Glucophage: detailed information

Package leaflet: Information for the user

GLUCOPHAGE 500 mg film-coated tablets

metformin hydrochloride
Read this leaflet carefully before you start taking this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

What Glucophage is and what it is used for
What you need to know before taking Glucophage
How to take Glucophage
Possible side effects
How to store Glucophage
Contents of the pack and other information

1. What Glucophage is and what it is used for

Glucophage contains metformin, a medicine used to treat diabetes. It belongs to a group of
active substances called biguanides.
Insulin is a hormone produced by the pancreas that enables the body to absorb glucose
(sugar) from the blood. The body uses glucose to produce energy or stores it for future use.
If you have diabetes, your pancreas does not produce enough insulin, or your body is unable
to use insulin properly. This results in high levels of glucose in the blood. Glucophage helps lower blood glucose to a level as close to normal as possible.
If you are overweight, taking Glucophage over a long period of time may also help reduce the risk of diabetes-related complications. Glucophage has been associated with both stabilization and modest reduction in body weight.
Glucophage is used to treat patients with type 2 diabetes (also known as “non-insulin-dependent diabetes”) when diet and exercise alone have not been sufficient to control blood glucose levels. It is particularly used in overweight patients.
Adults may take Glucophage alone or in combination with other antidiabetic medicines (oral medications or insulin).
Children aged 10 years and older and adolescents may take Glucophage alone or in combination with insulin.

2. What you need to know before taking Glucophage

Do not take Glucophage

if you are allergic (hypersensitive) to metformin or to any of the other ingredients of this medicine (listed in section 6)
if you have liver problems
if you have severely reduced kidney function
if you have uncontrolled diabetes, for example with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see "Risk of lactic acidosis" below) or ketoacidosis. Ketoacidosis is a condition in which substances called 'ketone bodies' accumulate in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusually fruity odour.
if your body has lost too much water (dehydration), for example due to prolonged or severe diarrhoea or if you have vomited repeatedly. Dehydration can cause kidney problems which may put you at risk of lactic acidosis (see section "Warnings and precautions").
if you have a severe infection, such as one affecting the lungs, bronchial system or kidneys. Severe infections can cause kidney problems which may put you at risk of lactic acidosis (see section "Warnings and precautions").
if you are being treated for acute heart failure or have recently had a heart attack, if you have serious circulatory problems (such as shock) or breathing difficulties. These conditions may lead to inadequate oxygen supply to tissues, increasing your risk of lactic acidosis (see section "Warnings and precautions").
if you drink large amounts of alcohol

If you are in any of the above conditions, consult your doctor before starting this medicine.
Make sure to ask your doctor for advice if:

you are due to have tests such as X-rays or diagnostic scans that require injection into the bloodstream of iodine-containing contrast agents
you are due to have surgery

You must stop taking Glucophage for a certain period of time before and after such tests or surgery. Your doctor will decide whether you need alternative treatment during this time. It is important that you follow your doctor's instructions precisely.

Warnings and precautions
Risk of lactic acidosis
Glucophage may cause a very rare but serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is also increased by uncontrolled diabetes, severe infections, prolonged fasting, alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition in which part of the body is deprived of oxygen (such as severe acute heart disease).
If you have any of the medical conditions described above, speak to your doctor for further instructions.

Stop taking Glucophage temporarily if you develop a medical condition that may be associated with dehydration (significant loss of body fluids), such as vomiting, diarrhoea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further instructions.

If you experience any of the symptoms of lactic acidosis, stop taking Glucophage and contact your doctor or go to the nearest hospital immediately, because lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

vomiting
stomach ache (abdominal pain)
muscle cramps
a general feeling of discomfort associated with severe fatigue
difficulty breathing
lowered body temperature (hypothermia) and slower heart rate

Lactic acidosis is a medical emergency and must be treated in hospital.

Contact your doctor immediately for further instructions if:

you know you have a hereditary genetic disease affecting mitochondria (the components that produce energy within cells), such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes) or maternally inherited diabetes and deafness (MIDD);
you develop any of the following symptoms after starting metformin: seizures, reduced cognitive ability, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), headache, or hearing loss.

