METFORMIN

Posology Adults with normal renal function (GFR≥90mL/min) Dosage Usual dosage:

The required daily dose ranges from 500mg to 3g. Therapy should be initiated with a low dose of one 500mg tablet three times a day or one 850 mg tablet twice a day. Depending on the metabolic state the dose can be increased stepwise at intervals of a few days up to two weeks until the therapeutically required dose has been reached.

The daily dose should be divided and taken with or after meals in order to minimise the gastro-intestinal side effects. Generally, daily doses of 1000mg to 1700mg are sufficient. If diabetic control is incomplete a cautious increase in dosage to a maximum of 2 to 3g daily is justified.

No additional benefit can usually be achieved by use of doses exceeding 3g daily. Once control has been achieved it may be possible to reduce the daily dose. Renal impairment A GFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter.

g. every 3-6 months. 4) should be reviewed before considering initiation of metformin. The staring dose is at most half of the maximum dose. <30 - Metformin is contraindicated In cases of metabolic decompensation: The metformin hydrochloride dosage may be reduced in cases of metabolic decompensation.

If only small daily doses are administered an omission of one metformin hydrochloride dose should be tried. This is of importance in elderly patients to reduce the risk of lactic acidosis.

Children and juveniles:

Metformin 500 mg film-coated tablets are not recommended for use in children.

Elderly patients:

Metformin 500 mg film-coated tablets are indicated for use in the elderly.

Further dosage information Combination with sulfonylureas:

Metformin 500 mg film-coated tablets may be used in combination with sulfonylureas if monotherapy with metformin hydrochloride does not lead to a satisfactory response. However, it should be noted that metformin hydrochloride and sulfonylureas have a different mode of action and therefore an additive or potentiating effect of these drugs might cause a hypoglycaemic shock.

Summary of the safety profile During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite which resolve spontaneously in most cases. To prevent them, it is recommended to take metformin in 2 or 3 daily doses and to increase slowly the doses.

List of adverse reactions The following adverse reactions may occur under treatment with metformin. Frequencies are defined as follows: very common ≥1/10; common ≥1/100, <1/10; uncommon ≥1/1,000, <1/100; rare ≥1/10,000, <1/1,000; very rare <1/10,000, not known (cannot be estimated from available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 4).

Nervous system disorders:

Common: Taste disturbance.

Gastrointestinal disorders:

Very common: Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain and loss of appetite. These undesirable effects occur most frequently during initiation of therapy and resolve spontaneously in most cases. To prevent them, 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.

Hepatobiliary disorders:

Very Rare: Isolated reports of liver function tests abnormalities or hepatitis resolving upon metformin discontinuation.

Skin and subcutaneous tissue disorders:

Very rare: Skin reactions such as erythema, pruritus, urticaria. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

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 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.

5). 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.

35), increased plasma lactate levels (>5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.

Patients with known or suspected mitochondrial diseases:

In patients with known mitochondrial diseases such as Mitochondrial Encephalopathy with Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome and Maternal inherited diabetes and deafness (MIDD), metformin is not recommended due to the risk of lactic acidosis exacerbation and neurologic complications which may lead to worsening of the disease.

In case of signs and symptoms suggestive of MELAS syndrome or MIDD after the intake of metformin, treatment with metformin should be withdrawn immediately and prompt diagnostic evaluation should be performed. 2. 3. Cardiac function Patients with heart failure are more at risk of hypoxia and renal insufficiency.

In patients with stable chronic heart failure, metformin may be used with a regular monitoring of cardiac and renal function. 3). Administration of iodinated contrast agents Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis.

1. • In patients with non-insulin-dependent diabetes (NIDDM, type II), if sulphonylurea therapy has completely failed. • Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis). • Diabetic precoma, coma and ketoacidosis.

• Impaired renal function of any degree. • Chronic liver disease. • Severe cardiovascular impairment. • Cardiac failure and recent myocardial infarction. • Severe peripheral vascular disease. • Severe renal failure (GFR < 30 mL/min) • Acute sever disorders, example infections with fever, pancreatitis or trauma.

• Dehydration. • History of or conditions associated with lactic acidosis such as shock or pulmonary insufficiency, alcoholism (acute or chronic), and conditions associated with hypoxaemia. • Reduced diet (< 1000 kcal or 4200 kJ per day).