METFORMIN HYDROCHLORIDE

Posology Adults with normal renal function (GFR≥ 90 mL/min) Monotherapy and combination with other oral antidiabetic agents The usual starting dose is 500mg or 850mg metformin hydrochloride 2 or 3 times daily given during or after meals.

This product is not suitable if a dose of 850mg is required, or other intermediate doses not divisible by 500mg or 1000mg, in this situation an appropriate tablet or oral solution product should be substituted. 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 3g daily taken as 2-3 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 is given at the usual starting dose of 500mg or 850mg 2-3 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.

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 one 500mg or 850mg 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 is 2g daily taken as 2-3 dived doses.

Method of administration The powder should be poured into a glass and 150 ml water should be added to obtain a clear to opalescent solution. The solution should be taken immediately after being prepared. If necessary, the solution may be stirred.

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 undesirable effects 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), not known (cannot be estimated from the available data).

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

Isolated reports: 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.

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. • 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 or respiratory failure, recent myocardial infarction, shock. • Hepatic insufficiency, acute alcohol intoxication, alcoholism.