Active OB

Active OB Uses, Dosage, Side Effects, Food Interaction and all others data.

Vitamin D is essential for normal bone growth and development and to maintain bone density. It is also necessary for utilization of both Calcium and Phosphorus. Vitamin D acts as a hormone and increases reabsorption of Calcium and Phosphorus by the kidneys and increased bone turnover.

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

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 .

Vitamin B12 (cyanocobalamin) is required for the maintenance of normal erthropoiesis, nucleprotein and myelin synthesis, cell reproduction and normal growth; Coenzyme; metabolic functions include protein synthesis and carbohydrate metabolism. Plays role in cell replication and hematopoiesis.

General effects

Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12 .

Parenteral cyanocobalamin effects

A mixture of fish oil and primrose oil, doconexent is used as a high-docosahexaenoic acid (DHA) supplement. DHA is a 22 carbon chain with 6 cis double bonds with anti-inflammatory effects. It can be biosythesized from alpha-linolenic acid or commercially manufactured from microalgae. It is an omega-3 fatty acid and primary structural component of the human brain, cerebral cortex, skin, and retina thus plays an important role in their development and function. The amino-phospholipid DHA is found at a high concentration across several brain subcellular fractions, including nerve terminals, microsomes, synaptic vesicles, and synaptosomal plasma membranes .

DHA in the central nervous system is found in the phospholipid bilayers where it modulates the physical environment and increase the free volume within the membrane bilayer. It influences the G-protein coupled receptor activity and affects transmembrane transport and cell interaction with the exterior world. It is also reported to promote apoptosis, neuronal differentiation and ion channel activity. Like other polyunsaturated fatty acids, DHA acts as a ligand at PPARs that plays an anti-inflammatory effect and regulate inflammatory gene expression and NFκB activation. DHA also gives rise to resolvins and related compounds (e.g., protectins) through pathways involving cyclooxygenase and lipoxygenase enzymes to resolve the inflammatory responses.

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.

Riboflavin is a B vitamin. It can be found in certain foods such as milk, meat, eggs, nuts, enriched flour, and green vegetables. Riboflavin is frequently used in combination with other B vitamins in vitamin B complex products. Vitamin B complex generally includes vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin/niacinamide), vitamin B5 (pantothenic acid), vitamin B6 (pyridoxine), vitamin B12 (cyanocobalamin), and folic acid. However, some products do not contain all of these ingredients and some may include others, such as biotin, para-aminobenzoic acid (PABA), choline bitartrate, and inositol.

Riboflavin is used for preventing low levels of riboflavin (riboflavin deficiency), cervical cancer, and migraine headaches. It is also used for treating riboflavin deficiency, acne, muscle cramps, burning feet syndrome, carpal tunnel syndrome, and blood disorders such as congenital methemoglobinemia and red blood cell aplasia. Some people use riboflavin for eye conditions including eye fatigue, cataracts, and glaucoma.

Other uses include increasing energy levels; boosting immune system function; maintaining healthy hair, skin, mucous membranes, and nails; slowing aging; boosting athletic performance; promoting healthy reproductive function; canker sores; memory loss, including Alzheimer's disease; ulcers; burns; alcoholism; liver disease; sickle cell anemia; and treating lactic acidosis brought on by treatment with a class of AIDS medications called NRTI drugs.

Riboflavin or vitamin B2 is an easily absorbed, water-soluble micronutrient with a key role in maintaining human health. Like the other B vitamins, it supports energy production by aiding in the metabolising of fats, carbohydrates, and proteins. Vitamin B2 is also required for red blood cell formation and respiration, antibody production, and for regulating human growth and reproduction. It is essential for healthy skin, nails, hair growth and general good health, including regulating thyroid activity. Riboflavin also helps in the prevention or treatment of many types of eye disorders, including some cases of cataracts.

Zinc oxide is used to treat or prevent minor skin irritations such as burns, cuts, poison ivy, poison oak, poison sumac, and diaper rash. It is also used as a sunscreen.

