Hicalol
Hicalol Uses, Dosage, Side Effects, Food Interaction and all others data.
Hicalol 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). Hicalol promotes intestinal absorption of Calcium and regulates bone mineralization.
Hicalol 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 . Hicalol 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 . Hicalol 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.
| Trade Name | Hicalol |
| Availability | Prescription only |
| Generic | Calcitriol |
| Calcitriol Other Names | 1-alpha-25-Dihydroxyvitamin D3, Calcitriol, Calcitriolum |
| Related Drugs | ergocalciferol, calcium carbonate, Caltrate, Drisdol, calcium lactate, Rocaltrol, calcifediol, Calcidol |
| Type | |
| Formula | C27H44O3 |
| Weight | Average: 416.6365 Monoisotopic: 416.329045274 |
| Protein binding | Calcitriol is approximately 99.9% bound in blood, mostly by an alpha-globulin vitamin D binding protein . |
| Groups | Approved, Nutraceutical |
| Therapeutic Class | Vitamin in bone formation, Vitamin-D preparations |
| Manufacturer | |
| Available Country | China, Taiwan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Hicalol is used for the correction of the abnormalities of Calcium and Phosphate metabolism in patients with renal osteodystrophy.
Hicalol is also used for the treatment of established post-menopausal osteoporosis, hypoparathyroidism, idiopathic hypoparathyroidism, pseudohypoparathyroidism, vitamin D dependent rickets.
Hicalol is also used to associated treatment for these conditions: Hypocalcemia, Osteodystrophy, Psoriasis Vulgaris (Plaque Psoriasis), Secondary Hyperparathyroidism (SHPT), Vitamin D Resistant Rickets
How Hicalol 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 Hicalol 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 Hicalol 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 . Hicalol 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.
Dosage
Hicalol dosage
Injection
The recommended intravenous initial dose of Hicalol 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 Hicalol. 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 Hicalol 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 Hicalol 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.
Side Effects
Since Hicalol 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.
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 .
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 Hicalol should avoid dehydration. Adequate fluid intake should be maintained.
Interaction
Concomitant treatment with a thiazide diuretic increases the risk of hypercalcaemia. Hicalol 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 Hicalol. Therefore higher doses of Hicalol 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 Hicalol.
Food Interaction
No interactions found.Hicalol Drug Interaction
Major: ergocalciferol, ergocalciferol, cholecalciferol, cholecalciferolUnknown: aspirin, aspirin, furosemide, furosemide, metoprolol, metoprolol, metoprolol, metoprolol, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid
Hicalol Disease Interaction
Major: arrhythmia, electrolyte imbalance, hypercalcemia, renal dysfunctionModerate: dialysis, hepatobiliary dysfunction
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 . Hicalol from maternal circulation may also enter the fetal circulation .
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 .
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 . Hicalol 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 .
Pregnancy & Breastfeeding use
Pregnancy category C. Hicalol has been found to be teratogenic in rabbits. There are no adequate and well-controlled studies in pregnant women. Hicalol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Contraindication
Hicalol is contraindicated in patients with known hypersensitivity to any of its ingredients. Hicalol is also contraindicated in all diseases associated with hypercalcemia.
Special Warning
Elderly patients: No specific dosage modifications are required in elderly patients.
Acute Overdose
Administration of Hicalol to patients in excess of their daily requirements can cause hypercalcaemia, hypercalciuria and hyperphospatemia. Since Hicalol 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.
Innovators Monograph
You find simplified version here Hicalol
Hicalol contains Calcitriol see full prescribing information from innovator Hicalol Monograph, Hicalol MSDS, Hicalol FDA label
