Zincobex(vet)

Uses

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

Pyridoxine (vitamin B6) is used to prevent or treat low levels of vitamin B6 in people who do not get enough of the vitamin from their diets. Most people who eat a normal diet do not need extra vitamin B6. However, some conditions (such as alcoholism, liver disease, overactive thyroid, heart failure) or medications (such as isoniazid, cycloserine, hydralazine, penicillamine) can cause low levels of vitamin B6. Vitamin B6 plays an important role in the body. It is needed to maintain the health of nerves, skin, and red blood cells.

Pyridoxine has been used to prevent or treat a certain nerve disorder (peripheral neuropathy) caused by certain medications (such as isoniazid). It has also been used to treat certain hereditary disorders (such as xanthurenic aciduria, hyperoxaluria, homocystinuria).

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).

Zincobex(vet) is also used to associated treatment for these conditions: Anemia, 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 supplementationBackache, Dizziness, Fever, Headache, Hepatic; Functional Disturbance, Hepatitis, Iron Deficiency Anemia (IDA), Ketosis, Macrocytic anemia, Menière's Disease, Menstrual Distress (Dysmenorrhea), Metabolic Acidosis, Motion Sickness, Nausea and vomiting, Neuralgia, Sciatic, Neuritis, Neurological Conditions caused by B Vitamin Deficiency, Secondary anemia, Soreness, Muscle, Toothache, Toxinfectious state, Trigeminal Neuralgia (TN), Vitamin B1 deficiency, Vitamin B12 Deficiency, Vitamin B6 Deficiency, Vitamin Deficiency, Minor aches and pains, Minor pain, Nutritional supplementation, Supplementation, Vitamin supplementation, Wellness of the LiverAnemia, 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 Zincobex(vet) works

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.

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

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

Zincobex(vet) dosage

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

ADULTS:

BY MOUTH:

• For hereditary sideroblastic anemia: Initially, 200-600 mg of vitamin B6 is used. The dose is decreased to 30-50 mg per day after an adequate response.
• For vitamin B6 deficiency: In most adults, the typical dose is 2.5-25 mg daily for three weeks then 1.5-2.5 mg per day thereafter. In women taking birth control pills, the dose is 25-30 mg per day.
• For abnormally high levels of homocysteine in the blood: For reducing high levels of homocysteine in the blood after childbirth, 50-200 mg of vitamin B6 has been taken alone. Also, 100 mg of vitamin B6 has been taken in combination with 0.5 mg of folic acid.
• For preventing macular degeneration: 50 mg of vitamin B6 in the form of pyridoxine has been used daily in combination with 1000 mcg of vitamin B12 (cyanocobalamin) 1000 mcg and 2500 mcg of folic acid for about 7 years.
• For hardening of the arteries (atherosclerosis): A specific supplement (Kyolic, Total Heart Health, Formula 108, Wakunga) containing 250 mg of aged garlic extract, 100 mcg of vitamin B12, 300 mcg of folic acid, 12.5 mg of vitamin B6, and 100 mg of L-argininedaily for 12 months.
• For kidney stones: 25-500 mg of vitamin B6 has been used daily.
• For nausea during pregnancy: 10-25 mg of vitamin B6 taken three or four times per day has been used. In people who don't respond to vitamin B6 alone, a combination product containing vitamin B6 and the drug doxylamine (Diclectin, Duchesnay Inc.) is used three or four times per day. Also, another product containing 75 mg of vitamin B6, 12 mcg of vitamin B12, 1 mg of folic acid, and 200 mg of calcium (PremesisRx, KV Pharmaceuticals) is used daily.
• For symptoms of premenstrual syndrome (PMS): 50-100 mg of vitamin B6 is used daily, alone or along with 200 mg of magnesium.
• For treating tardive dyskinesia: 100 mg of vitamin B6 per day has been increased weekly up to 400 mg per day, given in two divided doses.

INJECTED INTO THE MUSCLE:

• Hereditary sideroblastic anemia: 250 mg of vitamin B6 daily, reduced to 250 mg of vitamin B6 weekly once adequate response is achieved.

CHILDREN:

BY MOUTH:

• For kidney stones: Up to 20 mg/kg daily in children aged 5 years and up.

INJECTED INTO THE VEIN OR MUSCLE:

• For seizures that respond to vitamin B6 (pyridoxine-dependent seizures): 10-100 mg is recommended.

The daily recommended dietary allowances (RDAs) of vitamin B6 are:

• Infants 0-6 months, 0.1 mg
• Infants 7-12 months, 0.3 mg
• Children 1-3 years, 0.5 mg
• Children 4-8 years, 0.6 mg
• Children 9-13 years, 1 mg
• Males 14-50 years, 1.3 mg
• Males over 50 years, 1.7 mg
• Females 14-18 years, 1.2 mg
• Females 19-50 years, 1.3 mg
• Females over 50 years, 1.5 mg
• Pregnant women, 1.9 mg
• Breast-feeding women, 2 mg
• Some researchers think the RDA for women 19-50 years should be increased to 1.5-1.7 mg per day.

The recommended maximum daily intake is:

• Children 1-3 years, 30 mg
• Children 4-8 years, 40 mg
• Children 9-13 years, 60 mg

Adults, pregnant and breast-feeding women:

• 14-18 years, 80 mg
• over 18 years, 100 mg

Prophylaxis: 3 to 10 mg daily.

Mild chronic deficiency: 10 to 25 mg daily.

Severe deficiency: 200 to 300 mg daily.

Side Effects

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

Pyridoxine usually has no side effects when used in recommended doses.

If your doctor has prescribed this medication, remember that he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Pyridoxine can cause side effects when taken in large doses for a long time. Tell your doctor right away if any of these unlikely but serious side effects occur: headache, nausea, drowsiness, numbness/tingling of arms/legs.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

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

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 Rat LD50 = 4 gm/kg. Toxic effects include convulsions, dyspnea, hypermotility, diarrhea, ataxia and muscle weakness.

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

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

Before taking pyridoxine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

During pregnancy, this vitamin has been found to be safe when used in recommended doses.

This vitamin passes into breast milk and is considered to be safe during breast-feeding when used in recommended doses. Consult your doctor for more information.

Interaction

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

The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this vitamin include: altretamine, cisplatin, phenytoin.

This vitamin may interfere with certain laboratory tests (including urine test for urobilinogen), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this vitamin.

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

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

Pyridoxine main active metabolite, pyridoxal 5’-phosphate, is released into the circulation (accounting for at least 60% of circulating vitamin B6) and is highly protein bound, primarily to albumin.

Elimination Route

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 .

The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Pyridoxine is absorbed mainly in the jejunum. The Cmax of pyridoxine is achieved within 5.5 hours.

Absorbed mainly from duodenum, by both active and passive processes

Half Life

Approximately 6 days (400 days in the liver) .

The total adult body pool consists of 16 to 25 mg of pyridoxine. Its half-life appears to be 15 to 20 days.

Clearance

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 , .

Elimination Route

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 .

The major metabolite of pyridoxine, 4-pyridoxic acid, is inactive and is excreted in urine

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).

Lactation: Drug distributed in milk.

Category A: Controlled studies in women fail to demonstrate a risk to the foetus in the 1st trimester (and there is no evidence of a risk in later trimesters), and the possibility of foetal harm remains remote.

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

Contraindication

Leber's disease, tobacco amblyopia.

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

Thiamine injection should be protected from light and moisture.

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