Zinc oxide has astringent, soothing and protective properties and is used in topical preparations for eczema, slight excoriations, wounds and haemorrhoids. It also reflects ultraviolet radiation and can be used as a physical sunscreen.

Active OB
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
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Interaction With other Medicine
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Trade Name	Active OB
Generic	Corbic acid + cholecalciferol + .alpha.-tocopherol acetate + d- + thiamine mononitrate + riboflavin + pyridoxine hydrochloride + folic acid + cyanocobalamin + iron pentacarbonyl + zinc oxide + cupric sulfate + doconexent
Type	Capsule, liquid filled
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun.

Vitamin D with calcium is used to treat or prevent bone loss (osteoporosis). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth.

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 .

This preparation is used for Pernicious anemia,Vitamin B12 deficiency due to low intake from food,Thyrotoxicosis, Hemorrhage, Malignancy, Liver or kidney disease,Gastric bypass surgery, Total or partial gastrectomy, Gluten enteropathy or sprue, Folic acid deficiency, Macrocytic anaemia

Doconexent is an omega 3 fatty acid used in a variety of nutritional supplements to support central nervous system and cardiovascular health.

Used as a high-docosahexaenoic acid (DHA) oral supplement.

Prophylaxis of megaloblastic anaemia in pregnancy, Supplement for women of child-bearing potential, Folate-deficient megaloblastic anaemia, Prophylaxis of neural tube defect in pregnancy

Preventing and treating riboflavin deficiency and conditions related to riboflavin deficiency.

Cataracts, an eye disorder. People who eat more riboflavin as part of their diet seems to have a lower risk of developing cataracts. Also, taking supplements containing riboflavin plus niacin seems to help prevent cataracts.

High amounts of homocysteine in the blood (hyperhomocysteinemia). Some people are unable to convert the chemical homocysteine into the amino acid methionine. People with this condition, especially those with low riboflavin levels, have high amounts of homocysteine in the blood. Taking riboflavin for 12 weeks seems to reduce homocysteine levels by up to 40% in some people with this condition. Also, certain antiseizure drugs can increase homocysteine in the blood. Taking riboflavin along with folic acid and pyridoxine seems to lower homocysteine levels by 26% in people with high homocysteine levels due to antiseizure drugs.

Migraine headaches. Taking high-dose riboflavin (400 mg/day) seems to significantly reduce the number of migraine headache attacks. However, taking riboflavin does not appear to reduce the amount of pain or the amount of time a migraine headache lasts. Also, taking lower doses of riboflavin (200 mg/day) does not seem to reduce the number of migraine headache attacks.

Zinc Oxide helps to To treat or prevent skin irritations (e.g., burns, bed sore, cuts, poison ivy, diaper rash). Protects chafed skin due to diaper rash and helps seal out wetness.

