Colecalciferol

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[edit] BRAND NAMES

[edit] STRUCTURE

Colecalciferol.png

[edit] MECHANISM OF ACTION

Colecalciferol also called Vitamin D3 is produced in the skin by conversion of 7-dehydrocholesterol to vitamin D3 by ultraviolet light. In the absence of adequate sunlight exposure, vitamin D3 is an essential dietary nutrient.

Vitamin D3 is converted to 25-hydroxyvitamin D3 in the liver, and stored until needed. Conversion to the active calcium-mobilizing hormone 1,25-dihydroxyvitamin D3 (calcitriol) in the kidney is tightly regulated. The principal action of 1,25-dihydroxyvitamin D3 is to increase intestinal absorption of both calcium and phosphate as well as regulate serum calcium, renal calcium and phosphate excretion, bone formation and bone resorption.

Vitamin D3 is required for normal bone formation. Vitamin D insufficiency develops when both sunlight exposure and dietary intake are inadequate. Insufficiency is associated with negative calcium balance, bone loss, and increased risk of skeletal fracture. In severe cases, deficiency results in secondary hyperparathyroidism, hypophosphataemia, proximal muscle weakness and osteomalacia, further increasing the risk of falls and fractures in osteoporotic individuals. Supplemental vitamin D reduces these risks and their consequences. [1]

Onset of action – Hypercalcaemic: 12 to 24 hours; therapeutic effect may take 10 to 14 days.

Duration of action : Following oral administration: up to 6 months; repeated doses have a cumulative action. (Vitamin D can be stored in adipose and muscle tissue for long periods of time. It is slowly released from such storage sites and from the skin where it is formed in the presence of sunlight or ultraviolet light. Ergocalciferol and colecalciferol have a slow onset and a long duration of action; calcitriol and its analogue alfacalcidol, however, have a more rapid action and shorter half-lives.)

[edit] INDICATIONS

Colecalciferol is indicated for prevention and treatment of vitamin D deficiency states. Vitamin D deficiency may occur as a result of inadequate nutrition, intestinal malabsorption, or lack of exposure to sunlight, but does not occur in healthy individuals receiving an adequate balanced diet and exposure to sunlight. Colecalciferol is indicated also in combination with calcium for the treatment of osteoporosis

Requirements may be increased and / or supplementation may be necessary in the following persons or conditions (although clinical deficiencies are usually rare):

  • Postmenopausal women with increased risk of developing osteoporosis
  • Alcoholism.
  • Dark-skinned individuals.
  • Hepatic-bilary tract disease – hepatic function impairment, cirrhosis, obstructive jaundice.
  • Infants, breast-fed, with inadequate exposure to sunlight.
  • Intestinal disease – celiac, tropical sprue, regional enteritis, persistent diarrhoea.
  • Lack of exposure to sunlight combined with reduced vitamin D intake.
  • Renal function impairment.
  • In general, vitamin D absorption will be impaired in any condition in which fat malabsorption (steatorrhoea) occurs.

[edit] DOSAGE

  • Adults and elderly: 600-1000 IU per day (15-25 µg/day)
  • Pregnancy: the daily intake should not exceed 600 IU


Colecalciferol 1.25mg tablets:

  • Moderate/Severe Vitamin D insufficiency (less than 10 micrograms/litre of serum 25 hydroxy Vitamin D concentration): Dosage = 1 x Colecalciferol tablet a day for 10 days (loading), then 1 x Colecalciferol tablet a month (maintenance)
  • For Mild/Moderate Vitamin D insufficiency, (i.e. 10mcg/L or higher): Dosage = 1 x Colecalciferol tablet a month


Before vitamin D therapy is begun, elevated serum phosphate concentrations must be controlled.

Clinical response to vitamin D depends on adequate dietary calcium.

Because of individual variation in sensitivity to its effects, dosage of vitamin D must be adjusted on the basis of clinical response. Some infants are hyper reactive to even small doses. Careful titration is necessary to avoid overdosage, which induces hypercalcaemia and can cause hypercalciuria and hyperphosphataemia.

Dosage of vitamin D from dietary and other sources should be evaluated in determining the therapeutic dosage.

The serum calcium times phosphorus (Ca X P, in mg/dL) product should not exceed 60.

