Ergocalciferol

Introduction Overview

Generic Name

ergocalciferol

Brand Name

Calcidol, Calciferol, Drisdol, Vitamin D2

Dosage Form

oral capsule (50,000 international units), oral solution (200 mcg/mL)

Drug Class

Vitamins

Pharmacokinetics

Absorption:
Ergocalciferol, also known as vitamin D2, is absorbed efficiently through the gastrointestinal tract following oral administration. The absorption primarily occurs in the small intestine through passive diffusion aided by bile salts that emulsify dietary fats. The presence of fats in a meal can enhance absorption due to its lipophilic nature. Despite its fat-soluble properties, the bioavailability of ergocalciferol is generally high when taken orally as capsules or liquid formulations. Certain conditions such as malabsorption syndromes, including celiac disease or inflammatory bowel diseases, can significantly impair its absorption, necessitating careful clinical monitoring and adjustment of dosing.

Distribution:
Once absorbed, ergocalciferol is incorporated into chylomicrons and transported via the lymphatic system into the bloodstream. It binds extensively to vitamin D-binding protein (DBP) in plasma, which serves as the primary transporter to various tissues, including the liver and kidneys, where it undergoes activation. The volume of distribution is relatively large due to its sequestration in adipose tissue given its lipophilic nature. This sequestration can serve as a reservoir but may also influence plasma concentrations, especially in obese individuals, possibly requiring dose adjustments. Ergocalciferol can cross the placenta and is present in breast milk, concerns which necessitate caution during pregnancy and lactation.

Metabolism:
Ergocalciferol undergoes sequential hydroxylation to exert its biological activity. The first step occurs in the liver where ergocalciferol is hydroxylated by the enzyme 25-hydroxylase (CYP2R1) to form 25-hydroxyergocalciferol (25(OH)D2), the major circulating form and marker of vitamin D status. This metabolite is then transported to the kidneys, where it is further hydroxylated by 1-alpha-hydroxylase (CYP27B1) to the active hormone 1,25-dihydroxyergocalciferol (1,25(OH)2D2). This active form binds to vitamin D receptors (VDR) affecting gene transcription. The metabolism can be influenced by parathyroid hormone levels, calcium, phosphate concentrations, and fibroblast growth factor 23 (FGF23), all critical in maintaining mineral homeostasis.

Elimination:
Ergocalciferol and its metabolites are primarily eliminated via biliary excretion into the feces, with minimal renal elimination of the unchanged drug. The metabolites undergo further hydroxylation and conjugation reactions before excretion. The half-life of 25(OH)D2 ranges from approximately 15 to 25 days, reflecting its storage in fat tissues and slow release. Clearance can be affected by renal function and hepatic metabolic capacity, which is pertinent in patients with renal or hepatic impairment. Excessive intake can lead to accumulation and toxicity, underscoring the importance of monitoring serum levels during therapy.

Dosage Forms

Available Dosage Forms:
Ergocalciferol is commercially available in two primary formulations: oral capsules and oral solutions. The oral capsules contain a high-dose formulation of 50,000 international units (IU), often used in therapeutic or deficiency correction settings. The oral solution is available at a concentration of 200 micrograms (mcg) per milliliter, suitable for precise dose adjustments and in patients requiring liquid formulations for ease of administration.

Dosages for Adults and Adolescents:
The dosing regimen of ergocalciferol varies depending on the indication and severity of deficiency or clinical condition. For vitamin D deficiency or rickets, doses typically range from 50,000 IU weekly for several weeks to achieve repletion, followed by maintenance dosing. In hypoparathyroidism or hypophosphatemia, individualized dosing is required based on serum calcium and phosphate levels with frequent monitoring to avoid toxicity. Adults with malabsorption may require higher or prolonged dosing. It is critical to titrate doses carefully due to the narrow therapeutic window and risk of hypercalcemia.

Specific Patient Populations:
Children should only receive ergocalciferol under strict medical supervision with doses adjusted according to age, weight, and clinical response, particularly in rickets or familial hypophosphatemia. In pregnant and breastfeeding women, dosing must consider both maternal and fetal/neonatal safety due to potential vitamin D toxicity effects. Patients with renal impairment may require dose adjustments because of altered metabolism of vitamin D. Additionally, those with malabsorption syndromes might need alternative dosing regimens or formulations to ensure therapeutic efficacy.

The precise measurement of liquid formulations is essential, often requiring specialized dosing syringes rather than household utensils to ensure accurate dosing and prevent overdose risks.

Mechanism Of Action

Ergocalciferol is a form of vitamin D2 that functions primarily as a prohormone involved in mineral metabolism and bone health. Upon oral administration, ergocalciferol undergoes hepatic and renal activation to its biologically active form, 1,25-dihydroxyvitamin D2 (calcitriol), which then exerts its effects at the cellular level. This active metabolite binds with high affinity to the vitamin D receptor (VDR), a nuclear receptor widely expressed in multiple tissues including the intestines, bone, kidney, and parathyroid glands.

