FETAGRO SOFTGEL (Each softgel contains Biotin 5mg/ L-Methylfolate Calcium 1mg/ Methylcobalamin 1500mcg/ Pyridoxal-5-Phosphate 0.5mg/ DHA 200mg)

Indications

• Isolated carboxylase defects
• Defects of biotin metabolism
• Prevention of deficiency in complete biliary obstruction

Dosage

Children: Neonate: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily. Child: Initially 10 mg once daily, adjusted according to response; maintenance 5–20 mg daily, higher doses may be required.

Adults: For adults, the dosing may vary based on the condition being treated. General guidance is to refer to the BNF for specific dosing recommendations.

Mechanism of action

Biotin acts as a coenzyme for carboxylase enzymes, facilitating critical metabolic processes including gluconeogenesis, fatty acid synthesis, and amino acid catabolism.

Pharmacodynamics

Biotin is essential for the carboxylation of substrates in metabolic pathways, influencing energy metabolism and the synthesis of important biomolecules. It supports normal growth and development.

Pharmacokinetics

Biotin is absorbed in the intestine and is widely distributed in body tissues. It is not stored in large amounts, with excess being excreted in urine. The half-life and specific pharmacokinetic parameters can vary based on individual metabolism and dietary intake.

Adverse effects

• Rough skin
• Dry hair
• Enlarged liver
• Increases in erythrocyte sedimentation rate
• Increased serum calcium
• Increased serum alkaline phosphatase concentration

Precautions

• Excessive doses may be teratogenic
• High levels of vitamin A may cause birth defects

Pregnancy

No information available.

Breast-feeding

No information available.

Formulations

• Tablet
• Oral suspension
• Oral solution
• Solution for injection

Indications

• Folate deficiency
• Hyperhomocysteinemia
• Supporting treatment in certain neurological disorders
• Prevention of neural tube defects during pregnancy

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Levomefolic acid acts as a methyl donor in the conversion of homocysteine to methionine, a reaction that is catalyzed by vitamin B12-dependent methionine synthase. This process is essential for reducing homocysteine levels and facilitating the production of S-adenosylmethionine (SAMe), which participates in various methylation reactions, including neurotransmitter synthesis.

Pharmacodynamics

Levomefolate serves as an active metabolite in one-carbon metabolism, regulating key cellular functions such as DNA synthesis, gene expression, and amino acid metabolism. By acting as a cofactor in the synthesis of neurotransmitters like dopamine, serotonin, and norepinephrine, it plays a vital role in maintaining mental health and cognitive function. Additionally, it contributes to red blood cell formation and myelin synthesis.

Pharmacokinetics

Levomefolate is absorbed efficiently from the gastrointestinal tract and is known to cross the blood-brain barrier, which is significant for its role in neurological functions. It is metabolized in the liver and excreted through urine. Its pharmacokinetic profile is influenced by individual variations in folate metabolism and transport pathways.

Pregnancy

Levomefolic acid is generally considered safe during pregnancy as it is a natural form of folate.

Breast-feeding

Levomefolic acid is compatible with breastfeeding, as it is a natural metabolite of folate.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Vitamin B12 deficiency
• Megaloblastic anemia
• Peripheral neuropathy
• Neuropathic pain
• Multiple sclerosis

Dosage

Children: For paediatric patients, refer to the BNF for Children for appropriate dosing guidelines.

Adults: The typical adult dosage for methylcobalamin is 500 micrograms to 1,000 micrograms administered intramuscularly or subcutaneously, usually once daily for the initial treatment, followed by maintenance doses as needed.

Mechanism of action

Methylcobalamin serves as a cofactor for the enzyme methionine synthase, which catalyzes the conversion of homocysteine to methionine. This reaction is crucial in the synthesis of S-adenosylmethionine (SAMe), an important methyl donor in numerous methylation reactions within the body. Methylcobalamin also plays a role in myelin formation and the maintenance of nerve cells.

Pharmacodynamics

Methylcobalamin exhibits neuroprotective effects, promoting nerve regeneration and repair in peripheral neuropathy. It is believed to enhance nerve conduction and improve neurological function. The physiological effects are primarily attributed to its role in methylation processes and the synthesis of neurotransmitters.

Pharmacokinetics

Methylcobalamin is water-soluble and is absorbed in the intestine. The bioavailability can be affected by gastrointestinal health, and intrinsic factor is not required for its absorption. It is distributed throughout the body, with high concentrations in the liver, kidneys, and brain. The elimination half-life of methylcobalamin is approximately 6 hours, and it is excreted primarily in the urine.

Adverse effects

• Nausea
• Diarrhea
• Headache
• Dizziness
• Anxiety
• Rash
• Pruritus

Precautions

• Monitor patients with Leber's disease due to potential optic nerve damage.
• Caution in patients with allergies to cobalt or vitamin B12.
• Use with caution in patients with renal impairment.

Pregnancy

Methylcobalamin is classified as a category A drug. It is generally considered safe during pregnancy, but consultation with a healthcare provider is recommended.

Breast-feeding

Methylcobalamin is excreted in breast milk. It is generally considered safe during breastfeeding, but consultation with a healthcare provider is recommended.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Injections
• Sublingual tablets
• Oral solutions

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy
• Certain types of anemia
• Pyridoxine-dependent seizures
• Supplementation in pregnant women to alleviate nausea

Dosage

Children: Refer to established guidelines for specific dosing, as pyridoxal 5'-phosphate dosages can vary based on indication and patient-specific factors.

