MVI Adult

Uses

alpha-Tocopherol acetate is a form of vitamin E used to treat and prevent vitamin deficiencies.

The primary health-related use for which alpha-tocopherol acetate is formally indicated is as a dietary supplement for patients who demonstrate a genuine vitamin E deficiency. At the same time, vitamin E deficiency is generally quite rare but may occur in premature babies of very low birth weight (< 1500 grams), individuals with fat-malabsorption disorders (as fat is required for the digestive tract to absorb vitamin E), or individuals with abetalipoproteinemia - a rare, inherited disorder that causes poor absorption of dietary fat - who require extremely large doses of supplemental vitamin E daily (around 100 mg/kg or 5-10 g/day) . In all such cases, alpha-tocopherol is largely the preferred form of vitamin E to be administered.

Elsewhere, vitamin E's chemical profile as a fat-soluble antioxidant that is capable of neutralizing free radicals in the body continues to generate ongoing interest and study regarding how and whether or not the vitamin can help prevent or delay various chronic diseases associated with free radicals or other potential biological effects that vitamin E possesses like cardiovascular diseases, diabetes, ocular conditions, immune illnesses, cancer, and more . None of these ongoing studies have yet to elucidate any formally significant evidence, however .

Vitamin C is used for prevention and treatment of scurvy. It may be used for pregnancy, lactation, infection, trauma, burns, cold exposure, following surgery, fever, stress, peptic ulcer, cancer, methaemoglobinaemia and in infants receiving unfortified formulas. It is also prescribed for haematuria, dental caries, pyorrhea, acne, infertility, atherosclerosis, fractures, leg ulcers, hay fever, vascular thrombosis prevention, levodopa toxicity, succinyl-choline toxicity, arsenic toxicity etc. To reduce the risk of stroke in the elderly, long-term supplementation with Vitamin C is essential.

Biotin is a B-complex vitamin found in many multivitamin products.

For nutritional supplementation, also for treating dietary shortage or imbalance.

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

Dexpanthenol is used for-

• For prevention and treatment of diaper rash in infants.
• For prevention and treatment of cracked or sore nipples in nursing women.
• For prevention and treatment of chafed, cracked or split skin.
• For treatment of light skin wounds and dry skin

Ergocalciferol is a vitamin found in many supplement products.

Ergocalciferol is indicated for the treatment of hypoparathyroidism, refractory rickets, and familial hypophosphatemia.

Hypoparathyroidism is the result of inadequate parathyroid hormone production that occurs due to the presence of damage or removal of the parathyroid glands. This condition produces decreased calcium and increased phosphorus levels.

Rickets is a condition produced due to a deficiency in vitamin D, calcium or phosphorus. However, this condition can also be related to renal diseases. It is characterized to present weak or soft bones.

Familial hypophosphatemia is characterized by the impaired transport of phosphate and an altered vitamin D metabolism in the kidneys. The presence of this condition can derive in the presence of osteomalacia, bone softening and rickets.

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

Thiamine is specifically used in the treatment of the various manifestations of thiamine deficiency such as Beriberi and Wernick's encephalopathy, neuritis associated with pregnancy and pellagra. Supplementary Thiamine may be used prophylactically in conditions where there is low dietary intake or impaired gastro intestinal absorption of thiamine (e.g. alcohol) or where requirements are increased (pregnancy, carbohydrate rich diet).

