Glumet DC

Metformin hydrochloride.

White to off-white, round, biconvex, film-coated tablet with Pharmaniaga icon on one side and break line on the other.
Each tablet contains Metformin hydrochloride 500 mg.

Pharmacology: Metformin hydrochloride is a biguanide hypoglycaemic agent used in non-insulin-dependent diabetes mellitus. Its mode of action is not clear. It does not stimulate insulin release but does require that some insulin be present in order to exert its hypoglycaemic effect.
Possible mechanisms of action include delay in the absorption of glucose from the gastrointestinal tract, an increase in insulin sensitivity and glucose uptake into cells and inhibition of hepatic gluconeogenesis.
Metformin does not usually lower blood-glucose concentrations in non-diabetic subjects.
Pharmacokinetics: Metformin hydrochloride is slowly and incompletely absorbed from the gastrointestinal tract. After an oral dose of metformin, Tmax is reached in 2.5 hours. Absolute bioavailability of a single 500 mg or 850 mg dose is approximately 50 to 60% in healthy subjects, although this is reduced somewhat if taken with food.
After oral administration, metformin absorption is saturable and incomplete. The non-absorbed fraction recovered in faeces was 20-30%.
Following absorption, plasma protein binding is negligible and it is excreted unchanged in the urine. The plasma elimination half-life is reported to range from about 2 to 6 hours after oral administration. 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.

Indicated in the treatment of Type 2 diabetes mellitus. It is used to supplement treatment by diet modification when such modification has not proved effective on its own. Metformin may be used as monotherapy or in combination with other oral antidiabetic agents or 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.
In Type 1 diabetes, metformin may be given as an adjuvant to patients whose diabetes are poorly controlled.
In children from 10 years of age and adolescents, Metformin 500 mg film-coated tablet may be used as monotherapy or in combination with insulin.

Renal impairment: A CFR 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

Monotherapy and combination with other oral antidiabetic agents: 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.
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: Metformin 500 mg film-coated tablet can be used in children from 10 years of age and adolescents. The usual starting dose is one tablet of 500 mg or 850 mg once daily, given during meals 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 2 g daily, taken as 2 or 3 divided doses.
Route of Administration: Oral.

Hypoglycaemia has not been seen with metformin doses of up to 85 g, 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.

Diabetic ketoacidosis, diabetic pre-coma.
Hypersensitivity to metformin hydrochloride or to any of the excipients.
Renal failure or renal dysfunction.
Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock and intravascular administration of iodinated contrast agents.
Acute or chronic disease which may cause tissue hypoxia such as: cardiac or respiratory failure, recent myocardial infarction and 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).

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 reduced fluid intake), metformin should be temporarily discontinued and contact with a healthcare 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 may cause lactic acidosis.
Patients and/or caregivers 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 (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.

Renal function: GFR should be assessed before treatment initiation and regularly thereafter [see 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.
Other precautions: All patients should continue their diet with 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.
Use in Children: Metformin should not be used in children.
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.
Use in the Elderly: 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.

Pregnancy: To date, no relevant epidemiological data are available. Insulin is preferred for the treatment of diabetes in pregnancy in order to lower risk of foetal malformations associated with abnormal blood glucose level.
Lactation: Metformin is excreted into milk in lactating rats. Similar data are 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.

Metformin causes gastrointestinal adverse effects including nausea, vomiting, diarrhoea, abdominal pain and loss of appetite (>10%) 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.
Absorption of various substances including vitamin B12 may be impaired. Patients may experience a metallic taste and there may be weight loss.
Lactic acidosis can occur but is very rare.
Mild erythema has been reported in some hypersensitive individuals. However, the incidence of such effects is regarded as very rare (<0.01%).

Acute alcohol intoxication may increase the risk of lactic acidosis, particularly in case of fasting or malnutrition and hepatic insufficiency. To avoid consumption of alcohol and alcohol-containing medications.
Intravascular administration of iodinated contrast materials 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.
Glucocorticoids (systemic and local routes), beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. If necessary, the dosage of the antidiabetic drug need to be adjusted during therapy with the other drug and upon its discontinuation.
ACE-inhibitors may decrease the blood glucose level. If necessary, the dosage of the antidiabetic drug need to be adjusted during therapy with the other drug and upon its discontinuation.

Store below 30°C.
Protect from light.

Antidiabetic Agents

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

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