Calcrown
Calcrown Uses, Dosage, Side Effects, Food Interaction and all others data.
Calcitriol is one of the most important active metabolites of vitamin D3. It is normally formed in the kidney from its precursor, 25-hydroxycolecalciferol (25-HCC). Physiological daily production is normally 0.5-1.0 mcg and is somewhat higher during periods of increased bone synthesis (e.g. growth or pregnancy). Calcitriol promotes intestinal absorption of Calcium and regulates bone mineralization.
Calcitriol is a biologically active calcitrophic hormone with anti-osteoporotic, immunomodulatory, anticarcinogenic, antipsoriatic, antioxidant, and mood-modulatory activities. Its main sites of action are the intestine, bone, kidney and parathyroid hormone . Calcitriol is a ligand for the vitamin D nuclear receptor, which is expressed in, but not limited to, gastrointestinal (GI) tissues, bones, and kidneys . As an active form of vitamin D3, calcitriol elevates the plasma levels of calcium by stimulating intestinal calcium uptake, increasing reabsorption of calcium by the kidneys, and possibly increasing the release of calcium from skeletal stores. The duration of pharmacologic activity of a single dose of exogenous calcitriol is expected to be about 3 to 5 days .
In addition to its important role in calcium metabolism, other pharmacological effects of calcitriol have been studied in various conditions including cancer models. Various studies demonstrated expression of vitamin D receptors in cancer cell lines, including mouse myeloid leukemia cells . Calcitriol has been found to induce differentiation and/or inhibit cell proliferation in vitro and in vivo in many cell types, such as malignant cell lines carcinomas of the breast, prostate, colon, skin, and brain, myeloid leukemia cells, and others . In early human prostate cancer trials, administration of 1.5 µg/d calcitriol in male participants resulted in a reduction in the rate of PSA rise in most participants, however it was coincided with dose-limiting hypercalcemia in most participants . Hypercalcemia and hypercalcuria were evident in numerous initial trials, and this may be due to these trials not testing the drug at concentrations that are active in preclinical systems . Findings from preclinical data show an additive or synergistic antineoplastic action of calcitriol when combined with agents including dexamethasone, retinoids, and radiation, as well as several cytotoxic chemotherapy drugs such as platinum compounds .
Vitamin D deficiency has long been suspected to increase the susceptibility to tuberculosis. The active form of calcitriol, 1,25-(OH)2-D3, has been found to enhance the ability of mononuclear phagocytes to suppress the intracellular growth of Mycobacterium tuberculosis. 1,25-(OH)2-D3 has demonstrated beneficial effects in animal models of such autoimmune diseases as rheumatoid arthritis. Vitamin D appears to demonstrate both immune-enhancing and immunosuppressive effects.
Calcium carbonate reacts with gastric acid to produce a salt and water. For calcium carbonate the postulated chemical reaction is:
CaCO3 + 2HCl = CaCl2 + H2O + CO2
Indicated in raised calcium requirement e.g. during pregnancy and lactation, and in children and adolescents at time of rapid growth, inadequate intake of calcium in the diet due to malnutrition, prevention and treatment of osteoporosis, disorders of osteogenesis and tooth formation, latent tetany.
Gastric-peptic disease occurs as a result of an imbalance between protective factors, such as mucus, bicarbonate, and prostaglandin secretion, and aggressive factors, such as hydrochloric acid, pepsin, and Helicobacter pylori (H. pylori). Antacids work by restoring acid-base balance, attenuating the pepsin activity and increasing bicarbonate and prostaglandin secretion. The acid-neutralizing capacity of calcium carbonate is 58 mEq/15 ml.When used as a nutritional supplement, calcium carbonate acts by directly increasing calcium stores within the body.
Folic acid is essential for the production of certain coenzymes in many metabolic systems such as purine and pyrimidine synthesis. It is also essential in the synthesis and maintenance of nucleoprotein in erythropoesis. It also promotes WBC and platelet production in folate-deficiency anaemia.
