Introduction
Ergocalciferol (vitamin D2) is a secosteroid hormone and a form of vitamin D used primarily for the prevention and treatment of vitamin D deficiency. It is one of two major forms of vitamin D used in clinical practice, alongside cholecalciferol (vitamin D3). Ergocalciferol is derived from plant sources and fungal ergosterol and is available by prescription in various formulations, including oral capsules, tablets, and liquid solutions.
Mechanism of Action
Ergocalciferol requires two hydroxylation steps to become biologically active. First, it undergoes 25-hydroxylation in the liver by the enzyme CYP2R1 to form 25-hydroxyvitamin D (calcifediol). Subsequently, it undergoes 1α-hydroxylation primarily in the kidneys by CYP27B1 to form the active metabolite 1,25-dihydroxyvitamin D (calcitriol). Calcitriol binds to vitamin D receptors in target tissues, regulating gene expression and promoting intestinal absorption of calcium and phosphate, bone mineralization, and regulation of parathyroid hormone secretion.
Indications
- Treatment and prevention of vitamin D deficiency
- Treatment of hypoparathyroidism
- Management of refractory rickets (vitamin D-resistant rickets)
- Familial hypophosphatemia
- Hypocalcemia in premature infants
- Nutritional supplementation in malabsorption syndromes
Dosage and Administration
General dosing for deficiency:- Adults: 50,000 IU weekly for 8 weeks, then maintenance dose of 1,500-2,000 IU daily
- Children: 2,000 IU daily for 6 weeks
- Adults: 25,000-200,000 IU daily with calcium supplements
- Children: Dosage based on serum calcium levels
- Oral administration with meals containing fat for optimal absorption
- Available forms: capsules, tablets, oral solution
- Dosing adjustments required for renal impairment and malabsorption conditions
- Renal impairment: Requires careful monitoring; may need calcitriol instead
- Hepatic impairment: Monitor levels closely
- Elderly: May require higher doses due to reduced skin synthesis and absorption
Pharmacokinetics
Absorption: Absorbed in the small intestine via passive diffusion, enhanced by dietary fat Distribution: Bound to vitamin D-binding protein in circulation Metabolism: Hepatic hydroxylation to 25-hydroxyvitamin D, then renal hydroxylation to active form Elimination: Primarily biliary excretion; half-life of 25-hydroxyvitamin D is approximately 15 days Onset of action: Biochemical effects begin within hours; full therapeutic effects may take weeksContraindications
- Hypervitaminosis D
- Hypercalcemia
- Hypersensitivity to ergocalciferol or any component of the formulation
- Malabsorption syndromes without appropriate monitoring (relative contraindication)
Warnings and Precautions
- Risk of hypercalcemia and hypercalciuria
- Use with caution in patients with renal impairment, sarcoidosis, or other granulomatous diseases
- Monitor for signs of vitamin D toxicity (nausea, vomiting, constipation)
- May exacerbate arterial calcification and cardiovascular risk in susceptible patients
- Use caution in patients with history of kidney stones
- Concurrent use with thiazide diuretics may increase hypercalcemia risk
Drug Interactions
- Cholestyramine, colestipol: Decreased absorption of ergocalciferol
- Thiazide diuretics: Increased risk of hypercalcemia
- Corticosteroids: May reduce calcium absorption and counteract vitamin D effects
- Phenytoin, phenobarbital: Increased metabolism of vitamin D
- Calcium supplements: Increased risk of hypercalcemia
- Digoxin: Hypercalcemia may potentiate digitalis toxicity
- Magnesium-containing antacids: Risk of hypermagnesemia in renal impairment
Adverse Effects
Common:- Hypercalcemia
- Hypercalciuria
- Constipation
- Nausea
- vomiting
- Vitamin D toxicity (usually at levels >150 ng/mL 25-hydroxyvitamin D)
- Renal impairment or failure
- Pancreatitis
- Cardiac arrhythmias
- Soft tissue calcification
- Nephrolithiasis
Monitoring Parameters
- Serum 25-hydroxyvitamin D levels (target 30-50 ng/mL for most indications)
- Serum calcium (regular monitoring during treatment)
- 24-hour urinary calcium excretion
- Renal function (BUN, creatinine)
- Phosphorus levels
- Parathyroid hormone levels in relevant conditions
- Bone mineral density in long-term therapy
Patient Education
- Take with meals containing fat for better absorption
- Do not exceed prescribed dosage
- Report symptoms of hypercalcemia (nausea, vomiting, constipation, weakness)
- Maintain adequate dietary calcium intake as recommended
- Avoid concurrent use of other vitamin D supplements unless directed
- Regular monitoring is essential for safe therapy
- Store medication properly away from heat and light
- Inform all healthcare providers about ergocalciferol use
References
1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-281. 2. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press; 2011. 3. Rosen CJ. Clinical practice. Vitamin D insufficiency. N Engl J Med. 2011;364(3):248-254. 4. Kennel KA, Drake MT, Hurley DL. Vitamin D deficiency in adults: when to test and how to treat. Mayo Clin Proc. 2010;85(8):752-758. 5. National Institutes of Health Office of Dietary Supplements. Vitamin D Fact Sheet for Health Professionals. Updated August 2021. 6. Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92(1):4-8. 7. Jones G. Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr. 2008;88(2):582S-586S. 8. FDA prescribing information for ergocalciferol preparations.