Ergocalciferol, also known as vitamin D2, was discovered in the early 20th century and is used primarily to treat and prevent vitamin D deficiency and associated disorders such as rickets and osteomalacia. Its clinical development focused on its ability to increase calcium and phosphate absorption in the gut, thereby supporting bonemineralization. Ergocalciferol is available as oral capsules, tablets, or liquid formulations, and is often included in combination vitamin D therapies. Unlike drugs requiring genetic screening, ergocalciferol’s safety profile is generally well-established, with monitoring primarily aimed at serum calcium and vitamin D levels to avoid toxicity with excessive supplementation.
BRAND NAMES
Drisdol – one of the most widely recognized brands, used for vitamin D deficiency and rickets.
Calciferol – available in some regions as oral capsules or tablets.
Ergocal – generic or regional brand formulations.
MECHANISM OF ACTION
Ergocalciferol (vitamin D2) is converted in the liver to 25-hydroxyergocalciferol (calcifediol) and then in the kidneys to the active form 1,25-dihydroxyergocalciferol (calcitriol). The active form binds to vitamin D receptors (VDRs) in target tissues, regulating the expression of genes involved in calcium and phosphate absorption in the intestine, bone mineralization, and renal calcium reabsorption.
PHARMACOKINETICS
Absorption
Ergocalciferol (vitamin D2) is well absorbed from the gastrointestinal tract when taken orally, particularly when ingested with dietaryfats, as it is a fat-soluble vitamin. Peak plasma levels are typically reached within 12–24 hours after administration.
Distribution
Ergocalciferol (vitamin D2) has a very large volume of distribution (approximately 0.5–1 L/kg or higher), reflecting its extensive uptake into adipose tissue, liver, and muscle.
Metabolism
Ergocalciferol (vitamin D2) is metabolized through a two-step hydroxylation process. First, in the liver, it is converted to 25-hydroxyergocalciferol (calcifediol), the main circulating form. Then, in the kidneys, it undergoes further hydroxylation to form 1,25-dihydroxyergocalciferol (calcitriol), the biologically active form.
Elimination
Ergocalciferol (vitamin D2) and its metabolites are primarily eliminated via the bile into the feces, with only a small amount excreted in the urine. Due to its fat-soluble nature and storage in adipose tissue, elimination is slow, resulting in a prolonged half-life of several days to weeks.
PHARMACODYNAMICS
Ergocalciferol (vitamin D2) exerts its effects after conversion to its active form, 1,25-dihydroxyergocalciferol (calcitriol), which binds to vitamin D receptors (VDRs) in target tissues such as the intestine, bone, and kidneys.
ADMINISTRATION
Ergocalciferol (vitamin D2) is administered primarily orally in the form of capsules, tablets, or liquid preparations for the treatment and prevention of vitamin D deficiency. It is often taken with meals containing fat to enhance absorption due to its fat-soluble nature.
DOSAGE AND STRENGTH
Ergocalciferol (vitamin D2) is available in a variety of oral formulations, most commonly as capsules or tablets containing 400 IU, 800 IU, 1,000 IU, and high-dose 50,000 IU strengths.
DRUG INTERACTIONS
Ergocalciferol (vitamin D2) can interact with several medications that affect its absorption, metabolism, or calcium balance. Drugs such as bile acid sequestrants (e.g., cholestyramine) and orlistat can reduce absorption of ergocalciferol by interfering with fat absorption.
FOOD INTERACTIONS
Ergocalciferol (vitamin D2) is a fat-soluble vitamin, so its absorption is enhanced when taken with meals containing fat. Taking it on an empty stomach or with very low-fat meals may reduce bioavailability.
CONTRAINDICATIONS
Ergocalciferol (vitamin D2) is contraindicated in patients with hypercalcemia, as additional vitamin D can exacerbate elevated serum calcium levels, and in those with a history of vitamin D toxicity.
SIDE EFFECTS
Hypercalcemia – nausea, vomiting, weakness, and confusion
Hypercalciuria – increased urinary calcium excretion
Constipation – mild and occasional
Headache – uncommon
Fatigue – may occur with high doses
Dry mouth or metallic taste – rare
TOXICITY
Ergocalciferol (vitamin D2) toxicity, also known as hypervitaminosis D, typically results from excessive supplementation over an extended period. The primary manifestation is hypercalcemia, which can cause nausea, vomiting, weakness, confusion, polyuria, and dehydration. Chronic toxicity may lead to renal damage, nephrolithiasis, and vascular or soft tissue calcification due to calcium-phosphate deposition.
