VITAMIN D2
CASRN: 50-14-6
Human Health Effects:
Human Toxicity Excerpts:
HYPERCALCEMIA ... CONSTANT FINDING IN ... TOXIC SYMPTOMS. INITIAL SYMPTOMS USUALLY INCL
ANOREXIA, NAUSEA & VOMITING ... OFTEN MIMICS HYPERPARATHYROIDISM WITH POLYURIA &
POLYDIPSIA, MUSCULAR WEAKNESS, NERVOUSNESS & ITCHING, METASTATIC CALCIFICATION IN
KIDNEYS ... RENAL IMPAIRMENT & HYPERTENSION ... CEREBELLAR ATAXIA ... . /VITAMIN D/
... METASTATIC CALCIFICATION OCCURS IN CORNEA & CONJUNCTIVA IN FORM OF BAND
KERATOPATHY. OFTEN ACCOMPANIED BY WHITE FLECKS & CRYSTAL-LIKE OPACITIES IN THE BULBAR
CONJUNCTIVA. /VITAMIN D/
AMT ... WHICH ARE ONLY ABOUT 80 TO 100 TIMES RECOMMENDED DIETARY INTAKE, MAY LEAD TO
HYPERCALCEMIA & ... METASTATIC CALCIFICATION & RENAL CALCULI. ... DEMINERALIZATION
OF BONES ... & MULTIPLE FRACTURES ... FROM VERY SLIGHT TRAUMA. /VITAMIN D/
THERE IS A RELATIONSHIP BETWEEN EXCESS MATERNAL VITAMIN D INTAKE OR EXTREME SENSITIVITY
TO THE VITAMIN AND NONFAMILIAL CONGENITAL SUPRAVALVULAR AORTIC STENOSIS. IN INFANTS, THIS
ANOMALY IS OFTEN FOUND IN ASSOCIATION WITH OTHER STIGMATA OF HYPERCALCEMIA. /VITAMIN D/
Initial signs and symptoms ... consists of weakness, fatigue, lassitude, headache,
nausea, vomiting, and diarrhea. Obtundation and coma may develop. Early impairment of
renal function from hypercalcemia is manifest by polyuria, polydipsia, nocturia, decreased
urinary concentration ability, and proteinuria.
SERIOUS TOXICITY MAY RESULT FROM EXCESSIVE INGESTION OF VITAMIN, AND EVEN AS LITTLE AS
1800 USP UNITS PER DAY IN INFANTS MAY LEAD TO POSSIBLE INHIBITION OF GROWTH. /VITAMIN D/
VITAMIN D TOXICITY ... THERE IS EVIDENCE FOR HYPERREACTIVITY TO VITAMIN D IN
FAIR-SKINNED CHILDREN HAVING GREATER SUSCEPTIBILITY. /VITAMIN D/
Vitamin D ingested in excess results in hypercalcemia, which is caused by excessive
absorption of massive quantities of calcium by the intestine and enhanced bone resorption.
The symptoms of this intoxication include feeding difficulties, polydypsia, polyuria,
irritability, lassitude and poor weight gain. Because daily intakes of 400 IU (10 g) of
vitamin D2 or D3 are completely safe, and because as low as 100 IU (2.5 g) daily may
prevent rickets, it is difficult to justify recent studies that attempt to firmly
establish an upper limit of daily vitamin D intake in the normal neonate. Thus, despite
efforts to better understand the upper limits of daily vitamin D intake, a concentration
of 100 IU (2.5 g) of vitamin D per 100 kcal ingested, as is currently recommended by the
Committee on Nutrition of the American Academy of Pediatrics, seems entirely appropriate.
/Vitamin D/
MATERNAL HYPERCALCEMIA MAY ALSO RESULT IN SUPPRESSION OF PARATHYROID FUNCTION IN THE
NEWBORN WITH RESULTANT HYPOCALCEMIA, TETANY, AND SEIZURES. /VITAMIN D/
Drug Warnings:
USE ... FOR TREATMENT OF LUPUS VULGARIS IS OBSOLETE & ITS TOPICAL USE FOR OTHER
DERMATOSES IS NOT JUSTIFIED. /VITAMIN D/
Maternal Medication usually Compatible with Breast-Feeding: D (Vitamin): Reported Sign
or Symptom in Infant or Effect on Lactation: None; follow up in infant's serum calcium
level if mother receives pharmacological doses. /from Table 6/
POTENTIAL ADVERSE EFFECTS ON FETUS: Teratogenic in animals at high doses (4-15x
recommended human dose). In humans, maternal hypercalcemia during pregnancy may increase
fetal sensitivity to effects of vitamin D, suppression of parathyroid function or a
syndrome of elfin facies, mental retardation, and congenital supravalvular aortic
stenosis. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: No known problems at recommended
daily allowance. FDA Category: C (C = Studies in laboratory animals have revealed adverse
effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies
in pregnant women. The benefits from use of the drug in pregnant women may be acceptable
despite its potential risks, or there are no laboratory animal studies or adequate studies
in pregnant women.) /Vitamin D from table II/
Emergency Medical Treatment:
Emergency Medical Treatment:
| EMT Copyright Disclaimer: |
| Portions of the POISINDEX(R) database are provided here for general
reference. THE COMPLETE POISINDEX(R) DATABASE, AVAILABLE FROM MICROMEDEX, SHOULD BE
CONSULTED FOR ASSISTANCE IN THE DIAGNOSIS OR TREATMENT OF SPECIFIC CASES. Copyright
1974-1998 Micromedex, Inc. Denver, Colorado. All Rights Reserved. Any duplication,
replication or redistribution of all or part of the POISINDEX(R) database is a violation
of Micromedex' copyrights and is strictly prohibited. The following Overview, *** VITAMIN D ***, is relevant for this HSDB record chemical. |
| Life Support: |
o This overview assumes that basic life support measures
have been instituted.
|
| Clinical Effects: |
SUMMARY OF EXPOSURE
0.2.1.1 ACUTE EXPOSURE
o Vitamin D is used as a nutrient and/or dietary
supplement food additive and as a rodenticide. Most
human exposures occur primarily with ingestion of
Vitamin D in multivitamins. Toxic effects are usually
the result of over-supplementation, not acute ingestion
which rarely results in toxicity. Exposure to Vitamin
D used as a rodenticide may also occur.
o Vitamin D is toxic by the ingestion, intraperitoneal,
intravenous, and intramuscular routes. In ingestion
poisonings, symptoms include anorexia, nausea,
vomiting, and weight loss. Many of the other effects
of chronic vitamin D toxicity are due to induced
hypercalcemia. Polyneuropathy may be seen.
HEENT
0.2.4.2 CHRONIC EXPOSURE
o Conjunctivitis, keratopathy, elevated lens calcium, and
inhibition of growth of the human retinoblastoma cell
line grown in athymic mice have been observed.
CARDIOVASCULAR
0.2.5.1 ACUTE EXPOSURE
o Cardiac arrhythmias and myocardial infarction may be
seen with chronically high ingestion.
1. Changes in rat coronary arteries have been observed.
0.2.5.2 CHRONIC EXPOSURE
o Cardiac arrhythmias, myocardial infarction, and
mineralization of the endocardium and wall of large
blood vessels may be seen.
NEUROLOGIC
0.2.7.1 ACUTE EXPOSURE
o Symptoms are similar to hypercalcemia: anorexia,
fatigue, headache, itching, and weakness.
o Polyneuropathy has been reported after acute
intoxication.
GASTROINTESTINAL
0.2.8.1 ACUTE EXPOSURE
o Nausea, vomiting, and diarrhea may be seen.
1. Hemorrhagic gastritis has been seen in animal studies.
HEPATIC
0.2.9.1 ACUTE EXPOSURE
o Hepatomegaly has been reported in one case.
GENITOURINARY
0.2.10.1 ACUTE EXPOSURE
o Chronic exposures may produce metastatic calcification
of the renal tubules resulting in albuminuria,
nocturia, polydipsia, and polyuria.
0.2.10.2 CHRONIC EXPOSURE
o Chronic exposures may produce metastatic calcification
of the renal tubules resulting in albuminuria,
nocturia, polydipsia, and polyuria; nephropathy and
hyposthenuria have also been reported.
FLUID-ELECTROLYTE
0.2.12.1 ACUTE EXPOSURE
o Hypercalcemia is frequently reported following chronic
ingestion of excessive doses or following chronic
occupational exposure.