MVI Adult is also used to associated treatment for these conditions: Deficiency, Vitamin A, Vitamin Deficiency, Vitamin E Deficiency, Deficiency, Vitamin D, Nutritional supplementationCommon Cold, Deficiency, Vitamin A, Deficiency, Vitamin D, Fever, Flu caused by Influenza, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Oral bacterial infection, Scurvy, Vitamin C Deficiency, Vitamin Deficiency, Nutritional supplementation, Vitamin supplementationVitamin Deficiency, Nutritional supplementationAnemia, 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 supplementationAllergic Rhinitis (AR), Bursitis, Canker Sore, Contusions, Dermabrasion, Diaper Rash, Dry Skin, Edema, Hoarseness, Inflammation, Inflammation of Mouth, Insect Bites, Lateral Epicondylitis, Lesions of the Mucous Membranes, Nasal Congestion, Pharyngeal inflammation, Pruritus, Respiratory Tract Infections (RTI), Seasonal Allergic Rhinitis, Sinusitis, Skin Roughness, Sore Throat, Sunburn, Tendinitis, Tooth Extraction Site Healing, Traumatic Injuries caused by Dental Prosthesis, Urticaria, Vitamin Deficiency, Wounds caused by Surgery, Oral of the Tonsils, Dry, cracked skin, Dryness of the nose, Superficial Conjunctival injuries, Superficial Corneal injuries, Superficial Traumatic Injuries of the Nasal Mucosa, Superficial Wounds, Irrigation therapy, Nutritional supplementation, Oropharyngeal antisepsis, Vitamin supplementationDeficiency, Vitamin A, Deficiency, Vitamin D, Hypoparathyroidism, Hypophosphatemia, Familial, Vitamin D Resistant Rickets, Dietary supplementationAnaemia folate deficiency, Folate deficiency, Iron Deficiency (ID), Iron Deficiency Anemia (IDA), Latent Iron Deficiency, Neural Tube Defects (NTDs), Vitamin Deficiency, Methotrexate toxicity, Nutritional supplementationAnemia, B12 Deficiency Anemia, Beriberi, Cardiovascular Heart Disease caused by Thiamine Deficiency, Folic Acid Deficiency Anemia, Infantile Beriberi, Infection, Iron Deficiency (ID), Liver disorder, Neuritis caused by Pregnancy, Secondary anemia, Thiamine Deficiency, Vitamin Deficiency, Wernicke's encephalopathy, Nutritional supplementation, Vitamin supplementation, Dietary supplementation

How MVI Adult works

Vitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron . These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) . In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases . Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun . It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure .

Specifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions . The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins . Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids . Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical . This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids .

In addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E . For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes . In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity .

In addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium .

Vitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 . The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans .

Furthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions . The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets . Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production .

Given these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis .

Similarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications . In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA . Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use . Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action .

There have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals .

As of this time however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality) on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.

In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair by acting as a cofactor in the posttranslational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. These two forms of the vitamin are believed to be important in oxidation-reduction reactions. The vitamin is involved in tyrosine metabolism, conversion of folic acid to folinic acid, carbohydrate metabolism, synthesis of lipids and proteins, iron metabolism, resistance to infections, and cellular respiration.

Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.

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.

Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium.

Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties .

For its activity, ergocalciferol is required to be transformed to its major active circulating hydroxylated metabolite and transported to the target organs in order to bind to its target, the vitamin D receptor.

The activation of the vitamin D receptor is part of the vitamin D endocrine system and it is described by the production of a change in the transcription rates of the vitamin D receptor target genes. The target genes in the DNA affected by the presence of ergocalciferol are called vitamin D response elements which are dependent on co-modulators.

The vitamin D receptor is a transcription factor and member of the steroid hormone nuclear receptor family. It presents a DNA binding domain (VDRE) that, when activated, recruits coregulatory complexes to regulate the genomic activity.

Additionally, ergocalciferol presents nongenomic effects such as the stimulation of intestinal calcium transport via transcaltachia.

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.

It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions.

Dosage

MVI Adult dosage

vitamin C is usually administered orally. When oral administration is not feasible or when malabsorption is suspected, the drug may be administered IM, IV, or subcutaneously. When given parenterally, utilization of the vitamin reportedly is best after IM administration and that is the preferred parenteral route.

For intravenous injection, dilution into a large volume parenteral such as Normal Saline, Water for Injection, or Glucose is recommended to minimize the adverse reactions associated with intravenous injection.

The average protective dose of vitamin C for adults is 70 to 150 mg daily. In the presence of scurvy, doses of 300 mg to 1 g daily are recommended. However, as much as 6 g has been administered parenterally to normal adults without evidence of toxicity.

To enhance wound healing, doses of 300 to 500 mg daily for a week or ten days both preoperatively and postoperatively are generally considered adequate, although considerably larger amounts have been recommended. In the treatment of burns, doses are governed by the extent of tissue injury. For severe burns, daily doses of 1 to 2 g are recommended. In other conditions in which the need for vitamin C is increased, three to five times the daily optimum allowances appear to be adequate.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever the solution and container permit.

