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Ergocalciferol


General


Pronunciation

(er goe kal SIF e role)


Brand Names: U.S.

  • Calcidol [OTC]
  • Calciferol [OTC]
  • Drisdol [DSC]
  • Drisdol [OTC] [DSC]

Indications


Use: Labeled Indications

Dietary supplement: For use as a vitamin D supplement.

Familial hypophosphatemia: Treatment of familial hypophosphatemia.

Hypoparathyroidism: Treatment of hypoparathyroidism.

Rickets: Treatment of refractory rickets, also known as vitamin D-resistant rickets.


Contraindications


Hypercalcemia; malabsorption syndrome; abnormal sensitivity to the toxic effects of vitamin D; hypervitaminosis D

Note: Although the manufacturer 's labeling lists use in malabsorption syndrome as contraindicated, when dosed appropriately, ergocalciferol may be used in these patients (Holick 2011).

Documentation of allergenic cross-reactivity for vitamin D analogues is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.


Dosing and Administration


Dosing: Adult

Note: 1 mcg = 40 units

Dietary Reference Intake for Vitamin D: Oral (IOM, 2011):

Adults 19 to 70 years: RDA: 600 units/day

Pregnancy/Lactating: RDA: 600 units/day

Osteoporosis prevention (off-label use): Adults ≥50 years: 800 to 1000 units/day (NOF guidelines, 2014)

Vitamin D deficiency treatment (off-label dose): (Holick, 2011): Oral: 6000 units daily or 50,000 units once weekly for at least 8 weeks to achieve a 25(OH)D level >30 ng/mL; then maintenance dose of 1500 to 2000 units daily

Special populations (obese patients, patients on medications known to affect vitamin D metabolism, patients with malabsorption syndromes): 6000 to 10,000 units daily to achieve a 25(OH)D level >30 ng/mL; then maintenance dose of 3000 to 6000 units daily

Vitamin D deficiency/insufficiency in patients with CKD stages 3 to 4 (K/DOQI, 2003): Note: Dose is based on 25-hydroxyvitamin D serum level (25[OH]D): Oral (treatment duration should be a total of 6 months):

Serum 25(OH)D <5 ng/mL:

50,000 units/week for 12 weeks, then 50,000 units/month

Serum 25(OH)D 5 to 15 ng/mL:

50,000 units/week for 4 weeks, then 50,000 units/month

Serum 25(OH)D 16 to 30 ng/mL:

50,000 units/month

Hypoparathyroidism: Oral: 1.25 to 5 mg/day (50,000 to 200,000 units) with calcium supplements

Vitamin D-resistant rickets: Oral: 12,000 to 500,000 units/day


Dosing: Geriatric

Note: 1 mcg = 40 units

Dietary Reference Intake for Vitamin D: Oral (IOM, 2011):

≤70 years: Refer to adult dosing.

>70 years: RDA: 800 units/day


Dosing: Pediatric

Note: 1 mcg = 40 units

Dietary Reference Intake for Vitamin D: Oral:

Infants 0 to 12 months: Adequate intake: 400 units/day (IOM, 2011)

Breast-fed (fully or partially) Infants: Oral: 10 mcg/day (400 units/day) beginning in the first few days of life; continue supplementation until infant is weaned to ≥1 L/day or 1 quart/day of vitamin D-fortified formula or whole milk (after 12 months of age) (Wagner, 2008)

Nonbreast-fed Infants, Older Children ingesting <1000 mL of vitamin D-fortified formula or milk: Oral: 10 mcg/day (400 units/day) (Wagner, 2008)

Children with increased risk of vitamin D deficiency (chronic fat malabsorption, maintained on chronic antiseizure medications): Oral: Higher doses may be required; use laboratory testing [25 (OH)D, PTH, bone mineral status] to evaluate (Wagner, 2008)

Children and Adolescents 1 to 18 years: RDA: 600 units/day (IOM, 2011)

Vitamin D deficiency treatment (off-label use) (Holick, 2011):

Infants 0 to 1 year: 2000 units daily or 50,000 units once weekly for 6 weeks to achieve a 25(OH)D level >30 ng/mL; then maintenance dose of 400 to 1000 units daily.

Children and Adolescents 1 to 18 years: 2000 units daily or 50,000 units once weekly for at least 6 weeks to achieve a 25(OH)D level >30 ng/mL; then maintenance dose of 600 to 1000 units daily.

