Description: Ergocalciferol is a vitamin D analog. Vitamin D has two primary forms: cholecalciferol (vitamin D3), which is synthesized in the skin after exposure to ultraviolet light, and ergocalciferol (vitamin D2), which is produced from plant sterols and is the primary dietary source of vitamin D. Ergocalciferol is less expensive than dihydrotachysterol, calcifediol, and calcitriol. Activated ergocalciferol and calcitriol have equal activity and function; however, calcitriol may be preferable to ergocalciferol in the acute treatment of hypocalcemia because of its faster onset of action. Ergocalciferol may be less effective than other vitamin D analogs in patients with hepatic, biliary, or GI disease because bile is required for its absorption. Ergocalciferol is indicated for the prophylaxis and treatment of vitamin D deficiency, rickets, familial hypophosphatemia, hypoparathyroidism, osteomalacia, and is also used as a nutritional supplement. Ergocalciferol was approved by the FDA in 1940. Mechanism of Action: Activated ergocalciferol promotes renal reabsorption of calcium, increases intestinal absorption of calcium and phosphorus, and increases calcium and phosphorus mobilization from bone to plasma. The activated form of ergocalciferol acts similarly to calcitriol in that it appears to promote intestinal absorption of calcium through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. Some evidence suggests that the active moiety of ergocalciferol acts at the level of the cell nucleus to increase plasma calcium and phosphorus. Once plasma saturation of these electrolytes occurs, bone mineralization takes place. The synthesis of activated ergocalciferol is enhanced by elevated parathyroid hormone levels and low plasma phosphorus levels. Hypocalcemia causes release of parathyroid hormone, which stimulates the production of activated ergocalciferol. Pharmacokinetics: Ergocalciferol is administered orally and parenterally. Oral absorption occurs rapidly and completely in the presence of bile salts. The extent absorbed can be decreased in patients with hepatic, biliary, or GI disease. In these cases, IM administration may be needed. The onset of action following oral or IM administration is 10�24 hours. Maximal effects are usually observed in 4 weeks. The duration of action can extend up to 2 months or longer. Ergocalciferol enters the blood through chylomicrons of lymph. Vitamin D is stored primarily in the liver and fat depots. The parent compound and its metabolites are bound in plasma to alpha-globulins. Ergocalciferol is converted in the liver by the enzyme vitamin D-25-hydroxylase (cytochrome P450 27) to 25-hydroxyergocalciferol, an active, intermediate. Ergocalciferol is further converted to its most active form, 1,25-dihydroxyergocalciferol, in the kidneys. The intermediate metabolite of ergocalciferol may be distributed into breast milk following high doses (see Contraindications). All of the metabolites of ergocalciferol have not been identified. Elimination of vitamin D and its metabolites occurs principally through the bile, with the remainder excreted renally. The half-life is 19�48 hours. Indications...Dosage For the treatment of osteomalacia: Oral Dosage: Adults and children with normal absorption: 1000�5000 units PO once daily. Adults with malabsorption: 10,000�300,000 units PO once daily. Children with malabsorption: 10,000�25,000 units PO once daily. For the treatment of familial hypophosphatemia: Oral Dosage: Adults: 50,000�100,000 units PO once daily. Children: 40,000�80,000 units PO once daily. The daily dosage is increased in 10,000�20,000 unit increments at 3�4 month intervals until an adequate response is achieved. For the treatment of hypoparathyroidism: Oral Dosage: Adults: 25,000�200,000 units PO once daily along with calcium supplements. Children: 50,000�200,000 units PO once daily along with calcium supplements. For the treatment of vitamin D deficiency: Oral Dosage: Adults: 1000�2000 units PO once daily. Children: 1000�4000 units PO once daily. For the treatment of vitamin D-dependent rickets: Oral Dosage: Adults: 10,000�60,000 units PO once daily. The maximum recommended dosage is 150,000 units per day. Children: 3000�5000 units PO once daily. The maximum recommended dosage is 60,000 units per day. For nutritional supplementation: �the recommended adequate intake (AI) of vitamin D2 for nutritional supplementation in healthy individuals: NOTE: A recommended dietary allowance (RDA) has not been established for vitamin D2. Adequate intake (AI) should be used in place of RDA. NOTE: Dietary intake of vitamin D is unecessary for most healthy individuals who eat a healthy diet and have sufficient exposures to sunlight. Oral dosage, expressed as �g of cholecalciferol (40 IU = 1�g): Adults > 70 years: 15 �g PO per day. Adults 51�70 years: 10 �g PO per day. In postmenopausal women, a supplemental dose of 700 units PO once daily was more effective than dietary intake of 100 units PO once daily in preventing femoral neck bone mineral density loss.