Active OB is also used to associated treatment for these conditions: Calcium and Vitamin D Deficiencies, Deficiency of Vitamin D3, Deficiency, Vitamin A, Deficiency, Vitamin D, Fracture Bone, Hip Fracture, Hypoparathyroidism, Hypophosphatemia, Familial, Menopause, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Vertebral Fractures, Vitamin D Resistant Rickets, Vitamin Deficiency, Severe Bone Resorption, Spine fracture, Calcium supplementation, Nutritional supplementation, Vitamin D Supplementation, Vitamin supplementationCopper Deficiency, Skin disinfectionAnemia, Anemia, Pernicious, Combined Vitamin B1 and B12 deficiency, Convalescence, Diabetic Neuropathies, Folate deficiency, Iron Deficiency Anemia (IDA), Neuritis, Vitamin B1 deficiency, Vitamin B12 Deficiency, Vitamin B12 concentration, Vitamin B6 Deficiency, Vitamin Deficiency, Nutritional supplementation, Vitamin supplementationFredrickson classification type IV Hyperlipidemia, Fredrickson type IIb hyperlipidemia, Type III hyperlipidaemia, Nutritional supplementationAnaemia folate deficiency, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Latent Iron Deficiency, Neural Tube Defects (NTDs), Vitamin Deficiency, Methotrexate toxicity, Nutritional supplementationAriboflavinosis, Beriberi, Constipation, Functional Gastrointestinal Disorders, Joint Pain, Metabolic cardiomyopathy, Migraine, Neuralgia, Peripheral neuritis, Peripheral paralysis, Soreness, Muscle, Vitamin B complex deficiency, Vitamin B1 deficiency, Vitamin Deficiency, Wernicke's encephalopathy, Dietary and Nutritional Therapies, Nutritional supplementation, Vitamin supplementation, Dietary supplementationAcute Wounds, Burns first degree, Burns second degree, Dermatitis, Eczematous, Diaper Rash, Herpes Labialis, Injuries to the Nipple (Fissures and Cracks) Resulting Breastfeeding, Intertrigo, Pain, Pruritus, Sensitive Skin, Skin Irritation, Skin candida, Sunburn, Wounds, Chafing, Damaged skin, Dry, cracked skin, Facial rash, Heat rash, Superficial Wounds, Watery skin lesions, Astringent, Nutritional supplementation

How Active OB works

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 stimulate 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 .

In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively . Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts . Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels . Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys .

Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements . When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome . It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency . In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions .

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 .

Vitamin B12 serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate , an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency . Succinyl-CoA is also necessary for the synthesis of hemoglobin .

In tissues, vitamin B12 is required for the synthesis of methionine from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids . Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency , . This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form methionine and tetrahydrofolate. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells . A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

DHA and its conversion to other lipid signalling moleccules compete with the arachidonic acid cascade from endogenous phospholipids and shift the inflammatory state to being more anti-inflammatory. DHA inhibits endotoxin-stimulated production of IL-6 and IL-8 in human endothelial cells. Derivatives of DHA are anti-inflammatory lipid mediators. Lipid mediators resolvin D1 and protectin D1 all inhibit transendothelial migration of neutrophils, so preventing neutrophilic infiltration at sites of inflammation, resolvin D1 inhibits IL-1β production, and protectin D1 inhibits TNF and IL-1β production . Monoxydroxy derivative of DHA converted by LOX inhibit thromboxane-induced platelet aggregation. DHA supplementation has also shown to reduce the levels of serum C-reactive protein (CRP) and other circulating markers of inflammation such as neutrophils in hypertriglyceridemic men . DHA acts as a ligand at peroxisome proliferator-activated receptor (PPAR) gamma and alpha that regulate lipid signalling molecule-mediated transduction pathways and modulate inflammation. As a natural ligand, DHA induces a protective effect in retinal tissues by activating retinoid x receptors and subsequent ERK/MAPK signaling pathway in photoreceptors to promote their survival and differentiation, stimulating the expression of antiapoptotic proteins such as Bcl-2 and preserving mitochondrial membrane potential [A19453].

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.

Binds to riboflavin hydrogenase, riboflavin kinase, and riboflavin synthase. Riboflavin is the precursor of flavin mononucleotide (FMN, riboflavin monophosphate) and flavin adenine dinucleotide (FAD). The antioxidant activity of riboflavin is principally derived from its role as a precursor of FAD and the role of this cofactor in the production of the antioxidant reduced glutathione. Reduced glutathione is the cofactor of the selenium-containing glutathione peroxidases among other things. The glutathione peroxidases are major antioxidant enzymes. Reduced glutathione is generated by the FAD-containing enzyme glutathione reductase.

It acts by providing a physical barrier to prevent skin irritation and help heal damaged skin.

Dosage

Active OB dosage

Oral solution: Colecalciferol (Vitamin D3) is recommended 5-10 mcg or 1-2ml (200-400 IU)/day or as directed by the physician.

