ERGOCALCIFEROL
Clinical safety rating: safe
Animal studies have demonstrated safety
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.
| 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. |
| Molecular Weight | 396.65 |
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. |
| 1st trimester | Safe at recommended dietary allowance (RDA) doses; excessive doses may cause fetal hypercalcemia. |
| 2nd trimester | Safe at RDA doses; avoid megadoses. |
| 3rd trimester | Safe at RDA doses; avoid megadoses. |
Clinical note
Cholestyramine and mineral oil may reduce absorption Excessive intake can lead to hypercalcemia.
| Placental transfer | Ergocalciferol crosses the placenta; transfer is dose-dependent. |
| Breastfeeding | Ergocalciferol is excreted into breast milk in low amounts; at RDA doses, not expected to cause adverse effects in infant. Monitor infant for hypercalcemia if maternal doses exceed RDA. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Common Effects | Hypercalcemia |
| Serious Effects |
HypercalcemiaVitamin D toxicityMalabsorption syndromeSevere renal impairment (unless used for deficiency under monitoring)
| 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. |
| Food/Dietary | Excessive dietary calcium (e.g., dairy, fortified foods) may precipitate hypercalcemia. High-phosphate foods (e.g., soda, processed meats) may impair absorption. Grapefruit juice does not significantly interact. Alcohol may reduce vitamin D metabolism. |
Loading safety data…
| L1 (Compatible) |
| 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. |
| Fetal Monitoring | Monitor maternal serum calcium, phosphorus, 25-hydroxyvitamin D levels, and urine calcium. Fetal surveillance includes ultrasound for cardiac and renal anomalies in suspected overdose. Neonatal monitoring of serum calcium and parathyroid hormone after delivery. |
| Fertility Effects | No known adverse effects on fertility at recommended doses. Severe vitamin D deficiency may impair fertility through disruption of ovarian function and endometrial receptivity; supplementation restores normal reproductive function. |
| Clinical Pearls | Monitor serum calcium and 25-hydroxyvitamin D levels monthly during loading therapy. Toxicity risk is high with doses >10,000 IU/day; avoid co-administration with high-dose calcium supplements. Use cautiously in sarcoidosis, renal stones, or hyperparathyroidism. Ergocalciferol (vitamin D2) is less potent than cholecalciferol (D3); D2 has a shorter half-life and lower affinity for vitamin D-binding protein. |
| Patient Advice | Take exactly as prescribed; do not double the dose if missed. Do not take extra calcium or vitamin D supplements unless directed by your doctor. · Report symptoms of hypercalcemia: nausea, vomiting, constipation, weakness, confusion, or irregular heartbeats. · Limit dietary calcium intake if advised; avoid use of antacids containing calcium or magnesium. · Store at room temperature away from light and moisture. Do not use after expiration date. |