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Ergocalciferol (Vitamin D2) tablets, capsules and solution for oral use

Summary about Ergocalciferol

Ergocalciferol, also known as vaitamin D2 and calciferol, is a type of vitamin D found in food and used as a dietary supplement.

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 phosphorus 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 4 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.

 

 

Ergocalciferol is indicated for the treatment of hypoparathyroidism, refractory rickets, and familial hypophosphatemia. Hypoparathyroidism is the result of inadequate parathyroid hormone production that occurs due to the presence of damage or removal of the parathyroid glands. This condition produces decreased calcium and increased phosphorus levels. Rickets is a condition produced due to a deficiency in vitamin D, calcium or phosphorus. However, this condition can also be related to renal diseases. It is characterized to present weak or soft bones. Familial hypophosphatemia is characterized by the impaired transport of phosphate and an altered vitamin D metabolism in the kidneys. The presence of this condition can derive in the presence of osteomalacia, bone softening and rickets.

 

 

Ergocalciferol (Vitamin D2) tablets, capsules and solution

Active Ingredient

Ergocalciferol

Administration Route

Oral

Alcohol Warning

No known interactions.

Available Strength

Capsule, Oral:

1.25 mg (50000 UT)

62.5 mcg (2500 UT)

Solution, Oral:

200 mcg/mL (60 mL)

Tablet, Oral:

10 mcg (400 UT), 50 mcg (2000 UT)

Breastfeeding Warning

Caution is recommended. It is excreted into human milk.

Comments:
-Large maternal doses of vitamin D led to hypercalcemia in a child.
-Monitoring of the infant’s serum calcium may be needed.
-The US Recommended Daily Allowance for lactating women is 600 international units per day.

Clinical Pharmacology

Pharmacodynamics

After the activation of the vitamin D receptor, some of the biological changes produced by ergocalciferol include mobilization and accretion of calcium and phosphorus in the bone, absorption of calcium and phosphorus in the intestine, and reabsorption of calcium and phosphorus in the kidney.

Some other effects known to be produced due to the presence of vitamin D are osteoblast formation, fetus development, induction of pancreatic function, induction of neural function, improvement of immune function, cellular growth and cellular differentiation.

When compared to its vitamin D counterpart cholecalciferol, ergocalciferol has been shown to present a reduced induction of calcidiol and hence, it is less potent.

Ergocalciferol supplementation in patients with end-stage renal disease has been shown to generate a significant benefit in lab parameters of bone and mineral metabolism as well as improvement in glycemic control, serum albumin levels and reduced levels of inflammatory markers

Pharmacokinetics

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

Absorption: Absorbed in the small intestine; fat soluble; requires bile

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

Half-life, circulating: 25(OH)D: 2 to 3 weeks; 1,25-dihydroxyvitamin D ~4 hours

Excretion: Feces

Cost

Capsules (Drisdol Oral):

1.25 MG(50000 UT) (per each): $3.49

Capsules (Ergocalciferol Oral)

1.25 MG(50000 UT) (per each): $0.72

Solution (Calcidol Oral)

200 mcg/mL (per mL): $1.66

Solution (Calciferol Oral)

200 mcg/mL (per mL): $3.44

Solution (Ergocalciferol Oral)

200 mcg/mL (per mL): $0.59 – $1.67

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer’s AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Form

Capsules, Solution and Tablets for oral administration

Dose Schedule

Osteoporosis prevention (off-label use): Oral: Adults ≥50 years of age: 800 to 1,000 units/day

Vitamin D insufficiency/deficiency treatment (off-label use):  Repletion strategies may vary depending on desired target serum 25(OH)D levels as well as the clinical status of the patient. The optimal serum 25(OH)D level is controversial; the Institute of Medicine recommends a 25(OH)D level >20 ng/mL as sufficient in nearly all persons, whereas others have suggested targeting a level of ~30 ng/mL to minimize the risk of fractures, particularly in patients with. However, some data suggest levels >40 ng/mL (median level in one trial: ~48 ng/mL) are associated with increased risk of falls in postmenopausal women.