0.2.12.2 CHRONIC EXPOSURE
o Hypercalcemia, hypocalcemia, and hyperphosphatemia have
been observed.
HEMATOLOGIC
0.2.13.1 ACUTE EXPOSURE
o Normocytic, normochromic anemia has been described
after chronic intoxication.
0.2.13.2 CHRONIC EXPOSURE
o Normocytic, normochromic anemia has been described
after chronic intoxication.
MUSCULOSKELETAL
0.2.15.1 ACUTE EXPOSURE
o Widespread joint, periarticular, and nephro-calcinosis
occurred in one case. Demineralization of bone may
result in multiple fractures from very slight trauma.
METABOLISM
0.2.17.2 CHRONIC EXPOSURE
o Cessation of growth or weight loss have been noted in
experimental animals.
PSYCHIATRIC
0.2.18.1 ACUTE EXPOSURE
o Extreme depression, apathy, confusion, and fatigue may
be associated with chronic excessive intake of vitamin
D.
REPRODUCTIVE HAZARDS
o In humans, aortic stenosis was associated with high
doses of vitamin D in pregnancy. However, conflicting
results have been observed. In animal studies, toxic
effects including fetotoxicity, spontaneous abortion and
specific developmental abnormalities were observed.
CARCINOGENICITY
0.2.21.2 HUMAN OVERVIEW
o At the time of this review, no data were available to
assess the carcinogenic potential of this agent.
GENOTOXICITY
o At the time of this review, no data were available to
assess the mutagenic or genotoxic potential of this
agent.
|
| Laboratory: |
o Serum calcium and phosphate levels should be monitored
closely. Estimation of vitamin D levels is usually
restricted to a specialized (research) laboratory.
1. Vitamin D may also be measured in infant formula,
multivitamin-mineral formulations, cereals, mixed feed
components, and mixed feeds.
|
| Treatment Overview: |
SUMMARY EXPOSURE
o The following treatment information is for vitamin D in
general:
1. ORAL EXPOSURE -
a. Emesis, activated charcoal, and cathartics are seldom
necessary with acute ingestion unless extremely large
amounts are ingested (more than 100 times the RDA).
Rodenticide ingestion may be acutely toxic.
b. CHRONIC EXPOSURE -
(1) Initiate a low calcium diet.
(2) Urine acidification will enhance excretion. Consider
administration of ascorbic acid 500 milligrams four
times a day. Attempt to lower the urinary pH to
below 5.5.
(3) Calcium excretion may be increased by forced diuresis
with intravenous furosemide (20 to 40 milligrams IV
every 4 to 6 hours). Urine flow should be maintained
at greater than 3 milligrams/kilogram/hour.
(4) Measure urinary volumes, sodium, and potassium as
pooled samples at least once every day. Replace lost
fluids, sodium, and potassium by IV infusions.
(5) Prednisone - a dose of 1 milligram/kilogram/day to a
maximum of 20 milligram/day should be administered
for a short one to two week course thereby decreasing
plasma calcium. Rebound elevations in plasma calcium
may occur.
(6) Calcitonin - A 4 MRC units/kilogram body weight
intramuscular injection every 12 hours has been used
in one case of vitamin D intoxication with some
success.
(7) Severe hypercalcemia not responding to other
therapies has been treated with sodium EDTA or
mithramycin. These agents should be used with great
caution.
(8) Cholestyramine - Doses of 12 to 16 grams/day may be
effective in lowering serum calcium levels.
ORAL EXPOSURE
o Emesis, activated charcoal, and cathartics are seldom
necessary with acute ingestion unless extremely large
amounts are ingested (more than 100 times the RDA).
Rodenticide ingestion may be acutely toxic.
o CHRONIC EXPOSURE - Initiate a low calcium diet.
1. Urine acidification will enhance excretion. Consider
administration of ascorbic acid 500 mg four times a
day. Attempt to lower the urinary pH to below 5.5.
2. Calcium excretion may be increased by forced diuresis
with intravenous furosemide (20 to 40 mg IV every 4 to
6 hours). Urine flow should be maintained at greater
than 3 mL/kg/hr.
3. Measure urinary volumes, sodium, and potassium as
pooled samples at least once every day. Replace lost
fluids, sodium, and potassium by IV infusions.
4. Prednisone - A dose of 1 mg/kg/day to a maximum of 20
mg/day should be administered for a short one to two
week course, to decrease plasma calcium. Rebound
elevations in plasma calcium may occur.
5. Calcitonin - A 4 MRC units/kg body weight intramuscular
injection every 12 hours has been used in one case of
vitamin D intoxication with some success.
6. Severe hypercalcemia not responding to other therapies
has been treated with sodium EDTA or mithramycin.
These agents should be used with great caution.
7. CHOLESTYRAMINE - Doses of 12 to 16 g/day may be
effective in lowering serum calcium levels.
|
| Range of Toxicity: |
o The RDA is 400 IU/day for adults and children.
o Chronic ingestions of vitamin D in excess of 1600
units/day may cause toxicity. Daily ingestions in excess
of 2000 units in children or 75,000 units in adults may
produce toxic symptoms associated with hypervitaminosis D.
Limited data are available on the toxicity due to single
overdoses.
|
Antidote and Emergency Treatment:
CALCIFIC BAND KERATOPATHY ... CAN GRADUALLY DISAPPEAR AFTER POISONING ... OR IT CAN BE
REMOVED SURGICALLY BY SCRAPING CORNEA, OR IT CAN BE DISSOLVED IN 10 TO 20 MIN BY
APPLICATION OF 0.01 TO 0.05 M SODIUM EDETATE @ PHYSIOLOGIC PH AFTER REMOVAL OF EPITHELIUM
FROM CORNEA. /VITAMIN D/
Animal Toxicity Studies:
Non-Human Toxicity Excerpts:
... EXCESSIVE DOSES ... OVER EXTENDED PERIOD OF TIME, HYPERCALCEMIA & CALCIFICATION
OF BLOOD VESSELS, MUSCLES & OTHER TISSUES MAY RESULT IN EXPERIMENTAL ANIMAL. IN
HYPERVITAMINOSIS D CALCIUM SALTS ARE LAID DOWN IN MUCOPOLYSACCHARIDE MATRIX IN SOFT
TISSUES.
LETHAL DOSE IN DOG IS SAID TO BE ... 13 MG/KG (530,000 IU/KG) BODY WEIGHT. IMMEDIATE
EFFECTS ARE BLOODY DIARRHEA, ANOREXIA, THIRST, POLYURIA & PROSTRATION. IN SURVIVING
ANIMALS CALCIUM IS DEPOSITED AS IN CHRONIC HYPERVITAMINOSIS-D. /VITAMIN D/
SIMILAR LESIONS /OF CONGENITAL SUPRAVALVULAR AORTIC STENOSIS/ HAVE BEEN
PRODUCEDEXPERIMENTALLY IN OFFSPRING OF RABBITS TREATED WITH LARGE DOSES OF VITAMIN D
DURING PREGNANCY. /VITAMIN D/
... IN RABBITS ADMIN OF LARGE AMT OF VITAMIN D HAS PRODUCED BAND KERATOPATHY BUT ONLY
AFTER UVEITIS WAS INDUCED BY INJECTION OF EGG ALBUMIN INTO VITREOUS AND ONLY WHEN ANIMALS
WERE ALLOWED TO KEEP THEIR EYES OPEN PERMITTING EVAPORATION. /VITAMIN D/
Twenty pregnant Wistar rats were given 40,000 IU/day of vitamin D2 orally with their
diet during days 14-20 of gestation. Controls received the diet alone. Vitamin D2 caused a
depression in body weight and retarded ossification of the sacrococcigeal vertebrae and
proximal phalanges in the forepaw when compared to controls.
The present study was conducted in Wistar rat fetuses to investigate the growth
retardation induced by maternal fasting and/or massive doses of ergocalciferol
during the third trimester of pregnancy. Growth indices examined in 21 day fetuses were
body weight and ossification of sacrococcygeal vertebrae, supraoccipital bone, sternebrae
and proximal phalanges in the forepaw stained by alizarin red S. Growth retardation was
expressed in hours by comparison with the normal standard development, or in sigma by
calculating the relative difference from the control, utilizing the standard variance in
normal fetuses. Degrees of growth retardation expressed in the common scales were
different among the indices and between fasting and massive doses of ergocalciferol;
body weight and ossification of sacrococcygeal vertebrae were most severely retarded by
fasting and least by ergocalciferol.
