Ergocalciferol

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# Overview
Ergocalciferol is a bone density conservation agent that is FDA approved for the treatment of hypoparathyroidism, refractory rickets, also known as vitamin D resistant rickets, and familial hypophosphatemia.   Common adverse reactions include constipation, nausea, vomiting.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)

### Familial x-linked hypophosphatemic vitamin D refractory rickets
- Dosing Information
- Phosphorus and calcium homeostasis improved following long-term therapy with oral phosphorus 2 grams and vitamin D2 50,000 to 75,000 international units daily in patients with X-linked hypophosphatemic rickets and osteomalacia.
- High-dose vitamin D2 (50,000 to 300,000 international units daily) has been utilized in the treatment of vitamin D-resistant rickets in children and adults. Bone deformities improved in some patients with vitamin D2 therapy alone.

### Hypoparathyroidism
- Dosing Information
- The optimal daily dose of vitamin D2 required to maintain serum calcium within normal limits without adverse effects ranged from 2.5 to 6.25 mg in 16 patients with either pseudohypoparathyroidism, idiopathic hypoparathyroidism, or postoperative hypoparathyroidism.

### Vitamin D deficiency; Prophylaxis
- Dosing Information
- The recommended dose of ergocalciferol in patients with vitamin D deficiency as a result of pregnancy, lactation, obesity, stage 2 chronic kidney disease, inadequate sun exposure, or supplementation, age older than 50 years, and primary or tertiary hyperparathyroidism is 50,000 international units orally every week for 8 to 12 weeks. The dose may be repeated another 8 weeks, or up to 12 weeks if 25-hydroxyvitamin D levels are less than 30 nanograms/milliliter.
- Malabsorption Syndrome:
- The recommended dose for of ergocalciferol in patients with vitamin D deficiency due to malabsorption syndrome is 50,000 international units orally every day or every other day.
- Concomitant Use With Drugs That Activate Steroid and Xenobiotic Receptor, And Drugs Used In Transplantation:
- The recommended dose of ergocalciferol in patients with vitamin D deficiency on concomitant drugs that activate steroid and xenobiotic receptors and/or on drugs used in transplantation is 50,000 international units orally every 2 weeks for 8 to 10 weeks, or every week if 25-hydroxyvitamin D levels are less than 30 nanograms/milliliter.
- Granulomatous Disorders and Some Lymphomas:
- For patients with granulomatous disorders and some lymphomas, the recommended dose of ergocalciferol is 50,000 international units orally once a week for 4 weeks or every 2 to 4 weeks to maintain 25-hydroxyvitamin D levels between 20 and 30 nanograms/milliliter (ng/mL). Levels above 30 ng/mL may result in hypercalciuria and hypercalcemia.
- Kidney Disease:
- For nephrotic syndrome, the recommended dose is 50,000 international units orally twice a week for 8 to 12 weeks; may repeat another 8 to 12 weeks if 25-hydroxyvitamin D levels are less than 30 nanograms/milliliter (ng/mL).
- For stage 3 or 4 chronic kidney disease, the recommended dose of ergocalciferol when 25-hydroxyvitamin D (25-OHD) levels are less than 5 ng/mL is 50,000 international units orally every week for 12 weeks, then monthly for 6 months. When 25-OHD levels are between 5 and 15 ng/mL, the dose is 50,000 international units orally weekly for 4 weeks, then monthly for 6 months. When 25-OHD levels are between 16 and 30 ng/mL, the dose is 50,000 international units orally monthly for 6 months.
- For stage 5 chronic kidney disease, a dose of 50,000 international units orally weekly for 24 weeks increased serum concentrations of 25-hydroxyvitamin D while intact parathyroid hormone levels did not change in a retrospective study (n=344).

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Ergocalciferol in adult patients.

### NonGuideline-Supported Use
- There is limited information regarding Off-Label NonGuideline-Supported Use of Ergocalciferol in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
- Dosing Information
- For vitamin D-resistant rickets, doses of 25,000 to 100,000 units daily have been given with high phosphate intake and calcium supplementation.
- In children with genetic vitamin D-dependent rickets, 3000 to 50,000 units vitamin D daily has been given.
- Dosing Information
- Oral vitamin D 10,000 to 200,000 units daily has been recommended. However, dihydrotachysterol or other vitamin D metabolites are usually preferred.