Vitamin D deficiency/insufficiency in patients with CKD stages 3 to 4 (K/DOQI, 2005): Note: Dose is based on 25-hydroxyvitamin D serum level (25[OH]D): Oral (treatment duration should be a total of 3 months):

Serum 25(OH)D <5 ng/mL:

8000 units/day for 4 weeks, then 4000 units/day for 2 months or

50,000 units/week for 4 weeks, then 50,000 units twice a month for 2 months

Serum 25(OH)D 5 to 15 ng/mL:

4000 int units/day or

50,000 int units every other week

Serum 25(OH)D 16 to 30 ng/mL:

2000 units/day or

50,000 units every 4 weeks

Hypoparathyroidism: Oral: 1.25 to 5 mg/day (50,000 to 200,000 units) and calcium supplements

Vitamin D-resistant rickets: Oral: 12,000 to 500,000 units/day


Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer 's labeling.


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturers labeling.


Administration

Liquid vitamin D preparations have the potential for dosing errors when administered to infants. The FDA recommends using droppers that deliver no more than 400 international units per dose for products intended for infants.


Dietary Considerations

Vitamin D is found in egg yolks, fatty fish, fortified milk, fortified cereal, and infant formulas; it is also produced by exposure to sunlight (IOM, 2011). Multivitamin supplements containing vitamin D may be required for breast fed infants, those ingesting <1000 ml/day of vitamin D-fortified formula or milk, adolescents who do not obtain 400 units/day through vitamin D-fortified milk (100 int units/8 ounce serving), and children at increased risk of vitamin D deficiency.

Supplemental calcium and/or phosphorous may be required depending on the indication for therapy. Alternately, a low phosphate diet and/or the use of a nonaluminum-binding agent may be required.


Storage

Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from light.


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Drisdol: 50,000 units [DSC] [contains brilliant blue fcf (fd&c blue #1), soybean oil, tartrazine (fd&c yellow #5)]

Generic: 50,000 units

Solution, Oral:

Calcidol: 8000 units/mL (60 mL) [contains propylene glycol]

Calciferol: 8000 units/mL (60 mL) [contains propylene glycol]

Drisdol: 8000 units/mL (60 mL [DSC]) [contains propylene glycol]

Generic: 8000 units/mL (60 mL)

Tablet, Oral:

Generic: 400 units, 2000 units


Drug Interactions

Aluminum Hydroxide: Vitamin D Analogs may increase the serum concentration of Aluminum Hydroxide. Specifically, the absorption of aluminum may be increased, leading to increased serum aluminum concentrations. Avoid combination

Bile Acid Sequestrants: May decrease the serum concentration of Vitamin D Analogs. More specifically, bile acid sequestrants may impair absorption of Vitamin D Analogs. Management: Avoid concomitant administration of vitamin D analogs and bile acid sequestrants (e.g., cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Calcium Salts: May enhance the adverse/toxic effect of Vitamin D Analogs. Monitor therapy

Cardiac Glycosides: Vitamin D Analogs may enhance the arrhythmogenic effect of Cardiac Glycosides. Monitor therapy

Danazol: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Mineral Oil: May decrease the serum concentration of Vitamin D Analogs. More specifically, mineral oil may interfere with the absorption of Vitamin D Analogs. Management: Avoid concomitant, oral administration of mineral oil and vitamin D analogs. Consider separating the administration of these agents by several hours to minimize the risk of interaction. Monitor plasma calcium concentrations. Consider therapy modification

Multivitamins/Fluoride (with ADE): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the adverse/toxic effect of Vitamin D Analogs. Avoid combination

Orlistat: May decrease the serum concentration of Vitamin D Analogs. More specifically, orlistat may impair absorption of Vitamin D Analogs. Management: Monitor clinical response (including serum calcium) to oral vitamin D analogs closely if used with orlistat. If this combination must be used, consider giving the vitamin D analog at least 2 hrs before or after orlistat. Consider therapy modification

Sucralfate: Vitamin D Analogs may increase the serum concentration of Sucralfate. Specifically, the absorption of aluminum from sucralfate may be increased, leading to an increase in the serum aluminum concentration. Avoid combination

Thiazide and Thiazide-Like Diuretics: May enhance the hypercalcemic effect of Vitamin D Analogs. Monitor therapy

Vitamin D Analogs: May enhance the adverse/toxic effect of other Vitamin D Analogs. Avoid combination


Monitoring Parameters

Serum calcium and phosphorus at least every 2 weeks; x-ray bones monthly until stabilized; signs and symptoms of vitamin D intoxication.

Serum 25(OH)D should be monitored in patients at risk for vitamin D deficiency; Serum 1,25-dihydroxyvitamin D may be used in conditions such as acquired or inherited vitamin D disorders (eg, chronic kidney disease, vitamin D resistant rickets) or phosphate metabolism (Holick, 2011).

When treating vitamin D deficiency in children, monitor serum calcium, phosphorus and alkaline phosphatase (ALP) one month after starting therapy; serum calcium, phosphorous, magnesium, ALP, 25(OH)D, and PTH as well as x-ray (may also consider urine calcium/creatinine ratio) after 3 months; 25(OH)D yearly (Misra, 2008).

