YALTORMIN SR

Posology Adults with normal renal function (GFR≥ 90mL/min) Reduction in the risk or delay of the onset of type 2 diabetes • Metformin should only be considered where intensive lifestyle modifications for 3 to 6 months have not resulted inadequate glycaemic control.

• The therapy should be initiated with one tablet Yaltormin SR 500 mg once daily with the evening meal. • After 10 to 15 days dose adjustment on the basis of blood glucose measurements is recommended (OGTT and/or FPG and/or HbA1C values to be within the normal range).

A slow increase of dose may improve gastro-intestinal tolerability. The maximum recommended dose is 4 tablets (2000 mg) once daily with the evening meal. • It is recommended to regularly monitor (every 3-6 months) the glycaemic status (OGTT and/or FPG and/or HbA1C value) as well as the risk factors to evaluate whether treatment needs to be continued, modified or discontinued.

• A decision to re-evaluate therapy is also required if the patient subsequently implements improvements to diet and/or exercise, or if changes to the medical condition will allow increased lifestyle interventions to be possible.

Monotherapy and combination with other oral antidiabetic agents:

Yaltormin SR 750 mg is intended for patients who are already treated with metformin tablets (prolonged or immediate release). The dose of Yaltormin SR 750 mg should be equivalent to the daily dose of metformin tablets (prolonged or immediate release), up to a maximum dose of 1500 mg given with the evening meal.

After 10 to 15 days, it is recommended to check that the dose of Yaltormin SR 750 mg is adequate on the basis of blood glucose measurements.

Combination with insulin:

For patients already treated with metformin and insulin in combination therapy, the dose of Yaltormin SR 750 mg should be equivalent to the daily dose of metformin tablets up to a maximum of 1500 mg given with the evening meal, while insulin dosage is adjusted on the basis of blood glucose measurements.

Ovulation stimulation to support conception in women with PCOS:

The usual dose is 1,500-2000 mg once daily. A slow increase of dose may improve gastrointestinal tolerability. The maximum recommended dose is 2000 mg daily with the evening meal. Yaltormin SR should be considered for at least 6 months.

The decision to maintain therapy after conception and during pregnancy should be made clinically and on a case-by-case basis, taking into consideration the patient needs and an evaluation of the potential risks and benefits.

Elderly:

Due to the potential for decreased renal function in elderly subjects, the metformin dosage should be adjusted based on renal function. 4). 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. 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: In the absence of available data, Yaltormin SR should not be used in children.

Method of administration The tablets should be swallowed whole with a drink of water. They should not be chewed or crushed.

In post marketing data and in controlled clinical studies, adverse event reporting in patients treated with metformin SR was similar in nature and severity to that reported in patients treated with metformin immediate release. During treatment initiation, the most common adverse reactions are nausea, vomiting, diarrhoea, abdominal pain and loss of appetite, which resolve spontaneously in most cases.

The following adverse reactions may occur with Yaltormin SR. 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. Special warnings and precautions for use). 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. 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. 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.

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).

Elderly:

Due to the limited therapeutic efficacy data in the reduction of risk or delay of type 2 diabetes in patients 75 years and older, metformin initiation is not recommended in these patients.

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. 2 and

1 • Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis) • Diabetic pre-coma • Severe renal failure (GFR <30mL/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.