Vitomil AF
Vitomil AF Uses, Dosage, Side Effects, Food Interaction and all others data.
Cupric sulfate is a salt created by treating cupric oxide with sulfuric acid. This forms as large, bright blue crystals containing five molecules of water (CuSO4∙5H2O) and is also known as blue vitriol. The anhydrous salt is created by heating the hydrate to 150 °C (300 °F). Cupric sulfate is used primarily for agricultural purposes, as a pesticide, germicide, feed additive, and soil additive. Some of its secondary uses are as a raw material in the preparation of other copper compounds, as a reagent in analytic chemistry, as an electrolyte for batteries and electroplating baths, and in medical practice as a locally applied fungicide, bactericide, and astringent .
Copper is an essential trace element and an important catalyst for heme synthesis and iron absorption. After zinc and iron, copper is the third most abundant trace element found in the human body. Copper is a noble metal and its properties include high thermal and electrical conductivity, low corrosion, alloying ability, and malleability. Copper is a component of intrauterine contraceptive devices (IUD) and the release of copper is necessary for their important contraceptive effects. The average daily intake of copper in the USA is approximately 1 mg Cu with the diet being a primary source .
Interestingly, the dysregulation of copper has been studied with a focus on neurodegenerative diseases, such as Wilson’s disease, Alzheimer’s disease, and Parkinson’s disease. Data from clinical observations of the neurotoxic effects of copper may provide the basis for future treatments affecting copper and its homeostasis .
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.
An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.
Vitamin D ultimately comprises a group of lipid-soluble secosteroids responsible for a variety of biological effects, some of which include increasing the intestinal absorption of calcium, magnesium, and phosphate. With reference to human use, there are 2 main forms of vitamin D - vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). When non-specific references are made about 'vitamin d', the references are usually about the use of vitamin D3 and/or D2.
Vitamin D3 and D2 require hydroxylation in order to become biologically active in the human body. Since vitamin D can be endogenously synthesized in adequate amounts by most mammals exposed to sufficient quantities of sunlight, vitamin D functions like a hormone on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Vitamin D plays an essential physiological role in maintaining calcium homeostasis and metabolism. There are several different vitamin D supplements that are given to treat or to prevent osteomalacia and rickets, or to meet the daily criteria of vitamin D consumption.
The in vivo synthesis of the predominant two biologically active metabolites of vitamin D occurs in two steps. The first hydroxylation of vitamin D3 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 . 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 . 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 . There exists a period of 10 to 24 hours between the administration of vitamin D 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 . It is parathyroid hormone that is responsible for the regulation of such metabolism at the level of the kidneys .
| Trade Name | Vitomil AF |
| Generic | Kandungan: β-carotene + Vitamin B Compleks (Vitamin B + Vitamin B + Vitamin B + Vitamin B + Vitamin C + Vitamin D + Nicotinamide + Ca pantothenate + Folic acid + K iodide + Fe fumarate + cupric sulfate + Ca lactate + Na fluoride |
| Weight | 10.000iu, 1mononitrate10mg, 22.5mg, 6hcl15mg, 124mcg, 100mg, 400mg, 20mg, 7.5mg, 1mg, 100mg, 90mg, 0.1mg, 250mg, 1mg |
| Type | Caplet |
| Therapeutic Class | |
| Manufacturer | Mersifarma Tirmaku Mercusana |
| Available Country | Indonesia |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Cupric sulfate is a compound used as an intravenous copper supplement for Total Parenteral Nutrition (TPN).
Elemental use in copper deficiency
Copper and copper containing compounds are broadly used in medical practice. Metallic copper is used already for many years in dental fillings and in copper intrauterine devices (IUD) for reversible contraception. Ointments containing copper, which release copper ions that are absorbed by the skin in the management of cramps, disturbances of renal function, peripheral, venous hypostatic circulatory disturbances, rheumatic disease and swelling associated with trauma. There are also cosmetic facial creams containing copper as their main active ingredient .
Prophylaxis of megaloblastic anaemia in pregnancy, Supplement for women of child-bearing potential, Folate-deficient megaloblastic anaemia, Prophylaxis of neural tube defect in pregnancy
Nicotinamide is an ingredient found in a variety of cosmetic products.
Vitamin D is an ingredient found in a variety of supplements and vitamins.
Vitamin D is indicated for use in the treatment of hypoparathyroidism, refractory rickets (also known as vitamin D resistant rickets), and familial hypophosphatemia .
Vitomil AF is also used to associated treatment for these conditions: Copper Deficiency, Skin disinfectionAnaemia folate deficiency, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Latent Iron Deficiency, Neural Tube Defects (NTDs), Vitamin Deficiency, Methotrexate toxicity, Nutritional supplementationGastrointestinal insufficiency, Hepatic Insufficiency, Macrocytic anemia, Secondary anemia, Vitamin Deficiency, Severe debilitation, Dietary and Nutritional Therapies, Nutritional supplementation, Dietary supplementationDeficiency, Vitamin D
How Vitomil AF works
This drug is an essential trace element for the functioning of many metalloenzymes including ceruloplasmin, ferroxidase II, lysyl oxidase, monoamine oxidase, Zn-copper superoxide dismutase, tyrosinase, dopamine-β-hydroxylase, and cytochrome-c-oxidase.