Chewable tablet: Cholecalciferol (Vitamin D3) is recommended 100 IU (1 tablet) daily, or as directed by physician. Take the medicine with food or within 1 hour after a meal. Place the tablet in mouth swallow after chewing.

Injection:

Treatment of Cholecalciferol deficiency: 40,000 lU/week for 7 weeks, followed by maintenance therapy (1400-2000 lU/day). Follow-up 25 (OH) D measurements should be made approximately 3 to 4 months after initiating maintenance therapy to confirm that the target level has been achieved.
Prevention of Vitamin D deficiency: 20,000 lU/Month.
Treatment of Vitamin D deficiency:12-18 years: 20,000 IU, once every 2 weeks for 6 weeks. Prevention of Vitamin D deficiency, 12-18 years: 20,000 IU, once every 6 weeks.

Usual Adult Dose for Pernicious Anemia

Initial dose: 1000 mcg intramuscularly or deep subcutaneous once a day for 6 to 7 daysIf clinical improvement and reticulocyte response is seen from the above dosing:

100 mcg every other day for 7 doses, then
100 mcg every 3 to 4 days for 2 to 3 weeks, then
Maintenance dose: 100 to 1000 mcg monthly

Administer concomitant folic acid if needed. Chronic treatment should be done with an oral preparation in patients with normal intestinal absorption.

Usual Adult Dose for B12 Nutritional Deficiency: 25 to 2000 mcg orally daily

Usual Adult Dose for Schilling Test: 1000 mcg intramuscularly is the flushing dose

Usual Pediatric Dose for B12 Nutritional Deficiency: 0.5 to 3 mcg daily

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.

For treating low levels of riboflavin (riboflavin deficiency) in adults: 5-30 mg of riboflavin (Vitamin B2) daily in divided doses.

For preventing migraine headaches: 400 mg of riboflavin (Vitamin B2) per day. It may take up to three months to get best results.

For preventing cataracts: a daily dietary intake of approximately 2.6 mg of riboflavin (Vitamin B2) has been used. A combination of 3 mg of riboflavin (Vitamin B2) plus 40 mg of niacin daily has also been used.

The daily recommended dietary allowances (RDAs) of riboflavin (Vitamin B2) are:

Infants 0-6 months: 0.3 mg
Infants 7-12 months: 0.4 mg
Children 1-3 years: 0.5 mg
Children 4-8 years: 0.6 mg
Children 9-13 years: 0.9 mg
Men 14 years or older: 1.3 mg
Women 14-18 years: 1 mg
Women over 18 years: 1.1 mg
Pregnant women: 1.4 mg
Breastfeeding women: 1.6 mg

Apply thin layer topically every 8 hourly. Change wet and soiled diapers, promptly cleans the diaper area, allow to dry and apply ointment liberally as often as necessary, with each diaper change, especially at bedtime or any time when exposure to wet diapers may be prolonged.

May be taken with or without food.

Side Effects

Generally all nutritional supplements are considered to be safe and well tolerable. However, few side-effects can generally occur including 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 with the administration of Colecaciferol.

Arthralgia (12%), Dizziness (12%), Headache (12%), Nasopharyngitis (12%), Anaphylaxis, Angioedema, Congestive heart failure, Peripheral vascular disease,Pulmonary edema, Diarrhea, Dyspepsia, Polycythemia vera, Sore throat, Nervousness, Rhinitis, Glossitis, Hypoesthesia

GI disturbances, hypersensitivity reactions; bronchospasm.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Riboflavin may cause your urine to turn a yellow-orange color, but this is usually not a harmful side effect.

Usually well tolerated. Extremely low frequency of hypersensitivity reaction.

Toxicity

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae . Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia . 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 .

Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established . 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 . Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures .

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

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 .

LD50 Oral (mouse): > 5,000 mg/kg .

General toxicity

Vitamin B12 is generally non-toxic, even at higher doses. Mild, transient diarrhea, polycythemia vera, peripheral vascular thrombosis, itching, transitory exanthema, a feeling of swelling of entire body, pulmonary edema and congestive heart failure in early treatment stages, anaphylactic shock and death have been observed after vitamin B12 administration .