Ossification of sternebrae was moderately retarded by fasting and by ergocalciferol,
and ossification of supraoccipital bone was moderately retarded by fasting but not by ergocalciferol. Ossification of proximal phalanges in
the forepaw was least retarded by fasting and most severely retarded by ergocalciferol.
The observed retardations were progressions relatable to the duration of fasting. Combined
treatments of fasting and ergocalciferol showed
more deleterious effects on growth than fasting only or ergocalciferol
only and induced face anomalies. These findings show that growth retardations induced by
different nutritional disturbances may vary among indices and that comparisons of various
indices are important in the analysis of teratological experiments.
Metabolism/Pharmacokinetics:
Metabolism/Metabolites:
A POLAR, BIOLOGICALLY ACTIVE METABOLITE OF VITAMIN D2, 25-HYDROXYERGOCALCIFEROL, WHICH
IS ABOUT 1.5 TIMES MORE ACTIVE IN CURING RICKETS IN RATS, HAS BEEN ISOLATED FROM PIG
PLASMA.
... DIHYDROTACHYSTEROL, A DERIVATIVE OF VITAMIN D2, WILL PROMOTE BONE RESORPTION IN
VIVO IN HYPOPARATHYROID INDIVIDUALS.
VITAMIN D3 (OR D2) ... IS HYDROXYLATED @ THE 25 POSITION IN LIVER TO PRODUCE
25-HYDROXY-VIT D3 (OR D2) WHICH IS THE MAJOR METABOLITE CIRCULATING IN THE PLASMA. THE
METABOLITE IS FURTHER HYDROXYLATED IN THE KIDNEY TO 1,25-DIHYDROXY-VIT D3 (OR D2), THE
MOST ACTIVE METABOLITE IN INITIATING INTESTINAL TRANSPORT OF CALCIUM & PHOSPHATE &
MOBILIZATION OF MINERAL FROM BONE.
The effect of calcitriol (1,25-dihydroxyvitamin D3) on the conversion of ergocalciferol (vitamin D2) to 25-hydroxyvitamin D in
20 normal subjects receiving 2 separate doses of ergocalciferol,
one with and one without concomitant administration of calcitriol is described. The
concurrent administration of the 2 drugs made no difference to serum calcitriol
concentrations.
Absorption, Distribution & Excretion:
ADEQUATE INTESTINAL ABSORPTION OF VITAMIN IN OIL IS DEPENDENT UPON PRESENCE OF BILE.
... VITAMIN D IS READILY ADSORBED WHEN ADMIN IN FORM OF AQ DISPERSION IN WHICH ONE OF
DISPERSING AGENTS SUCH AS TWEEN (POLYSORBATE 80) OR SPAN IS EMPLOYED. /VITAMIN D/
VITAMIN D ... DISAPPEARS FROM PLASMA WITH HALF-LIFE OF 19-25 HR, BUT IT IS STORED IN
BODY FOR PROLONGED PERIODS (6 MO OR LONGER IN RAT) ... APPARENTLY IN FAT DEPOSITS.
/VITAMIN D/
BILE IS ESSENTIAL FOR ADEQUATE INTESTINAL ABSORPTION. ... PRIMARY ROUTE OF EXCRETION
... IS IN BILE, & ONLY SMALL PERCENTAGE OF AN ADMIN DOSE IS FOUND IN URINE. /VITAMIN
D/
VIT D WHICH IS ABSORBED THROUGH INTESTINAL WALL FROM DIETARY SOURCES OR WHICH IS FORMED
IN SKIN FROM 7-DEHYDROCHOLESTROL ENTERS CIRCULATORY SYSTEM, & EXCESSES ARE STORED. ...
IN ANIMAL BODY FATS, PRINCIPALLY IN LIVER. /VITAMIN D/
FAT-SOLUBLE VITAMINS ... D ... ARE ABSORBED FROM THE SKIN ... . /VITAMIN D/
BOTH VITAMIN D2 & VITAMIN D3 ARE ABSORBED FROM THE SMALL INTESTINE.
A longitudinal, randomized, double blind, placebo controlled study was conducted for 6
months to monitor ultraviolet B light exposure in human milk-fed infants both with and
without supplemental vitamin D2, and to measure longitudinally the bone mineral content,
growth, and serum concentrations of calcium, phosphorus, 25-hydroxyvitamin D3,
25-hydroxyvitamin D2, 1,25-dihydroxyvitamin D, and parathyroid hormone. Sequential
sampling was performed of 46 human milk-fed white infants; 24 received 400 IU/day of
vitamin D2, and 22 received placebo. An additional 12 patients were followed who received
standard infant formula. 83% of patients completed a full 6 months of the study.
Ultraviolet B light exposure and measurements of growth did not differ between groups. At
6 months, the human milk groups did not differ significantly in bone mineral content or
serum concentrations of parathyroid hormone or 1,25-dihydroxyvitamin D, although total
25-hydroxyvitamin D values were significantly less in the unsupplemented human milk group
(23.53 + or - 9.94 vs 36.96 + or - 11.86 ng/ml; p< 0.01). However, 25-hydroxyvitamin D3
serum concentrations were significantly higher in the unsupplemented human milk-fed group
compared with the supplemented group (21.77 + or - 9.73 vs 11.74 + or - 10.27 ng/ml, p<
0.01) by 6 months of age. It was concluded that unsupplemented, human milk-fed infants had
no evidence of vitamin D deficiency during the first 6 months of life.
Biological Half-Life:
VITAMIN D ... DISAPPEARS FROM PLASMA WITH HALF-LIFE OF 19-25 HR, BUT IT IS STORED IN
BODY FOR PROLONGED PERIODS (6 MO OR LONGER IN RAT) ... APPARENTLY IN FAT DEPOSITS.
/VITAMIN D/
Mechanism of Action:
VITAMIN D IS ANTIRACHITIC VITAMIN ... PROMOTING CALCIFICATION OF BONY STRUCTURES. IT IS
FORMED BY ACTION OF SUN'S UV RAYS ON PRECURSOR STEROLS IN SKIN. /VITAMIN D/
... ACTIVE FORM OF VITAMIN D HAS TWO FUNCTIONS. ... MAINTAIN CIRCULATING LEVEL OF
CALCIUM IN BLOOD. ... LOW BLOOD CALCIUM ACTS TO RELEASE PARATHORMONE, WHICH INITIATES
VITAMIN D ACTIVATION. ... NORMAL BONE CALCIFICATION REQUIRES VITAMIN D. IT INSURES THAT CA
& PO4 ARE PRESENT IN BLOOD ... SO THAT BONE MAY BE FORMED./VITAMIN D/
THE MECHANISMS BY WHICH VITAMIN D ACTS TO MAINTAIN NORMAL CONCN OF CALCIUM &
PHOSPHATE IN PLASMA ARE TO FACILITATE THEIR ABSORPTION BY THE SMALL INTESTINE, TO ENHANCE
THEIR MOBILIZATION FROM BONE, AND TO DECREASE THIER EXCRETION BY THE KIDNEY. /VITAMIN D/
The mechanism of action of calcitriol, the activated form of vitamin D, resembles that
of the steroid and thyroid hormones. Thus, calcitriol binds to cytosolic receptors within
target cells, and the receptor-hormone complex interacts with the DNA of certain genes to
either enhance or inhibit their transcription. Structural analysis of the calcitriol
receptor indicates that it belongs to the same supergene family as the steroid receptors.
Calcitriol also appears to exert a few effects that occur too rapidly to be explained by
genomic actions. /Calcitriol/
The mechanisms responsible for mobilization of bone salts have been only partially
defined, and the interaction of multiple factors appears to be involved. Paradoxically,
the cells responsible for bone resorption (osteoclasts) are not directly acted upon by
calcitriol and do not appear to contain calcitriol receptors. Instead, calcitriol causes
an increase in the number of osteoclasts available to resorb bone; this may result from an
action upon myeloid hematopoietic precursor cells that are induced to differentiate toward
functional osteoclasts. The cells responsible for bone formation (osteoblasts) do contain
receptors, and calcitriol causes them to elaborate several proteins, including
osteocalcin, a vitamin K-dependent protein that contains gamma-carboxyglutamic acid
residues. The exact role of this protein is not known, but other unidentified substances
are also elaborated that appear to stimulate the function of osteoclasts. In addition,
calcitriol acts synergistically with gamma-interferon to increase the production of
interleukin-1, a lymphokine that promotes bone resorption.