If you are undergoing major surgery, you must stop taking Glucophage during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Glucophage. Glucophage alone does not cause hypoglycaemia (low blood glucose levels). However, if you take Glucophage together with other diabetes medicines that can cause hypoglycaemia (such as sulphonylureas, insulin, meglitinides), there is a risk of hypoglycaemia. If you experience symptoms of hypoglycaemia such as weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances or difficulty concentrating, it is usually helpful to eat or drink something containing sugar.

During treatment with Glucophage, your doctor will check your kidney function at least once a year, or more frequently if you are elderly and/or have impaired kidney function.

Other medicines and Glucophage
If you are due to receive an injection into the bloodstream of iodine-containing contrast agents, for example during X-rays or diagnostic scans, you must stop taking Glucophage before and after the test. Your doctor will decide when to stop and when you can restart treatment with Glucophage.

Inform your doctor if you are taking, have recently taken, or might take any other medicine. You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust your Glucophage dose. It is particularly important to mention the use of:

medicines that increase urine production (diuretics)
medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
certain medicines for high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)
beta-2 agonists such as salbutamol or terbutaline (used to treat asthma)
corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma)
medicines that may alter the amount of Glucophage in your blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib)
other medicines used to treat diabetes

Glucophage and alcohol
Avoid excessive consumption of alcohol and of medicines containing alcohol during treatment with Glucophage, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or are planning a pregnancy, consult your doctor before taking this medicine so that they can make any necessary treatment adjustments or monitor your blood glucose levels.
This medicine is not recommended if you are breastfeeding or intend to breastfeed your baby.

Driving and using machines
Glucophage alone does not cause hypoglycaemia (low blood glucose levels). This means it does not impair your ability to drive or operate machinery.
However, take particular care if you take Glucophage together with other diabetes medicines that can cause hypoglycaemia (such as sulphonylureas, insulin, meglitinides). Symptoms of hypoglycaemia include weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances, or difficulty concentrating. Do not drive or operate machinery if you begin to experience these symptoms.

3. How to take Glucophage

Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Glucophage cannot replace the benefits of a healthy lifestyle. Continue to follow all dietary advice given by your doctor and exercise regularly.

Recommended dose
Children aged 10 years and older, and adolescents, usually start with 500 mg or 850 mg of Glucophage once daily. The maximum daily dose is 2000 mg, taken in 2 or 3 divided doses. Treatment of children aged between 10 and 12 years is recommended only on specific medical advice, as experience in this age group is limited.
Adults usually start with 500 mg or 850 mg of Glucophage two or three times daily. The maximum daily dose is 3000 mg, taken in 3 divided doses.
If you have reduced kidney function, your doctor may prescribe a lower dose.
If you are also taking insulin, your doctor will advise you on how to start taking Glucophage.

Monitoring

Your doctor will regularly monitor your blood glucose levels and adjust your dose of Glucophage accordingly. You should consult your doctor regularly. This is particularly important for children and adolescents, or if you are elderly.
Your doctor will also check your kidney function at least once a year. You may need more frequent checks if you are elderly or if your kidneys do not function normally.

How to take Glucophage
Take the tablets during or after a meal. This will help you avoid gastrointestinal side effects.
Do not crush or chew the tablets. Swallow each tablet with a glass of water.

If you take one dose per day, take it in the morning (with breakfast).
If you take two doses per day, take them in the morning (with breakfast) and in the evening (with dinner).
If you take three doses per day, take them in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If, after some time, you think that the effect of Glucophage is too strong or too weak, consult your doctor or pharmacist.

If you take more Glucophage than you should
If you have taken more Glucophage than you should, you may develop lactic acidosis. Symptoms of lactic acidosis are non-specific and include vomiting, stomach pain (abdominal pain) with muscle cramps, general feeling of malaise with extreme fatigue, and difficulty breathing.
Further symptoms include lowered body temperature and slowed heart rate. If you experience any of these symptoms, seek immediate medical attention, as lactic acidosis can lead to coma. Stop taking Glucophage immediately and contact a doctor or go to the nearest hospital without delay.

If you forget to take Glucophage
Do not take a double dose to make up for a forgotten dose. Take the next dose at the usual scheduled time.

If you have any doubts about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. The following side effects may occur:
Glucophage may cause a very rare (may affect up to 1 in 10,000 people), but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Glucophage and seek immediate medical attention from your doctor or the nearest hospital, because lactic acidosis can lead to coma.

