Armovit

Uses

Copper is a transition metal found in a variety of supplements and vitamins, including intravenous solutions for total parenteral nutrition (TPN).

For use in the supplementation of total parenteral nutrition and in contraception with intrauterine devices .

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

Iodine is an ingredient of nutritional supplements that is also used for disinfection.

Investigated for use/treatment in breast disorders (unspecified) and pain (acute or chronic).

Manganese is a transition metal used for supplementation of manganese during Total Parenteral Nutrition (TPN).

Indicated for use as a supplement to intravenous solutions given for Total Parenteral Nutrition (TPN). Administration helps to maintain plasma levels and to prevent depletion of endogenous stores and subsequent deficiency symptoms.

Phosphorus is a medication indicated in the treatment of hypophosphatemia.

Rutin is a flavonoid found in over-the-counter vitamin supplements.

Effective for:

• Vitamin A deficiency. Taking vitamin A by mouth is effective for preventing and treating symptoms of vitamin A deficiency. Vitamin A deficiency can occur in people with protein deficiency, diabetes, over-active thyroid, fever, liver disease, cystic fibrosis, or an inherited disorder called abetalipoproteinemia.

Possibly Effective for:

• Breast cancer. Premenopausal women with a family history of breast cancer who consume high levels of vitamin A in their diet seem to have reduced risk of developing breast cancer. It is not known if taking vitamin A supplements has the same benefit.
• Cataracts. Research suggests that high intake of vitamin A in the diet is linked to a lower risk of developing cataracts.
• Diarrhea related to HIV. Taking vitamin A along with conventional medicines seems to decrease the risk of death from diarrhea in HIV-positive children with vitamin A deficiency.
• Malaria. Taking vitamin A by mouth seems to decrease malaria symptoms in children less than 3 years-old living in areas where malaria is common.
• Measles. Taking vitamin A by mouth seems to reduce the risk of measles complications or death in children with measles and vitamin A deficiency.
• Precancerous lesions in the mouth (oral leukoplakia). Research suggests that taking vitamin A can help treat precancerous lesions in the mouth.
• Recovery from laser eye surgery (photoreactive keratectomy). Taking vitamin A by mouth along with vitamin E seems to improve healing after laser eye surgery.
• Complications after pregnancy. Taking vitamin A seems to reduce the risk of diarrhea and fever after pregnancy in malnourished women.
• Complications during pregnancy. Taking vitamin A by mouth seems to reduce the risk of death and night blindness during pregnancy in malnourished women.
• Eye disease affecting the retina (retinitis pigmentosa). Research suggests that taking vitamin A can slow the progression of an eye disease that causes damage to the retina.

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 .

As a dietary supplement:

• Vitamin E deficiency resulting from impaired absorption.
• Increased requirements due to diet rich in polyunsaturated fats.
• For healthy hair & skin
• As an Antioxidant
• Hemolytic anemia due to Vitamin E deficiency

Therapeutic use

: Heavy metal poisoning, Hepatotoxin poisoning, Hemolytic anemia, Oxygen therapy and replacement therapy in nutritional deficiency states for the betterment of skin and hair.

Armovit is also used to associated treatment for these conditions: Emergency Contraception, IUD, Trace Element Deficiency, 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 supplementationInfection in minor cuts, scrapes, or burns, Antisepsis, Antimycotic, Prophylaxis of bacterial skin infectionsMineral supplementation, Total parenteral nutrition therapy, Vitamin supplementation, Dietary supplementationBone Loss, Nutritional supplementationAnemia, General Surgery, Pregnant State, Vitamin supplementationDeficiency, Vitamin A, Deficiency, Vitamin D, Degenerative Retinal Disorders, Disorder of the Epithelium, Disorder of the Mesoderm, Inner ear disorder, Vitamin Deficiency, Vitamin E Deficiency, Nutritional supplementationDeficiency, Vitamin DVitamin Deficiency, Long-chain omega-3 fatty acid supplementation, Dietary supplementation