It is involved in erythropoiesis & leukopoiesis, bone mineralization, elastin and collagen cross-linking, oxidative phosphorylation, catecholamine metabolism, melanin formation & antioxidant protection of cells .
Cupric sulfate may also have a role in iron turnover, ascorbic acid metabolism, phospholipid metabolism, myelin formation, glucose homeostasis, and cellular immune defense .
After the metal passes through the basolateral membrane it is transported to the liver, attached to serum albumin. The liver is the critical organ for the homeostasis of copper. The copper is then prepared for excretion through the bile or incorporation into various proteins. The transport of copper to the peripheral tissues is accomplished through the plasma attached to serum albumin, ceruloplasmin or low-molecular-weight complexes .
In the dermis, copper promotes dermal fibroblasts proliferation, upregulates collagen (types I, II, and V) and elastin fiber components (elastin, fibrillins) production by fibroblasts, through the induction of TGF-β, promotes heat shock protein-47, important for collagen fibril formation, serves as a cofactor of LOX enzyme required for extracellular matrix protein cross-linking, stabilizes the skin ECM once formed, as increased crosslinking of collagen and elastin matrices occurs in a copper dose dependant manner, serves as a cofactor of superoxide dismutase, an antioxidant enzyme in the skin, essential for protection against free radicals, inhibits cellular oxidative effects such as membrane damage and lipid peroxidation, acts as a cofactor of tyrosinase, a melanin biosynthesis essential enzyme responsible for skin and hair pigmentation .
In reference to its role as a biocide, copper is an essential nutrient for many organisms. It acts as a cofactor in respiration, and therefore copper is required for aerobic metabolism. Accumulation of copper ions or intracellular release of free copper ions from proteins lead to cell damage. Copper catalyzes reactions that result in the production of hydroxyl radicals through the Fenton and Haber-Weiss reactions. The highly reactive oxygen intermediates lead to lipid peroxidation and oxidation of proteins. Free copper ions oxidize sulfhydryl groups, such as cysteine, in proteins or the cellular redox buffer glutathione. In particular, copper ions inactivate proteins by damaging Fe-S clusters in cytoplasmic hydratases .
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.
Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight.
Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease . Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone . Increases in parathyroid hormone stimulates the mobilization of skeletal calcium and the renal excretion of phosphorus . This enhanced mobilization of skeletal calcium leads towards porotic bone conditions .
Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet . At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation . This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma .
Dosage
Vitomil AF dosage
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
GI disturbances, hypersensitivity reactions; bronchospasm.
Toxicity
Acute oral toxicity (LD50): 300 mg/kg in rats .
Copper sulfate ingestion (accidental or deliberate) is a rare form of poisoning usually limited to the Indian subcontinent. Though the rates are on the decline, it is essential that physicians are aware of its lethal complications and management strategies. The main complications of copper sulfate ingestion include intravascular hemolysis, methemoglobinaemia, acute kidney injury, and rhabdomyolysis .
Severe gastrointestinal effects may occur with acute overdosage. In extreme or long-term overdosage, symptoms may be similar to those of Wilson's disease, a disease in which the liver does not filter copper adequately and copper accumulates in the liver, brain, eyes, and other organs. Gradually, high copper levels may cause life-threatening organ damage .
Ingestion of more than 15 mg of copper has been reported to be toxic to humans. In a survey of human clinical case studies, 5.3 mg/day was the lowest oral dose at which local gastrointestinal irritation was seen. Ingestion of gram quantities of copper sulfate resulted in death by suicide, whereas less severe effects were reported from estimated copper doses of 40 to 50 mg from ingestion of carbonated beverages in contact with copper containers. Limited data are available on the chronic toxicity of copper. The hazard from dietary intakes of up to 5 mg/day appears to be low .
Treatment of cupric sulfate toxicity is symptomatic and may involve the use of a chelating agent (e.g. penicillamine, trientine and zinc) to remove any excessive metal that has been absorbed. In addition, dialysis may be useful .
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
The use of pharmacological or nutraceutical vitamin d and/or even excessive dietary intake of vitamin d is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin d, and hypervitaminosis D .
Hypersensitivity to vitamin d is one plausible etiologic factor in infants with idiopathic hypercalcemia - a case in which vitamin d use must be strictly restricted .
As vitamin d intake is available via fortified foods, dietary supplements, and clinical drug sources, serum concentrations and therapeutic dosages should be reviewed regularly and readjusted as soon as there is clinical improvement . Dosage levels are required to be individualized on an individual patient by patient basis as caution must be exercised to prevent the presence of too much vitamin d in the body and the various potentially serious toxic effects associated with such circumstances .
In particular, the range between therapeutic and toxic doses is quite narrow in vitamin d resistant rickets . When high therapeutic doses are used, progress should be followed with frequent blood calcium determinations .
When treating hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may be required .