Very common side effects (may affect more than 1 in 10 people)

Digestive problems such as nausea, vomiting, diarrhoea, stomach ache (abdominal pain), and loss of appetite. These side effects occur most often at the beginning of treatment with Glucophage. It may help to divide your doses throughout the day and to take Glucophage during or immediately after meals. If symptoms persist, stop taking Glucophage and consult your doctor.

Common side effects (may affect up to 1 in 10 people)

Altered taste. Reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling sensations (paraesthesia), or pale or yellowish skin). Your doctor may carry out certain tests to determine the cause of your symptoms, as some of these may also be caused by diabetes or other unrelated health problems.

Very rare side effects (may affect up to 1 in 10,000 people)

Lactic acidosis. This is a very rare but serious complication, particularly if the kidneys are not functioning properly. The symptoms of lactic acidosis are non-specific (see section “Warnings and precautions”).
Abnormal liver function tests or hepatitis (inflammation of the liver; may cause fatigue, loss of appetite, weight loss, with or without yellowing of the skin or whites of the eyes). If you experience such symptoms, stop taking Glucophage and contact your doctor;
Skin reactions such as redness of the skin (erythema), itching, or itchy rash (urticaria).

Children and adolescents
Limited data in children and adolescents have shown that adverse events were similar in nature and severity to those reported in adults.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glucophage

Keep this medicine out of the sight and reach of children. If a child is being treated with Glucophage, parents and caregivers must supervise the use of this medicine.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton, bottle, or blister after "EXP". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Glucophage contains

The active substance is metformin hydrochloride. One Glucophage 500 mg film-coated tablet contains 500 mg of metformin hydrochloride, equivalent to 390 mg of metformin base.
The other ingredients are povidone K 30, magnesium stearate, hypromellose.

Description of the appearance of Glucophage and contents of the pack
Glucophage 500 mg film-coated tablets are white, circular, and convex in shape.
The tablets are available in blister packs containing 1 (x100), 9, 20, 21, 30, 40, 50, 56, 60, 84, 90, 100, 120, 200, 500, 600 or 1000 tablets, and in plastic bottles with child-resistant closures containing 21, 30, 40, 50, 60, 100, 120, 300, 400, 500, 600 or 1000 tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Bruno Farmaceutici S.p.A.
Via delle Ande, 15
00144 Rome
Italy

Manufacturer
Merck Santé s.a.s.
2 rue du Pressoir Vert
45400 Semoy
France
or
Merck S.L.
Poligono Merck
Mollet Del Vallès 08100 Barcelona
Spain

This medicinal product is authorized in the European Economic Area countries under the following names:
Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Latvia, Luxembourg, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Sweden, United Kingdom (Northern Ireland): Glucophage
Hungary: Merckformin

Package leaflet: Information for the user

GLUCOPHAGE 850 mg film-coated tablets

metformin hydrochloride
Please read this entire leaflet carefully before taking this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, consult your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet

What Glucophage is and what it is used for
What you need to know before taking Glucophage
How to take Glucophage
Possible side effects
How to store Glucophage
Contents of the pack and other information

1. What Glucophage is and what it is used for

Glucophage contains metformin, a medicine used to treat diabetes. It belongs to a group of
active substances known as biguanides.
Insulin is a hormone produced by the pancreas that enables the body to absorb glucose
(sugar) from the blood. The body uses glucose to produce energy or stores it for future use.
If you have diabetes, your pancreas does not produce enough insulin, or your body is unable
to use the insulin it produces effectively. This leads to high levels of glucose in the blood. Glucophage helps lower blood glucose, bringing it to a level as close to normal as possible.
If you are an overweight adult, taking Glucophage over a long period of time also helps reduce the risk of diabetes-related complications. Glucophage has been associated with both stabilization and modest body weight loss.
Glucophage is used to treat patients with type 2 diabetes (also called "non-insulin-dependent diabetes") when diet and exercise alone have not been sufficient to control blood glucose levels. It is particularly used in overweight patients.
Adults may take Glucophage alone or in combination with other antidiabetic medicines (oral medications or insulin).
Children aged 10 years and older and adolescents may take Glucophage alone or in combination with insulin.

