Calcydon K2

Calcydon K2 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.

Lycopene is a naturally occuring red carotenoid pigment that is responsible in red to pink colors seen in tomatoes, pink grapefruit, and other foods . Having a chemical formula of C40H56, lycopene is a tetraterpene assembled from eight isoprene units that are solely composed of carbon and hydrogen. Lycophene may undergo extensive isomerization that allows 1056 theoretical cis-trans configurations; however the all-trans configuration of lycopene is the most predominant isomer found in foods that gives the red hue. Lycopene is a non-essential human nutrient that is classified as a non-provitamin A carotenoid pigment since it lacks a terminal beta ionone ring and does not mediate vitamin A activity. However lycophene is a potent antioxidant molecule that scavenges reactive oxygen species (ROS) singlet oxygen. Tomato lycopene extract is used as a color additive in food products.

Mecobalamin is the neurologically active form of vitamin B12 and occurs as a water-soluble vitamin in the body. It is a cofactor in the enzyme methionine synthase, which functions to transfer methyl groups for the regeneration of methionine from homocysteine. In anaemia, it increases erythrocyte production by promoting nucleic acid synthesis in the bone marrow and by promoting maturation and division of erythrocytes.

Calcydon K2
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Calcydon K2
Generic	Calcium Citrate Malate + Eicosapentaenoic Acid + Docosahexaenoic Acid + Lycopene + Mecobalamin + L-methylfolate Calcium + Pyridoxal-5-phosphate + Vitamin K2-7 + Calcitriol
Weight	500mg
Type	Tablet
Therapeutic Class
Manufacturer	Medicure Life Sciences India Private Limited
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.

Lycopene is an ingredient found in a variety of supplements and vitamins.

Mecobalamin is used for-

Peripheral Neuropathies
Diabetic Neuropathy
Verteberal Syndrome
Nerve Compression Syndrome
Multiple sclerosis
Amyotrophic lateral sclerosis
Parkinson’s disease
Alzheimer’s disease
Diabetic retinopathy
Entrapment neuropathy
Drug induced neuropathy
Megaloblastic anemia due to Vitamin B12 deficiency

Calcydon K2 is also used to associated treatment for these conditions: Hypocalcemia, Osteodystrophy, Psoriasis Vulgaris (Plaque Psoriasis), Secondary Hyperparathyroidism (SHPT), Vitamin D Resistant RicketsNutritional supplementationVitamin B12 Deficiency, Nutritional supplementation

How Calcydon K2 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.

Dosage

Calcydon K2 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.

Tablet: The usual adult dosage is one 500 mcg tablet three times daily. The dosage should be adjusted according to the age of patient and the severity of symptoms.

Injection:

Peripheral neuropathies: The usual adult dosage is one ampoule equivalent to 500 mcg of Mecobalamin, administered intramuscularly or intravenously three times a week.The dosage should be adjusted according to the age of patient and the severity of symptoms.
Megaloblastic anemia: The usual adult dosage is one ampoule equivalent to 500 mcg of Mecobalamin, administered intramuscularly or intravenously three times a week. After about two months of administration, dosage should be changed to one ampoule equivalent to 500 mcg of Mecobalamin every one to three months as maintenance therapy

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.

Generally Mecobalamin is well tolerated. However, a few side effects like GI discomfort (including anorexia, nausea or diarrhea) & rash may be seen after administration of Mecobalamin.

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 Calcitriol should avoid dehydration. Adequate fluid intake should be maintained.

The medicine should not be used for months if there is no response at all after its use for a certain period of time.

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.

Decreased GI tract absorption with neomycin, aminosalicylic acid, H2-blockers and colchicine. Reduced serum concentrations with oral contraceptives. Reduced effects in anaemia with parenteral chloramphenicol.

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 .

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 . 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 .

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.

Not recommended during pregnancy & lactation.

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 any component of this product.

Special Warning

Elderly patients: No specific dosage modifications are required in elderly patients.

Use in children: Not recommended.

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.