Vitamin D

VITAMIN D

General Monograph

Vitamin

Action And Clinical Pharmacology: Vitamin D is a fat-soluble vitamin and has properties of both vitamins and minerals. The term vitamin D collectively refers to a group of structurally similar chemicals and their metabolites which includes alfacalcidol (1hydroxycholecalciferol), calcitriol (1,25-dihydroxycholecalciferol), cholecalciferol (vitamin D3), dihydrotachysterol (DHT) and ergocalciferol (vitamin D2). These agents have antirachitic properties.

The biologic activity of 40 IU vitamin D equals that of 1 µg of ergocalciferol or cholecalciferol.

Vitamin D is essential for the absorption and utilization of calcium and phosphate and aids in the mobilization of bone calcium and maintenance of serum calcium concentrations.

Cholecalciferol (vitamin D3) is synthesized in the skin on exposure to ultraviolet radiation. Cholecalciferol is also present in fish liver oils. Ergocalciferol (vitamin D2) is produced by ultraviolet irradiation of a provitamin D sterol (ergosterol) which occurs in yeast and fungi. Both of these agents which have equal biologic activity are metabolized in the liver to calcifediol (25-hydroxycholecalciferol) which is then hydroxylated in the kidney to calcitriol (1,25-dihydroxycholecalciferol). Calcitriol is considered the most active form. Dihydrotachysterol is produced by synthetic reduction of ergocalciferol. Patients with chronic renal disease cannot convert calcifediol to calcitriol. Alfacalcidol (1hydroxyvitamin D3), a synthetic analogue of calcitriol, is rapidly converted in the liver to calcitriol, bypassing the renal conversion step.

Because alfacalcidol, calcitriol and dihydrotachysterol do not require renal hydroxylation, they are useful in patients with renal failure.

Pharmacokinetics: Vitamin D analogs are readily absorbed from the small intestine if fat absorption is normal. Bile is required for absorption. Cholecalciferol and ergocalciferol are activated by the 2-step process described above. Dihydrotachysterol and alfacalcidol are activated by the liver. Vitamin D is eliminated renally and by biliary excretion.

Indications And Clinical Uses: Vitamin D analogs are used in treatment of refractory rickets (vitamin D resistant rickets), familial hypophosphatemia and hypoparathyroidism, and in the management of hypocalcemia and renal osteodystrophy in patients with chronic renal failure undergoing dialysis. Vitamin D is used in conjunction with calcium in the management and prevention of primary or corticosteroid-induced osteoporosis. Vitamin D supplementation is indicated when dietary intake is insufficient, e.g., breast-fed infants.

Contra-Indications: Known hypersensitivity to vitamin D or any of its analogues and derivatives. Hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin D, hypervitaminosis D. The manufacture of ergocalciferol states that it is contraindicated in patients with decreased renal function.

Precautions: Vitamin D analogs are usually nontoxic in physiologic doses. Chronic or acute administration of excessive doses may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae.

The therapeutic index of vitamin D analogs is narrow, and there is great interindividual variation in the dose that will lead to chronic toxicity. Daily doses of ergocalciferol ranging from 1.25 to 2.5 mg in adults and 25 µg in children may result in hypervitaminosis. Other vitamin D analogs with shorter duration of action may have a lower propensity to accumulate and to cause hypercalcemia.

Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, hypotonia. Later and possibly more serious manifestations include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification and seizures.

Periodic monitoring of serum calcium, phosphate, magnesium, alkaline phosphatase is recommended for patients taking vitamin D analogs. Serum calcium should be maintainedin the range of 2.25 to 2.5 mmol/L and not allowed to exceed 2.75 mmol/L.

Drug Interactions: Antacids (Magnesium-containing): Hypermagnesemia may develop when these agents are used concurrently with vitamin D, particularly in patients with chronic renal failure.

Anticonvulsants (Phenytoin, Phenobarbital): Decreased vitamin D effects may occur when certain anticonvulsants are administered, as they may induce hepatic microsomal enzymes and accelerate the conversion of vitamin D to inactive metabolites.

Cholestyramine, Colestipol, Mineral Oil: Intestinal absorption of vitamin D may be impaired. Patients on cholestyramine or colestipol should be advised to allow as much time as possible between the ingestion of these drugs and vitamin D.

Digoxin: Vitamin D should be used with caution in patients on digoxin as hypercalcemia (which may result with vitamin D use) may precipitate cardiac arrhythmias.

Thiazide Diuretics: Concurrent administration of thiazide diuretics and vitamin D to hypoparathyroid patients may cause hypercalcemia which may be transient or may require discontinuation of vitamin D.

Different vitamin D analogs should be administered concurrently.

Pregnancy: Safety of doses in excess of 400 IU (10 µg) of vitamin D daily during pregnancy has not been established. Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus and other effects.

Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany and seizures.

Lactation: Vitamin D is deficient in maternal milk; therefore breast-fed infants may require supplementation. Use of excessive amounts of vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of vitamin D analogs in excess of 10 µg daily should not be administered to nursing women.

Adverse Reactions: Vitamin D analogs are well tolerated in normal daily doses. Chronic excessive dosing can lead to toxicity (see Precautions).

Symptoms And Treatment Of Overdose: Symptoms: Acute intoxication with vitamin D analogs may cuase hypervitaminosis D (See Precautions).

Treatment: Treatment of acute or chronic intoxication includes withdrawal of the vitamin D analog and any calcium supplements, administration of oral or i.v. fluids and possibly corticosteroids or calciuric diuretics such as furosemide and ethacrynic acid. Peritoneal or hemodialysis with calcium free dialysate will help remove calcium.

If acute ingestion is recent, gastric lavage or emesis may minimize further absorption. If the drug has already passed through the stomach, administration of mineral oil may promote fecal elimination.

Hypercalcemia is usually reversible; however if metastatic calcification has occurred, severe renal or cardiac failure or even death may result.

Dosage And Administration: In preventing vitamin deficiencies, adequate dietary intake is preferred over supplementation whenever possible. For a listing of dietary sources of vitamin D, see Vitamin Food Sources in the Clin-Info section.

For a listing of the daily requirements of vitamin D and other vitamins, see Recommended Nutrient Intake in the Clin-Info section. It should be noted that expert groups are now recommending a daily intake of 400 to 800 IU vitamin D to optimize calcium absorption and prevent primary or corticosteroid-induced osteoporosis. Daily doses of 400 to 800 IU and sometimes higher are used in conjunction with calcium and other measures in the treatment of osteoporosis.

At doses used for active treatment of deficiency, the range between therapeutic and toxic doses is narrow.

Dosage of vitamin D analogs must be individualized with careful monitoring of serum calcium levels. Careful titration is necessary to avoid overdosage. Dietary and other sources of vitamin D must be considered. Calcium intake should be adequate.

Ergocalciferol: For vitamin D deficiency, 5 000 IU (125 g) daily until a biochemical and radiographic response is achieved.

For vitamin D resistant rickets, 12 000 to 500 000 IU (0.3 to 12.5 mg) daily.

For hypoparathyroidism, 50 000 to 200 000 IU (1.25 to 5 mg) daily. Calcium supplementation is also required.

Alfacalcidol: For hypocalcemia and osteodystrophy in patients with chronic renal failure undergoing dialysis: Initial: 1 g daily, the dosage being increased in increments of 0.5 g every 2 to 4 weeks as necessary, up to 2 g daily. Rarely a dose of 3 g/day is required. Maintenance: 0.25 g to 1 g/day.

Calcitriol: Adults: For management of hypocalcemia and osteodystrophy in patients with chronic renal failure on dialysis: Initial: 0.25 g daily; the daily dose may be increased by 0.25 g every 4 to 8 weeks as necessary.

Maintenance: 0.5 to 1 g daily. Patients with normal or only slightly reduced serum calcium levels may respond to 0.25 g every other day.

For hypoparathyroidism and vitamin D resistant rickets, initially, 0.25 g daily; the dosage may be increased by 0.25 g/day at 2- to 4-week intervals if necessary.

Children: Initiation of Treatment: For x-linked hypophosphatemic rickets, 0.01 to 0.02 g/kg/day (mean 0.018 g/kg/day). For vitamin D dependency rickets type I, 0.010 to 0.025 g/kg/day (mean 0.017 g/kg/day). For hypoparathyroidism, 0.03 to 0.05 g/kg/day (mean 0.04 g/kg/day). If biochemical improvement has not occurred in 2 weeks, the dose is increased by 25% and re-evaluated in 2 weeks. Maintenance: For x-linked hypophosphatemic rickets, 0.01 to 0.05 g/kg/day (mean 0.022 g/kg/day). For vitamin D dependency rickets type I, 0.0046 to 0.015 g/kg/day. For hypoparathyroidism, 0.014 to 0.04 g/kg/day (mean 0.025 g/kg/day).

Dihydrotachysterol: For treatment of acute, chronic and latent forms of post-operative tetany, idiopathic tetany and hypoparathyroidism: Initial: 0.75 to 2.5 mg daily for several days.

Maintenance: 0.25 mg weekly to 1 mg/day depending on serum calcium levels.

VITAMIN D General Monograph, Vitamin

Posted by

Connected Diseases :

Vitamin Deficiency

General Illness Information: Description: Vitamin deficiency (avitaminosis, beriberi) is a disease caused by a severe shortage of vitamins in the body, which leads to serious…