Folic acid is a water-soluble B-complex vitamin found in foods such as liver, kidney, yeast, and leafy, green vegetables. Also known as folate or Vitamin B9, folic acid is an essential cofactor for enzymes involved in DNA and RNA synthesis. More specifically, folic acid is required by the body for the synthesis of purines, pyrimidines, and methionine before incorporation into DNA or protein. Folic acid is the precursor of tetrahydrofolic acid, which is involved as a cofactor for transformylation reactions in the biosynthesis of purines and thymidylates of nucleic acids. Impairment of thymidylate synthesis in patients with folic acid deficiency is thought to account for the defective deoxyribonucleic acid (DNA) synthesis that leads to megaloblast formation and megaloblastic and macrocytic anemias. Folic acid is particularly important during phases of rapid cell division, such as infancy, pregnancy, and erythropoiesis, and plays a protective factor in the development of cancer. As humans are unable to synthesize folic acid endogenously, diet and supplementation is necessary to prevent deficiencies. In order to function properly within the body, folic acid must first be reduced by the enzyme dihydrofolate reductase (DHFR) into the cofactors dihydrofolate (DHF) and tetrahydrofolate (THF). This important pathway, which is required for de novo synthesis of nucleic acids and amino acids, is disrupted by anti-metabolite therapies such as Methotrexate as they function as DHFR inhibitors to prevent DNA synthesis in rapidly dividing cells, and therefore prevent the formation of DHF and THF.
In general, folate serum levels below 5 ng/mL indicate folate deficiency, and levels below 2 ng/mL usually result in megaloblastic anemia.
| Trade Name | Calcrown |
| Generic | Calcitriol + Calcium Carbonate + Methylcobalamin + Folic Acid + Omega 3 Fatty Acids |
| Type | Tablet |
| Therapeutic Class | |
| Manufacturer | Renowed Lifescience |
| Available Country | India |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Calcitriol is used for the correction of the abnormalities of Calcium and Phosphate metabolism in patients with renal osteodystrophy.
Calcitriol is also used for the treatment of established post-menopausal osteoporosis, hypoparathyroidism, idiopathic hypoparathyroidism, pseudohypoparathyroidism, vitamin D dependent rickets.
Adult: One Calcium Carbonate 500 tablet or as directed by the physician. For the prevention of osteoporosis, 1-3 Calcium Carbonate 500 tablet is recommended generally as a dietary supplement . Doses for children is half of those for adults. A large dose should not be taken without physician\'s advice.
Adolescent: One to two Calcium Carbonate tablet daily.
Children: One Calcium Carbonate tablet daily.
Prophylaxis of megaloblastic anaemia in pregnancy, Supplement for women of child-bearing potential, Folate-deficient megaloblastic anaemia, Prophylaxis of neural tube defect in pregnancy
Calcrown is also used to associated treatment for these conditions: Hypocalcemia, Osteodystrophy, Psoriasis Vulgaris (Plaque Psoriasis), Secondary Hyperparathyroidism (SHPT), Vitamin D Resistant RicketsAcid Reflux, Acid indigestion, Bloating, Calcium Deficiency, Calcium Metabolism Disorders, Calcium and Vitamin D Deficiencies, Colic, Dyspepsia, Gastric Ulcer, Gastroesophageal Reflux, Heartburn, Hemorrhoids, Hot Flushes, Hyperacidity, Hyperphosphataemia, Hypovitaminosis D, Low Bone Density, Osteodystrophy, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Postoperative Gas, Proctitis, Vertebral Fractures, Calcium loss, Gastrointestinal ulceration, Dietary supplementationAnaemia folate deficiency, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Latent Iron Deficiency, Neural Tube Defects (NTDs), Vitamin Deficiency, Methotrexate toxicity, Nutritional supplementation
How Calcrown works
The mechanism of action of calcitriol in the treatment of psoriasis is accounted for by their antiproliferative activity for keratinocytes and their stimulation of epidermal cell differentiation. The anticarcinogenic activity of the active form of Calcitriol appears to be correlated with cellular vitamin D receptor (VDR) levels. Vitamin D receptors belong to the superfamily of steroid-hormone zinc-finger receptors. VDRs selectively bind 1,25-(OH)2-D3 and retinoic acid X receptor (RXR) to form a heterodimeric complex that interacts with specific DNA sequences known as vitamin D-responsive elements. VDRs are ligand-activated transcription factors. The receptors activate or repress the transcription of target genes upon binding their respective ligands. It is thought that the anticarcinogenic effect of Calcitriol is mediated via VDRs in cancer cells. The immunomodulatory activity of calcitriol is thought to be mediated by vitamin D receptors (VDRs) which are expressed constitutively in monocytes but induced upon activation of T and B lymphocytes. 1,25-(OH)2-D3 has also been found to enhance the activity of some vitamin D-receptor positive immune cells and to enhance the sensitivity of certain target cells to various cytokines secreted by immune cells.
