Ergocalciferol | Pharmacology Mentor

Generic Name

vitamin D2

Mechanism

Prohormone conversion: Ergocalciferol is first hydroxylated in the liver to 25‑hydroxyergocalciferol (calcifediol), then in the kidney to the active hormone 1α,25‑dihydroxyergocalciferol (calcitriol).
Calcium–phosphate homeostasis: The active metabolite binds the vitamin‑D receptor (VDR) in intestinal, renal, and bone cells, promoting transcription of genes that increase intestinal absorption of calcium and phosphate.
Bone remodeling: Calcitriol stimulates osteoclast activity indirectly, aiding in bone mineralization and reversing osteomalacia.

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Pharmacokinetics

Parameter	Details
Absorption	Lipid‑soluble; absorbed with dietary fat in the small intestine.
Distribution	Stores in adipose tissue and liver; widely distributed in body fluids.
Metabolism	1st‑pass hydroxy‑(CYP2R1) → 25‑OH‑vitamin D₂; then 1α‑hydroxylation (CYP27B1) to active form.
Half‑life	25‑OH‑vitamin D₂: ~15–20 days; active 1α,25‑OH₂‑vitamin D₂: ~1–2 days.
Elimination	Primarily biliary excretion; minor renal clearance of metabolites.

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Indications

Treatment of secondary hyperparathyroidism in chronic kidney disease (CKD) when patients cannot tolerate vitamin D₃.
Prevention/treatment of vitamin D deficiency: osteomalacia, rickets (in adults or children on vitamin D‑sparing diets or who avoid ergocalciferol‑rich fish).
Use in patients with malabsorption or those at risk of vitamin D‑3 intolerance (e.g., severe hyperlipidemia or lipoprotein disorders).

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Contraindications

Hypercalcemia or hyperphosphatemia.
Ocular or cardiac calcification (e.g., metastatic calcification).
Granulomatous disease (e.g., sarcoidosis, tuberculosis) due to autonomous production of calcitriol.
Advanced CKD stage 4+: active monitoring required; vitamin D₃ usually preferred.

Warnings
• Monitor serum calcium, phosphate, and PTH to avoid *calciphylaxis* in dialysis patients.
• Potential for *vitamin D toxicity* if doses are supra‑physiologic.

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Dosing

Setting	Dose	Route	Frequency
Adults & children (CKD or deficiency)	50 000 IU orally weekly	Oral capsule/tablet	1×/week
Rickets or severe deficiency	5 000 IU daily (or 50 000 IU weekly)	Oral	1×/week or daily
Maintenance (post‑repletion)	600–1 000 IU daily	Oral	1×/day
Alternate regimen	1 000 IU oral daily	Oral	1×/day

• Take with a fatty meal to enhance absorption.
• Re‑assessment of 25‑OH‑D₂ levels after 6–8 weeks to titrate dose.

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Adverse Effects

Common
• Hypercalcemia (if overdosed).
• GI upset (nausea, constipation).
• Fatigue or headache (rare).

Serious
• Hypercalcemia → renal stones, nephrocalcinosis.
• Hyperphosphatemia in CKD leading to soft‑tissue calcification.
• Vitamin D toxicity (nephrogenic diabetes insipidus, hypertension).

Mitigation: Routine labs and dose adjustment.

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Monitoring

Parameter	Target/Notes
Serum 25‑OH‑D₂	20–50 ng/mL (optimal). Recheck 6–12 weeks after initiation.
Serum calcium	8.5–10.5 mg/dL (or 2.2–2.6 mmol/L).
Serum phosphate	2.5–4.5 mg/dL (or 0.8–1.5 mmol/L).
PTH (if CKD)	Trend downward; baseline and every 3–6 months.
Kidney function (CrCl, eGFR)	Monitor every 3–6 months in CKD.

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Clinical Pearls

Food synergy: Take ergocalciferol with a high‑fat meal; bile acids help micellar solubilization, boosting absorption 2–3× compared with an empty stomach.
Folate interaction: Unlike vitamin D₃, ergocalciferol does not interfere with folic acid metabolism; this is useful in patients on high‑dose folate supplements.
Storage benefit: As a plant‑derived molecule, ergocalciferol is cheaper and available in lower‑cost generic formulations, often making it the first‑line supplement in resource‑limited settings.
Elderly caution: Older adults typically require higher daily doses (≥ 1 000 IU) because of reduced skin synthesis and decreased dietary intake; monitor closely to avoid toxicity.
Differential diagnosis: Persistently low vitamin D despite supplementation may indicate malabsorption (celiac, Crohn) or inadequate fat ingestion; evaluate lipid profile.

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