Adults: Refer to established guidelines for specific dosing, as pyridoxal 5'-phosphate dosages can vary based on indication and patient-specific factors.

Mechanism of action

Pyridoxal 5'-phosphate functions primarily as a coenzyme in various enzymatic reactions. It is involved in transamination, decarboxylation, and racemization reactions, facilitating the conversion of amino acids and the production of neurotransmitters. It also plays a role in the metabolism of tryptophan to niacin and the synthesis of sphingolipids.

Pharmacodynamics

The pharmacodynamic effects of pyridoxal 5'-phosphate are closely tied to its role as a cofactor in enzymatic reactions. Its deficiency can lead to neurological disorders, impaired immune function, and anemia. Adequate levels are associated with improved mood, cognitive function, and overall metabolic health.

Pharmacokinetics

Pyridoxal 5'-phosphate is absorbed in the intestine and is widely distributed throughout the body, including the brain. It is metabolized primarily in the liver, where it can be converted into other forms of vitamin B6. The elimination half-life is variable and can depend on individual metabolic rates. Excess vitamin B6 is excreted in urine as pyridoxal and pyridoxic acid.

Adverse effects

• Peripheral neuropathy
• Photosensitivity
• Gastrointestinal disturbances
• Nausea
• Headache
• Drowsiness

Interactions

• May interact with certain antiepileptic drugs, potentially reducing their effectiveness
• May affect the metabolism of levodopa, reducing its effectiveness
• Can interact with isoniazid, potentially reducing the effectiveness of pyridoxine therapy

Precautions

• Use caution in patients with liver disease
• Monitor for neuropathy with prolonged use
• Consider vitamin B6 status in patients with malabsorption syndromes

Pregnancy

Pyridoxal 5'-phosphate is generally considered safe during pregnancy when used at recommended doses.

Breast-feeding

Pyridoxal 5'-phosphate is excreted in breast milk, but is considered safe for breastfeeding mothers when used at recommended doses.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Capsules
• Injectable solutions

Mechanism of action

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. In human tissues biotin is a cofactor for the enzymatic carboxylation of four substrates: pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA. As such, it plays an important role in both carbohydrate and fat metabolism. Carbon dioxide fixation occurs in a two-step reaction, the first involving binding of carbon dioxide to the biotin moiety of the holoenzyme, and the second involving transfer of the biotin-bound carbon dioxide to an appropriate acceptor. Biotin functions in carbon dioxide fixation reactions in intermediate metabolism, transferring the carboxyl group to acceptor molecules. It acts similarly in decarboxylation reactions. Biotin is essential in human metabolism for its part in the previously described enzymatic steps, in catalyzing deamination of amino acids, and in oleic acid synthesis. Biotin is a cofactor for the enzymatic carboxylation of pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA, and, therefore, plays an important role in carbohydrate and fat metabolism. Protein folding in the endoplasmic reticulum (ER) depends on Ca2+; uptake of Ca2+ into the ER is mediated by sarco/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3). The 5'-flanking region of the SERCA3 gene (ATP2A3) contains numerous binding sites for the transcription factors Sp1 and Sp3. Biotin affects the nuclear abundance of Sp1 and Sp3, which may act as transcriptional activators or repressors. Here we determined whether biotin affects the expression of the SERCA3 gene and, thus, protein folding in human lymphoid cells. Jurkat cells were cultured in media containing 0.025 nmol/L biotin (denoted "deficient") or 10 nmol/L biotin ("supplemented"). The transcriptional activity of the full-length human SERCA3 promoter was 50% lower in biotin-supplemented cells compared to biotin-deficient cells. Biotin-dependent repressors bind to elements located 731 to 1312 bp upstream from the transcription start site in the SERCA3 gene. The following suggest that low expression of SERCA3 in biotin-supplemented cells impaired folding of secretory proteins in the ER, triggering unfolded protein response: (i) sequestration of Ca2+ in the ER decreased by 14 to 24% in response to biotin supplementation; (ii) secretion of interleukin-2 into the extracellular space decreased by 75% in response to biotin supplementation; (iii) the nuclear abundance of stress-induced transcription factors increased in response to biotin supplementation; and (iv) the abundance of stress-related proteins such ubiquitin activating enzyme 1, growth arrest and DNA damage 153 gene, X-box binding protein 1 and phosphorylated eukaryotic translation initiation factor 2alpha increased in response to biotin supplementation. Collectively, this study suggests that supplements containing pharmacological doses of biotin may cause cell stress by impairing protein folding in the ER. Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have

Pharmacodynamics

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.

Mechanism of action

Levomefolic acid plays a critical role in methylating homocysteines into methionine by acting as a methyl donor in a reaction catalyzed by vitamine B12-dependent methionine synthase. Homocysteine must either be further metabolized via transulfuration to become cysteine, taurine, and glutathione via a B6-dependent process, or re-methylated to become methionine again. Methionine formed from remethylation of homocysteine by levomefolic acid forms the downstream metabolite S-adenosylmethionine (SAMe), which is involved in numerous biochemical methyl donation reactions, including reactions forming monoamine neurotransmitters. Studies suggest that high plasma levels of homocysteine is associated with increased incidences of arterial plaque formation.

Pharmacodynamics

Levomefolic acid is an active metabolite of folic acid and a methyl group donor in one-carbon metabolism reactions. It regulates important cellular functions such as DNA biosynthesis, gene expression regulation, amino acid synthesis and metabolism, and myelin synthesis and repair. As a only form of folate that can cross the blood-brain barrier, it acts as a cofactor in the production of monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. Levomefolic acid is also involved in red blood cell formation.