How Armovit works

Copper is absorbed from the gut via high affinity copper uptake protein and likely through low affinity copper uptake protein and natural resistance-associated macrophage protein-2 . It is believed that copper is reduced to the Cu1+ form prior to transport. Once inside the enterocyte, it is bound to copper transport protein ATOX1 which shuttles the ion to copper transporting ATPase-1 on the golgi membrane which take up copper into the golgi apparatus. Once copper has been secreted by enterocytes into the systemic circulation it remain largely bound by ceruloplasmin (65-90%), albumin (18%), and alpha 2-macroglobulin (12%).

Copper is an essential element in the body and is incorporated into many oxidase enzymes as a cofactor . It is also a component of zinc/copper super oxide dismutase, giving it an anti-oxidant role. Copper defiency occurs in Occipital Horn Syndrome and Menke's disease both of which are associated with impaired development of connective tissue due to the lack of copper to act as a cofactor in protein-lysine-6-oxidase. Menke's disease is also associated with progressive neurological impairment leading to death in infancy. The precise mechanisms of the effects of copper deficiency are vague due to the wide range of enzymes which use the ion as a cofactor.

Copper appears to reduce the viabilty and motility of spermatozoa . This reduces the likelihood of fertilization with a copper IUD, producing copper's contraceptive effect . The exact mechanism of copper's effect on sperm are unknown.

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.

Molecular iodine is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rats.It has also been shown to have beneficial effects in fibrocystic human breast disease.

Vision:Vitamin A (all-trans retinol) is converted in the retina to the 11-cis-isomer of retinaldehyde or 11-cis-retinal. 11-cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to 11-cis-retinol in the dark, and then oxidized to 11-cis-retinal. 11-cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-cis retinal rapidly.
Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted.

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 .

The mechanism of action for most of vitamin E's effects are still unknown. Vitamin E is an antioxidant, preventing free radical reactions with cell membranes. Though in some cases vitamin E has been shown to have pro-oxidant activity.

One mechanism of vitamin E's antioxidant effect is in the termination of lipid peroxidation. Vitamin E reacts with unstable lipid radicals, producing stable lipids and a relatively stable vitamin E radical. The vitamin E radical is then reduced back to stable vitamin E by reaction with ascorbate or glutathione.

Dosage

Armovit 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.

Vitamin A deficiency For severe deficiency with corneal changes: 500,000 unit/day for 3 days, followed by 50,000 unit/day for 2 wk and then 10,000-20,000 unit/day for 2 mth as follow-up therapy.

For cases without corneal changes: 10,000-25,000 unit/day until clinical improvement occurs (usually 1 -2 wk).

Betterment of Cardiovascular health: 400 mg - 800 mg / day

Deficiency syndrome in adults: 200 mg - 400 mg / day

Deficiency syndrome in children: 200 mg / day

Thalassemia: 800 mg / day

Sickle-cell anemia: 400 mg / day

Betterment of Skin & Hair: 200 mg - 400 mg / day (Topical use is also established for beautification)

Chronic cold in adults: 200 mg / day

May be taken with or without food.

Side Effects

GI disturbances, hypersensitivity reactions; bronchospasm.

Hypervitaminosis A characterised by fatigue, irritability, anorexia, weight loss, vomiting and other Gl disturbances, low-grade fever, hepatosplenomegaly, skin changes, alopoecia, dry hair, cracking and bleeding lips, SC swelling, nocturia, pains in bones and joints.

Overdoses (>1g) have been associated with minor side effects, including hypertension, fatigue, diarrhea and myopathy

Toxicity

Copper toxicity is belevied to be due to fenton-type redox reactions occuring with high copper concentrations which produce damaging reactive oxygen species .