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

Check with the doctor or pharmacist if you are unsure how to use Dexpanthenol.

The usual dosage is generally:

• Diaper rash: Apply a thin layer on the baby’s bottom at every diaper change.
• Nipples: Apply a thin layer on the nipples after each nursing session. Wash the nipples thoroughly before the next nursing session.
• Dry/cracked skin or light wounds and chafed skin: Apply to the dry areas and/or to the wound up to 3 times a day.

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.

Prophylaxis: 3 to 10 mg daily.

Mild chronic deficiency: 10 to 25 mg daily.

Severe deficiency: 200 to 300 mg daily.

May be taken with or without food.

Side Effects

Ascorbic acid does not seem to have any important adverse effects at dosages less than 4 mg/day. Larger dose may cause diarrhoea or formation of renal calculi of calcium oxalate in patients with renal impairment. Ingestion of more than 600 mg daily have a diuretic action.

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

As with any medicine, use of Dexpanthenol may cause side effects in some users. Do not be alarmed by the list of side effects. You may not suffer from any of them. Discontinue use and refer to a doctor immediately in the event of: Allergic reaction and/or allergic skin reaction such as: atopic dermatitis, allergic dermatitis, pruritus, redness, rash, eczema, urticaria, local irritation or blistering. If a side effect occurs, worsens, or if you suffer from a side effect not mentioned in this leaflet, consult with the doctor.

GI disturbances, hypersensitivity reactions; bronchospasm.

Vitamin B1 does not have adverse effects when given orally, but in a few fatal cases anaphylactic reactions have occurred after intravenous administration of large doses (400 mg) in sensitive patients, especially children, and in one case following an intramuscular dose of 125 mg. The risk of such reactions increases with repeated administration of the drug by parenteral route. Transient mild soreness may occur at the site of intramuscular administration

Toxicity

Tocopherols are considered as non-toxic but if very high doses (approximately >2 g/kg/day) are administered, there are reports of hemorrhagic activity . Reproductive and developmental toxicity tests are negative . These negative results were also observed in the analysis of mutagenicity and carcinogenicity . The majority of these tests were animal feeding studies .

Prolonged skin contact may cause irritation.

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 .

Mouse LD50 : 9gm/kg (Intraperitoneal) Mouse: LD50 7gm/kg (Intravenous) Mouse: LD50 15gm/kg (Oral) Rabbit LD50 4gm/kg (Oral)

The reported LD50 for orally administered ergocalciferol in the rat is of 10 mg/kg. Overdosage with this agent is reported to produce hypervitaminosis characterized by hypercalcemia, renal impairment, calcification of soft tissues, a decline in the rate of linear growth and increase in bone mineralization.

Once an overdose state is registered, immediate withdrawal of vitamin D is required along with a calcium diet, generous intake of fluids and symptomatic treatment. The administration of loop diuretics is an option to increase renal calcium excretion. On the other hand, dialysis and administration of citrates, sulfates, phosphates, corticosteroids, EDTA and mithramycin are recommended.

There haven't been long term studies analyzing the carcinogenic and mutagenic potential of ergocalciferol or its effects in fertility.

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

Thiamine toxicity is uncommon; as excesses are readily excreted, although long-term supplementation of amounts larger than 3 gram have been known to cause toxicity. Oral mouse LD₅₀ = 8224 mg/kg, oral rat LD₅₀ = 3710 mg/kg.

Precaution

Ingestion of megadose (more than 1000 mg daily) of vitamin C during pregnancy has resulted in scurvy in neonates. Vitamin C in mega-doses has been contraindicated for patients with hyperoxaluria. Vitamin C itself is a reactive substance in the redox system and can give rise to false positive reactions in certain analytical tests for glucose, uric acid, creatine and occult blood.

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.

Interaction

Potentially hazardous interactions: Ascorbic acid is incompatible in solution with aminophylline, bleomycin, erythromycin, lactobionate, nafcillin, nitrofurantoin sodium, conjugated oestrogen, sodium bicarbonate, sulphafurazole diethanolamine, chloramphenicol sodium succinate, chlorthiazide sodium and hydrocortisone sodium succinate.

