Glucon

Glucon

metformin

Manufacturer:

Avex

Distributor:

Apex
Full Prescribing Info
Contents
Metformin hydrochloride.
Description
GLUCON Tablet 500MG contains Metformin HCl 500mg.
GLUCON Tablet 850MG contains Metformin HCl 850mg.
Action
Pharmacology: Pharmacodynamics: Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.
Metformin may act via 3 mechanisms: reduction of hepatic glucose production by inhibiting gluconeogenesis and glycogenolysis; in muscle, by increasing insulin sensitivity, improving peripheral glucose, uptake and utilisation; 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 humans, independently of its action on glycaemia, metformin has favourable 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, Tmax is reached in 2.5 hours. Absolute bioavailability of a 500mg or 850mg metformin tablet is approximately 50-60% in healthy subjects. After an oral dose, the non-absorbed fraction recovered in faeces was 20-30%.
After oral administration, metfomin 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 metformin plasma levels (Cmax) 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 of 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 Vd ranged between 63-276 L.
Metabolism: Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination: Renal clearance of metformin is > 400ml/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.
Paediatrics: Single dose study: After single doses of metformin 500mg, paediatric patients have shown similar pharmacokinetic profile to that observed in healthy adults.
Multiple dose study: Data are restricted to one study. After repeated doses of 500mg BID for 7 days in paediatric patients the peak plasma concentration (Cmax) and systemic exposure (AUC0-t) were reduced by approximately 33% and 40%, respectively compared to diabetic adults who received repeated doses of 500mg BID for 14 days. As the dose is individually titrated based on the glycaemic control, this is on limited clinical relevance.
Indications/Uses
Treatment of type 2 diabetes mellitus, when dietary management and exercise alone does not result in adequate glycaemic control.
In adults, Glucon film-coated tablets may be used as monotherapy or in combination with other oral anti-diabetic agents or with insulin.
In children from 10 years of age and adolescents, Glucon film-coated tablets may be used as monotherapy or in combination with insulin.
A reduction of diabetic complications has been shown in overweight type 2 diabetic patients treated with metformin as first-line therapy after diet failure.
Dosage/Direction for Use
Adults: Monotherapy and combination with other oral antidiabetic agents: The usual starting dose is one tablet 2 or 3 times daily given during or after meals. After 10 to 15 days the dose should be adjusted on the basis of blood glucose measurements. A slow increase of dose may improve gastrointestinal tolerability.
The maximum recommended dose of metformin is 3 g daily.
If transfer from another oral antidiabetic agent is intended: discontinue the other agent and initiate metformin at the dose indicated as previously mentioned.
Renal impairment: A GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. In patients at an increased risk of further progression of renal impairment and in the elderly, renal function should be assessed more frequently, e.g. every 3-6 months. (See table.)