Binding of 1,25-dihydroxyergocalciferol to VDR leads to heterodimerization with the retinoid X receptor (RXR). This complex then binds to vitamin D response elements (VDREs) in the promoter regions of vitamin D-regulated genes, modulating their transcription. The primary genomic effects facilitate increased intestinal absorption of calcium and phosphate by upregulating calcium-binding proteins and transporters in enterocytes. This elevation in serum calcium and phosphate levels supports proper mineralization of bone and maintenance of neuromuscular function.

Moreover, ergocalciferol influences bone remodeling by affecting osteoblast and osteoclast activity, promoting bone formation and resorption balance. It also inhibits parathyroid hormone secretion by providing negative feedback in response to increased serum calcium. Clinical studies reveal that ergocalciferol supplementation corrects hypocalcemia and improves bone mineral density in patients with hypoparathyroidism and rickets.

Comparatively, ergocalciferol shares similar mechanisms with cholecalciferol (vitamin D3) but differs slightly in metabolism and affinity to DBP, influencing its pharmacokinetic profile. Research suggests that while both forms ultimately become active, vitamin D3 has a longer half-life and higher potency in raising and maintaining serum 25-hydroxyvitamin D levels in some populations. Nonetheless, ergocalciferol remains widely utilized, especially in high-dose therapeutic regimens, due to availability and efficacy documented in clinical trials.

Pharmacological Actions

Acts as a prohormone of vitamin D facilitating calcium and phosphate homeostasis.
Enhances intestinal absorption of dietary calcium and phosphate by inducing expression of calcium-binding proteins.
Regulates bone remodeling by modulating osteoblast and osteoclast function.
Suppresses parathyroid hormone secretion through negative feedback mechanisms.
Increases renal tubular reabsorption of calcium and phosphate, reducing urinary losses.
Influences immune system modulation via vitamin D receptor activation in immune cells.
Facilitates mineralization of bone matrix, preventing disorders such as rickets or osteomalacia.
Restores calcium and phosphate levels in deficiency states such as hypoparathyroidism and hypophosphatemia.
Serves as adjunct therapy in familial hypophosphatemia to improve phosphate metabolism.
Modulates gene transcription involved in growth, differentiation, and cell cycle regulation.
Interacts with other endocrine pathways to maintain electrolyte and bone metabolism balance.
Potentially exhibits antioxidant and anti-inflammatory properties through indirect mechanisms.

Therapeutic Or Clinical Uses

Treatment of hypoparathyroidism causing hypocalcemia.
Management of rickets and osteomalacia due to vitamin D deficiency.
Correction of hypophosphatemia in conditions such as familial hypophosphatemia.
Supplementation in vitamin D deficiency states to restore normal serum levels.
Adjunct therapy in mineral and bone disorders associated with chronic kidney disease.
Prevention of vitamin D deficiency in populations at risk, including malabsorption syndromes.
Supportive treatment in disorders leading to impaired calcium metabolism.
Addressing vitamin D insufficiency in patients with osteoporosis.
Part of comprehensive therapy including calcium supplementation for bone health.
Investigational use in certain autoimmune and inflammatory conditions due to immunomodulatory effects.
Management of neonatal and pediatric vitamin D deficiency-related skeletal disorders.
Use in patients with malnutrition or conditions causing dietary vitamin D insufficiency.

Side Or Adverse Effects

Hypercalcemia manifesting as weakness, fatigue, nausea, and vomiting.
Metallic taste in the mouth indicating early signs of vitamin D toxicity.
Constipation and gastrointestinal discomfort.
Muscle and bone pain due to altered calcium metabolism.
Weight loss associated with overdose.
Allergic reactions including urticaria, facial swelling, and respiratory difficulties.
Rare risk of nephrolithiasis due to hypercalciuria.
Confusion and altered mental status in severe toxicity.
Electrolyte imbalances such as hyperphosphatemia.
Potential cardiovascular effects including arrhythmias related to calcium imbalance.
Headache and dizziness in some patients.
Risk of soft tissue calcification with prolonged high doses.
Skin rash or pruritus as a hypersensitivity reaction.
Elevations in serum calcium warrant frequent monitoring during therapy.
Respiratory distress in allergic or severe hypersensitivity cases.

Precautions

Avoid use in patients with hypercalcemia or hypervitaminosis D.
Use cautiously in individuals with malabsorption syndromes due to variable absorption.
Monitor serum calcium and phosphate levels regularly during treatment.
Adjust doses carefully as there is a narrow margin between therapeutic and toxic doses.
Inform patients about symptoms of vitamin D overdose for early detection.
Caution advised in patients with renal impairment due to altered metabolism.
Consider potential allergies to formulation excipients such as peanut or soybean oil.
Pregnant and breastfeeding women should use only under medical advice due to fetal/neonatal risks.
Not recommended for use in children without physician supervision.
Avoid concomitant use with other vitamin D supplements unless directed by healthcare provider.
Careful consideration in patients with heart disease due to calcium homeostasis effects.
Monitor for electrolyte imbalances, especially in prolonged therapy.
Educate patients on adherence to prescribed dosing to prevent adverse effects.
Evaluate for drug interactions that may impair vitamin D absorption or metabolism.
Adjust dosing in diabetic patients if formulation contains sugars or phenylalanine (in aspartame).