2. What you should know before taking Glucophage

Do not take Glucophage

if you are allergic (hypersensitive) to metformin or any of the other ingredients of this medicine (listed in section 6);
if you have liver problems;
if you have severely reduced kidney function;
if you have uncontrolled diabetes, for example with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called 'ketone bodies' build up in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusually fruity odour;
if your body has lost too much water (dehydration), for example due to prolonged or severe diarrhoea or if you have vomited repeatedly. Dehydration can cause kidney problems which may increase your risk of lactic acidosis (see section “Warnings and precautions”);
if you have a severe infection, such as one affecting the lungs, bronchial system or kidneys. Severe infections can cause kidney problems which may increase your risk of lactic acidosis (see section “Warnings and precautions”);
if you are being treated for acute heart failure or have recently had a heart attack, if you have serious circulatory problems (such as shock) or breathing difficulties. These conditions may cause inadequate oxygen supply to tissues, increasing your risk of lactic acidosis (see section “Warnings and precautions”);
if you drink large amounts of alcohol.

If you are in any of the above conditions, consult your doctor before starting this medicine.
Make sure to seek medical advice if:

you are scheduled for tests such as X-rays or diagnostic scans requiring injection of iodine-containing contrast agents into the bloodstream;
you are scheduled for surgery.

You must stop taking Glucophage for a certain period before and after such tests or surgery. Your doctor will decide whether you need alternative treatment during this time. It is important that you follow your doctor’s instructions precisely.

Warnings and precautions
Risk of lactic acidosis
Glucophage may cause a very rare but serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is also increased by uncontrolled diabetes, severe infections, prolonged fasting, alcohol consumption, dehydration (see below for further information), liver problems, and any other medical condition in which a part of the body is deprived of oxygen (such as severe acute heart disease).
If you have any of the medical conditions listed above, consult your doctor for further instructions.

Temporarily stop taking Glucophage if you have a medical condition that may lead to dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, exposure to heat, or if you are drinking less fluid than usual. Consult your doctor for further instructions.

If you experience any of the symptoms of lactic acidosis, stop taking Glucophage immediately and contact your doctor or the nearest hospital, as lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

vomiting
stomach ache (abdominal pain)
muscle cramps
a general feeling of discomfort associated with severe fatigue
difficulty breathing
reduced body temperature (hypothermia) and slower heart rate.

Lactic acidosis is a medical emergency and must be treated in hospital.

Contact your doctor immediately for further instructions if:

you know you have a hereditary genetic disease affecting mitochondria (the components that produce energy within cells), such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes) or Maternal Inherited Diabetes and Deafness (MIDD);
you experience any of the following symptoms after starting metformin: seizures, reduced cognitive function, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

If you are undergoing major surgery, you must stop taking Glucophage during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Glucophage. Glucophage alone does not cause hypoglycaemia (low blood glucose levels). However, if you take Glucophage together with other diabetes medicines that can cause hypoglycaemia (such as sulfonylureas, insulin, meglitinides), there is a risk of hypoglycaemia. If you experience symptoms of hypoglycaemia such as weakness, dizziness, increased sweating, rapid heartbeat, vision disturbances, or difficulty concentrating, it is usually helpful to eat or drink something containing sugar.

During treatment with Glucophage, your doctor will check your kidney function at least annually, and more frequently if you are elderly and/or have impaired kidney function.

Other medicines and Glucophage
If you are due to receive an injection of iodine-containing contrast agents into the bloodstream, for example during X-rays or diagnostic scans, you must stop taking Glucophage before and after the test. Your doctor will decide when you should stop and when you can restart treatment with Glucophage.

Inform your doctor if you are taking, have recently taken, or might take any other medicine. You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust the dose of Glucophage. It is particularly important to mention the use of:

medicines that increase urine production (diuretics);
medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib);
certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists);
beta-2 agonists such as salbutamol or terbutaline (used to treat asthma);
corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma);
medicines that may alter the amount of Glucophage in the blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib);
other medicines used to treat diabetes.

Glucophage and alcohol
Avoid excessive consumption of alcohol and alcohol-containing medicines during treatment with Glucophage, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine so that your treatment can be adjusted if necessary, or your blood glucose levels monitored.
This medicine is not recommended if you are breastfeeding or intend to breastfeed your baby.