Therefore, some experts recommend a range of 20 to 40 ng/mL as a reasonable target in most patients. Ergocalciferol (vitamin D2) is considered an alternative agent to the use of cholecalciferol (vitamin D3) by some experts due to limited data showing slightly higher levels of serum 25(OH)D achieved with D3, especially when higher doses or longer intervals are used. In patients with normal absorption, for every 100 units/day of vitamin D ingested the serum 25(OH)D level is expected to increase by ~0.7 to 1 ng/mL. The dose-response declines as the 25(OH)D concentration increases above 40 ng/mL (100 nmol/L). The following recommendations are based primarily on expert opinion and clinical experience:

Initial dosing (according to baseline serum 25(OH)D level):

Serum 25(OH)D 20 to 30 ng/mL: Initial: Supplementation dosing: Oral: 600 to 800 units once daily; a repeat serum 25(OH)D level is not required or 1,000 to 2,000 units once daily; may consider a repeat serum 25(OH)D level in ~3 months to determine if the target level has been achieved.

Serum 25(OH)D 10 to <20 ng/mL: Initial:Supplementation dosing: Oral: 800 to 1,000 units once daily or 2,000 units once daily; a repeat serum 25(OH)D level should be drawn after ~3 months. If target serum 25(OH)D level has not been achieved, may increase to 2,000 units once daily or administer therapeutic dosing of 50,000 units once weekly for 6 to 8 weeks.

OR

Therapeutic dosing (ie, high-dose ergocalciferol): Oral: 50,000 units once weekly (or 5,000 to 7,000 units once daily) for ~8 weeks followed by decreased maintenance dosing as needed to maintain target serum 25(OH)D level.

Serum 25(OH)D <10 ng/mL or in patients with deficiency symptoms : Initial: Therapeutic dosing (ie, high-dose ergocalciferol): Oral: 50,000 units once weekly (or 5,000 to 7,000 units once daily) for 6 to 8 weeks to achieve target serum 25(OH)D level; a repeat serum 25(OH)D level should be drawn after ~3 months to assure target serum 25(OH)D level has been met.

Maintenance dosing: Maintenance dosing is highly patient specific and dependent on target 25(OH)D level and may range from 600 to 800 units/day to 1,000 to 2,000 units/day

Special populations (eg, obese patients, patients on medications known to affect vitamin D metabolism, patients with malabsorption syndromes or gastrectomy): Higher doses or longer durations may be necessary for adequate repletion.

Vitamin D deficiency/insufficiency in patients with chronic kidney disease (off-label use): 

In patients without severe and progressive hyperparathyroidism, including chronic kidney disease (CKD) stages G3 to G5 and dialysis or transplant patients, KDIGO guidelines recommend correcting vitamin D deficiency and insufficiency with treatment strategies recommended for the general population using ergocalciferol (or cholecalciferol) while avoiding hypercalcemia and ensuring phosphate levels are in the normal range. An individualized monitoring approach to direct treatment is also recommended. In patients in whom serum parathyroid hormone levels are progressively rising and remain persistently elevated despite correction of modifiable factors (eg, hyperphosphatemia, vitamin D deficiency), calcitriol or vitamin D analogs are suggested instead of ergocalciferol (or cholecalciferol).

Hypoparathyroidism: Active vitamin D preparations (ie, alfacalcidolcalcitriol) in conjunction with calcium supplementation are recommended therapy. Addition of ergocalciferol (or cholecalciferol) may be considered for supplemental therapy.

Drug Class

A11CC — Vitamin D and analogues

Drug Unit

mg, mcg, IU, UT,  USP units

Food Warning

No known interactions with food.

Included In
Health Insurance Plan

In general, Medicare plans do not cover this drug.

Interacting Drugs

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. Risk X: 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 (eg, cholestyramine). Separate administration of these agents by several hours to minimize the potential risk of interaction. Monitor plasma calcium concentrations. Risk D: Consider therapy modification

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

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

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

Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Risk D: Consider therapy modification

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. Risk D: Consider therapy modification

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

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

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

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

Is Available Generically

Yes

Is Proprietary

No

Label Details

http://s3-us-west-2.amazonaws.com/drugbank/fda_labels/DB00153.pdf?1556227665

Legal Status

Legal.

Is not subject to the Controlled Substances Act.

Manufacturer

Strides Pharma Science Limited

Maximum Intake

In healthy patients 4000 IU is the safe upper limit according to the Institute of Medicine, which is needed to maintain optimal blood levels.