Maintenance of normal serum phosphorus levels by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatic calcification .
Mineral oil interferes with the absorption of lipid-soluble vitamins, including vitamin d preparations .
The administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with vitamin d can result in hypercalcemia .
At this time, no long term animal studies have been performed to evaluate vitamin potential for carcinogens, mutagenesis, or fertility .
As various animal reproduction studies have demonstrated fetal abnormalities in several species associated with hypervitaminosis D, the use of vitamin d in excess of the recommended dietary allowance during normal pregnancy should be avoided . The safety in excess of 400 USP units of vitamin d daily during pregnancy has not been established . The abnormalities observed are similar to the supravalvular aortic stenosis syndrome described in infants that is characterized by supravalvular aortic stenosis, elfin facies, and mental retardation .
In a nursing mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Caution is subsequently required when contemplating the use of vitamin d in a nursing woman, and the necessity of monitoring infants' serum calcium concentration if vitamin d is administered to a breastfeeding woman .
Adverse reactions associated with the use of vitamin d are primarily linked to having hypervitaminosis D occurring [FDA Lanel]. In particular, hypervitaminosis D is characterized by effects specific effects on specific organ systems. At the renal system, hypervitaminosis D can cause impairment of renal function with polyuria, nocturne, polydipsia, hypercalciuria, reversible asotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or even irreversible renal insufficiency which may result in death . Elsewhere, hypervitaminosis D can also cause CNS mental retardation . At the level of soft tissues, it can widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs . In the skeletal system, bone demineralization (osteoporosis) in adults can occur while a decline in the average rate of linear growth and increased mineralization of bones, dwarfism, vague aches, stiffness, and weakness can occur in infants and children . Finally, hypervitaminosis D can also lead to nausea, anorexia, and constipation at the gastrointestinal level as well as mild acidosis, anemia, or weight loss via metabolic processes .
The LD(50) in animals is unknown .
Precaution
Treatment resistance may occur in patients with depressed haematopoiesis, alcoholism, deficiencies of other vitamins. Neonates.
Interaction
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
The body of a 70 kg healthy individual contains approximately 110 mg of copper, 50% of which is found in the bones and muscles, 15% in the skin, 15% in the bone marrow, 10% in the hepatic system, and 8% in the brain .
The distribution of copper is affected by sex, age, and the amount of copper in the diet. Brain and liver have the highest tissue levels (about one-third of the total body burden), with lesser concentrations found in the heart, spleen, kidneys, and blood. The iris and choroid of the eye have very high copper levels .
Erythrocyte copper levels are generally stable, however, plasma levels fluctuate widely in association with the synthesis and release of ceruloplasmin. Plasma copper levels during gestation may be 2-3 times levels measured before pregnancy, due to the increased synthesis of ceruloplasmin .
Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.
Elimination Route
Primarily absorbed in the small intestine .
Based on studies with radioactive isotopes of copper, most copper is absorbed from the stomach and duodenum of the gastrointestinal tract.
Maximum blood copper levels are observed within 1 to 3 hours following oral administration, and about 50 percent of ingested copper was absorbed. Copper absorption is proposed to occur by two mechanisms, one energy- dependent and the other enzymatic. Factors that can interfere with copper absorption include competition for binding sites with zinc, interactions with molybdenum and sulfates, chelation with phytates, and inhibition by ascorbic acid (vitamin C) .
Copper absorbed from the gastrointestinal tract is transported rapidly to blood serum and deposited in the liver bound to metallothionein .
From 20 to 60% of the dietary copper is absorbed .
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.
Vitamin D3 and D2 are readily absorbed from the small intestine (proximal or distal) .
Half Life
The biological half-life of copper from the diet is 13-33 days with biliary excretion being the primary route of elimination .
Although certain studies suggest the half-life of 1,25-hydroxyvitamin D3 may be approximately 15 hours, the half-life of 25-hydroxyvitamin D3 appears to have a half-life of about 15 days . Intriguingly however, the half-lives of any particular administration of vitamin d can vary and in general the half-lives of vitamin D2 metabolites have been demonstrated to be shorter overall than vitamin D3 half-lives with this being affected by vitamin d binding protein concentrations and genotype in particular individuals .
Clearance
Some studies propose an estimated clearance rate for 1,25-dihydroxyvitamin D as 31 +/- 4 ml/min in healthy adults .
Elimination Route
This drug is 80% eliminated via the liver in bile. Minimal excretion by the kidney . Metabolism studies show that persons with daily intakes of 2-5 mg of copper per day absorbed 0.6 to 1.6 mg (32%), excreted 0.5 to 1.3 mg in the bile, passed 0.1 to 0.3 mg directly into the bowel, and excreted 0.01 to 0.06 mg in the urine. As the data indicate, urinary excretion plays a negligible role in copper clearance, and the main route of excretion is in the bile. Other nonsignificant excretory routes include saliva, sweat, menstrual flow, and excretion into the intestine from the blood .
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.
The primary excretion route of vitamin D is via the bile into the feces .
Pregnancy & Breastfeeding use
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
Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.
Storage Condition
Store at 15-30° C.
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