Driving and using machines
Glucophage alone does not cause hypoglycaemia (low blood glucose levels). This means it does not impair your ability to drive or operate machinery.
However, take particular care if you take Glucophage together with other diabetes medicines that can cause hypoglycaemia (such as sulfonylureas, insulin, meglitinides). Symptoms of hypoglycaemia include weakness, dizziness, increased sweating, rapid heartbeat, vision disturbances, or difficulty concentrating. Do not drive or operate machinery if you begin to experience these symptoms.

3. How to take Glucophage

Always take this medicine exactly as instructed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
Glucophage cannot replace the benefits of a healthy lifestyle. Continue to follow all the dietary
advice given to you by your doctor and exercise regularly.
Recommended dose
Children aged 10 years and older and adolescents usually start with 500 mg or 850 mg of Glucophage once daily. The maximum daily dose is 2000 mg taken in 2 or 3 divided doses. Treatment of children aged between 10 and 12 years is recommended only on specific advice of the doctor, as experience in this age group is limited.
Adults usually start with 500 mg or 850 mg of Glucophage two or three times daily. The maximum daily dose is 3000 mg taken in 3 divided doses.
If you have reduced kidney function, your doctor may prescribe a lower dose.
If you are also taking insulin, your doctor will advise you on how to start taking Glucophage.
Monitoring

Your doctor will carry out regular blood glucose tests and adjust your dose of Glucophage according to your blood sugar levels. Consult your doctor regularly. This is particularly important for children and adolescents or if you are elderly.
Your doctor will also check at least once a year how well your kidneys are working. You may need more frequent checks if you are elderly or if your kidneys do not function normally.

If you take one dose per day, take it in the morning (with breakfast);
If you take two doses per day, take them in the morning (with breakfast) and in the evening (with dinner);
If you take three doses per day, take them in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If, after some time, you think the effect of Glucophage is too strong or too weak,
consult your doctor or pharmacist.
If you take more Glucophage than you should
If you have taken more Glucophage than you should, you may develop lactic acidosis. Symptoms
of lactic acidosis are non-specific and include vomiting, stomach ache (abdominal pain) with muscle cramps, general feeling of illness with extreme tiredness and difficulty breathing.
Further symptoms include reduced body temperature and heart rate. If you experience any of these symptoms, seek immediate medical attention, as lactic acidosis can lead to coma. Stop taking Glucophage and contact a doctor or the nearest hospital immediately.
If you forget to take Glucophage
Do not take a double dose to make up for a forgotten dose. Take the next dose at the scheduled time.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may occur:
Glucophage may cause a very rare (may occur in up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Glucophage and must immediately contact your doctor or go to the nearest hospital, because lactic acidosis can lead to coma.

Very common side effects (may affect more than 1 in 10 people)

Gastrointestinal problems such as nausea, vomiting, diarrhoea, stomach ache (abdominal pain), and loss of appetite. These side effects occur more frequently at the beginning of treatment with Glucophage. It may help to divide the doses throughout the day and to take Glucophage during or immediately after meals. If symptoms persist, stop taking Glucophage and consult your doctor.

Common side effects (may affect up to 1 in 10 people)

Altered taste. Reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling sensations (paraesthesia), or pale or yellowish skin). Your doctor may prescribe certain tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.

Very rare side effects (may affect up to 1 in 10,000 people)

Lactic acidosis. This is a very rare but serious complication, particularly if the kidneys are not functioning properly. Symptoms of lactic acidosis are non-specific (see section “Warnings and precautions”);
Abnormalities in liver function tests or hepatitis (inflammation of the liver; may cause fatigue, loss of appetite, weight loss, with or without yellowing of the skin or whites of the eyes). If you experience such symptoms, stop taking Glucophage and contact your doctor;
Skin reactions such as redness of the skin (erythema), itching, or itchy rash (urticaria).