[1635] Adults <= 50 years: 5 �g PO per day. Adolescents: 5 �g PO per day. Children: 5 �g PO per day. Infants : 5 �g PO per day. Infants fed human milk and exposed to about 35 minutes of sunlight per day generally produce adequate amounts of vitamin D in skin. For breastfed or formula-fed infants who have regular, small exposures to sunshine, supplemental vitamin D is not necessary. �for nutritional supplementation of vitamin D2 to prevent low serum levels in patients receiving total parenteral nutrition (TPN): Intravenous dosage: Adults: 5 �g IV per day admixed with parenteral nutrition. For the treatment of Fanconi syndrome�: Oral Dosage: Adults: 50,000�200,000 Units PO once daily. Children: 25,000�50,000 Units PO once daily. For the treatment of postmenopausal osteoporosis�: Oral Dosage: Adults: 1000�10,000 units PO once daily or 50,000 units PO 2 times weekly with calcium supplements. A Dutch study suggests that even doses as low as 400 IU per day may exert beneficial effects on bone density in women 70 years and above. No calcium supplements were given in this study although it was determined that participants averaged about 1 g of calcium intake per day.[1038] For the treatment of renal osteodystrophy� associated with renal failure: Oral Dosage: Adults: Initially, 20,000 units PO per day. The usual maintenance dosage is 10,000�300,000 units PO per day. Children: 4000�40,000 units PO per day. Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed. �non-FDA-approved indication Administration NOTE: International Units (IU), a previous measurement system for fat soluble vitamins, has been replaced by a more accurate measure, the metric system. Each �g of ergocalciferol is equivalent to 40 IU of Vitamin D. Dosage should be individualized to maintain serum calcium concentrations of 9�10 mg/dL. Oral administration �All dosage forms: May be administered without regard to meals. �Oral solution: Administer using calibrated measuring device provided by the manufacturer to ensure dosage accuracy. The solution may be mixed with cereal, juice, or food. Intramuscular administration �This route is usually reserved for patients with hepatic, GI, or biliary disease because these patients should not receive ergocalciferol orally. �Because the injection is oil-based, avoid intravenous injection. �Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Intramuscular injection: �Inject slowly and deeply into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel. Contraindications Ergocalciferol should not be given to patients with hypercalcemia or hypervitaminosis D. Hypercalcemia can lead to soft tissue calcification and other toxicities. This should be considered when contemplating the use of vitamin D under these conditions. Ergocalciferol should be administered with caution to patients with cardiac disease or those receiving digoxin because hypercalcemia with cardiac arrhythmias can result. Ergocalciferol should be used with extreme caution in patients with arteriosclerosis due to the possibility of the condition being exacerbated by elevated serum cholesterol concentrations. Vitamin D is classified as pregnancy category C. Problems in humans from normal daily intake of vitamin D have not been documented; however, hypercalcemia during pregnancy has been associated with suppression of parathyroid hormone in the neonate, resulting in mental retardation and congenital aortic stenosis. The risks to benefits of untreated hypoparathyroidism or hypophosphatemia in the mother should be considered before using vitamin D. This vitamin is distributed in small amounts into breast milk. The use of vitamin D during breast-feeding is controversial. Large doses of ergocalciferol should be avoided because its active metabolite, 25-hydroxyergocalciferol, may be distributed into breast milk. Serum calcium concentrations in the infant should be monitored when using vitamin D in a nursing mother. Vitamin D should be used cautiously in patients with hyperphosphatemia due to the risk of metastatic calcification, and it should be