Ocuvel

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.

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

Xanthophylls are taken for nutritional supplementation, and also for treating dietary shortage or imbalance.

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.

Ocuvel 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 supplementationEmergency 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 supplementationFolate supplementation therapy, Mineral supplementation, Nutritional supplementation, Vitamin supplementationMineral supplementation, Oral Nutritional Supplementation, Vitamin 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 Ocuvel 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.

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.

Xanthophylls have antioxidant activity and react with active oxygen species, producing biologically active degradation products. They also can inhibit peroxidation of membrane phospholipids and reduce lipofuscin formation, both of which contribute to their antioxidant properties. Lutein is naturally present in the macula of the human retina. It filters out potentially phototoxic blue light and near-ultraviolet radiation from the macula. The protective effect is due in part, to the reactive oxygen species quenching ability of these carotenoids. Lutein is more stable to decomposition by pro-oxidants than are other carotenoids such as beta-carotene and lycopene. Lutein is abundant in the region surrounding the fovea, and lutein is the predominant pigment at the outermost periphery of the macula. Zeaxanthin, which is fully conjugated (lutein is not), may offer somewhat better protection than lutein against phototoxic damage caused by blue and near-ultraviolet light radiation. Lutein is one of only two carotenoids that have been identified in the human lens, may be protective against age-related increases in lens density and cataract formation. Again, the possible protection afforded by lutein may be accounted for, in part, by its reactive oxygen species scavenging abilities. Carotenoids also provide protection from cancer. One of the mechanisms of this is by increasing the expression of the protein connexin-43, thereby stimulating gap junctional communication and preventing unrestrained cell proliferation.

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

Dosage

Ocuvel 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.

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.

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

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.

GI disturbances, hypersensitivity reactions; bronchospasm.

Usually well tolerated. Extremely low frequency of hypersensitivity reaction.

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 .

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

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.

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

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.

Antiepileptics, oral contraceptives, anti-TB drugs, alcohol, aminopterin, methotrexate, pyrimethamine, trimethoprim and sulphonamides may result to decrease in serum folate contrations. Decreases serum phenytoin concentrations.

Volume of Distribution

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 .

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

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%

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.

No significant percutaneous absorption from topically applied zinc oxide.

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)

Intended for local use only, no systemic absorption.

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 .

Intended for local use only, no systemic absorption.

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 .

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.

Intended for local use only, no systemic absorption.

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).

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

Contraindication

Undiagnosed megaloblastic anaemia; pernicious, aplastic or normocytic anaemias.

Known hypersensitivity to any component of the preparation

Acute Overdose

No overdose related problem is yet reported.

Storage Condition

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

Store at 15-30° C.

keep in a cool and dry place, away from light.

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