ALMETIN

Posology Adults with normal renal function (GFR≥ 90 mL/min) Monotherapy and combination with other oral antidiabetic agents The usual starting dose is 500 mg or 850 mg metformin hydrochloride 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 hydrochloride is 3 g daily, taken as 3 divided doses.

If transfer from another oral antidiabetic agent is intended: discontinue the other agent and initiate metformin at the dose indicated above. Combination with insulin Metformin and insulin may be used in combination therapy to achieve better blood glucose control.

Metformin hydrochloride is given at the usual starting dose of 500 mg or 850 mg 2 or 3 times daily, while insulin dosage is adjusted on the basis of blood glucose measurements. Elderly Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function.

4). 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. GFR mL/min Total maximum daily dose (to be divided into 2 – 3 daily doses) Additional considerations 60 – 89 3000 mg Dose reduction may be considered in relation to declining renal function. 4) should be reviewed before considering initiation of metformin.

The starting dose is at most half of the maximum dose. < 30 - Metformin is contraindicated. Paediatric population Monotherapy and combination with insulin • Metformin can be used in children from 10 years of age and adolescents. • The usual starting dose is 500 mg or 850 mg metformin hydrochloride once 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 hydrochloride is 2 g daily, taken as 2 or 3 divided doses.

Method of administration For oral use.

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.

The following adverse reactions may occur under treatment with metformin. Frequencies are defined as follows: very common: (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000) frequency not known (cannot be estimated from the 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 Paediatric population In published and post marketing data and in controlled clinical studies in a limited paediatric population aged 10 – 16 years treated during 1 year, adverse event reporting was similar in nature and severity to that reported in adults.

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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store'.

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. 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 media Intravascular administration of iodinated contrast agents may lead to contrast induced nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis. 2 and

1. • Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis). • Diabetic pre-coma. • Severe renal failure (GFR < 30 mL/min). • Acute conditions with the potential to alter renal function such as: dehydration, severe infection, shock.

• Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic disease) such as: decompensated heart failure, respiratory failure, recent myocardial infarction, shock. • Hepatic insufficiency, acute alcohol intoxication, alcoholism.