avoided in patients with renal osteodystrophy with hyperphosphatemia. Treatment with vitamin D may be initiated after stabilization of phosphorus levels. Use of excessive doses acutely or for a prolonged period can result in vitamin D-induced hypercalcemia manifest as nephrocalcinosis and other calcifications. These adverse reactions can be significant in patients with renal failure, even with usual dosages. Ergocalciferol should be used with caution in patients with renal disease or renal stones. Patients with sarcoidosis, and possibly other granulomatuous diseases, may have increased sensitivity to the effects of vitamin D. Ergocalciferol should be used with caution in patients with hypoparathyroidism. Calcium, dihydrotachysterol, or parathyroid hormone may need to be added to therapy. Interactions The use of other vitamin D analogs with ergocalciferol is not recommended because of the increased potential for additive effects and toxicity. In addition, due to ergocalciferol-induced increased serum phosphorus levels, concurrent administration of phosphorus salts may increase the toxicity of ergocalciferol. Magnesium-containing antacids and supplemental magnesium salts should be used cautiously in patients receiving ergocalciferol. Because vitamin D analogs can increase serum magnesium concentrations, the combined use of ergocalciferol and magnesium-containing antacids should be avoided, if possible, in patients with chronic renal failure. The concurrent use of vitamin D with calcium-containing antacids or other calcium salts can cause hypercalcemia; in some patients, however, this combination can be beneficial. The chronic use of aluminum-containing antacids for hyperphosphatemia in conjunction with vitamin D can lead to increased aluminum concentrations and toxicity. This is of primary significance in patients with renal failure. Anticonvulsants, such as phenobarbital, phenytoin, and primidone, can decrease the activity of vitamin D by increasing its metabolism. In rare cases, this has caused anticonvulsant-induced rickets and osteomalacia. Vitamin D supplementation may be required in patients with inadequate dietary intake of vitamin D who are receiving chronic treatment with anticonvulsants. Ergocalciferol should be administered with caution to patients with cardiac disease or those receiving cardiac glycosides. Ergocalciferol may cause hypercalcemia which may affect the actions of the cardiac glycoside and/or lead to cardiac arrhythmias. Cholestyramine, colestipol, or mineral oil can decrease the intestinal absorption of ergocalciferol. If used concurrently, administration of the two agents should be staggered for the longest time interval possible. Orlistat decreases the body's absorption of dietary fat, which also affects the absorption of fat soluble vitamins. Concomitant use of thiazide diuretics and ergocalciferol in patients with hypoparathyroidism can result in hypercalcemia, which is likely due to increased release of calcium from the bone. This condition may be transient or require discontinuation of the vitamin D analog. Adverse Reactions Hypervitaminosis D, manifest as hypercalcemia, can occur. Early signs of hypercalcemia include fatigue, somnolence, headache, anorexia, xerostomia, metallic taste, nausea/vomiting, abdominal cramps, constipation, diarrhea, vertigo, tinnitus, ataxia, exanthema, myalgia, arthralgia, and irritability. Polyuria, photophobia, anorexia, rhinorrhea, hyperthermia, cardiac arrhythmias, and hypertension are all late symptoms of hypercalcemia. Ergocalciferol should be discontinued if symptoms become severe. Therapy with ergocalciferol should be started at the lowest dose and serum calcium levels monitored throughout treatment. Dietary calcium intake also should be estimated and adjusted, if necessary, to avoid hypercalcemic effects. In conditions of hypercalcemia, reduction in calcium intake in the diet is advocated along with an increase in fluid intake. Vitamin D increases the absorption of phosphorus and can cause hyperphosphatemia, especially in those with renal failure. Dosage adjustments may be required for patients receiving aluminum-containing antacids for the treatment of hyperphosphatemia.
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Ergocalciferol, Vitamin D2 Calciferol�, Drisdol�, Ergocalciferol by Schein | Erogo D� 1635. Dawson-Hughes B, Harris SS, Krall EA, et al. Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 1995;61:1140�5. 1038. Ooms ME et al. Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 1995;80:1052�8. |