Click on icon to see table/diagram/image

Combination with insulin: Metformin and insulin may be used in combination therapy to achieve better blood glucose control. Metformin is given at the usual starting dose of one tablet 2-3 times daily, while Insulin dosage is adjusted on the basis of blood glucose measurements.
Children and adolescents: Monotherapy and combination with insulin: Glucon film-coated tablets can be used in children from 10 years of age and adolescents.
The usual starting dose is one tablet of 500mg or 850mg once daily, given during meals or after meals.
After 10 to 15 days the dose should be adjusted in the basis of blood glucose measurements. A slow increase of dose may improve gastrointestinal tolerability. The maximum recommended dose of metformin is 2g daily, taken as 2 or 3 divided doses.
Mode of Administration: Oral.
Overdosage
Hypoglycaemia has not been seen with metformin doses of up to 85g, although lactic acidosis has occurred in such circumstances. High overdose or concomitant risks of metformin may lead to lactic acidosis. Lactic acidosis is a medical emergency and must be treated in hospital.
The most effective method to remove lactate and metformin is haemodialysis.
Contraindications
Hypersensitivity to metformin hydrochloride or to any of the excipients.
Diabetic ketoacidosis, diabetic pre-coma.
Renal failure or renal dysfunction (creatinine clearance < 60ml/min).
Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock, intravascular administration of iodinated contrast agents.
Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction, shock.
Hepatic insufficiency, acute alcohol intoxication, alcoholism.
Lactation.
Severely reduced kidney function (GFR <30 mL/min).
Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)
Warnings
Lactic acidosis: Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.
In case of dehydration (severe diarrhoea or vomiting, fever or reduce fluid intake), metformin should be temporarily discontinued and contact with a health care professional is recommended.
Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and NSAIDs) should be initiated with caution in metformin-treated patients. Other risk factors for lactic acidosis are excessive alcohol intake, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as well as concomitant use of medicinal products that cause lactic acidosis. Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking metformin and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH (<7.35), increased plasma lactate levels (>5mmol/L) and an increased anion gap and lactate/pyruvate ratio
Special Precautions
Diagnosis: Lactic acidosis is characterised by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory findings are decreased blood pH. plasma lactate levels above 5 mmoI/L and an increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, metformin should be discontinued and the patient should be hospitalised immediately.
Renal function: As metformin is excreted by the kidney, serum creatinine levels should be determined before initiating treatment and regularly thereafter: at least annually in patients with normal renal function, at least two to four times a year in patients with serum creatinine levels at the upper limit of normal and in elderly subjects.
Decreased renal function in elderly subjects is frequent and asymptomatic. Special caution should be exercised in situations where renal function may become impaired, for example when initiating antihypertensive therapy or diuretic therapy and when starting therapy with an NSAID.
GFR should be assessed before treatment initiation and regularly thereafter [See Recommended Dosage under Dosage & Administration].
Metformin is contraindicated in patients with GFR<30 ml/min and should be temporarily discontinued in the presence of conditions that alter renal function [See Contraindications].
Administration of iodinated contrast agent: As the intravascular administration of iodinated contrast materials in radiologic studies can lead to renal failure, metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Surgery: Metformin hydrochloride should be discontinued 48 hours before elective surgery with general anaesthesia and should not be usually resumed earlier than 48 hours afterwards.
Children and adolescents: The diagnosis of type 2 diabetes mellitus should be confirmed before treatment with metformin is initiated. No effect of metformin on growth and puberty has been detected during controlled clinical studies of one-year duration but no long-term data on these specific points are available. Therefore, a careful follow-up of the effect of metformin on these parameters in metformin treated children, especially pre-pubescent children, is recommended.
Children aged between 10 and 12 years: Only 15 subjects aged between 10 and 12 years were included in the controlled clinical studies conducted in children and adolescents. Although metformin efficacy and safety in children below 12 did not differ from efficacy and safety in older children, particular caution is recommended when prescribing to children aged between 10 and 12 years.
Other precautions: All patients should continue their diet with a regular distribution of carbohydrate intake during the day. Overweight patients should continue their energy-restricted diet.
The usual laboratory tests for diabetes monitoring should be performed regularly.
Metformin alone never causes hypoglycaemia, although caution is advised when it is used in combination with insulin or sulfonylureas.
Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. Regular assessment of renal function is necessary.
Use In Pregnancy & Lactation
To date, no relevant epidemiological data are available. Animal studies do not indicate harmful effects with respect to pregnancy, embryonal or foetal development, parturition or postnatal development.
When the patient plans to become pregnant and during pregnancy, diabetes should not be treated with metformin but insulin should be used to maintain blood glucose levels as close to normal as possible in order to lower the risk of foetal malformations associated with abnormal blood glucose levels.
Metformin is excreted into milk in lactating rats. Similar data is not available in humans and a decision should be made whether to discontinue nursing or to discontinue metformin, taking into account the importance of the compound to the mother.
Side Effects
Similarly to all medicines, Metformin might cause side effects.
Gastrointestinal symptoms such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite are very common: these occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent these gastrointestinal symptoms, it is recommended that metformin be taken in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability.
Metallic taste is common. Mild erythema is very rare.
A decrease of vitamin B12 absorption with decrease of serum levels has been observed in patients treated long- term with metformin and appears generally to be without clinical significance.
Lactic acidosis is very rare.
If any of the previously mentioned side effects are trouble some, severe, or do not wear off as treatment goes on tell a doctor. If the patient have any other side effects not listed in this patient information leaflet, notify a doctor or pharmacist.
Drug Interactions
Concomitant use not recommended: Alcohol: Increased risk of lactic acidosis in acute alcohol intoxication, particularly in case of: fasting or malnutrition, hepatic insufficiency.
Avoid consumption of alcohol and alcohol-containing medications.
Iodinated contrast agents: Intravascular administration of iodinated contrast agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Metformin should be discontinued prior to, or at the time of the test and not reinstituted until 48 hours afterwards, and only after renal function has been re-evaluated and found to be normal.
Combinations requiring precautions for use: Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation. ACE-inhibitors may decrease the blood glucose levels. If necessary, adjust the dosage of the antidiabetic drug during therapy with the other drug and upon its discontinuation.
Storage
Store below 30°C. Protect it from light and humidity.
MIMS Class
ATC Classification
A10BA02 - metformin ; Belongs to the class of biguanides. Used in the treatment of diabetes.
Presentation/Packing
FC tab 500 mg (white, coloured, round, biconvex, 11.0 mm diameter, with breakline on one side) 10 x 10's, 50 x 10's. 850 mg (white, round, biconvex, 13.5mm diameter) x 10 x 10's.
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