25-HCC /25-HYDROXYCHOLECALCIFEROL/ APPEARS TO FACILITATE PHOSPHATE RESORPTION IN RENAL
TUBULE. ... 1,25-DIHYDROXYCHOLECALCIFEROL (1,25-HCC) ... FINDS ITS WAY TO INTESTINAL
MUCOSAL CELLS, BONE & SKELETAL MUSCLE WHERE IT IS STORED FOR REGULATING CALCIUM
ABSORPTION & MOBILIZATION. /VITAMIN D/
The effects of vitamin D2 on plasma 25-hydroxyvitamin and 1,25-dihydroxyvitamin D
levels and the relationship of 1,25-dihydroxyvitamin D to calcium and phosphorus
absorption and retention were studied in 11 very low birth weight infants who received a
preterm infant formula and 380-480 IU/day of vitamin D2 for 3 wk. Plasma 25-hydroxyvitamin
D and 1,25-dihydroxyvitamin D levels were normal at the beginning of the study. Although
25-hydroxyvitamin D concentrations did not change, plasma 1,25-dihydroxyvitamin D values
increased throughout the study. The concentrations of the latter were not related to
calcium or phosphorus absorption and retention, but were a linear function of
postconceptional age. It was concluded that 25-hydroxyvitamin D and 1,25-dihydroxyvitamin
D status and activity are maintained in the very low birth weight infant during treatment
with 380-480 IU/day vitamin D2; plasma 1,25-dihydroxyvitamin D levels are not related to
calcium absorption but are linearly related to maturity.
The effect of short term treatment with pharmacological doses of vitamin D2 or vitamin
D3 on the serum concentration of 1,25(OH)2D metabolites was examined in epileptic patients
on chronic anticonvulsant drug therapy. Nine patients were studied before and after
treatment with vitamin D2 4000 IU daily for 24 wk and 10 before and after treatment with
vitamin D3 in the same dose. Before treatment the serum concentrations of 1,25(OH)2D and
25(OH)D were significantly lower in epileptics than in normal subjects (p< 0.01).
Vitamin D2 treatment increased the serum concentration of 1,25(OH)2D2, but a corresponding
decrease in 1,25(OH)2D3 resulted in an unchanged serum concentration of total 1,25(OH)2D.
The serum concentration of 25(OH)D2 and 25(OH)D increase significantly, whereas there was
a small decrease in 25(OH)D3. Vitamin D3 treatment did not change the serum concentration
of 1,25(OH)2D3 whereas serum 25(OH)D3 increased significantly. The correlation between the
serum ratio of 1,25(OH)2D2/1,25(OH)2D3 and 25(OH)D2/25(OH)D3 estimated on vitamin D2
treated epileptic patients and normal subjects was highly significant (p< 0.01). The
data indicate that the serum concentration of 1,25(OH)2D2 and 1,25(OH)2D3 are directly
proportional to the amount of their precursors 25(OH)D2 and 25(OH)D3 and that the
concentration of total 1,25(OH)2D is tightly regulated.
Interactions:
The effects of glutethimide therapy, 500 mg/day, on the metabolism of vitamin D in a 77
yr old female patient who had taken an overdose of vitamin D2 are reported. Hypercalcemia
in this patient was associated with raised serum concentrations of total 25-hydroxyvitamin
D and total 1,25-dihydroxyvitamin D. Eight days after administration of glutethimide,
plasma gamma-glutamyltransferase activity rose above the upper limit of normal, peaking at
90 IU/l on days 18-22 of therapy. The plasma calcium concentration fell to within the
normal range on day 13. The serum concentration of 1,25-dihydroxyvitamin D began to fall
within 4 days, and after 8 days it was near the lower limit of the reference range, at 70
pmol/l. The serum concentration of total 25-hydroxyvitamin D did not change appreciably
until hepatic enzymes were induced; thereafter it fell gradually. Although the
25-hydroxyvitamin D concentration remained high, the concentration of
1,25-dihydroxyvitamin D did not rise again but remained within the lower part of the
normal range.
The effect of a high cholesterol diet and corticosteroids on the toxicity of vitamin D2
in rats was studied. Vitamin D2 was administered orally at the dosage of 5X10+4 to 60X10+4
IU/kg, once daily for 4 days. Animals fed cholesterol showed a decrease in mortality due
to vitamin D2 treatment. Dietary cholesterol inhibited toxic responses such as a
diminished growth rate following anorexia, elevated serum calcium level and calcium
deposition in tissues, which were produced by a sublethal dose of vitamin D2 (20X10+4
IU/kg, once daily for 4 days). Animals pretreated with the high cholesterol diet from 2 wk
before the first vitamin D2 administration showed much more symptomatic relief than those
given this diet after the first vitamin D2 administration. On the other hand,
dexamethasone as well as corticosterone remarkably increased the mortality due to vitamin
D2. The degree of vitamin D2 toxicity, enhanced by dexamethasone, was correlated with the
degree of hypercalcemia and tissue calcification. Therefore, the inhibitory effect of
cholesterol is not likely to be due to activation of the cholesterol corticosterone system
in the adrenal gland.
Pharmacology:
Therapeutic Uses:
WITH ADEQUATE CALCIUM-PHOSPHORUS INTAKE ... UNCOMPLICATED RICKETS CAN BE CURED BY
ORDINARY DAILY INTAKE OF 400 IU OF VITAMIN D. LARGER DOSES (ABOUT 1600 IU OR MORE DAILY)
ARE MORE RAPIDLY EFFECTIVE ... . /VITAMIN D/
USUAL DAILY REQUIREMENT ... FOR ALL AGE GROUPS IS 400 UNITS DAILY, ALTHOUGH
REQUIREMENTS MAY RISE TO 800 UNITS DAILY DURING PREGNANCY & LACTATION. ... TREATMENT
OF RICKETS & OSTEOMALACIA USUAL DOSE IS 1500 TO 5000 UNITS DAILY. ... IN REFRACTORY
RICKETS MUCH LARGER DOSES ARE OFTEN USED.
MEDICATION (VET): ... RECOMMENDED FOR PROPHYLAXIS OF MILK FEVER IN COWS. ... PREVENT
ATROPHIC RHINITIS IN PIGS. ... AID FRACTURE HEALING IN CATS & DOGS.
MEDICATION (VET): TO BE EFFECTIVE ... SUPPLEMENTATION WITH CA & PO4. ... FISH MEALS
& IRRADIATED YEAST MAY BE USED AS SUPPLEMENTAL ... SOURCE. ... DIETS ARE ROUTINELY
SUPPLEMENTED ... 1400-1600 IU/KG. THERAPY FOR RICKETS ... LEVEL 10-20 TIMES DAILY
REQUIREMENT, ALTERNATE DAYS FOR 1 WK. /VITAMIN D/
REQUIREMENT ... CAN BE MET ENTIRELY BY SKIN IRRADIATION, SO THAT NEED FOR INGESTED
VITAMIN D IS INFLUENCED BY AMT OF EXPOSURE TO UV LIGHT. ... 400 IU/DAY IS SUFFICIENT TO
MEET REQUIREMENTS OF PRACTICALLY ALL HEALTHY INDIVIDUALS, ASSUMING NO EXPOSURE TO UV
LIGHT. /VITAMIN D/
A form of Vitamin D indicated in the treatment of rickets, familial hypophosphatemia,
and hypoparathyroidism.
In adults and children with nutritional rickets or osteomalacia and normal GI
absorption, oral administration of 25 ug of ergocalciferol
daily results in normal serum calcium and phosphate concentrations in about 10 days,
radiographic evidence of healing of bone within 2-4 wk, and complete healing in about 6
months. However, 50-125 ug daily for 6-12 wk is commonly administered for more prompt
healing. Diet should be corrected and, after healing has occurred, supplemental doses of ergocalciferol may be discontinued in patients with
normal GI absorption. In adults with severe malabsorption and vitamin D deficiency,
dosages of 250 ug to 7.5 mg orally or 250 ug im daily have been given to correct
osteomalacia. In children with malabsorption, oral ergocalciferol
dosages of 250-625 ug daily have been recommended. In vitamin D-deficient infants with
tetany and rickets, calcium should be administered orally or iv to control tetany. Vitamin
D deficiency is then treated orally with 50-125 ug of ergocalciferol
daily until the bones have healed, or 250 ug may be given daily for about 3 wk. Rarely,
when compliance with ergocalciferol therapy is
not predictable, a single 7.5 to 15 mg oral dose of ergocalciferol
in oil solution has been used to treat rickets in children.