Useful interactions: Ascorbic acid increases the apparent half-life of paracetamol and enhances iron absorption from the gastrointestinal tract.

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.

No hazardous drug interactions have been reported. Vitamin B1 acts synergistically with other vitamins of the B-complex group and its potential for causing adverse effects is considerably reduced.

Volume of Distribution

When three particular doses alpha-tocopherol were administered to healthy male subjects, the apparent volumes of distribution (ml) observed were: (a) at a single administered dose of 125 mg, the Vd/f was 0.070 +/- 0.002, (b) at dose 250. mg, the Vd/f was 0.127 +/- 0.004, and (c) at dose 500 mg, the Vd/f was 0.232 +/- 0.010 .

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

Dexpanthenol is readily converted to pantothenic acid which is widely distributed into body tissues, mainly as coenzyme A. Highest concentrations are found in the liver, adrenal glands, heart, and kidneys.

The amount of circulating ergocalciferol is very limited as this compound is rapidly stored in fat tissue such as adipose tissue, liver and muscle. This is very obvious in reports that indicate that circulating ergocalciferol is significantly reduced in obese patients.

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

Elimination Route

When vitamin E is ingested, intestinal absorption plays a principal role in limiting its bioavailability . It is known that vitamin E is a fat-soluble vitamin that follows the intestinal absorption, hepatic metabolism, and cellular uptake processes of other lipophilic molecules and lipids . The intestinal absorption of vitamin E consequently requires the presence of lipid-rich foods .

In particular, stable alpha-tocopherol acetate undergoes hydrolysis by bile acid-dependant lipase in the pancreas or by an intestinal mucosal esterase . Subsequent absorption in the duodenum occurs by way of transfer from emulsion fat globules to water-soluble multi- and unilamellar vesicles and mixed micelles made up of phospholipids and bile acids . As the uptake of vitamin E into enterocytes is less efficient compared to other types of lipids, this could potentially explain the relatively low bioavailability of vitamin E . Alpha-tocopherol acetate itself is embedded in matrices where its hydrolysis and its uptake by intestinal cells are markedly less efficient than in mixed micelles . Subsequently, the intestinal cellular uptake of vitamin E from mixed micelles follows in principle two different pathways across enterocytes: (a) via passive diffusion, and (b) via receptor-mediated transport with various cellular transports like scavenger receptor class B type 1, Niemann-Pick C1-like protein, ATP-binding cassette (ABC) transporters ABCG5/ABCG8, or ABCA1, among others .

Vitamin E absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion . Defects at any step can lead to impaired absorption. . Chylomicron secretion is required for vitamin E absorption and is a particularly important factor for efficient absorption. All of the various vitamin E forms show similar apparent efficiencies of intestinal absorption and subsequent secretion in chylomicrons . During chylomicron catabolism, some vitamin E is distributed to all the circulating lipoproteins .

Chylomicron remnants, containing newly absorbed vitamin E, are then taken up by the liver . Vitamin E is secreted from the liver in very low density lipoproteins (VLDLs). Plasma vitamin E concentrations depend upon the secretion of vitamin E from the liver, and only one form of vitamin E, alpha-tocopherol, is ever preferentially resecreted by the liver . The liver is consequently responsible for discriminating between tocopherols and the preferential plasma enrichment with alpha-tocopherol . In the liver, the alpha-tocopherol transfer protein (alpha-TTP) likely is in charge of the discriminatory function, where RRR- or d-alpha-tocopherol possesses the greatest affinity for alpha-TTP .

It is nevertheless believed that only a small amount of administered vitamin E is actually absorbed. In two individuals with gastric carcinoma and lymphatic leukemia, the respective fractional absorption in the lymphatics was only 21 and 29 percent of label from meals containing alpha-tocopherol and alpha-tocopheryl acetate, respectively .

Additionally, after feeding three separate single doses of 125 mg, 250 mg, and 500 mg to a group of healthy males, the observed plasma peak concentrations (ng/mL) were 1822 +/- 48.24, 1931.00 +/- 92.54, and 2188 +/- 147.61, respectively .