### Vitamin D deficiency; Prophylaxis
- Dosing Information
- Prevention and Maintenance:
- Adequate Sun Exposure:
- In breast-feeding infants with sensible sun exposure, up to 1 year old, administer cholecalciferol 400 international units orally every day. Up to 1000 to 2000 international units/day of cholecalciferol is safe. The recommended maintenance dose is 400 to 1000 international units/day of cholecalciferol.
- In children with adequate sun exposure, the recommended daily dose of cholecalciferol is 200 international units orally. Sun exposure to the arms and legs for 5 to 30 minutes (depending on time of day, season, latitude, and skin pigmentation) between 10 in the morning to 3 in the afternoon twice a week is considered adequate.
- Inadequate Sun Exposure:
- In children without adequate sun exposure or dark skin, the recommended daily dose is 800 to 1000 international units orally. Up to 1000 to 2000 international units/day of cholecalciferol is safe. The recommended maintenance dose is 400 to 1000 international units/day of cholecalciferol. Sun exposure to the arms and legs for 5 to 30 minutes (depending on time of day, season, latitude, and skin pigmentation) between 10 in the morning to 3 in the afternoon twice a week is considered adequate.
- Due to limited natural dietary sources of vitamin D and recommendations to decrease sun exposure due to skin cancer risks, the American Academy of Pediatrics recommended total daily intake requirement of vitamin D in all infants (breast-fed and bottlefed), children, and adolescents is at least 400 international units/day beginning in the first few days of life and continuing throughout childhood. The goal is to maintain the indicator of vitamin D deficiency, serum 25- hydroxyvitamin D serum concentrations at 50 nanomoles/liter or greater (20 nanograms/milliliter or greater):
- Breast-fed and partially breast-fed infants should be supplemented with vitamin D 400 international units/day and continued until the infant is weaned to at least 1 liter/day or 1 quart/day of vitamin D-fortified formula or whole milk. Whole milk should not be used in infants until after 12 months of age. In infants with obesity concerns or a family history of obesity, dyslipidemia, or cardiovascular disease, reduced-fat milk is appropriate.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
- There is limited information regarding Off-Label Guideline-Supported Use of Ergocalciferol in pediatric patients.

### NonGuideline-Supported Use
- There is limited information regarding Off-Label NonGuideline-Supported Use of Ergocalciferol in pediatric patients.

# Contraindications
- Ergocalciferol is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin D, and hypervitaminosis D.

# Warnings
- Hypersensitivity to vitamin D may be one etiologic factor in infants with idiopathic hypercalcemia. In these cases vitamin D must be strictly restricted.
- Keep out of the reach of children.

### Precautions
GENERAL PRECAUTIONS
- Vitamin D administration from fortified foods, dietary supplements, self-administered and prescription drug sources should be evaluated. Therapeutic dosage should be readjusted as soon as there is clinical improvement. Dosage levels must be individualized and great care exercised to prevent serious toxic effects. IN VITAMIN D RESISTANT RICKETS THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW. When high therapeutic doses are used progress should be followed with frequent blood calcium determinations.
- In the treatment of hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihy-drotachysterol may be required.
- Maintenance of a normal serum phosphorous level by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatis calcification.
- Adequate dietary calcium is necessary for clinical response to vitamin D therapy.
- Protect from light.