In children with familial hypophosphatemia (vitamin D-resistant rickets), the usual
initial oral dosage of ergocalciferol is 1-2 mg
daily with phosphate supplements; daily dosage is increased in 250 to 500 ug increments at
3 to 4 mo intervals until an adequate response is obtained. After growth is complete,
dosage of ergocalciferol can often be reduced.
In adults, oral ergocalciferol dosages of 250 ug
to 1.5 mg daily have been given with phosphate supplements .
In adults with Fanconi syndrome, oral ergocalciferol
dosages of 1.25-5 mg (and in some patients 10 mg) daily have been given along with
treatment of acidosis. In children with Fanconi syndrome oral ergocalciferol
dosages of 625 ug to 1.25 mg daily have been used.
For the treatment of vitamin D-dependent rickets in adults, oral ergocalciferol
dosages of 250 ug to 1.5 mg daily have been recommended; some patients may require up to
12.5 mg daily. However, prolonged administration of dosages greater than 2.5 mg daily is
likely to result in toxicity. Children may respond to oral dosages of 75-125 ug daily;
however, some require up to 1.5 mg daily.
In patients with rickets or osteomalacia secondary to anticonvulsant therapy, oral ergocalciferol dosages of 50 ug to 1.25 mg daily may
be required. Some clinicians recommend prophylactic administration of 25 ug of ergocalciferol daily or 250 ug weekly in patients
receiving long-term anticonvulsant therapy .
/Exptl therapy:/ In patients with osteoporosis oral ergocalciferol
dosages of 25-250 ug daily or 1.25 mg 2 times weekly have been used with calcium and
fluoride supplements.
For the management of hypoparathyroidism or pseudohypoparathyroidism in adults, oral ergocalciferol dosages of 625 ug to 5 mg (and in some
patients up to 10 mg) daily may be required with calcium supplements and/or im or iv
parathyroid hormone. Children with hypoparathyroidism or pseudohypoparathyroidism are
usually treated with 1.25-5 mg of oral ergocalciferol
daily and calcium supplements. Prolonged administration of ergocalciferol
dosages greater than 2.5 mg daily in adults or children is likely to result in toxicity.
Dosage should be gradually decreased as serum calcium concentrations approach normal.
To treat early renal osteodystrophy in adults with renal failure, an initial oral ergocalciferol dosage of 500 ug daily has been
recommended. Dosage is then adjusted according to the serum calcium concentration, To
maintain normal serum calcium concentrations, oral ergocalciferol
dosages of 250 ug to 7.5 mg of ergocalciferol
have been recommended; however, some patients have required up to 12.5 mg daily. In
children with renal failure, oral ergocalciferol
dosages of 100 ug to 1 mg daily have been used to maintain normal serum calcium
concentrations.
To prevent osteomalacia in adults with normal Gl absorption (including pregnant and
lactating women) when exposure to sunlight is inadequate, oral ergocalciferol
dosages of 10 ug daily are sufficient. In adults with severe malabsorption syndromes, at
least a 5 to 10 fold increase in the physiologic dose of ergocalciferol
is usually needed to prevent osteomalacia, and some clinicians have recommended oral ergocalciferol dosages of 250 ug to 2.5 mg daily. In
some patients, im administration of the drug may be preferred. In infants and healthy
children, an oral ergocalciferol dosage of 10 ug
daily prevents rickets and provides for optimal growth; although this amount may be
obtained from fortified milk, breast fed infants may require supplemental ergocalciferol. For normal bone development, most
premature infants require 12-20 ug of ergocalciferol
daily; however, premature infants who are abnormally susceptible to hypocalcemia may
require oral dosages up to 750 ug daily to prevent rickets.
Hypocalcemia, chronic (treatment); hypophosphatemia (treatment); osteodystrophy
(treatment); or Rickets (prophylaxis and treatment).
Tetany (prophylaxis and treatment) - Dihydrotachysterol is indicated (and ergocalciferol are used) for treatment of chronic and
latent form of postoperative tetany and idiopathic tetany. Ergocalciferol
is indicated for prevention and treatment of vitamin D deficiency state. ... Vitamin D
therapy, alone, as treatment for osteoporosis is not generally recommeded; however,
Vitamin D supplements in dose of 400 to 800 Units may be used as part of the prevention
and treatment of osteoporosis in patients with an inadequate vitamin D and/or calcium
intake.
Osteomalacia due to prolonged use of anticonvulsants, hypoparathyroidism. /Ergocalciferol/
Renal function impairment; renal osteodystrophy (use not included in US product label).
/Ergocalciferol/
Drug Warnings:
USE ... FOR TREATMENT OF LUPUS VULGARIS IS OBSOLETE & ITS TOPICAL USE FOR OTHER
DERMATOSES IS NOT JUSTIFIED. /VITAMIN D/
Maternal Medication usually Compatible with Breast-Feeding: D (Vitamin): Reported Sign
or Symptom in Infant or Effect on Lactation: None; follow up in infant's serum calcium
level if mother receives pharmacological doses. /from Table 6/
POTENTIAL ADVERSE EFFECTS ON FETUS: Teratogenic in animals at high doses (4-15x
recommended human dose). In humans, maternal hypercalcemia during pregnancy may increase
fetal sensitivity to effects of vitamin D, suppression of parathyroid function or a
syndrome of elfin facies, mental retardation, and congenital supravalvular aortic
stenosis. POTENTIAL SIDE EFFECTS ON BREAST-FED INFANT: No known problems at recommended
daily allowance. FDA Category: C (C = Studies in laboratory animals have revealed adverse
effects on the fetus (teratogenic, embryocidal, etc.) but there are no controlled studies
in pregnant women. The benefits from use of the drug in pregnant women may be acceptable
despite its potential risks, or there are no laboratory animal studies or adequate studies
in pregnant women.) /Vitamin D from table II/
Interactions:
The effects of glutethimide therapy, 500 mg/day, on the metabolism of vitamin D in a 77
yr old female patient who had taken an overdose of vitamin D2 are reported. Hypercalcemia
in this patient was associated with raised serum concentrations of total 25-hydroxyvitamin
D and total 1,25-dihydroxyvitamin D. Eight days after administration of glutethimide,
plasma gamma-glutamyltransferase activity rose above the upper limit of normal, peaking at
90 IU/l on days 18-22 of therapy. The plasma calcium concentration fell to within the
normal range on day 13. The serum concentration of 1,25-dihydroxyvitamin D began to fall
within 4 days, and after 8 days it was near the lower limit of the reference range, at 70
pmol/l. The serum concentration of total 25-hydroxyvitamin D did not change appreciably
until hepatic enzymes were induced; thereafter it fell gradually. Although the
25-hydroxyvitamin D concentration remained high, the concentration of
1,25-dihydroxyvitamin D did not rise again but remained within the lower part of the
normal range.
The effect of a high cholesterol diet and corticosteroids on the toxicity of vitamin D2
in rats was studied. Vitamin D2 was administered orally at the dosage of 5X10+4 to 60X10+4
IU/kg, once daily for 4 days. Animals fed cholesterol showed a decrease in mortality due
to vitamin D2 treatment. Dietary cholesterol inhibited toxic responses such as a
diminished growth rate following anorexia, elevated serum calcium level and calcium
deposition in tissues, which were produced by a sublethal dose of vitamin D2 (20X10+4
IU/kg, once daily for 4 days). Animals pretreated with the high cholesterol diet from 2 wk
before the first vitamin D2 administration showed much more symptomatic relief than those
given this diet after the first vitamin D2 administration. On the other hand,
dexamethasone as well as corticosterone remarkably increased the mortality due to vitamin
D2. The degree of vitamin D2 toxicity, enhanced by dexamethasone, was correlated with the
degree of hypercalcemia and tissue calcification. Therefore, the inhibitory effect of
cholesterol is not likely to be due to activation of the cholesterol corticosterone system
in the adrenal gland.