Warnings

Do not use ergocalciferol in patients with known hypersensitivity to vitamin D compounds.
Contraindicated in hypercalcemia and hypervitaminosis D to avoid toxicity.
Excessive dosing can lead to serious or life-threatening hypercalcemia.
Overdose symptoms can include nausea, vomiting, weakness, confusion, and cardiac arrhythmias.
Use only the recommended dose; therapeutic index is narrow.
Monitor patients closely during therapy with frequent laboratory evaluations.
Avoid in patients with malabsorption syndromes unless benefits outweigh risks.
Potential for cross-reactivity in patients allergic to peanut or soybean oil excipients.
Pregnant women must consult healthcare provider; excessive vitamin D is harmful to fetus.
Ergocalciferol passes into breast milk and may cause adverse effects in nursing infants.
Children should not receive ergocalciferol without strict medical supervision.
Drug interactions may alter ergocalciferol levels; spacing medications may be required.
Risk of soft tissue calcification with long-term overdose.
Instruct patients not to self-adjust dosage without medical guidance.
If signs of overdose or toxicity appear, seek immediate medical attention.

Contraindication

Known allergy or hypersensitivity to ergocalciferol or other vitamin D products.
Hypercalcemia (elevated blood calcium levels).
Hypervitaminosis D or excessive vitamin D levels in the body.
Conditions causing malabsorption that severely impair vitamin D uptake without monitoring.
Patients with a history of vitamin D intoxication.
Use in infants or children without medical supervision.
Severe renal impairment where 1-alpha hydroxylation is impaired unless monitored carefully.
Patients with certain granulomatous diseases causing endogenous vitamin D excess.
Individuals with hyperphosphatemia not controlled by other means.
Concurrent use with drugs that cause hypercalcemia unless medically justified.
Presence of active hyperparathyroidism not managed by therapy.
Avoid in patients with severe cardiovascular disease linked to electrolyte abnormalities.
Use contraindicated in those with excipient allergies (e.g., to peanut oil).
Patients undergoing excessive vitamin D supplementation without medical guidance.
Do not administer in combination with other unmonitored vitamin D or calcium supplements.

Drug Interactions

Diuretics, especially thiazides, can increase risk of hypercalcemia when combined with ergocalciferol.
Mineral oil may reduce the absorption of vitamin D, decreasing efficacy.
Cholestyramine and other bile acid sequestrants may impair vitamin D absorption.
Orlistat and other weight-loss agents that reduce fat absorption can decrease vitamin D uptake.
Anticonvulsants like phenytoin and phenobarbital may induce hepatic enzymes, enhancing vitamin D metabolism and reducing its levels.
Glucocorticoids can antagonize vitamin D actions and reduce calcium absorption.
Magnesium deficiency can impair vitamin D metabolism; magnesium supplementation may be required.
Concurrent use with other vitamin D supplements or calcium-containing products may potentiate hypercalcemia risk.
Certain antifungals and HIV protease inhibitors may affect vitamin D metabolism through CYP450 interactions.
Cholesterol-lowering agents may compete for absorption and affect vitamin D concentrations.
Drugs that reduce gastrointestinal absorption (e.g., laxatives) can interfere with ergocalciferol efficacy.
Antacids containing aluminum may interact with vitamin D affecting mineral balance.
Use of digitalis glycosides with vitamin D therapy increases risk of cardiac arrhythmias if hypercalcemia occurs.
Concomitant use with methotrexate might increase risk of toxicity through altered metabolism.
Immunosuppressants may interact by modulating vitamin D receptor signaling pathways.

Preparations Of The Drug

Oral capsules containing 50,000 international units (IU) of ergocalciferol, intended for weekly or monthly dosing in deficiency states.
Oral liquid solution with concentration of 200 micrograms (mcg) per milliliter for flexible dosing in patients requiring liquid formulation.
Capsule formulations may contain excipients such as peanut or soybean oil; caution in patients with allergies.
Liquid preparations may contain sugars, aspartame (phenylalanine), and food dyes requiring caution in patients with diabetes or phenylketonuria.
Available under brand names including Calcidol, Calciferol, Drisdol, and generic vitamin D2 formulations.
Packaging designed to protect against moisture and light to preserve stability.
Supplied for both prescription and hospital use with specified storage conditions at room temperature.
Formulations intended for oral administration only; not for parenteral use.
Dosage strengths selected based on clinical indication, ranging from high-dose therapeutic to maintenance levels.
Measure liquid dosage carefully using dosing syringe or calibrated measuring device to ensure accuracy.
Storage recommendations include keeping away from heat, moisture, and direct sunlight to maintain drug potency.
Patient information leaflets included to educate on proper use, potential side effects, and storage.
Manufactured under good manufacturing practices (GMP) ensuring consistent quality and efficacy.
Periodically updated formulations may vary excipient profiles to improve tolerability or stability.
Available in multi-dose bottles and blister packaging to facilitate adherence and safe administration.