Children and adolescents
Limited data in children and adolescents have shown that adverse events were similar in nature and severity to those reported in adults.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glucophage

Keep this medicine out of the sight and reach of children. If a child is being treated with Glucophage, parents and caregivers must supervise the use of this medicine.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton, bottle, or blister after "EXP". The expiry date refers to the last day of that month.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Glucophage contains

The active substance is metformin hydrochloride. One Glucophage 850 mg film-coated tablet contains 850 mg of metformin hydrochloride, equivalent to 662.9 mg of metformin base;
The other components are povidone K 30, magnesium stearate, hypromellose.
Description of the appearance of Glucophage and contents of the pack

Glucophage 850 mg film-coated tablets are white, circular and convex in shape.
The tablets are available in blister packs containing 1 (x100), 8, 9, 10, 14, 20, 21, 30, 40, 50, 56, 60, 84, 90, 100, 120, 300, 600 or 1000 tablets, and in plastic bottles with child-resistant closure containing 30, 60, 200, 300 or 600 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Bruno Farmaceutici S.p.A.
Via delle Ande, 15
00144 Rome
Italy

Manufacturer
Merck Santé s.a.s.
2 rue du Pressoir Vert
45400 Semoy
France
or
Merck S.L.
Poligono Merck
Mollet Del Vallès
08100 Barcelona
Spain

This medicinal product is authorised in the European Economic Area countries under the following names:
Spain: Dianben
Austria, Belgium, Bulgaria, Cyprus, Czech Republic, France, Germany, Greece, Iceland, Ireland, Italy, Luxembourg, Norway, Poland, Romania, Slovakia, Slovenia, Sweden, United Kingdom (Northern Ireland): Glucophage
Hungary: Merckformin
Portugal: Risidon

Package leaflet: Information for the user

GLUCOPHAGE 1000 mg film-coated tablets

metformin hydrochloride
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet

What Glucophage is and what it is used for
What you need to know before taking Glucophage
How to take Glucophage
Possible side effects
How to store Glucophage
Contents of the pack and other information

1. What Glucophage is and what it is used for

Glucophage contains metformin, a medicine used to treat diabetes. It belongs to a group of
active substances called biguanides.
Insulin is a hormone produced by the pancreas that enables the body to absorb glucose
(sugar) from the blood. The body uses glucose to produce energy or stores it for future use.
If you have diabetes, your pancreas does not produce enough insulin, or your body cannot
use the insulin it produces effectively. This leads to high levels of glucose in the blood. Glucophage helps lower blood glucose, bringing it to as near-normal a level as possible.
If you are an overweight adult, taking Glucophage over a long period of time also helps reduce the risk of diabetes-related complications. Glucophage has been associated with both stabilization and modest reduction in body weight.
Glucophage is used to treat patients with type 2 diabetes (also called “non-insulin-dependent diabetes”) when diet and exercise alone have not been sufficient to control blood glucose levels. It is particularly used in overweight patients.
Adults may take Glucophage alone or in combination with other antidiabetic medicines (oral medications or insulin).
Children aged 10 years and older and adolescents may take Glucophage alone or in combination with insulin.

2. What you should know before taking Glucophage

Do not take Glucophage

if you are allergic (hypersensitive) to metformin or to any of the other ingredients of this medicine (listed in section 6).
if you have liver problems.
if you have severely reduced kidney function.
if you have uncontrolled diabetes, for example with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called 'ketone bodies' accumulate in the blood and may lead to diabetic pre-coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness and breath with an unusual fruity odour.
if your body has lost too much water (dehydration), for example due to prolonged or severe diarrhoea or if you have vomited repeatedly. Dehydration can cause kidney problems which may increase your risk of lactic acidosis (see section “Warnings and precautions”).
if you have a severe infection, such as an infection affecting the lungs, bronchial system or kidneys. Severe infections can cause kidney problems which may increase your risk of lactic acidosis (see section “Warnings and precautions”).
if you are being treated for acute heart failure or have recently had a heart attack, or if you have serious circulatory problems (such as shock) or breathing difficulties. These conditions may cause tissue hypoxia (lack of oxygen supply to tissues), which may increase your risk of lactic acidosis (see section “Warnings and precautions”).
if you drink large amounts of alcohol.

If you are in any of the above conditions, consult your doctor before starting this medicine.
Make sure to ask your doctor for advice if:

you are scheduled for tests such as X-rays or diagnostic scans requiring injection of iodinated contrast agents into the bloodstream
you are scheduled for surgery

Warnings and precautions
Risk of lactic acidosis
Glucophage may cause a very rare but serious side effect called lactic acidosis, particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is also increased by uncontrolled diabetes, severe infections, prolonged fasting, alcohol consumption, dehydration (see below for further information), liver problems, and any medical condition causing tissue hypoxia (such as severe acute heart disease).
If you have any of the medical conditions listed above, consult your doctor for further instructions.