Carcinogenesis and mutagenesis

Long term studies in animals examining the carcinogenic potential of any of the vitamin B12 formulations have not completed to date. There is no evidence from long-term use in patients with pernicious anemia that vitamin B12 has carcinogenic potential. Pernicious anemia is known to be associated with an increased incidence of stomach carcinoma, however, this malignancy has been attributed to the underlying cause of pernicious anemia and has not been found to be related to treatment with vitamin B12 .

Use in pregnancy

No adverse effects have been reported with ingestion of normal daily requirements during pregnancy .

A note on the use of the nasal spray in pregnancy

Although vitamin B12 is an essential vitamin and requirements are increased during pregnancy, it is currently unknown whether the nasal spray form can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. The nasal spray form should be given to a pregnant woman only if clearly needed, as it is considered a pregnancy category C drug in this form. Sufficient well-controlled studies have not been done to this date in pregnant women .

Use in lactation

Vitamin B12 has been found distributed into the milk of nursing women in concentrations similar to the maternal blood vitamin B12 concentrations. No adverse effects have been reported to date with intake of normal required doses during lactation .

Oral LD50 value in rats is 7,060 mg/kg and 3,450 mg/kg in mouse. Adverse effects include anemia, cough, CNS depression, drowsiness, headache, heart damage, lassitude (weakness, exhaustion), liver damage, narcosis, reproductive effects and teratogenic effects.

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

Acute oral toxicity (LD50): 7950 mg/kg [Mouse].

Precaution

People with the following conditions should exercise caution when considering taking vitamin D supplements: High blood Calcium or Phosphorus level, Heart problems, Kidney disease.

Vitamin D must be taken with adequate amounts of both Calcium and Magnesium supplementation. When Calcium level is low (due to insufficient vitamin D and calcium intake), the body activates the parathyroid gland, which produces PTH (parathyroid hormone). This hormone kick starts vitamin D hormone production and assists removal of Calcium from the bones to be used in more important functions such as neutralizing body acidity.

Intensive treatment of B12-deficient megaloblastic anemia may cause hypokalemia and sudden death. Use with caution in patients with Leber optic nerve atrophy. Thrombocytosis may occur with treatment of severe vitamin B12 megaloblastic anemia

Treatment resistance may occur in patients with depressed haematopoiesis, alcoholism, deficiencies of other vitamins. Neonates.

For external use only. Avoid contact with the eyes. Stop use and ask a doctor if condition worsens or does not improve within 7 days. Keep out of the reach of children. If swallowed, get medical help or contact a poison control center right away

Interaction

Cholecalciferol is known to interact with Carbamazepine, Dactinomycin, Diuretics, Fosphenytoin, Miconazole, Phenobarbital, Phenytoin, Primidone

Absorption reduced by antibiotics, aminosalicylic acid, anticonvulsants, biguanides, cholestyramine, cimetidine, colchicine, K salts, methyldopa.

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.

Rate and extent of absorption may be affected by propantheline bromide.

Volume of Distribution

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 .

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 .

Cobalamin is distributed to tissues and stored mainly in the liver and bone marrow .

DHA is the most abundant n−3 fatty acid in membranes and is present in all organs. It is also the most variable among organs and is particularly abundant in neural tissue, such as brain and retina, where it is several hundred-fold more abundant than EPA .

Tetrahydrofolic acid derivatives are distributed to all body tissues but are stored primarily in the liver.

Intended for local use only, no systemic absorption.

Elimination Route

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal . Moreover, bile is necessary for absorption as well .

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 .

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 .

Vitamin B12 is quickly absorbed from intramuscular (IM) and subcutaneous (SC) sites of injection; with peak plasma concentrations achieved about 1 hour after IM injection .

