FRUBIOSE VIT D 1000 U.I

Ergocalciferol is an inactivated vitamin

D analog.

It is synthesized by some plants in the presence of UVB light.

The production of ergocalciferol was prompted by the identification of dietary deficiency, more specifically vitamin D, as the main causative factor for the development of rickets.

Ergocalciferol was isolated for the first time from yeast in and its structure was elucidated in 1932.

Ergocalciferol is considered the first vitamin

D analog and is differentiated from cholecalciferol by the presence of a double bond between C22 and C23 and the presence of a methyl group at C24.

These modifications reduce the affinity of ergocalciferol for the vitamin D binding protein resulting in faster clearance, limits its activation, and alters its catabolism.

The first approved product containing ergocalciferol under the FDA records was developed by US Pharm Holdings and was FDA approved in 1941.

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.

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.

Ergocalciferol is absorbed in the intestine and carried to the liver in chylomicrons.

Its intestinal absorption does not present limitations unless the presence of conditions related to fat malabsorption.

However, for absorption to take place, the presence of bile is required.

The amount of circulating ergocalciferol is very limited as this compound is rapidly stored in fat tissue such as adipose tissue, liver and muscle.

This is very obvious in reports that indicate that circulating ergocalciferol is significantly reduced in obese patients.

Ergocalciferol is inactive and hence, the first step in the body is ruled by the conversion of this parent compound to 25-hydroxyvitamin D by the action of CYP2R1 followed by the generation of the major circulating metabolite, 1,25-dihydroxyvitamin D or calcitrol.

The generation of this major metabolite is ruled by the activity of CYP27B1 which is a key 1-hydroxylase and CYP24A1 which is responsible for the 25-hydroxylation.

As part of the minor metabolism, ergocalciferol is transformed into 25-hydroxyvitamin D in the liver by the activity of D-25-hydroxylase and CYP2R1.

As well, the formation of 24(R),25dihydroxyvitamin D is performed mainly in the kidneys by the action of 25-(OH)D-1-hydroxylase and 25-(OH)D-24-hydroxylase.

Additionally, there are reports indicating significant activity of 3-epimerase in the metabolism of ergocalciferol which modifies the hydroxy group in C3 from the alpha position to a beta.

The epimers formed seemed to have a reduced affinity for the vitamin D plasma proteins and to the vitamin D receptor.

An alternative activation metabolic pathway has been reported and this process is characterized by the activity of CYP11A1 and its hydroxylation in the C-20.

This 20-hydroxylated vitamin D seems to have similar biological activity than calcitriol.

Hover over products below to view reaction partners Ergocalciferol 25-hydroxyvitamin D Calcitrol 24(R),25dihydroxyvitamin D beta-ergocalciferol 20-hydroxyvitamin D.

The active form of ergocalciferol, calcitrol, cannot be maintained for long periods in storage tissue mainly in periods of dietary or UVB deprivation.

Therefore, ergocalciferol and its metabolites are excreted via the bile with a minor contribution of renal elimination.

This major fecal elimination is explained due to the cubilin-megalin receptor system-mediated renal reuptake of vitamin D metabolites bound to vitamin D binding protein.

Ergocalciferol can be found circulation for 1-2 days.

This quick turnover is presented due to hepatic conversion and uptake by fat and muscle cells where it is transformed to the active form.

There are no formal reports regarding the clearance rate of ergocalciferol.

Due to the structural similarity, it is recommended to consult this parameter with cholecalciferol.

On the other hand, the proposed renal clearance of calcitriol is of 31 ml/min.

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The reported

LD50 for Oral administered ergocalciferol in the rat is of 10 mg/kg.

Once an overdose state is registered, immediate withdrawal of vitamin D is required along with a calcium diet, generous intake of fluids and symptomatic treatment.

The administration of loop diuretics is an option to increase renal calcium excretion.

On the other hand, dialysis and administration of citrates, sulfates, phosphates, corticosteroids, EDTA and mithramycin are recommended.

There haven't been long term studies analyzing the carcinogenic and mutagenic potential of ergocalciferol or its effects in fertility.

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.

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

Rickets: 12,000 to 500,000 USP units daily.

Hypoparathyroidism: 50,000 to 200,000 USP units daily concomitantly with calcium lactate 4 g, 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.

Each green, oval softgel is imprinted with PA140 and contains 1,250 mcg (50,000 USP units vitamin D) of ergocalciferol, USP, and is available in NDC 71335-2246-1: 4 Capsules in a BOTTLE NDC 71335-2246-2: 12 Capsules in a BOTTLE NDC 71335-2246-3: 8 Capsules in a BOTTLE Store at 25° C (77° F); excursions permitted to 15° to 30° C (59° to 86° F) .

Protect from light and moisture.

Dispense in a tight, light-resistant container as defined in the USP.

Repackaged/Relabeled by: Bryant Ranch Prepack Burbank, CA 91504.

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.

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.

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 infant's serum calcium concentration is required in that case (Goldberg, 1972).

Pediatric doses must be individualized See DOSAGE AND ADMINISTRATION.

Clinical studies of

Ergocalciferol capsules, USP did not include sufficient numbers of subjects aged 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.