Children at increased risk of vitamin D deficiency (chronic fat malabsorption, chronic antiseizure medication use) require serum 25(OH)D, PTH, and bone mineral status to evaluate. If vitamin D supplement required, then 25(OH)D levels should be repeated at 3-month intervals until normal. PTH and bone mineral status should be monitored every 6 months until normal. (Wagner, 2008).

Vitamin D deficiency/insufficiency in patients with CKD stages 3 to 4: Measure serum 25(OH)D levels after 3 months of treatment in children or after 6 months in adults. Measure corrected total calcium and phosphorous after 1 month and then at least every 3 months in children and at least every 3 months in adults. Discontinue ergocalciferol (or any vitamin D supplements) if the corrected total serum calcium level is >10.2 mg/dL. (K/DOQI, 2003; K/DOQI, 2005).

Serum 25(OH)D in patients on long term anticonvulsant medications, antifungals, cholestyramine, glucocorticoids, or medications to treat the human immunodeficiency virus (HIV); the catabolism of the metabolite 25(OH)D may be increased (Holick, 2011).


Adverse Reactions


Frequency not defined: Endocrine & metabolic: Hypervitaminosis D


Warnings/Precautions


Disease-related concerns:

- Hyperphosphatemia: Normal serum phosphorous concentrations must be maintained in patients treated for hyperphosphatemia to prevent metastatic calcification.

- Hypoparathyroidism: Concomitant treatment with intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may also be required when treating hypoparathyroidism.

- Obesity: Adults with a BMI >30 kg/m2 are at high risk for vitamin D deficiency due to storage of vitamin D in adipose tissue. Doses higher than the RDA may be required, but must be carefully monitored to avoid toxicity (Holick, 2011).

- Renal impairment: Metabolism of vitamin D may be altered in patients with chronic kidney disease. Supplementation with ergocalciferol may be needed; close monitoring is required (KDOQI, 2003).

- Rickets: The range between therapeutic and toxic doses is narrow in vitamin D-resistant rickets; adjust dose based on clinical response to avoid toxicity.

Concurrent drug therapy issues:

- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

- Propylene glycol: Oral solutions may contain propylene glycol; toxicities may occur if large doses of vitamin D are required. Alternate dosage forms/products should be used (Misra, 2008).

- Tartrazine: Products may contain tartrazine, which may cause allergic reactions in certain individuals.

Other warnings/precautions:

- Appropriate use: Adequate calcium supplementation is required; calcium and phosphorous levels must be monitored during therapy. All sources of vitamin D (eg, dietary supplements, fortified foods, medication) should be evaluated.

- Toxicity: Effects of vitamin D can last ≥2 months after therapy is discontinued.


Pregnancy Risk Factor

C


Pregnancy Considerations

Adverse events were observed in some animal reproduction studies. The ergocalciferol (vitamin D2) metabolite, 25(OH)D, crosses the placenta; maternal serum concentrations correlate with fetal concentrations at birth (Misra, 2008; Wagner, 2008).

Vitamin D deficiency in a pregnant woman may lead to a vitamin D deficiency in the neonate (Misra, 2008; Wagner, 2008). Serum 25(OH)D concentrations should be measured in pregnant women considered to be at increased risk of deficiency (ACOG, 2011). The amount of vitamin D contained in prenatal vitamins may not be adequate to treat a deficiency during pregnancy; although larger doses may be needed, current guidelines recommend a total of 1000 to 2000 units/day until more safety data is available (ACOG, 2011; Holick, 2011). In women not at risk for deficiency, doses larger than the RDA should be avoided during pregnancy (ACOG, 2011).


Actions


Pharmacology

Ergocalciferol (vitamin D2) is a provitamin. The active metabolite, 1,25-dihydroxyvitamin D (calcitriol), stimulates calcium and phosphate absorption from the small intestine, promotes secretion of calcium from bone to blood; promotes renal tubule phosphate resorption.


Absorption

Absorbed in the small intestine; fat soluble; requires bile (IOM, 2011)


Metabolism

Inactive until hydroxylated hepatically to 25-hydroxyvitamin D [25(OH)D; calcifediol] then renally to the active metabolite 1,25-dihydroxyvitamin D (calcitriol)


Excretion

Feces (IOM, 2011)


Onset of Action

10 to 24 hours; Maximum effect: ~1 month following daily doses


Half-Life Elimination

Circulating: 25(OH)D: 2 to 3 weeks; 1,25-dihydroxyvitamin D ~4 hours (Holick, 2011)


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Have patient report immediately to prescriber signs of hypercalcemia, significant asthenia, severe dizziness, intolerable headache, urinary retention, oliguria, polyuria, lack of appetite, polydipsia, or weight loss (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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