Berocca

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

vitamin C, the water-soluble vitamin, is readily absorbed from the gastrointestinal tract and is widely distributed in the body tissues. It is believed to be involved in biological oxidations and reductions used in cellular respiration. It is essential for the synthesis of collagen and intracellular material. Vitamin C deficiency develops when the dietary intake is inadequate and when increased demand is not fulfilled. Deficiency leads to the development of well defined syndrome known as scurvy, which is characterized by capillary fragility, bleeding (especially from small blood vessels and the gums), anaemia, cartilage and bone lesions and slow healing of wounds.

Ascorbic Acid (vitamin C) is a water-soluble vitamin indicated for the prevention and treatment of scurvy, as ascorbic acid deficiency results in scurvy. Collagenous structures are primarily affected, and lesions develop in bones and blood vessels. Administration of ascorbic acid completely reverses the symptoms of ascorbic acid deficiency.

A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.

Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast.

Calcium (Ca2+) plays a pivotal role in the physiology and biochemistry of organisms and the cell. It plays an important role in signal transduction pathways, where it acts as a second messenger, in neurotransmitter release from neurons, contraction of all muscle cell types, and fertilization. Many enzymes require calcium ions as a cofactor, those of the blood-clotting cascade being notable examples. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.

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

General effects

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

Parenteral cyanocobalamin effects

An important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake.

Pantothenic acid, also called pantothenate or vitamin B5 (a B vitamin), is a water-soluble vitamin discovered by Roger J. Williams in 1919. For many animals, pantothenic acid is an essential nutrient as it is required to synthesize coenzyme-A (CoA), as well as to synthesize and metabolize proteins, carbohydrates, and fats. Pantothenic acid is the amide between pantoic acid and β-alanine and commonly found as its alcohol analog, the provitamin panthenol, and as calcium pantothenate. Small quantities of pantothenic acid are found in nearly every food, with high amounts in whole-grain cereals, legumes, eggs, meat, royal jelly, avocado, and yogurt. Pantothenic acid is an ingredient in some hair and skin care products. Only the dextrorotatory (D) isomer of pantothenic acid possesses biological activity. while the levorotatory (L) form may antagonize the effects of the dextrorotatory isomer.

Pantothenic acid is used in the synthesis of coenzyme A (CoA). CoA is thought to act as a carrier molecule, allowing the entry of acyl groups into cells. This is of critical importance as these acyl groups are used as substrates in the tricarboxylic acid cycle to generate energy and in the synthesis of fatty acids, cholesterol, and acetylcholine. Additionally, CoA is part of acyl carrier protein (ACP), which is required in the synthesis of fatty acids in addition to CoAs use as a substrate.

Pantothenic acid in the form of CoA is also required for acylation and acetylation, which, for example, are involved in signal transduction and enzyme activation and deactivation, respectively.

Pyridoxine is a water-soluble vitamin which functions in the metabolism of carbohydrates, proteins and fats. It is essential in Hb formation and GABA synthesis within the CNS. It also aids in the release of glycogen stored in the liver and muscles.

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.

Berocca
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Berocca
Generic	Ascorbic Acid + Biotin + Calcium + Cyanocobalamin + Magnesium Oxides and Hydroxides + Nicotinamide + Pantothenic Acid + Pyridoxine + Riboflavin (Vitamin B2) + Thiamine HCl (Vitamin B1)
Weight	500mg, 0.15mg, 100mg, 10mcg, 50mg, 23mg, 10mg, 15mg, , 7.5mg, 8.5mg, 150mcg, 400mcg, 100
Type	Tablet, Oral Capsule, Oral Gum, Oral Liquid, Oral Oil, Oral Solution, Oral Tablet, Chewable, Dispersible, Extended Release, Sublingual Tablet, Tablet Effervescent
Therapeutic Class
Manufacturer	Bayer Health Care, Bayer Indonesia
Available Country	Pakistan, United States, Indonesia
Last Updated:	September 19, 2023 at 7:00 am

Uses

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.

Calcium is a mineral found in over-the-counter supplements or prescription formulations used for the treatment of specific medical conditions related to calcium deficiency.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. It is vital in cell signaling, muscular contractions, bone health, and signalling cascades.

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

Nicotinamide is an ingredient found in a variety of cosmetic products.

Pantothenic acid is a vitamin B5 found in various nutritional supplements.

Studied for the treatment of many uses such as treatment of testicular torsion, diabetic ulceration, wound healing, acne, obesity, diabetic peripheral polyneuropathy. It has also been investigated for its hypolipidemic effects and as cholesterol lowering agent.

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).

Berocca is also used to associated treatment for these conditions: Common 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 supplementationCalcium Deficiency, Deficiency, Vitamin D, Osteodystrophy, Osteomalacia, Osteoporosis, Chronic Hypocalcemia, Chronic Hypocalcemia caused by anticonvulsant medications, Care of the Joint, Mineral supplementation, 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 supplementationGastrointestinal insufficiency, Hepatic Insufficiency, Macrocytic anemia, Secondary anemia, Vitamin Deficiency, Severe debilitation, Dietary and Nutritional Therapies, Nutritional supplementation, Dietary supplementationNutritional 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 Liver

How Berocca works

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.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.

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.

Pantothenic acid is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.

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).

Dosage

Berocca 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

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

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

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.

Toxicity

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 .

No Tolerable Upper Level Intake (UL) has been established for the vitamin.

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

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

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

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.

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.

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

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 .

Dietary pantothenic acid is primarily in the form of CoA or ACP and must be converted into free pantothenic acid for absorption. CoA and ACP are hydrolyzed into 4'-phosphopantetheine which is then dephosphorylated into pantetheine and subsequently hydrolyzed again to free pantothenic acid by Pantetheinase in the intestinal lumen. Free pantothenic acid is absorbed into intestinal cells via a saturable, sodium-dependent active transport system with passive diffusion acting as a secondary pathway. As intake increases up to 10-fold absorption rate can decrease to as low as 10% due to transporter saturation.

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.

Half Life

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

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

The kidney excretes 250 mmol a day in urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d.

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

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.

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.