FEDATE COMBINATION PRODUCT SYRUP

Indications

• Vitamin B6 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Idiopathic sideroblastic anaemia
• Prevention of penicillamine-induced neuropathy in Wilson's disease
• Metabolic diseases such as cystathioninuria and homocystinuria
• Premenstrual syndrome

Mechanism of action

Pyridoxine hydrochloride is converted in the body to pyridoxal phosphate, which is the active form of vitamin B6. It serves as a cofactor for more than 100 enzymatic reactions, particularly those involved in the metabolism of amino acids, the synthesis of neurotransmitters (such as serotonin, dopamine, and gamma-aminobutyric acid), and the production of hemoglobin. Its role in neurotransmitter synthesis makes it crucial for normal brain function and mood regulation.

Pharmacodynamics

Pyridoxine hydrochloride exerts its effects by facilitating the conversion of amino acids into neurotransmitters and is involved in the synthesis of heme. It impacts the metabolism of tryptophan to serotonin and is essential for the production of norepinephrine and gamma-aminobutyric acid, which are vital for proper neurological function. Deficiency of vitamin B6 can lead to neurological symptoms, including peripheral neuropathy and cognitive disturbances.

Pharmacokinetics

Pyridoxine hydrochloride is readily absorbed from the gastrointestinal tract. It is primarily metabolized in the liver, where it is converted to its active form, pyridoxal phosphate. The elimination half-life of pyridoxine is approximately 15-20 days, and it is excreted primarily through the urine. Renal impairment may affect the metabolism and excretion of pyridoxine, necessitating dose adjustments.

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

• Caution in renal impairment (increased risk of hyperkalaemia)
• Interrupt treatment during periods of low food intake (such as fasting, anorexia, and nausea) to reduce risk of hypoglycaemia
• Monitor liver function tests monthly during high-dose therapy

Pregnancy

Manufacturer advises avoiding use in pregnancy due to potential risk of birth defects; however, no adverse effects have been reported at normal dietary levels.

Breast-feeding

Theoretical risk of toxicity in infants if mothers take large doses.

Storage

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

Formulations

• Pyridoxine hydrochloride 10 mg tablets
• Pyridoxine hydrochloride 20 mg tablets
• Pyridoxine hydrochloride 50 mg tablets
• Pyridoxine hydrochloride oral solution 20 mg per 1 ml

Indications

• Vitamin B12 deficiency
• Megaloblastic anemia due to vitamin B12 deficiency
• Neurological disorders related to vitamin B12 deficiency
• Pernicious anemia
• Dietary deficiency in strict vegetarians or malabsorptive conditions

Dosage

Children: Refer to the BNF for Children for specific dosing information tailored to pediatric patients.

Adults: Refer to the BNF for specific dosing information according to the condition being treated.

Mechanism of action

Cyanocobalamin acts as a cofactor for two critical enzymes: methionine synthase and L-methylmalonyl-CoA mutase. Methionine synthase facilitates the conversion of homocysteine to methionine, while L-methylmalonyl-CoA mutase is involved in the conversion of methylmalonyl-CoA to succinyl-CoA. This action is vital for proper cellular metabolism and the maintenance of myelin sheaths in nerve cells.

Pharmacodynamics

Cyanocobalamin is essential for normal cellular metabolism, particularly in the synthesis of nucleic acids and the regulation of fatty acid synthesis. It plays a role in the formation of myelin, the protective sheath that surrounds nerves, thereby influencing neurological health. Deficiency results in symptoms such as fatigue, weakness, and neurological disturbances due to impaired DNA synthesis and myelination.

Pharmacokinetics

Cyanocobalamin is absorbed in the ileum of the small intestine, where intrinsic factor, a glycoprotein secreted by the stomach, is crucial for its absorption. Once absorbed, it is transported in the bloodstream bound to transcobalamin II. The liver stores significant amounts of vitamin B12, releasing it as needed. The half-life of cyanocobalamin is variable, but it can range from several days to a few weeks, depending on body stores and physiological needs.