Temporarily stop taking Glucophage if you develop a medical condition that may lead to dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, heat exposure, or reduced fluid intake. Consult your doctor for further instructions.

If you experience any symptoms of lactic acidosis, stop taking Glucophage immediately and seek medical attention at once from your doctor or the nearest hospital, as lactic acidosis may lead to coma.
Symptoms of lactic acidosis include:

vomiting
stomach ache (abdominal pain)
muscle cramps
a general feeling of malaise associated with severe fatigue
difficulty breathing
low body temperature (hypothermia) and slow heart rate

Lactic acidosis is a medical emergency and must be treated in hospital.

Seek immediate medical advice if:

you know you have a hereditary genetic mitochondrial disease (components responsible for energy production within cells), such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD);
you develop any of the following symptoms after starting metformin: seizures, cognitive decline, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

If you are undergoing major surgery, you must stop taking Glucophage during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Glucophage. Glucophage alone does not cause hypoglycaemia (low blood glucose levels). However, if you take Glucophage together with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylureas, insulin, meglitinides), there is a risk of hypoglycaemia. If you experience symptoms of hypoglycaemia such as weakness, dizziness, increased sweating, rapid heartbeat, blurred vision or difficulty concentrating, it is usually helpful to eat or drink something containing sugar.

During treatment with Glucophage, your doctor will check your kidney function at least once a year, and more frequently if you are elderly and/or have impaired kidney function.

Other medicines and Glucophage
If you are due to receive an injection of iodinated contrast agents into the bloodstream, for example during X-rays or diagnostic scans, you must stop taking Glucophage before and after the procedure. Your doctor will decide when to stop and when you can resume treatment with Glucophage.

Inform your doctor if you are taking, have recently taken or might take any other medicines. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Glucophage. It is particularly important to mention the use of:

medicines that increase urine production (diuretics).
medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib).
certain medicines used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).
beta-2 agonists such as salbutamol or terbutaline (used to treat asthma).
corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma).
medicines that may alter the blood levels of Glucophage, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).
other medicines used to treat diabetes.

Glucophage and alcohol
Avoid excessive consumption of alcohol and medicines containing alcohol during treatment with Glucophage, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine so that necessary adjustments to your treatment can be made or your blood glucose levels monitored.
This medicine is not recommended if you are breastfeeding or intend to breastfeed your baby.

Driving and using machines
Glucophage alone does not cause hypoglycaemia (low blood glucose levels). This means it does not impair your ability to drive or operate machinery.
However, take particular care if you take Glucophage together with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylureas, insulin, meglitinides). Symptoms of hypoglycaemia include weakness, dizziness, increased sweating, rapid heartbeat, blurred vision or difficulty concentrating. Do not drive or operate machinery if you begin to experience these symptoms.

3. How to take Glucophage

Always take this medicine exactly as instructed by your doctor. If you have any doubts,
consult your doctor or pharmacist.
Glucophage cannot replace the benefits of a healthy lifestyle. Continue to follow all dietary
advice given by your doctor and exercise regularly.
Recommended dose
Children aged 10 years and older and adolescents usually start with 500 mg or 850 mg of Glucophage once daily. The maximum daily dose is 2000 mg taken in 2 or 3 divided doses. Treatment of children aged between 10 and 12 years is recommended only on specific medical advice, as experience in this age group is limited.
Adults usually start with 500 mg or 850 mg of Glucophage two or three times daily. The maximum daily dose is 3000 mg taken in 3 divided doses.
If you have reduced kidney function, your doctor may prescribe a lower dose.
If you are also taking insulin, your doctor will advise you on how to start taking Glucophage.
Monitoring

Your doctor will carry out regular blood glucose tests and adjust your Glucophage dose according to your blood sugar levels. Consult your doctor regularly. This is particularly important for children and adolescents or if you are elderly.
Your doctor will also check your kidney function at least once a year. You may need more frequent checks if you are elderly or if your kidneys do not function normally.

How to take Glucophage
Take the tablets during or after meals. This will help you avoid gastrointestinal side effects.
Do not crush or chew the tablets. Swallow each tablet with a glass of water.

