ABIANO

Posology Adults 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 3000 mg daily, taken as 3 divided doses. If transfer from another oral antidiabetic agent is intended: the other agent should be discontinued and metformin hydrochloride may be initiated at the dose indicated above.

Combination with insulin Metformin hydrochloride 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 metformin hydrochloride 2 or 3 times daily, while insulin dosage is adjusted on the basis of blood glucose measurements.

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 The total maximum daily dose (divided in 1, 2 or 3 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 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 hydrochloride is 2 g daily, taken as 2 or 3 divided doses. 2 cannot always be achieved with this product, yet such doses can be achieved with other available drug products. Method of administration The effervescent tablets can be divided into two equal doses.

The remaining part of the effervescent tablet if not used immediately, should be discarded. The effervescent tablets must be dissolved in a glass of water and the solution should then be drunk immediately after complete dissolution of the tablets.

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, <1/10; uncommon >1/1,000, <1/100; rare >1/10,000, <1/1,000; very rare <1/10,000. 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 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, urticarial. 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 is a very rare, but serious (high mortality rate in the absence of prompt treatment), metabolic complication that can occur due to metformin hydrochloride accumulation. Reported cases of lactic acidosis in patients on metformin hydrochloride have occurred primarily in diabetic patients with impaired renal failure, or acute worsening of renal function.

Special caution should be paid to situations where renal function may become impaired, for example in case of dehydration (severe diarrhoea or vomiting), or when initiating antihypertensive therapy or diuretic therapy and when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).

In the acute conditions listed, metformin hydrochloride should be temporarily discontinued. 5). 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, plasma lactate levels above 5mmol/l, and an increased anion gap and lactate/pyruvate ratio. 9). Physicians should alert the patients and/or care-givers on the risk and on the symptoms of lactic acidosis.

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. Renal function eGFR 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 creatinine clearance levels at the lower limit of normal and in elderly subjects.

3. 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 a non-steroidal anti-inflammatory drug (NSAID).

Cardiac function Patients with heart failure are more at risk of hypoxia and renal insufficiency. In patients with stable chronic heart failure, metformin hydrochloride may be used with a regular monitoring of cardiac and renal function.

3). Administration of iodinated contrast media The intravascular administration of iodinated contrast agents can lead to contrast induced nephropathy. This may induce metformin accumulation and may increase the risk for 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.