70% to 90%

Systemic - approximately 50%

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 .

Dexpanthenol is soluble in water and alcohol, although insoluble in fats and oil based substances. With the appropriate vehicle, Dexpanthenol is easily penetrated into the skin. Rate of penetration and absorption is reduced when Dexpanthenol is administered as an oil/water formula.

Ergocalciferol is absorbed in the intestine and carried to the liver in chylomicrons. Its intestinal absorption does not present limitations unless the presence of conditions related to fat malabsorption. However, for absorption to take place, the presence of bile is required.

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.

Absorbed mainly from duodenum, by both active and passive processes

Half Life

The apparent half-life of RRR- or d-alpha-tocopherol in normal subjects is approximately 48 hours .

16 days (3.4 hours in people who have excess levels of vitamin C)

Approximately 6 days (400 days in the liver) .

Half life have not been reported

Ergocalciferol can be found circulation for 1-2 days. This quick turnover is presented due to hepatic conversion and uptake by fat and muscle cells where it is transformed to the active form.

Clearance

When three specific doses of 125 mg, 250 mg, and 500 mg of alpha-tocopherol were administered as single doses to a group of healthy males, the resultant times of clearance observed, respectively, were: 0.017 +/- 0.015 l/h, 0.011 +/- 0.001 l/h, and 0.019 +/- 0.001 l/h .

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 , .

There are no formal reports regarding the clearance rate of ergocalciferol. Due to the structural similarity, it is recommended to consult this parameter with cholecalciferol. On the other hand, the proposed renal clearance of calcitriol is of 31 ml/min.

Elimination Route

The major route of excretion of ingested vitamin E is fecal elimination because of its relatively low intestinal absorption . Excess alpha-tocopherol, as well as forms of vitamin E not preferentially used, are probably excreted unchanged in bile .

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 .

Milk of nursing mothers receiving a normal diet contains about 2 ug of pantothenic acid per mL. About 70% of an oral dose of pantothenic acid is excreted unchanged in urine and about 30% in feces.

The active form of ergocalciferol, calcitrol, cannot be maintained for long periods in storage tissue mainly in periods of dietary or UVB deprivation. Therefore, ergocalciferol and its metabolites are excreted via the bile with a minor contribution of renal elimination. This major fecal elimination is explained due to the cubilin-megalin receptor system-mediated renal reuptake of vitamin D metabolites bound to vitamin D binding protein.

After a single oral dose of 100 mcg of folic acid in a limited number of normal adults, only a trace amount of the drug appeared in the urine. An oral dose of 5 mg in 1 study and a dose of 40 mcg/kg of body weight in another study resulted in approximately 50% of the dose appearing in the urine. After a single oral dose of 15 mg, up to 90% of the dose was recovered in the urine. A majority of the metabolic products appeared in the urine after 6 hours; excretion was generally complete within 24 hours. Small amounts of orally administered folic acid have also been recovered in the feces. Folic acid is also excreted in the milk of lactating mothers.

Pregnancy & Breastfeeding use

The drug is safe in normal doses in pregnant women, but a daily intake of 5 gm or more is reported to have caused abortion. The drug may be taken safely during lactation.

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.

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).

The drug may be given safely to neonates, children, pregnant and lactating women and elderly patients.

Contraindication

Leber's disease, tobacco amblyopia.

Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.

There is no absolute contraindication but the risk of anaphylaxis is increased by repeated parenteral administration. Mild allergic phenomena, such as sneezing or mild asthma are warning signs that further may give rise to anaphylactic shock. To avoid this possibility it is advisable to start a second course of injection with a dose considerably lower than that previously used. Because of the above, vitamin B1 injection should not be given intravenously except in the case of comatose patients. Once thiamine deficiency is corrected there is no need for parenteral administration or for the administration of amounts in excess of daily requirement.

Storage Condition

Should be stored in a dry place below 30˚C.

Do not store above 30 degree Celsius. Keep away from light and out of the reach of children.

Store at 15-30° C.

Thiamine injection should be protected from light and moisture.

Innovators Monograph

You find simplified version here MVI Adult