Bionecessity:
STATE OF DEFICIENCY: ... LEADS TO INADEQUATE ABSORPTION OF CALCIUM FROM INTESTINAL
TRACT & RETENTION OF PHOSPHORUS IN KIDNEY ... FAULTY MINERALIZATION OF BONE
STRUCTURES. ... DELAYED CLOSURE OF FONTANELLES & SOFTENING OF SKULL, SOFT FRAGILE
BONES WITH BOWING OF LEGS & SPINAL CURVATURE ... RESTLESSNESS & NERVOUS
IRRITABILITY. /VITAMIN D/
STATE OF DEFICIENCY: VITAMIN D DEFICIENCY, RICKETS ... DISEASE OF GROWING ANIMALS. ...
LOW BLOOD CA & PO4 CONCN. THICKENING OF ENDOCHONDRAL JUNCTIONS, BOWING OF LARGE BONES,
STIFFENING & SWELLING OF JOINTS. FRACTURES OCCUR MORE FREQUENTLY. ... IN ADULT ANIMALS
DEFICIENCY OF VITAMIN D IS CALLED OSTEOMALACIA. /VITAMIN D/
STATE OF DEFICIENCY: MORE ACUTE FORMS OF VITAMIN D DEFICIENCY DISEASE AFFECT CA &
PO4 MOBILIZATION; LACTATION PARESIS ... & PARTURIENT PARESIS ... . /VITAMIN D/
STATE OF DEFICIENCY: VET: ... ASSOCIATED CONDITIONS ... LAMENESS, STIFFNESS, BOWED
LEGS, SWOLLEN JOINTS, ARCHED BACKS, GENERAL UNTHRIFTINESS ... POOR HAIR COATS & LOSS
OF SKIN TONE. ... REPRODUCTIVE PERFORMANCE & BREEDING EFFICIENCY ... ADVERSELY
AFFECTED ... GESTATION PERIOD ... AFFECTED ... POORLY DEVELOPED OFFSPRING WITH LIMITED VIT
D RESERVES.
STATE OF DEFICIENCY: DEFICIENCY CAUSES HYPOCALCEMIA & HYPOPHOSPHATEMIA, WHICH
STIMULATES PARATHYROID HORMONE SECRETION TO RESTORE PLASMA CALCIUM LEVELS AT THE EXPENSE
OF BONE. THIS CAUSES RICKETS IN INFANTS & CHILDREN AND OSTEOMALACIA IN ADULTS.
/VITAMIN D/
STATE OF DEFICIENCY: CHRONIC OBSTRUCTIVE JAUNDICE & PRIMARY BILIARY CIRRHOSIS CAN
BE ASSOCIATED WITH MALABSORPTION OF VITAMIN D AND OSTEOMALACIA. /VITAMIN D/
... D2 ... STEROLS ... REQUIRED BY MOST VERTEBRATES HAVING BONY SKELETON. ... SUPPLIED
VIA DIET OR BY SUITABLE IRRADIATION OF BODY.
MEMBERS OF DARK-SKINNED RACES INHABITING NORTHERN CLIMATES HAVE SLIGHTLY HIGHER
REQUIREMENT FOR VITAMIN D BECAUSE MELANIN INTERFERES WITH IRRADIATION. /VITAMIN D/
Vitamin D is the name applied to two related fat-soluble substances, cholecalciferol
and calciferol. ... The principal provitamin
found in animal tissues is 7-dehydrocholesterol, which is synthesized in the skin.
Exposure of the skin to sunlight converts 7-dehydrocholesterol to cholecalciferol (vitamin
D3). ... Ergosterol ... is the provitamin for vitamin D2 (calciferol).
Ergosterol and vitamin D2 differ from 7-dehydrocholesterol and vitamin D3, respectively,
only by each having a double bond between C 22 and C 23 and a methyl group at C 24.
Vitamin D2 is the active constituent in a number of commercial vitamin preparations as
well as in irradiated bread and irradiated milk. ... In some species the antirachitic
potencies of vitamin D2 and vitamin D3 differ greatly from each other. In man there is no
practical difference between the two, and vitamin D /is/ used as the collective term for
vitamins D2 and D3.
USUAL DAILY REQUIREMENT ... FOR ALL AGE GROUPS IS 400 UNITS DAILY, ALTHOUGH
REQUIREMENTS MAY RISE TO 800 UNITS DAILY DURING PREGNANCY & LACTATION. ... TREATMENT
OF RICKETS & OSTEOMALACIA USUAL DOSE IS 1500 TO 5000 UNITS DAILY. ... IN REFRACTORY
RICKETS MUCH LARGER DOSES ARE OFTEN USED.
400 IU/DAY IS SUFFICIENT TO MEET REQUIREMENTS OF PRACTICALLY ALL HEALTHY INDIVIDUALS,
ASSUMING NO EXPOSURE TO UV LIGHT. /VITAMIN D/
REQUIREMENT ... CAN BE MET ENTIRELY BY SKIN IRRADIATION, SO THAT NEED FOR INGESTED
VITAMIN D IS INFLUENCED BY AMT OF EXPOSURE TO UV LIGHT. ... 400 IU/DAY IS SUFFICIENT TO
MEET REQUIREMENTS OF PRACTICALLY ALL HEALTHY INDIVIDUALS, ASSUMING NO EXPOSURE TO UV
LIGHT. /VITAMIN D/
Antirachitic vitamin; (vet): nutritional factor (antirachitic). Low activity in
poultry.
Environmental Fate & Exposure:
Environmental Standards & Regulations:
CERCLA Reportable Quantities:
Releases of CERCLA hazardous substances are subject to the release reporting
requirement of CERCLA section 103, codified at 40 CFR part 302, in addition to the
requirements of 40 CFR part 355. Ergocalciferol
is an extremely hazardous substance (EHS) subject to reporting requirements when stored in
amounts in excess of its threshold planning quantity (TPQ) of 1,000/10,000 lbs.
FDA Requirements:
Manufacturers, packers, and distributors of drug and drug products for human use are
responsible for complying with the labeling, certification, and usage requirements as
prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat.
1040 et seq., as amended; 21 U.S.C. 321-392).
Vitamin D2 used as a dietary supplement in food for human consumption is generally
recognized as safe when used in accordance with good manufacturing practice.
Vitamin D2 used as a nutrient and/or dietary supplement in animal drugs, feeds, and
related products is generally recognized as safe when used in accordance with good
manufacturing or feeding practice.
Chemical/Physical Properties:
Molecular Formula:
C28-H44-O
Molecular Weight:
396.63
Color/Form:
PRISMS FROM ACETONE
WHITE CRYSTALS
Odor:
ODORLESS
Taste:
Medications associated with a metallic or bitter taste include ... vitamin D.
Melting Point:
115-118 DEG C
Solubilities:
INSOL IN WATER; 1 ML ACETONE DISSOLVES 0.0695 G @ 7 DEG C; SLIGHTLY SOL IN VEGETABLE
OILS.
SOL IN FAT SOLVENTS SUCH AS ETHER, ALCOHOL, CHLOROFORM
SOL IN FATTY ACIDS
Spectral Properties:
INDEX OF REFRACTION: 1.5101 @ 25 DEG C/D
SPECIFIC OPTICAL ROTATION: +82.6 @ 25 DEG C/D (ACETONE, 3%); +102.5 @ 20 DEG C/D
(ALCOHOL); SPECIFIC OPTICAL ROTATION: +52 @ 20 DEG C/D (CHLOROFORM); MAX ABSORPTION
(HEXANE): 264.5 NM (E= 458.9 +/- 7.5, 1%, 1 CM)
MAX ABSORPTION (METHANOL): 235 NM (A 600 1%, 1 CM)
MAX ABSORPTION (ALCOHOL): 265 NM (LOG E= 4.27)
IR: 14471 (Sadtler Research Laboratories Prism Collection)
UV: 5-899 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New
York)
NMR: 364 (Varian Associates NMR Spectra Catalogue)
MASS: 3081 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)
MASS: 838 (National Bureau of Standards EPA-NIH Mass Spectra Data Base, NSRDS-NBS-63)
Other Chemical/Physical Properties:
Sublimes
SUBLIMES IN VERY HIGH VACUUM (0.0006 MM) WITHOUT DECOMP; NOT PRECIPITATED BY DIGITONIN
(DIFFERENT FROM ERGOSTEROL)
Chemical Safety & Handling:
Stability/Shelf Life:
SHOWS SIGNS OF DECOMP WHEN STORED FOR FEW DAYS @ ROOM TEMP, STORAGE WITH INERT GAS
IMPROVES STABILITY
DETERIORATION OF PURE CRYSTAL IS NEGLIGIBLE AFTER STORAGE OF /9 MO/ IN AMBER EVACUATED
AMPULS @ REFRIGERATOR TEMPERATURE
Affected by air and light.