To control elevated serum phosphate concentrations in patients undergoing dialysis, a phosphate binding agent should be used. The dosage of the binding agent may need to be increased during vitamin D therapy since phosphate absorption is enhanced.

Deficiency due to malabsorption states or liver disease often requires higher doses for treatment, of up to 1 mg (40 000 units) daily. Doses of up to 2.5mg (100 000 units) daily may be used in the treatment of hypocalcaemia due to hypoparathyroidism.

Colecalciferol does not need to be administered with food.

[edit] CONTRAINDICATIONS

Colecalciferol is contraindicated when there is biochemical evidence of hypercalcemia, hyperphosphataemia, or evidence of vitamin D overdose

[edit] WARNINGS AND PRECAUTIONS

During long term treatment, serum and urinary calcium levels and kidney function should be monitored. This monitoring is particularly important in the elderly, in cases of combined treatment with cardiac glycosides or diuretics and in patients who are frequently subject to the formation of kidney stones. The dose should be reduced or treatment interrupted if urinary calcium exceeds 7.5mmol/24h (300mg/24h), in the presence of hypercalcaemia or if there are signs of problems with renal function.

Use with caution in patients with renal insufficiency and the effects on calcium and phosphate homeostasis should be monitored. In patients with severe renal insufficiency, other forms of vitamin D3 (i.e Alfacalcidol) must be used. Also use with caution in patients with sarcoidosis, in whom serum and urinary calcium should be monitored

[edit] INTERACTIONS

  • Use with caution in patients being treated with thiazide diuretics (e.g., hydrochlorothiazide). as they may have an increased risk of developing hypercalcemia. Plasma-calcium concentrations should be monitored in patients receiving the drugs concurrently.
  • Some antiepileptics may increase vitamin D requirements (e.g. carbamazepine, phenobarbitone, phenytoin, and primidone) due to the induction of hepatic detoxification enzymes.
  • Concomitant administration of colestyramine, orlistat and mineral oil may interfere with the intestinal absorption of Colecalciferol.
  • A case of severely decreased prothrombin has been reported as due to a possible interaction of vitamin D with warfarin and calcium carbonate.
  • Colecalciferol should be used with extreme caution in patients on digitalis (Digoxin - Lanoxin), as hypercalcemia may trigger cardiac arrhythmias.

[edit] PREGNANCY AND LACTATION

  • Colecalciferol may be used during pregnancy and lactation. However, the daily intake should not exceed 600 IU. In pregnancy, an overdose of colecalciferol must be avoided

[edit] SIDE EFFECTS

Uncommon (≥1/1,000 to <1/100): hypercalcaemia, hypercalciuria.

Rare (≥1/10,000 to <1/1,000): constipation, flatulence, nausea, abdominal pain, diarrhoea, pruritus, rash and urticaria.


Ingestion of excessive doses of vitamin D either as an acute overdose or over prolonged periods can result in severe toxicity.

Chronic vitamin D-induced hypercalcaemia may result in generalised vascular calcification, nephrocalcinosis, and other soft tissue calcification that may lead to hypertension and renal failure. These effects are more likely to occur when the hypercalcaemia is accompanied by hyperphosphataemia.

Growth may be arrested in children, especially after prolonged administration of 45mcg (1800 units) of colecalciferol per day.

Death may occur as a result of renal or cardiovascular failure caused by vitamin D toxicity.

Dosage necessary to cause toxicity varies with individual sensitivity, but in individuals without malabsorption problems, 250mcg (10,000 units) a day for more than several weeks or months is the maximum dose.


The early and late signs and symptoms associated with vitamin D intoxication and hypercalcemia may include:

  • Early: Pruritus, weakness, headache, "red-eyes", somnolence, nausea, cardiac arrhythmia, vomiting, excessive thirst, dry mouth, constipation, muscle pain, bone pain and metallic taste.
  • Late: Polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis, corneal calcification, photophobia, rhinorrhea, pancreatitis, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis.

[edit] RELATED LINKS

Calcium and phosphate homeostasis, including discussion of vitamin D metabolism and the actions of PTH
How osteoporosis develops

[edit] BIBLIOGRAPHY

[edit] REFERENCES

  1. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001180/WC500023479.pdf