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Vitamin D3 (cholecalciferol) tablets for oral use

Summary about Vitamin D3

Vitamin D3, also known as cholecalciferol and colecalciferol, is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement.

Vitamin D3, also known as cholecalciferol and colecalciferol, is a type of vitamin D which is made by the skin when exposed to sunlight; it is also found in some foods and can be taken as a dietary supplement.

 

 

Together with calcium, Vitamin D3 is used to treat or prevent bone loss (osteoporosis). Vitamin D3 is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth. Vitamin D drops (or other supplements) are given to breast-fed infants because breast milk usually has low levels of vitamin D.

 

 

Vitamin D3 (cholecalciferol) tablets

Active Ingredient

Cholecalciferol

Administration Route

Oral

Alcohol Warning

No known interactions.

Available Strength

10 mcg (400 UT), 25 mcg (1000 UT), 50 mcg (2000 UT), 1.25mg (5000 UT)

Breastfeeding Warning

The required dose of vitamin D during lactation has not been adequately studied; doses similar to those for pregnant women have been suggested.

Chronic ingestion of large doses of vitamin D by the mother may lead to hypercalcemia in the breastfed infant.

Use is not recommended unless the clinical condition of the woman requires treatment.

Excreted into human milk: Yes

Comments:
-Make allowance for any maternal dose if prescribing this product to a breast fed infant.
-Consider monitoring the infant’s serum calcium if the mother is receiving pharmacologic doses of vitamin D.
-Vitamin D supplementation is recommended in exclusively breast fed infants.

Clinical Pharmacology

Pharmacodynamics

The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 cholecalciferol (or D2) occurs in the liver to yield 25-hydroxyvitamin D while the second hydroxylation happens in the kidneys to give 1, 25-dihydroxyvitamin D. These vitamin D metabolites subsequently facilitate the active absorption of calcium and phosphorus in the small intestine, serving to increase serum calcium and phosphate levels sufficiently to allow bone mineralization. Conversely, these vitamin D metabolites also assist in mobilizing calcium and phosphate from bone and likely increase the reabsorption of calcium and perhaps also of phosphate via the renal tubules. There exists a period of 10 to 24 hours between the administration of cholecalciferol and the initiation of its action in the body due to the necessity of synthesis of the active vitamin D metabolites in the liver and kidneys. It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys

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

1.25 MG(50000 UT) (per each): $1.08

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Dosage Form

Tablets for oral use

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. Cholecalciferol (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 cholecalciferol): 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 cholecalciferol): 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 cholecalciferol (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 cholecalciferol (or cholecalciferol).

Hypoparathyroidism: Active vitamin D preparations (ie, alfacalcidolcalcitriol) in conjunction with calcium supplementation are recommended therapy. Addition of cholecalciferol (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

https://www.geneesmiddeleninformatiebank.nl/smpc/h113281_smpc_en.pdf

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

Non Proprietary Name

Cholecalciferol

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

https://www.geneesmiddeleninformatiebank.nl/smpc/h113281_smpc_en.pdf

Prescription Status

Rx and OTC

Proprietary Name

BProtected Pedia D-Vite, Bio-D-Mulsion, Bio-D-Mulsion Forte, Carlson D, Celebrate Vitamin D3 Quick-Melt, D 1000 IU, D-Vita Drops, D2000, D3, D3-5, D3-50, D400, Ddrops, Decara, Delta D3, Enfamil D-Vi-Sol, Maximum D3, Replesta, Replesta Children’s, Replesta NX, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, Vitamin D3, Wellesse Vitamin D3

Related Drugs

Calcitriol, Calcifediol, Alfacalcidiol, Dihydrotachysterol

RxCUI

1244014

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 cholecalciferol 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]. Medroxyprogesterone Information from Drugs.com; c1996-2019 [Updated: 10 March 2019, Cited: 28 November 2019]. Available from: https://www.drugs.com/medroxyprogesterone.html

Drugbank.ca [Internet Medroxyprogesterone Information from Drugbank.ca; c1996-2019 [Updated: 28 November 2019, Cited: 28 November 2019]. Available from: https://www.drugbank.ca/drugs/DB00603

Uptodate.com [Internet]. Cholecalciferol Information from Uptodate.com; c1996-2019 [Updated: 21 November 2019, Cited: 28 November 2019]. Available from: https://www.uptodate.com/contents/medroxyprogesterone-acetate-drug-information?search=medroxyprogesterone&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#F191983

Cundy T, Farquhar CM, Cornish J, Reid IR. Short-term effects of high dose oral medroxyprogesterone acetate on bone density in premenopausal women. J Clin Endocrinol Metab. 1996 Mar;81(3):1014-7

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