Ergocalciferol decomposes on exposure to air
and light, and preparations of the drug should be protected from air and light
Storage Conditions:
Ergocalciferol capsules, oral solution, and
tablets should be stored in tight, light-resistant containers at a temperature less than
40 deg C, preferably between 15-30 deg C.
Ergocalciferol injection should be protected
from light and stored at a temperature less than 40 deg C, preferably between 15-30 deg C.
Occupational Exposure Standards:
Manufacturing/Use Information:
Major Uses:
MEDICATION
Also as rodenticide /alone or in combination with warfarin/.
MEDICATION (VET)
Manufacturers:
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, (317) 276-2000
Vitamins Inc, Hq, 200 East Randolph Dr, Chicago, IL 60601, (312) 861-0700; Production
site: 809 West 58th St, Chicago, IL 60621
Methods of Manufacturing:
/IS/ THE SYNTHETIC FORM OF VITAMIN D. PREPARED FROM ERGOSTEROL BY UV IRRADIATION IN A
SUITABLE SOLVENT. ... THE BEST WAVE LENGTHS FOR PRODUCTION OF VIT D2 SEEM TO BE FROM 275
TO 300 NM ... PREPN BY ELECTRON BOMBARDMENT OF ERGOSTEROL USING LONGER WAVES ... .
Usually obtained from yeast which synthesizes it from simple sugars such as glucose.
General Manufacturing Information:
INTERNATIONAL & USP UNITS OF VITAMIN D ARE EQUIVALENT IN ACTIVITY TO 0.025 UG OF
CRYSTALLINE VITAMIN D2.
ERGOSTEROL, WHICH IS PRESENT IN YEASTS & FUNGI, IS PROVITAMIN FOR VITAMIN D2 (CALCIFEROL). ... VITAMIN D2 IS ACTIVE CONSTITUENT IN A
NUMBER OF COMMERCIAL VITAMIN PREPARATIONS AS WELL AS IN IRRADIATED BREAD & IRRADIATED
MILK.
VITAMIN D IS GENERIC TERM FOR CLOSELY RELATED STEROIDS THAT HAVE ANTIRACHITIC ACTIVITY.
... FORMED AS PROVITAMINS .... CONVERSION OF PROVITAMINS BY UV LIGHT IS WELL ESTABLISHED.
/VITAMIN D/ PLANT PROVITAMIN IS ERGOCALCIFEROL.
VITAMIN D2 CRYSTALS HAVE A POTENCY OF 40 UNITS OF VITAMIN D (USP)/UG.
BECAUSE OF VITAMIN D2'S SENSITIVITY TO OXYGEN & LIGHT, USP ALLOWS TRACES OF
ANTIOXIDANTS IN CRYSTALLINE CMPD.
Formulations/Preparations:
ERGOCALCIFEROL (CALCIFEROL;
DRISDOL) IS PURE VITAMIN D2. ... AVAILABLE IN
CAPSULES OR TABLETS THAT CONTAIN 1.25 MG (50,OOO USP UNITS) EACH. AN ORAL SOLUTION (8,000
UNITS/ML) OF THE VITAMIN IN PROPYLENE GYYCOL IS ALSO AVAILABLE. AN INJECTION IN OIL
(500,000 UNITS/ML) IS AVAILABLE FOR IM ADMINISTRATION. ... DIHYDROTACHYSTEROL (DHT;
HYTAKEROL) IS THE PURE CRYSTALLINE CMPD OBTAINED BY REDUCTION OF VITAMIN D2 ... AVAILABLE
AS TABLETS (0.125 TO 0.4 MG), CAPSULES (0.125 MG), AN ORAL SOLN (0.2 MG/ML) & A SOLN
IN OIL (0.2 MG/ML).
... MAY BE OBTAINED AS CRYSTALS, STANDARDIZED OIL SOLUTIONS, EMULSIONS OR BEADLETS. ...
USUALLY STABILIZED WITH ANTIOXIDANTS. /VITAMIN D/
... FOUR MAIN TYPES OF VITAMIN D PREPARATIONS: (1) FISH LIVER OILS ... (2) MULTIVITAMIN
... (3) PREPARATIONS CONTAINING VITAMIN D & CALCIUM SALTS ... (4) PREPARATION
CONTAINING VITAMIN D ACTIVITY ALONE.
GRADES: UNITED STATES PHARMACOPEIA, "FOOD CHEMICAL CODEX", AS VITAMIN D2.
COMMERCIAL SOLN ARE USUALLY MADE WITH PROPYLENE GLYCOL OR SESAME OIL.
Dosage Forms-Capsules: 1.25mg (50,000 USP Units); Solution; Tablets: 1.25 mg (50,000
USP Units)
CALCIFEROL Tablets contain 1.25 mg (50,000
USP units) of Ergocalciferol (Vitamin D2), CALCIFEROL In Oil Injection is a sterile solution of
Vitamin D2 in sesame oil for intramuscular use only. Each ml of CALCIFEROL
In Oil contains 500,000 USP units of Ergocalciferol.
CALCIFEROL Drops, oral solution, contains 8,000
USP units of Vitamin D2 in Propylene Glycol, per ml (200 USP units per drop)
Ergocalciferol capsules usually consist of
the drug in an edible oil solution encapsulated with gelatin. Commercially available ergocalciferol solution is a clear solution of the
drug in an edible vegetable oil or in propylene glycol. Ergocalciferol
injection is a sterile solution of the drug in sesame oil.
Ergocalciferol is also commercially available
in combination with other vitamins and minerals, analgesic-antipyretics, amino acids,
infant formulas, laxatives, and protein supplements.
Parenteral Injection, 12.5 mg (500,000 units) per ml, Calciferol
(in oil), Schwarz.
Oral Capsules: 1.25 mg (50,000 units), Deltalin
Gelseals, Lilly; Drisdol, Winthrop; Solution:
200 ug (8000 units) per mL, Calciferol Drops
(with propylene glycol), Schwarz; Drisdol,
Winthrop; Tablets: 1.25 mg (50,000 units), Calciferol,
Schwarz.
Capsules, 25000 and 50000 IU. Liquid, 8000 IU/ml. Ampules, 500000 IU/ml and 500000 IU/5
ml.
U. S. Imports:
(1984) 9.16X10+7 g /Vitamin D-2 and D-3, synthetic/
Laboratory Methods:
Clinical Laboratory Methods:
DETERMINATION OF VITAMIN D2 & D3 IN MILK BY USING REVERSE PHASE HPLC.
Analytic Laboratory Methods:
HPLC SEPARATION AND IDENTIFICATION OF VITAMINS D2 AND D3 IN PRESENCE OF FAT SOLUBLE
VITAMINS IN DOSAGE FORMS. AS LITTLE AS 2 NG EACH OF VIT D2 & D3 CAN BE SEPARATED &
IDENTIFIED.
A GC METHOD IS DESCRIBED FOR THE DETERMINATION OF VIT D2 (ERGOCALCIFEROL)
IN CAPSULES & INJECTIONS.
GLC PROCEDURE TO DETERMINE VITAMIN D2 & D3 IN INFANT FEEDINGS.
A GLC PROCEDURE FOR DETERMINATION OF VIT D2.
Determination of vitamin D2 and vitamin D3 in foods, feeds, and pharmaceuticals, using
HPLC.
Determination of vitamins D2 and D3 in feedingstuffs by HPLC.
Special References:
Special Reports:
Parfitt AM; Use of Calciferol and its
Metabolites and Analogs in Osteoporosis: Current Status. Drugs 36: 513-20 (1988). The
rationale for the use of ergocalciferol (calciferol), calcifediol and calcitriol for the
treatment of osteoporosis is reviewed.