A study suggests that calcitriol plays an immunoregulatry role by suppressing the aryl hydrocarbon receptor (AhR) expression in human Th9, a pro-inflammatory CD4 T cell subset . This suppression subsequently leads to repressed expression of BATF, a transcription factor essential for Th9 . Calcitriol has also been found to induce monocyte differentiation and to inhibit lymphocyte proliferation and production of cytokines, including interleukin IL-1 and IL-2, as well as to suppress immunoglobulin secretion by B lymphocytes.
Calcium carbonate is a basic inorganic salt that acts by neutralizing hydrochloric acid in gastric secretions. It also inhibits the action of pepsin by increasing the pH and via adsorption. Cytoprotective effects may occur through increases in bicarbonate ion (HCO3-) and prostaglandins. Neutralization of hydrochloric acid results in the formation of calcium chloride, carbon dioxide and water. Approximately 90% of calcium chloride is converted to insoluble calcium salts (e.g. calcium carbonate and calcium phosphate).
Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase (DHFR). These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.
Dosage
Calcrown dosage
Injection
The recommended intravenous initial dose of Calcitriol injection, depending on the severity of the hypocalcemia and/or secondary hyperparathyroidism, is 1 mcg (0.02 mcg/kg) to 2 mcg administered three times weekly, approximately every other day. Doses as small as 0.5 mcg and as large as 4 mcg three times weekly have been used as an initial dose. If a satisfactory response is not observed, the dose may be increased by 0.5 to 1 mcg at two to four week intervals.
Capsule
Adult
Renal osteodystrophy: The initial daily dose is 0.25 mcg of Calcitriol. In patients with normal or only slighty reduced Calcium level, doses of 0.25 mcg every other day are sufficient. If no satisfactory response in the biochemical parameters and clinical manifestations of the disease is observed within 2-4 weeks, the daily dosage may be increased by 0.25 mcg at 2-4 week intervals.
Post-menopausal osteoporosis: The recommended dose of Calcitriol is 0.25 mcg twice daily.
Serum calcium and creatinin levels should be determined at 1-3 and 6 months and at 6 monthly intervals thereafter.
Hypoparathyroidism & Rickets: The recommended initial dose of Calcitriol is 0.25 mcg per day in the morning. In patients with renal osteodystrophy or hypoparathyroidism and rickets if within 2-4 weeks no satisfactory response is observed by usual dose then dose may be increased at two to four week intervals.
Elderly patients
No specific dosage modifications are required in elderly patents.
Children
Dosage in children has not been established.
Calcium Carbonate is always used orally and when used as an antacid the recommended doses for adults are equivalent to 540-2000 mg Calcium Carbonate per day, doses for children being half of those for adults. As a dietary supplement, such as for the prevention of osteoporosis, 1250-3750 mg Calcium Carbonate (500-1500 mg calcium) daily is recommended in general, but again this will need to be tailored to the individual patient depending on any specific disease such as Calcium deficiency, malabsorption or parathyroid function. In pregnancy and lactation therecommended daily dose of calcium is 1200-1500 mg. In chronic renal failure the doses used vary from 2.5 - 9.0 gm Calcium Carbonate per day and need to be adjusted according to the individual patient. To maximize effective phosphate binding in this context the Calcium Carbonate should be given with meals.
Supplement for women of child-bearing potential: 0.4 mg daily.
Folate-deficient megaloblastic anaemia: 5 mg daily for 4 mth, up to 15 mg daily in malabsorption states. Continued dosing at 5 mg every 1-7 days may be needed in chronic haemolytic states, depending on the diet and rate of haemolysis.