Adverse effects

• Headache
• Nausea
• Diarrhea
• Fatigue
• Itching or rash at the injection site

Interactions

• Chloramphenicol may impair the effectiveness of cyanocobalamin
• Prolonged use of certain medications such as metformin may decrease vitamin B12 absorption

Precautions

• Use caution in patients with a history of allergic reactions to cobalt or cobalamin
• Monitor patients with renal impairment or conditions that may affect absorption

Pregnancy

Cyanocobalamin is considered safe during pregnancy and is essential for fetal development.

Breast-feeding

Cyanocobalamin is excreted in breast milk, but it is generally considered safe for breastfeeding mothers.

Storage

Store at room temperature, away from light. Protect from freezing.

Formulations

• Injection solution
• Oral tablets
• Sublingual tablets
• Nasal spray

Indications

• Hypertriglyceridemia
• Mixed dyslipidemia
• Hyperlipidemia

Dosage

Children: Refer to the BNF for Children for paediatric dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations.

Mechanism of action

Fenofibrate acts as a peroxisome proliferator-activated receptor alpha (PPARα) agonist. This activation enhances the oxidation of fatty acids in the liver and muscle tissues, leading to a decrease in triglyceride levels and an increase in HDL cholesterol. It also reduces the synthesis of very low-density lipoprotein (VLDL) in the liver, contributing to its lipid-lowering effects.

Pharmacodynamics

Fenofibrate promotes the breakdown of lipids, influencing lipid metabolism. It increases lipoprotein lipase activity, which facilitates the hydrolysis of triglycerides in lipoproteins, thus lowering triglyceride levels. The increase in HDL cholesterol contributes to improved cardiovascular health, as HDL is known for its protective role against atherosclerosis.

Pharmacokinetics

Fenofibrate is well absorbed following oral administration, with peak plasma concentrations occurring approximately 4 to 6 hours post-dose. It is extensively metabolized in the liver, primarily to its active metabolite fenofibric acid. The elimination half-life ranges from 20 to 30 hours, allowing for once-daily dosing in most cases. The drug is largely excreted via the kidneys, necessitating caution in patients with renal impairment.

Pregnancy

Federate should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider for individualized assessment.

Breast-feeding

It is not known whether Federate is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy associated with isoniazid therapy
• Supplementation in specific dietary deficiencies

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidance.

Adults: Refer to the BNF for specific dosing details, typically 10-50 mg daily for deficiency.

Mechanism of action

Pyridoxine, mainly in its active form pyridoxal 5'-phosphate, is involved in numerous biochemical reactions, including amino acid metabolism, glycogen breakdown, nucleic acid synthesis, and the production of key neurotransmitters. It aids in the synthesis of hemoglobin and sphingolipids, and its deficiency can impair several physiological processes, including immune response and vascular health.

Pharmacodynamics

Pyridoxine is utilized for the prevention and treatment of vitamin B6 deficiency, particularly in individuals undergoing treatment with isoniazid, which can deplete vitamin B6 levels. It may also have beneficial effects on blood pressure and lipid profiles, as studies have shown it can lower both systolic and diastolic blood pressure, inhibit platelet aggregation, and improve cholesterol levels. Additionally, it plays a role in enhancing immune function and protecting endothelial cells from injury.

Pharmacokinetics

Pyridoxine is rapidly absorbed from the gastrointestinal tract. It is transported to tissues where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The vitamin is primarily excreted in urine as pyridoxine and its metabolites. Its half-life varies depending on the individual’s nutritional status and other factors. Adequate dietary intake is essential for maintaining optimal levels in the body.

Pregnancy

Pyridoxine is generally considered safe during pregnancy. However, high doses should be avoided unless specifically prescribed.

Breast-feeding

Pyridoxine is excreted in breast milk, but at normal dietary levels it is considered safe for breastfeeding mothers.

Storage

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

Formulations

• Tablets
• Oral solution
• Injectable form

Mechanism of action

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).

Pharmacodynamics

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.