If you take one dose per day, take it in the morning (with breakfast)
If you take two divided doses per day, take them in the morning (with breakfast) and in the evening (with dinner)
If you take three divided doses per day, take them in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If, after some time, you think the effect of Glucophage is too strong or too weak,
consult your doctor or pharmacist.
If you take more Glucophage than you should
If you have taken more Glucophage than you should, you may develop lactic acidosis. Symptoms
of lactic acidosis are non-specific and include vomiting, stomach pain (abdominal pain) with muscle cramps, general feeling of malaise with extreme fatigue, and breathing difficulties.
Further symptoms include lowered body temperature and slowed heart rate. If
you experience any of these symptoms, seek immediate medical attention, as lactic acidosis can lead to coma. Stop taking Glucophage and contact a doctor or the nearest hospital immediately.
If you forget to take Glucophage
Do not take a double dose to make up for a forgotten dose. Take the next dose at the scheduled time.
If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects may occur:
Glucophage may cause a very rare (may occur in up to 1 in 10,000 people) but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Glucophage and must immediately contact your doctor or go to the nearest hospital, because lactic acidosis can lead to coma.

Very common side effects (may affect more than 1 in 10 people)

Gastrointestinal problems such as nausea, vomiting, diarrhoea, stomach ache (abdominal pain), and loss of appetite. These side effects occur most frequently at the beginning of Glucophage treatment. It may help to divide the daily dose throughout the day and to take Glucophage during or immediately after meals. If symptoms persist, stop taking Glucophage and consult your doctor.

Common side effects (may affect up to 1 in 10 people)

Altered taste.
Reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), red and sore tongue (glossitis), tingling sensations (paraesthesias), or pale or yellowish skin). Your doctor may prescribe certain tests to determine the cause of symptoms, as some of these may also be caused by diabetes or other unrelated health problems.

Very rare side effects (may affect up to 1 in 10,000 people)

Lactic acidosis. This is a very rare but serious complication, particularly if the kidneys are not functioning properly. Symptoms of lactic acidosis are non-specific (see section “Warnings and precautions”).
Abnormal liver function tests or hepatitis (liver inflammation; may cause fatigue, loss of appetite, weight loss, with or without yellowing of the skin or whites of the eyes). If you experience such symptoms, stop taking Glucophage and contact your doctor;
Skin reactions such as redness of the skin (erythema), itching, or itchy rash (urticaria).

Children and adolescents
Limited data in children and adolescents have shown that adverse events were similar in nature and severity to those reported in adults.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at the website
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Glucophage

Keep this medicine out of the sight and reach of children. If a child is being treated with Glucophage, parents and caregivers must supervise the use of this medicine.
This medicine does not require any special storage conditions.
Do not use this medicine after the expiry date stated on the carton, bottle or blister after "EXP". The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What Glucophage contains

The active substance is metformin hydrochloride. One Glucophage 1000 mg film-coated tablet contains 1000 mg of metformin hydrochloride, equivalent to 780 mg of metformin base.
The other components are povidone K 30, magnesium stearate, hypromellose, macrogol 400 and macrogol 8000.

Description of the appearance of Glucophage and contents of the pack
Glucophage 1000 mg film-coated tablets are white, oval-shaped and biconvex, with a break line on both sides of the tablet and the imprint '1000' on one side, measuring 19 mm x 10.5 mm and 6.4 mm in height. The tablet can be divided into two equal doses.
The tablets are available in blister packs containing 1 (x30), 20, 30, 50, 60, 90, 100, 120, 180 or 600 tablets, or in plastic bottles with child-resistant closures containing 20, 30, 50, 60, 90, 100, 120, 180 or 600 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Bruno Farmaceutici S.p.A.
Via delle Ande, 15
00144 Rome
Italy

Manufacturer
Merck Santé s.a.s.
2 rue du Pressoir Vert
45400 Semoy
France
or
Merck S.L.
Poligono Merck
Mollet Del Vallès 08100 Barcelona
Spain

This medicinal product is authorised in the European Economic Area countries under the following names:
Austria, Bulgaria, Cyprus, Czech Republic, Finland, France, Germany, Greece, Iceland, Ireland, Italy, Latvia, Norway, Poland, Romania, Slovakia, Slovenia, Sweden: Glucophage
Hungary: Merckformin
Portugal: Risidon