Prophylaxis of neural tube defect in pregnancy: 4 or 5 mg daily starting before pregnancy and continued through the 1st trimester.
Prophylaxis of megaloblastic anaemia in pregnancy: 0.2-0.5 mg daily.
May be taken with or without food.
Side Effects
Since Calcitriol exerts vitamin D activity, adverse effects may occur which are similar to those found when an excessive dose of vitamin D is taken, i.e. hypercalcaemia syndrome or calcium intoxication (depending on the severity and duration of hypercalcaemia). Occasional acute symptoms include anorexia, headache, nausea, vomiting, abdominal pain or stomach ache and constipation.
In rare cases, flatulence, diarrhoea or constipation.
GI disturbances, hypersensitivity reactions; bronchospasm.
Toxicity
LD50 (oral, rat) = 620 μg/kg; LD50 (intraperitoneal, rat) > 5 mg/kg .
Symptoms of calcitriol toxicity mirrors the early and late signs and symptoms of vitamin D intoxication associated with hypercalcemia . Early signs include weakness, headache, somnolence, nausea, vomiting, dry mouth, constipation, muscle pain, bone pain and metallic taste. Late signs are characterized by polyuria, polydipsia, anorexia, weight loss, nocturia, conjunctivitis (calcific), pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido, elevated BUN, albuminuria, hypercholesterolemia, elevated SGOT and SGPT, ectopic calcification, hypertension, cardiac arrhythmias and, rarely, overt psychosis .
IPR-MUS LD50 85 mg/kg,IVN-GPG LD50 120 mg/kg, IVN-MUS LD50 239 mg/kg, IVN-RAT LD50 500 mg/kg, IVN-RBT LD50 410 mg/kg
Precaution
Immobilised patients, e.g. those who have undergone surgery, are particularly exposed to the risk of hypercalcaemia. Patients with normal renal function who are taking Calcitriol should avoid dehydration. Adequate fluid intake should be maintained.
In the presence of mild hypercalciuria, excretion levels must be carefully monitored and where necessary the dose of calcium carbonate should be reduced or treatment should be stopped. Patients with a history of stone formation should also be recommended to increase their fluid intake. High dosage of vitamin D should be avoided during Calcium therapy unless specifically indicated.
Treatment resistance may occur in patients with depressed haematopoiesis, alcoholism, deficiencies of other vitamins. Neonates.
Interaction
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Calcitriol dosage must be determined with care in patients undergoing treatment with digitalis, as hypercalcaemia in such patients may precipitate cardiac arrhythmias. Administration of enzyme inducers such as phenytoin or phenobarbital may lead to increased metabolism and hence reduced serum concentrations of Calcitriol. Therefore higher doses of Calcitriol may be necessary if these drugs are administered simultaneously. Colestyramine can reduce intestinal absorption of fat-soluble vitamins and therefore may impair intestinal absorption of Calcitriol.
Oral calcium can reduce internal absorption of tetracycline and fluoride prepa-rations and an interval of at least 3 hours should therefore be allowed between ingestion of these medications. Vitamin D increases internal absorption of calcium. The intestinal uptake of calcium may be reduced by concomitant ingestion of certain foods (e.g. spinach, milk and milk products).
Antiepileptics, oral contraceptives, anti-TB drugs, alcohol, aminopterin, methotrexate, pyrimethamine, trimethoprim and sulphonamides may result to decrease in serum folate contrations. Decreases serum phenytoin concentrations.
Volume of Distribution
Upon intravenous administration, the volume of distribution of calcitriol was 0.49±0.14 L/kg in healthy male volunteers and 0.27±0.06 l/kg in uraemic male patients participating in a pharmacokinetic study . There is some evidence that calcitriol is transferred into human milk at low levels (ie, 2.2±0.1 pg/mL) in mothers . Calcitriol from maternal circulation may also enter the fetal circulation .
Calcium is rapidly distributed taken up by skeletal tissues following absorption and distribution into extracellular fluids. Bone contains 99% of the body's calcium and the remaining 1% is approximately equally distributed between intracellular and extracellular fluids.
Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.
Elimination Route
Upon administration, calcitriol is rapidly absorbed from the intestines. When a single oral dose of 0.5 mcg of calcitriol was administered, the mean serum concentrations of calcitriol rose from a baseline value of 40.0±4.4 (SD) pg/mL to 60.0±4.4 pg/mL at 2 hours, and declined to 53.0±6.9 at 4 hours, 50±7.0 at 8 hours, 44±4.6 at 12 hours and 41.5±5.1 at 24 hours . Following administration of single doses of 0.25 to 1.0 mcg of calcitriol, the peak plasma concentrations were reached within 3 to 6 hours . In a pharmacokinetic study, the oral bioavailability was 70.6±5.8% in healthy male volunteers and 72.2±4.8% in male patients with uraemia .
Maximal absorption occurs at doses of 500 mg or less taken with food. Oral bioavailability depends on intestinal pH, the presence of food and dosage.
Folic acid is absorbed rapidly from the small intestine, primarily from the proximal portion. Naturally occurring conjugated folates are reduced enzymatically to folic acid in the gastrointestinal tract prior to absorption. Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose; peak levels are generally reached within 1 hour.
Half Life
After administration of single oral doses, the elimination half life was 5-8 hours .
Clearance
The metabolic clearance rate was 23.5±4.34 ml/min in healthy male volunteers and 10.1±1.35 ml/min in male patients with uraemia . In the pediatric patients undergoing peritoneal dialysis receiving dose of 10.2 ng/kg (SD 5.5 ng/kg) for 2 months, the clearance rate was 15.3 mL/hr/kg .
Elimination Route
In normal subjects, approximately 27% and 7% of the radioactivity appeared in the feces and urine, respectively, within 24 hours . Calcitriol undergoes enterohepatic recycling and biliary excretion. The metabolites of calcitriol are excreted primarily in feces. Cumulative excretion of radioactivity on the sixth day following intravenous administration of radiolabeled calcitriol averaged 16% in urine and 49% in feces .
Excreted mainly in the feces. The majority of renally filtered calcium is reabsorbed in the ascending limb of the loop of Henle and the proximal and distal convoluted tubules. Also secreted by sweat glands.
After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic acid is also excreted in the milk of lactating mothers.
Pregnancy & Breastfeeding use
Pregnancy category C. Calcitriol has been found to be teratogenic in rabbits. There are no adequate and well-controlled studies in pregnant women. Calcitriol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnant women : Calcium containing drugs are used widely in pregnancy by way of calcium supplement or antacid therapy. No relationship between malformation in general and calcium exposure has been noted.
Lactating mother : There is no contraindication to the use of calcium carbonate in lactating mother.
Pregnancy Category A. Adequate and well-controlled human studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters).
Contraindication
Calcitriol is contraindicated in patients with known hypersensitivity to any of its ingredients. Calcitriol is also contraindicated in all diseases associated with hypercalcemia.
Hypersensitivity to the Calcium Carbonate or any inactive ingredient of the medication. Hypercalcemia (e.g. in hyperparathyroidism, overdosage of vitamin D, demineralizing tumours such as plasmacytomas and bone metastases), severe hypercalcuria, several renal insufficiency.
Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.
Special Warning
Elderly patients: No specific dosage modifications are required in elderly patients.
USE IN CHILDREN: Calcium carbonate has been extensively studied in children and infants with chronic renal failure and is both safe and effective.
USE IN ELDERLY: In case of elderly patients with renal failure when calcium carbonate is taken constipation may be troublesome one for this group. For this reason, monitoring of serum calcium and phosphate is of course indicated for elderly patients.
Acute Overdose
Administration of Calcitriol to patients in excess of their daily requirements can cause hypercalcaemia, hypercalciuria and hyperphospatemia. Since Calcitriol is a derivative of vitamin D, the signs and symptoms of overdose are the same as for an overdose of vitamin D.
Storage Condition
Store between 15-30° C. Protect from moisture, heat and light. Do not freeze.
Store in a cool, dry place in controlled room temperature.
Store at 15-30° C.
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