# Adverse Reactions

## Clinical Trials Experience
Hypervitaminosis D is characterized by effects on the following organ system:
- Renal: Impairment of renal function with polyuria, nocturia, polydipsia, hypercalciuria, reversible azotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or irreversible renal insufficiency which may result in death.
- CNS: Mental retardation.
- Soft Tissues: Widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs.
- Skeletal: Bone demineralization (osteoporosis) in adults occurs concomitantly. Decline in the average rate of linear growth and increased mineralization of bones in infants and children (dwarfism), vague aches, stiffness, and weakness.
- Gastrointestinal: Nausea, anorexia, constipation.
- Metabolic: Mild acidosis, anemia, weight loss.
- To report SUSPECTED ADVERSE REACTIONS, contact TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537, or drug.safety@tevapharm.com or FDA at 1-800-FDA-1088 or

## Postmarketing Experience
- There is limited information regarding Postmarketing Experience of Ergocalciferol in the drug label.

# Drug Interactions
- Mineral oil interferes with the absorption of fat-soluble vitamins, including vitamin D preparations. Administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with ergocalciferol may cause hypercalcemia.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA):
- Animal reproduction studies have shown fetal abnormalities in several species associated with hypervitaminosis D. These are similar to the supravalvular aortic stenosis syndrome described in infants by Black in England (1963). This syndrome was characterized by supravalvular aortic stenosis, elfin facies, and mental retardation. For the protection of the fetus, therefore, the use of vitamin D in excess of the recommended dietary allowance during normal pregnancy should be avoided unless, in the judgment of the physician, potential benefits in a specific, unique case outweigh the significant hazards involved. The safety in excess of 400 USP units of vitamin D daily during pregnancy has not been established.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
- There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ergocalciferol in women who are pregnant.

### Labor and Delivery
- There is no FDA guidance on use of Ergocalciferol during labor and delivery.

### Nursing Mothers
- Caution should be exercised when ergocalciferol is administered to a nursing woman. In a mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Monitoring of the infants serum calcium concentration is required in that case (Goldberg, 1972).

### Pediatric Use
- Pediatric doses must be individualized.

### Geriatic Use
- Clinical studies of Ergocalciferol capsules, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. A few published reports have suggested that the absorption of orally administered vitamin D may be attenuated in elderly compared to younger individuals. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

### Gender
- There is no FDA guidance on the use of Ergocalciferol with respect to specific gender populations.

### Race
- There is no FDA guidance on the use of Ergocalciferol with respect to specific racial populations.

### Renal Impairment
- There is no FDA guidance on the use of Ergocalciferol in patients with renal impairment.

### Hepatic Impairment
- There is no FDA guidance on the use of Ergocalciferol in patients with hepatic impairment.

### Females of Reproductive Potential and Males
- There is no FDA guidance on the use of Ergocalciferol in women of reproductive potentials and males.

### Immunocompromised Patients
- There is no FDA guidance one the use of Ergocalciferol in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- THE RANGE BETWEEN THERAPEUTIC AND TOXIC DOSES IS NARROW.
- Vitamin D Resistant Rickets: 12,000 to 500,000 USP units daily.
- Hypoparathyroidism: 50,000 to 200,000 USP units daily concomitantly with calcium lactate 4g, six times per day.
- DOSAGE MUST BE INDIVIDUALIZED UNDER CLOSE MEDICAL SUPERVISION.
- Calcium intake should be adequate. Blood calcium and phosphorous determinations must be made every 2 weeks or more frequently if necessary. X-rays of the bones should be taken every month until condition is corrected and stabilized.

### Monitoring
- Caution should be exercised when ergocalciferol is administered to a nursing woman. In a mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Monitoring of the infants serum calcium concentration is required in that case (Goldberg, 1972).

