 days. Intramuscular: Not applicable; ergocalciferol is not administered via this route.
Duration of Action	Duration of effect on calcium homeostasis lasts 2 to 3 months after cessation of dosing, due to accumulation in adipose tissue and slow release.

Classification & Brands

Dosing & administration

400-800 IU orally once daily for vitamin D deficiency prevention; 50,000 IU orally once weekly for 8 weeks for deficiency treatment.

Dosage form	CAPSULE
Renal impairment	No dose adjustment required for GFR >15 mL/min; avoid in severe renal impairment (GFR <15 mL/min) due to risk of hypercalcemia.
Liver impairment	No dose adjustment required for Child-Pugh A or B; use with caution in Child-Pugh C as hepatic 25-hydroxylation may be impaired.
Pediatric use	400 IU orally once daily for prevention; 50,000 IU orally once weekly for 6-8 weeks for deficiency treatment (weight-based not typically adjusted), but dosing per clinical guidelines.
Geriatric use	Same as adult dosing; consider 800-1000 IU daily due to reduced cutaneous synthesis and higher fracture risk.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Cholestyramine and mineral oil may reduce absorption Excessive intake can lead to hypercalcemia.

Breastfeeding	Ergocalciferol and its metabolite 25-hydroxyergocalciferol are excreted in breast milk. M/P ratio not well defined. At maternal doses up to 4000 IU/day, infant vitamin D levels are supplemented; higher doses may cause hypercalcemia in the infant. Use with caution; monitor infant serum calcium.
Teratogenic Risk	Ergocalciferol (vitamin D2) is not teratogenic at recommended doses. Excessive maternal intake (≥4000 IU/day) may cause fetal hypercalcemia, aortic stenosis, and supravascular aortic stenosis in the first trimester. Second and third trimester overexposure can lead to neonatal hypercalcemia, nephrocalcinosis, and intellectual disability.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Hypercalcemia
Serious Effects

Absolute Contraindications

["Hypercalcemia or hypercalciuria","Hypersensitivity to ergocalciferol or any component of the formulation","Malabsorption syndrome (relative contraindication)","Evidence of vitamin D toxicity"]

Clinical Precautions

Precautions

["Monitor serum calcium and phosphate levels regularly to avoid hypercalcemia and hyperphosphatemia.","Use with caution in patients with impaired renal function, sarcoidosis, or other granulomatous diseases.","Risk of vitamin D toxicity with excessive doses.","May lead to soft tissue calcification if hypercalcemia occurs.","Use caution in patients with hypercalcemia or evidence of vitamin D toxicity.","Patients on digitalis glycosides are at increased risk of arrhythmias if hypercalcemia develops."]

Clinical Tips & Counseling

Drug interactions

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