Mechanism of Action

For its activity, ergocalciferol is required to be transformed to its major active circulating hydroxylated metabolite and transported to the target organs in order to bind to its target, the vitamin D receptor.

The activation of the vitamin D receptor is part of the vitamin D endocrine system and it is described by the production of a change in the transcription rates of the vitamin D receptor target genes.The target genes in the DNA affected by the presence of ergocalciferol are called vitamin D response elements which are dependent on co-modulators.

The vitamin D receptor is a transcription factor and member of the steroid hormone nuclear receptor family. It presents a DNA binding domain (VDRE) that, when activated, recruits coregulatory complexes to regulate the genomic activity.

Additionally, ergocalciferol presents nongenomic effects such as the stimulation of intestinal calcium transport via transcaltachia.

Non Proprietary Name

Ergocalciferol

Overdosage

Symptoms of overdose may include:
  • loss of appetite
  • nausea
  • weakness
  • weight loss
  • muscle aches and stiffness
  • constipation
  • pale skin
  • increased urination (especially at night) or increased thirst
  • intellectual disability

Pregnancy Category


Safety has not been established during pregnancy. Use only if the benefit outweighs the risk to the fetus.AU TGA pregnancy category: Exempt
US FDA pregnancy category: C

Pregnancy Warning

-Avoid use of vitamin D in excess of the recommended dietary allowance.
-The safety of vitamin D doses in excess of 400 international units has not been established.Animal studies have shown fetal abnormalities associated with hypervitaminosis D, similar to supravalvular aortic stenosis syndrome. There are no controlled data in human pregnancy.AU Exempt: Medications exempted from pregnancy classification are not absolutely safe for use in pregnancy in all circumstances. Some exempted medicines, for example the complementary medicine, St John’s Wort, may interact with other medicines and induce unexpected adverse effects in the mother and/or fetus.US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Prescribing Info

http://s3-us-west-2.amazonaws.com/drugbank/fda_labels/DB00153.pdf?1556227665

Prescription Status

Rx and/or OTC

Proprietary Name

Calcidol, Calciferol, Drisdol

Related Drugs

Calcitriol, Calcifediol, Alfacalcidiol, Dihydrotachysterol

RxCUI

201327

4018

1101867

1043244

1246250

1246247

33272

209884

Warning


Concerns related to adverse effects:
  • Vitamin D toxicity: May occur with excessive doses; symptoms may include nausea, vomiting, loss of appetite, constipation, dehydration, fatigue, irritability, confusion, weakness, and/or weight loss. Effects of vitamin D can last ≥2 months after therapy is discontinued.

Disease-related concerns:

  • Hyperphosphatemia: Normal serum phosphorous concentrations must be maintained in patients treated for hyperphosphatemia to prevent metastatic calcification.
  • Obesity: Adults with a BMI >30 kg/m2are 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.
  • 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 (KDIGO 2009).

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

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution.

 

References:

Drugs.com [Internet]. Ergocalciferol Information from Drugs.com; c1996-2019 [Updated: 16 Jul 2018, Cited: 28 November 2019]. Available from: https://www.drugs.com/mtm/ergocalciferol.html

Drugbank.ca [Internet]. Ergocalciferol Information from Drugbank.ca; c1996-2019 [Updated: 27 November 2019, Cited: 28 November 2019]. Available from: https://www.drugbank.ca/drugs/DB00153

Uptodate.com [Internet]. Ergocalciferol Information from Uptodate.com; c1996-2019 [Updated: 21 November 2019, Cited: 28 November 2019]. Available from: https://www.uptodate.com/contents/vitamin-d2-ergocalciferol-patient-drug-information?search=ergocalciferol&topicRef=10150&source=related_link

Binkley N, Gemar D, Engelke J, et al. Evaluation of ergocalciferol or cholecalciferol dosing, 1,600 IU daily or 50,000 IU monthly in older adults. J Clin Endocrinol Metab. 2011;96(4):981–988. doi:10.1210/jc.2010-0015

Brandão-Lima PN, Santos BDC, Aguilera CM, Freire ARS, Martins-Filho PRS, Pires LV. Vitamin D Food Fortification and Nutritional Status in Children: A Systematic Review of Randomized Controlled Trials. Nutrients. 2019 Nov 14;11(11). pii: E2766. doi: 10.3390/nu11112766

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