# IV Compatibility
- There is limited information regarding IV Compatibility of Ergocalciferol in the drug label.

# Overdosage
- The effects of administered vitamin D can persist for two or more months after cessation of treatment.
Hypervitaminosis D is characterized by:
- Hypercalcemia with anorexia, nausea, weakness, weight loss, vague aches and stiffness, constipation, mental retardation, anemia, and mild acidosis.
- Impairment of renal function with polyuria, nocturia, polydipsia, hypercalciuria, reversible azotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or irreversible renal insufficiency which may result in death.
- Widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs. Bone demineralization (osteoporosis) in adults occurs concomitantly.
- Decline in the average rate of linear growth and increased mineralization of bones in infants and children (dwarfism).
- The treatment of hypervitaminosis D with hypercalcemia consists in immediate withdrawal of the vitamin, a low calcium diet, generous intake of fluids, along with symptomatic and supportive treatment. Hypercalcemic crisis with dehydration, stupor, coma, and azotemia requires more vigorous treatment. The first step should be hydration of the patient. Intravenous saline may quickly and significantly increase urinary calcium excretion. A loop diuretic (furosemide or ethacrynic acid) may be given with the saline infusion to further increase renal calcium excretion. Other reported therapeutic measures include dialysis or the administration of citrates, sulfates, phosphates, corticosteroids, EDTA (ethylenediaminetetraacetic acid), and mithramycin via appropriate regimens. With appropriate therapy, recovery is the usual outcome when no permanent damage has occurred. Deaths via renal or cardiovascular failure have been reported.
- The LD50 in animals is unknown. The toxic oral dose of ergocalciferol in the dog is 4 mg/kg.

# Pharmacology

## Mechanism of Action
- The in vivo synthesis of the major biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of ergocalciferol takes place in the liver (to 25-hydroxyvitamin D) and the second in the kidneys (to 1,25-dihydroxyvitamin D). Vitamin D metabolites promote the active absorption of calcium and phosphorous by the small intestine, thus elevating serum calcium and phosphate levels sufficiently to permit bone mineralization. Vitamin D metabolites also mobilize calcium and phosphate from bone and probably increase the reabsorption of calcium and perhaps also of phosphate by the renal tubules.
- There is a time lag of 10 to 24 hours between the administration of vitamin D and the initiation of its action in the body due to the necessity of synthesis of the active metabolites in the liver and kidneys. Parathyroid hormone is responsible for the regulation of this metabolism in the kidneys.

## Structure
- ERGOCALCIFEROL CAPSULES, USP, is a synthetic calcium regulator for oral administration.
- Ergocalciferol is a white, colorless crystal, insoluble in water, soluble in organic solvents, and slightly soluble in vegetable oils. It is affected by air and by light. Ergosterol or provitamin D2 is found in plants and yeast and has no antirachitic activity.
- There are more than 10 substances belonging to a group of steroid compounds, classified as having vitamin D or antirachitic activity.
- One USP Unit of vitamin D2 is equivalent to one International Unit (IU), and 1 mcg of vitamin D2 is equal to 40 IU.
- Each softgel, for oral administration, contains Ergocalciferol, USP 1.25 mg (equivalent to 50,000 USP units of Vitamin D), in an edible vegetable oil.
- Ergocalciferol, also called vitamin D2, is 9, 10-secoergosta-5,7,10(19),22-tetraen-3-ol,(3,5Z,7E,22E)-; (C28H44O) with a molecular weight of 396.65, and has the following structural formula:
- Inactive Ingredients: Refined soybean oil, gelatin, glycerin, purified water, D&C Yellow #10, and FD&C Blue #1.

## Pharmacodynamics
- There is limited information regarding Pharmacodynamics of Ergocalciferol in the drug label.

## Pharmacokinetics
- There is limited information regarding Pharmacokinetics of Ergocalciferol in the drug label.

## Nonclinical Toxicology
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
- No long-term animal studies have been performed to evaluate the drug's potential in these areas.

# Clinical Studies
- There is limited information regarding Clinical Studies of Ergocalciferol in the drug label.

# How Supplied
- Each green, oval softgel is imprinted with PA140 and contains 1.25 mg (50,000 USP units vitamin D) of ergocalciferol, USP, and is available in bottles of 100 (50111-990-01) Softgels.

## Storage
- Store at 25 C (77 F); excursions permitted to 15 - 30 C (59 - 86  F) 
- Protect from light and moisture.
- Dispense in a tight, light-resistant container as defined in the USP.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
- There is limited information regarding Patient Counseling Information of Ergocalciferol in the drug label.

# Precautions with Alcohol
- Alcohol-Ergocalciferol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
Calciferol,
Drisdol,
Vitamin D.

# Look-Alike Drug Names
- A  B

# Drug Shortage Status

# Price