Synonyms and Identifiers:
Synonyms:
ACTIVATED ERGOSTEROL
**PEER REVIEWED**
D-ARTHIN
**PEER REVIEWED**
BUCO-D
**PEER REVIEWED**
CALCIFEROL
**PEER REVIEWED**
CALCIFERON 2
**PEER REVIEWED**
CONDACAPS
**PEER REVIEWED**
CONDOCAPS
**PEER REVIEWED**
CONDOL
**PEER REVIEWED**
CRTRON
**PEER REVIEWED**
CRYSTALLINA
**PEER REVIEWED**
DARAL
**PEER REVIEWED**
DAVITAMON D
**PEER REVIEWED**
DAVITIN
**PEER REVIEWED**
DECAPS
**PEER REVIEWED**
DEE-OSTEROL
**PEER REVIEWED**
DEE-RON
**PEER REVIEWED**
DEE-RONAL
**PEER REVIEWED**
DEE-ROUAL
**PEER REVIEWED**
DELTALIN
**PEER REVIEWED**
DE-RAT CONCENTRATE
**PEER REVIEWED**
DERATOL
**PEER REVIEWED**
DETALUP
**PEER REVIEWED**
DIACTOL
**PEER REVIEWED**
DIVIT URTO
**PEER REVIEWED**
DORAL
**PEER REVIEWED**
DRISDOL
**PEER REVIEWED**
ERGOCALCIFEROL
**PEER REVIEWED**
ERGORONE
**PEER REVIEWED**
ERGOSTEROL ACTIVATED
**PEER REVIEWED**
ERGOSTEROL, IRRADIATED
**PEER REVIEWED**
ERTRON
**PEER REVIEWED**
FORTODYL
**PEER REVIEWED**
GELTABS
**PEER REVIEWED**
HI-DERATOL
**PEER REVIEWED**
INFRON
**PEER REVIEWED**
IRRADIATED ERGOSTA-5,7,22-TRIEN-3-BETA-OL
**PEER REVIEWED**
IRRADIATED ERGOSTEROL
**PEER REVIEWED**
METADEE
**PEER REVIEWED**
MINA D2
**PEER REVIEWED**
MULSIFEROL
**PEER REVIEWED**
MYKOSTIN
**PEER REVIEWED**
OLEOVITAMIN D
**PEER REVIEWED**
OLEOVITAMIN D2
**PEER REVIEWED**
OSTELIN
**PEER REVIEWED**
RADIOSTOL
**PEER REVIEWED**
RADSTERIN
**PEER REVIEWED**
9,10,SECOERGOSTA-5,7,10(19),22-TETRAEN 3-BETA-OL
**PEER REVIEWED**
9,10-Secoergosta-5,7,10(19),22-tetra-en-3-ol
**PEER REVIEWED**
9,10-SECOERGOSTA-5,7,10(19),22-TETRAEN-3-OL, (3BETA,5Z,7E,22E)-
**PEER REVIEWED**
SHOCK-FEROL
**PEER REVIEWED**
Sterogyl
**PEER REVIEWED**
D-TRACETTEN
**PEER REVIEWED**
Vio-D
**PEER REVIEWED**
Viosterol
**PEER REVIEWED**
Formulations/Preparations:
ERGOCALCIFEROL (CALCIFEROL;
DRISDOL) IS PURE VITAMIN D2. ... AVAILABLE IN
CAPSULES OR TABLETS THAT CONTAIN 1.25 MG (50,OOO USP UNITS) EACH. AN ORAL SOLUTION (8,000
UNITS/ML) OF THE VITAMIN IN PROPYLENE GYYCOL IS ALSO AVAILABLE. AN INJECTION IN OIL
(500,000 UNITS/ML) IS AVAILABLE FOR IM ADMINISTRATION. ... DIHYDROTACHYSTEROL (DHT;
HYTAKEROL) IS THE PURE CRYSTALLINE CMPD OBTAINED BY REDUCTION OF VITAMIN D2 ... AVAILABLE
AS TABLETS (0.125 TO 0.4 MG), CAPSULES (0.125 MG), AN ORAL SOLN (0.2 MG/ML) & A SOLN
IN OIL (0.2 MG/ML).
... MAY BE OBTAINED AS CRYSTALS, STANDARDIZED OIL SOLUTIONS, EMULSIONS OR BEADLETS. ...
USUALLY STABILIZED WITH ANTIOXIDANTS. /VITAMIN D/
... FOUR MAIN TYPES OF VITAMIN D PREPARATIONS: (1) FISH LIVER OILS ... (2) MULTIVITAMIN
... (3) PREPARATIONS CONTAINING VITAMIN D & CALCIUM SALTS ... (4) PREPARATION
CONTAINING VITAMIN D ACTIVITY ALONE.
GRADES: UNITED STATES PHARMACOPEIA, "FOOD CHEMICAL CODEX", AS VITAMIN D2.
COMMERCIAL SOLN ARE USUALLY MADE WITH PROPYLENE GLYCOL OR SESAME OIL.
Dosage Forms-Capsules: 1.25mg (50,000 USP Units); Solution; Tablets: 1.25 mg (50,000
USP Units)
CALCIFEROL Tablets contain 1.25 mg (50,000
USP units) of Ergocalciferol (Vitamin D2), CALCIFEROL In Oil Injection is a sterile solution of
Vitamin D2 in sesame oil for intramuscular use only. Each ml of CALCIFEROL
In Oil contains 500,000 USP units of Ergocalciferol.
CALCIFEROL Drops, oral solution, contains 8,000
USP units of Vitamin D2 in Propylene Glycol, per ml (200 USP units per drop)
Ergocalciferol capsules usually consist of
the drug in an edible oil solution encapsulated with gelatin. Commercially available ergocalciferol solution is a clear solution of the
drug in an edible vegetable oil or in propylene glycol. Ergocalciferol
injection is a sterile solution of the drug in sesame oil.
Ergocalciferol is also commercially available
in combination with other vitamins and minerals, analgesic-antipyretics, amino acids,
infant formulas, laxatives, and protein supplements.
Parenteral Injection, 12.5 mg (500,000 units) per ml, Calciferol
(in oil), Schwarz.
Oral Capsules: 1.25 mg (50,000 units), Deltalin
Gelseals, Lilly; Drisdol, Winthrop; Solution:
200 ug (8000 units) per mL, Calciferol Drops
(with propylene glycol), Schwarz; Drisdol,
Winthrop; Tablets: 1.25 mg (50,000 units), Calciferol,
Schwarz.
Capsules, 25000 and 50000 IU. Liquid, 8000 IU/ml. Ampules, 500000 IU/ml and 500000 IU/5
ml.
RTECS Number:
NIOSH/KE1050000
Administrative Information:
Hazardous Substances Databank Number: 819
Last Revision Date: 20010516
Last Review Date: Reviewed by SRP on 12/10/1993
Update History:
Complete Update on 05/16/2001, 1 field added/edited/deleted.
Complete Update on 08/26/1999, 1 field added/edited/deleted.
Complete Update on 10/13/1998, 1 field added/edited/deleted.
Complete Update on 02/27/1998, 1 field added/edited/deleted.
Complete Update on 10/17/1997, 1 field added/edited/deleted.
Complete Update on 04/01/1997, 1 field added/edited/deleted.
Complete Update on 03/11/1997, 2 fields added/edited/deleted.
Complete Update on 01/19/1996, 1 field added/edited/deleted.
Complete Update on 04/20/1995, 1 field added/edited/deleted.
Complete Update on 04/20/1995, 1 field added/edited/deleted.
Complete Update on 03/20/1995, 1 field added/edited/deleted.
Complete Update on 12/22/1994, 1 field added/edited/deleted.
Complete Update on 10/19/1994, 1 field added/edited/deleted.
Complete Update on 08/23/1994, 1 field added/edited/deleted.
Complete Update on 05/12/1994, 38 fields added/edited/deleted.
Field Update on 03/21/1994, 1 field added/edited/deleted.
Field update on 12/16/1992, 1 field added/edited/deleted.
Complete Update on 10/10/1990, 1 field added/edited/deleted.
Complete Update on 04/16/1990, 1 field added/edited/deleted.
Field update on 12/29/1989, 1 field added/edited/deleted.
Complete Update on 11/09/1989, 4 fields added/edited/deleted.
Complete Update on 10/14/1986
Record Length: 87775
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