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 toxicity to vitamin A can occur when adults or children ingest >100x or >20x the RDA, respectively, over a period of hours or a few days. The RDA for vitamin A differs depending on age and sex and can range from 300 - 900 μg retinol activity equivalents (RAE) per day. Symptoms of acute systemic toxicity generally include mucocutaneous involvement (e.g. xerosis, cheilitis, skin peeling) and may involve mental status changes. Children are typically more susceptible to acute vitamin A toxicity - daily intakes of as little as 1500 IU/kg have been observed to result in toxicity.

Chronic vitamin A toxicity can develop following the long-term ingestion of high vitamin A doses. While there is a wide variation in the lowest toxic vitamin A dose, the ingestion of >25 000 IU daily for 6 years or 100,000 IU daily for 6 months is considered to be toxic. Chronic vitamin A toxicity can affect many organ systems and can lead to the development of osteoporosis and CNS effects (e.g. headaches).

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 .

There is no data available for effects in pregnancy, breast feeding, hepatic impairment, or renal impairment. However, it appears that the process of vitamin E elimination is strict and self regulating enough that vitamin E toxicity is exceedingly rare. Studies showing adverse effects from excess vitamin E generally involve people consuming more than 1000mg/day for weeks to months.

Precaution

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

Cholestatic jaundice; fat-malabsorption conditions. Monitor patients closely for toxicity. Liver impairment and children.

Vitamin E may enhance the anticoagulant activity of anticoagulant drugs. Caution is advised in premature infants with high dose Vitamin E supplementation, because of reported risk of necrotizing enterocilitis.

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.

Decreased absorption with neomycin. Increased risk of hypervitaminosis A with synthetic retinoids eg, acitretin, isotretinoin and tretinoin. Increased risk of toxicity when used with alcohol.

Vitamin E may impair the absorption of Vitamin A. Vitamin K functions impairement happens at the level of prothrombin formation and potentiates the effect of Warfarin.

Volume of Distribution

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

0.41L/kg in premature neonates given a 20mg/kg intramuscular injection.

Elimination Route

Copper absorption varies inversely with intake. Absorption range is 12-65%.

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.

Readily absorbed from the normal gastrointestinal tract

Vitamin D3 and D2 are readily absorbed from the small intestine (proximal or distal) .

10-33% of deuterium labelled vitamin E is absorbed in the small intestine. Absorption of Vitamin E is dependant upon absorption of the fat in which it is dissolved. For patients with poor fat absorption, a water soluble form of vitamin E may need to be substituted such as tocopheryl polyethylene glycol-1000 succinate.

In other studies the oral bioavailability of alpha-tocopherol was 36%, gamma-tocotrienol was 9%. The time to maximum concentration was 9.7 hours for alpha-tocopherol and 2.4 hours for gamma-tocotrienol.

Half Life

1.9 hours

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 .

44 hours in premature neonates given a 20mg/kg intramuscular injection. 12 minutes in intravenous injection of intestinal lymph.

Clearance

Some studies propose an estimated clearance rate for 1,25-dihydroxyvitamin D as 31 +/- 4 ml/min in healthy adults .

6.5mL/hr/kg in premature neonates given a 20mg/kg intramuscular injection.

Elimination Route

Copper appears to be eliminated primarily through bile .

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 .

Alpha tocopherol is excreted in urine as well as bile in the feces mainly as a carboxyethyl-hydrochroman (CEHC) metabolite, but it can be excreted in it's natural form .

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).

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).

Use in pregnancy: Vitamin E may be used in pregnancy in the normally recommended dose but the safety of high dose therapy has not been established.

Use in lactation: There appears to be no contraindication to breast feeding by mothers taking the normally recommended dose.

Contraindication

Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.

Hypervitaminosis A; pregnancy (dose exceeding RDA).

No known contraindications found.

Special Warning

Use in Children: Vitamin E is safe for children

Acute Overdose

Large doses of vitamin E (more than 1 gm/day) have been reported to increase bleeding tendency in vitamin K deficient patients such as those taking oral anticoagulants.

Storage Condition

Store at 15-30° C.

Store at a cool and dry place, Protect from light and moisture.

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