Neoform 500

White to off-white film-coated tablet, round, biconvex and plain on both sides.
Each film-coated tablet contains: Metformin Hydrochloride, USP 500 mg.

Oral Hypoglycemic (Biguanide).
Pharmacology: Pharmacodynamics: Metformin is a biguanide with antihyperglycemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycemia.
Metformin may act via 3 mechanisms: Reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; increasing insulin sensitivity in muscles, improving peripheral glucose uptake and utilization and delay of intestinal glucose absorption.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase. Metformin increases the transport capacity of all types of membrane glucose transporters (GLUT).
In clinical studies, use of metformin was associated with either a stable body weight or modest weight loss.
In humans, independently of its action on glycemia, metformin has favorable effects on lipid metabolism. This has been shown at therapeutic doses in controlled, medium-term or long-term clinical studies; metformin reduces total cholesterol, LDL cholesterol and triglyceride levels.
Pharmacokinetics: Absorption: After an oral dose of metformin, maximum plasma concentration (C_max) is reached in 2.5 hours (T_max). Absolute bioavailability of a 500 mg or 850 mg metformin tablet is approximately 50-60% in healthy subjects. After an oral dose, the non-absorbed fraction recovered in feces was 20-30%.
After an oral administration, metformin absorption is saturable and incomplete. It is assumed that the pharmacokinetics of metformin absorption is non-linear.
At the usual metformin doses and dosing schedules, steady state plasma concentrations are reached within 24 to 48 hours and are generally less than 1 μg/mL. In controlled clinical trials, maximum plasma levels (C_max) did not exceed 4 μg/mL even at maximum doses.
Food decreases the extent and slightly delays the absorption of metformin. Following administration of a dose of 850 mg, a 40% lower plasma peak concentration, a 25% decrease in AUC (area under the curve) and a 35 minute prolongation in the time to peak plasma concentration were observed. The clinical relevance of these decreases is unknown.
Distribution: Plasma protein binding is negligible. Metformin partitions into erythrocytes. The blood peak is lower than the plasma peak and appears at approximately the same time. The red blood cells most likely represent a secondary compartment of distribution. The mean volume of distribution [Vd] ranged from 63 to 276 L.
Metabolism: Metabolism is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination: Renal clearance of metformin is >400 mL/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. Following an oral dose, the apparent terminal elimination half-life is approximately 6.5 hours.
When renal function is impaired, renal clearance is decreased in proportion to that of creatinine and thus the elimination half-life is prolonged, leading to increased levels of metformin in plasma.
Toxicology: Preclinical Safety Data: Preclinical safety data revealed no special hazard for humans based on conventional studies on safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity in reproduction.

Diet-failed, non-insulin dependent, Diabetes Mellitus patients, especially if overweight alone as initial therapy with sulphonylurea.

Given by mouth in the treatment of non-insulin dependent diabetes mellitus in an initial dosage of 500 mg two or three times a day or 850 mg once or twice a day with or after meals, gradually increased if necessary to a maximum of 2 or 3 g daily or as prescribed by the physician.

Hypoglycemia has not been seen with metformin doses up to 85 g, although lactic acidosis has occurred in such circumstances. High overdose of metformin or concomitant risks may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in a hospital. The most effective way to remove lactate and metformin from the blood is hemodialysis.

Diabetic coma, ketoacidosis, impaired renal function, chronic liver disease. Cardiac failure, recent myocardial infarction, alcoholism, tissue hypoxia, lactic acidosis. Severe infections, trauma, surgery, dehydration.

Metformin Hydrochloride should not be used in insulin dependent diabetes mellitus. Metformin Hydrochloride should not be used in patients with heart failure, dehydration, acute or chronic alcoholism, or any other condition, likely to predispose to lactic acidosis.

Uncontrolled diabetes during pregnancy (gestational or permanent) is associated with increased risk of congenital abnormalities and perinatal mortality.
A limited amount of data from the use of metformin in pregnant women does not indicate an increased risk of congenital abnormalities. Animal studies do not indicate harmful effects with respect to pregnancy, embryonic or fetal development, parturition or postnatal development (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). However, when the patient plans to become pregnant and during pregnancy, it is recommended that diabetes is not treated with metformin but insulin will be used to maintain blood glucose levels as close to normal as possible, to reduce the risk of malformations of the fetus.
Metformin is excreted into human breast milk. No adverse effects were observed in breastfed newborns/infants. However, as only limited data are available, breast-feeding is not recommended during metformin treatment. A decision on whether to discontinue breast-feeding should be made, taking into account the benefit of breast-feeding and the potential risk to adverse effects on the child.

Metformin causes gastrointestinal adverse effects with anorexia, nausea, and vomiting; absorption of various substances including vitamin B₁₂ may be impaired. Patients may experience a metallic taste and there may be weight loss. Hypoglycemia is less of a problem with metformin than with the sulfonylureas. Lactic acidosis, sometimes fatal, has occurred but to a lesser extent than with phenformin and it is generally accepted that the lactic acidosis usually occurred in patients whose condition contraindicated the use of metformin particularly those with renal impairment.

Use of biguanide concomitantly with other drugs that lower blood-glucose concentrations increases the risk of hypoglycaemia, while drugs that increase blood glucose concentrations may reduce the effect of biguanide therapy. In general, fewer drug interactions have been reported with biguanides than with sulfonylureas. Alcohol may increase the risk of lactic acidosis as well as hypoglycaemia. Care should be taken if biguanides are given concomitantly with drugs that may impair renal function.

Store at temperatures not exceeding 30°C.

Antidiabetic Agents

A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.

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