KINADYN-OS

D, in general, is a secosteroid generated in the skin when 7-dehydrocholesterol located there interacts with ultraviolet irradiation.

• like that commonly found in sunlight 9.

Both the endogenous form of vitamin

D (that results from 7-dehydrocholesterol transformation), vitamin D3 (cholecalciferol), and the plant-derived form, vitamin D2 (ergocalciferol), are considered the main forms of vitamin d and are found in various types of food for daily intake 9.

Structurally, ergocalciferol differs from cholecalciferol in that it possesses a double bond between C22 and C23 and has an additional methyl group at C24 9.

Finally, ergocalciferol is pharmacologically less potent than cholecalciferol, which makes vitamin D3 the preferred agent for medical use 9.

Appropriate levels of vitamin

D must be upheld in the body in order to maintain calcium and phosphorus levels in a healthy physiologic range to sustain a variety of metabolic functions, transcription regulation, and bone metabolism 4, 9, 10, 11, 12, 13, 14.

However, studies are also ongoing to determine whether or not cholecalciferol may also play certain roles in cancer, autoimmune disorders, cardiovascular disease, and other medical conditions that may be associated with vitamin D deficiency 9.

Cholecalciferol use is indicated for the treatment of specific medical conditions like refractory rickets (or vitamin D resistant rickets), hypoparathyroidism, and familial hypophosphatemia 12, 13.

Concurrently, as one of the most commonly utilized forms of vitamin D, cholecalciferol is also very frequently used as a supplement in individuals to maintain sufficient vitamin d levels in the body or to treat vitamin D deficiency, as well as various medical conditions that can be associated directly or indirectly with vitamin d insufficiency like osteoporosis and chronic kidney disease, among others 2, 3, 15.

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 12, 13, 14.

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 12, 13, 14.

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 12, 13, 14.

There exists a period of 10-24 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 12, 13, 14.

It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys 12, 13, 14.

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal 12, 13, 14.

Moreover, bile is necessary for absorption as well 12, 13, 14.

In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol 7.

Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L 5.

Within the liver, cholecalciferol is hydroxylated to calcifediol (25-hydroxycholecalciferol) by the enzyme vitamin D-25-hydroxylase 12, 13, 14.

At the kidney, calcifediol subsequently serves as a substrate for 1-alpha-hydroxylase, yielding calcitriol (1,25-dihydroxycholecalciferol), the biologically active form of vitamin D3 12, 13, 14.

Hover over products below to view reaction partners Cholecalciferol (23S)-23,25-dihdroxy-24-oxovitamine D3 23-(beta-glucuronide) Calcifediol Calcitriol.

It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces 8.

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days 8 while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days 10.

Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals 6.

Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day 5.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae 12, 13, 14.

Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia 12, 13, 14.

Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures 12, 13, 14.

Safety of doses in excess of 400 IU (10 mcg) of vitamin D3 daily during pregnancy has not been established 12, 13, 14.

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 12, 13, 14.

Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures 12, 13, 14.

D is deficient in maternal milk; therefore, breastfed infants may require supplementation.

Use of excessive amounts of Vitamin

D in nursing mothers may result in hypercalcemia in infants.

D3 in excess of 10 µg daily should not be administered daily to nursing women.

Patients with hypercalcemia.

The recommended initial dose of calcium acetate for the adult dialysis patient is 2 capsules with each meal.

Increase the dose gradually to lower serum phosphorus levels to the target range, as long as hypercalcemia does not develop.

Most patients require 3-4 capsules with each meal.

Starting dose is 2 capsules with each meal.

Titrate the dose every 2-3 weeks until acceptable serum phosphorus level is reached.

Each capsule is of size ‘00el’ hard gelatin capsule shell with blue opaque cap and white opaque body imprinted with “667 mg” on cap and “IG 377” on body in black ink filled with white to off white powder.

Supplied in

Bottles of 60 (NDC 69097-862-03) and 200 (NDC 69097-862-83).

Store at 20° to 25°C (68° to 77°F) .

Calcium acetate capsules contain calcium acetate.

Animal reproduction studies have not been conducted with calcium acetate, and there are no adequate and well controlled studies of calcium acetate use in pregnant women.

Patients with end stage renal disease may develop hypercalcemia with calcium acetate treatment.

Maintenance of normal serum calcium levels is important for maternal and fetal well being.

Hypercalcemia during pregnancy may increase the risk for maternal and neonatal complications such as stillbirth, preterm delivery, and neonatal hypocalcemia and hypoparathyroidism.

Calcium acetate treatment, as recommended, is not expected to harm a fetus if maternal calcium levels are properly monitored during and following treatment.

A calcium acetate capsule contains calcium acetate and is excreted in human milk.

Human milk feeding by a mother receiving calcium acetate is not expected to harm an infant, provided maternal serum calcium levels are appropriately monitored.

Safety and effectiveness in pediatric patients have not been established.

Clinical studies of calcium acetate did not include sufficient numbers of subjects aged and over to determine whether they respond differently from younger subjects.

Other clinical experience has not identified differences in responses between elderly and younger patients.

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.