Orally administered vitamin B12 binds to intrinsic factor (IF) during its transport through the stomach. The separation of Vitamin B12 and IF occurs in the terminal ileum when calcium is present, and vitamin B12 is then absorbed into the gastrointestinal mucosal cells. It is then transported by transcobalamin binding proteins . Passive diffusion through the intestinal wall can occur, however, high doses of vitamin B12 are required in this case (i.e. >1 mg). After the administration of oral doses less than 3 mcg, peak plasma concentrations are not reached for 8 to 12 hours, because the vitamin is temporarily retained in the wall of the lower ileum .

Like other omega-3 fatty acids, DHA is hydrolyzed from the intestines and delivered through the lymphatic circulation. Plasma DHA concentrations increase in a dose-dependent and saturable manner.

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 B2 is readily absorbed from the upper gastrointestinal tract.

No significant percutaneous absorption from topically applied zinc oxide.

Half Life

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days 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 .

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 .

The biological half-life of copper from the diet is 13-33 days with biliary excretion being the primary route of elimination .

Approximately 6 days (400 days in the liver) .

Approximately 20 hours .

66-84 minutes

Intended for local use only, no systemic absorption.

Clearance

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 .

During vitamin loading, the kidney accumulates large amounts of unbound vitamin B12. This drug is cleared partially by the kidney, however, multiligand receptor megalin promotes the reuptake and reabsorption of vitamin B12 into the body , .

Intended for local use only, no systemic absorption.

Elimination Route

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

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 .

This drug is partially excreted in the urine . According to a clinical study, approximately 3-8 mcg of vitamin B12 is secreted into the gastrointestinal tract daily via the bile. In patients with adequate levels of intrinsic factor, all except approximately 1 mcg is reabsorbed. When vitamin B12 is administered in higher doses that saturate the binding capacity of plasma proteins and the liver, the unbound vitamin B12 is eliminated rapidly in the urine. The body storage of vitamin B12 is dose-dependent .

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.

Intended for local use only, no systemic absorption.

Pregnancy & Breastfeeding use

There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses. Colecalciferol should be used during pregnancy only if the benefits outweigh the potential risk to the fetus.

It should be assumed that exogenous Colecalciferol passes into the breast milk. In view of the potential for hypercalcaemia in the mother and for adverse reactions from Colecalciferol in nursing infants, mothers may breastfeed while taking Colecalciferol, provided that the serum Calcium levels of the mother and infant are monitored.

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).

Lactation: Drug distributed in milk.

Riboflavin is LIKELY SAFE for pregnant or breast-feeding women when taken in the amounts recommended. The recommended amounts are 1.4 mg per day for pregnant women and 1.6 mg per day in breast-feeding women. Riboflavin is POSSIBLY SAFE when taken by mouth in larger doses, short-term. Some research shows that riboflavin is safe when taken at a dose of 15 mg once every 2 weeks for 10 weeks.

This medication should be used with precautions only if clearly needed during pregnancy or while breast feeding

Contraindication

Colecalciferol is contraindicated in all diseases associated with hypercalcaemia. It is also contraindicated in patients with known hypersensitivity to Colecalciferol (or medicines of the same class) and any of the constituent excipients. Colecalciferol is contraindicated if there is evidence of vitamin D toxicity.

Leber's disease, tobacco amblyopia.

Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.

Known hypersensitivity to any component of the preparation

Acute Overdose

Symptoms: anorexia, headache, vomiting, constipation, dystrophy (weakness, loss of weight), sensory disturbances, possibly fever with thirst, polyuria, dehydration, apathy, arrested growth and urinary tract infections. Hypercalcaemia ensues, with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.

Treatment: Immediate gastric lavage or induction of vomiting to prevent further absorption. Liquid paraffin should be administered to promote faecal excretion. Repeated serum calcium determinations are advisable. If elevated calcium levels persist in the serum, phosphates and corticosteroids may be administered and measures instituted to bring about adequate diuresis.

No overdose related problem is yet reported.