Glucophage 1000 mg

Package leaflet: Information for the user

GLUCOPHAGE 1000 mg, 1000 mg, film-coated tablets
(Metformini hydrochloridum)
Please read all of 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 further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Glucophage is and what it is used for
2. What you need to know before taking Glucophage
3. How to take Glucophage
4. Possible side effects
5. How to store Glucophage
6. Contents of the pack and other information

1. What Glucophage is and what it is used for

Glucophage contains metformin, a medicine used in the treatment of diabetes. It belongs to a group of medicines called biguanides.
Insulin is a hormone produced by the pancreas that enables the body to take up glucose (sugar) from the blood. The body uses glucose to produce energy or stores it for later use.
In people with diabetes, the pancreas does not produce enough insulin or the body cannot properly use the insulin it produces. This leads to abnormally high levels of glucose in the blood. Glucophage helps reduce blood glucose levels to values as close to normal as possible.
In overweight adults, long-term use of Glucophage also reduces the risk of diabetes-related complications. Treatment with Glucophage is associated with stable body weight or even moderate weight reduction.
Glucophage is used in the treatment of patients with type 2 diabetes (also known as "non-insulin-dependent diabetes") in whom adequate control of blood glucose levels cannot be achieved by diet and physical activity alone. It is particularly used in patients who are overweight.
Adults may take Glucophage either as monotherapy or in combination with other antidiabetic medicines (oral medications or insulin).
Children aged 10 years and older and adolescents may take Glucophage either as monotherapy or in combination with insulin.

2. Important information before using Glucophage

When not to use Glucophage:

• if the patient is allergic to metformin or any of the other ingredients of this medicine (listed in section 6),
• in case of liver dysfunction,
• if the patient has significantly reduced kidney function,
• if the patient has uncontrolled diabetes, for example severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, sudden 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 which may lead to diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or an unusual fruity odour of the breath,
• in case of excessive fluid loss from the body (dehydration), e.g. due to prolonged or severe diarrhoea or repeated vomiting. Dehydration may lead to impaired kidney function, which may increase the risk of lactic acidosis (see below "Warnings and precautions"),
• in case of severe infection, e.g. pneumonia, bronchitis or kidney infection. Severe infections may lead to impaired kidney function, which may increase the risk of lactic acidosis (see below "Warnings and precautions"),
• in case of treatment for acute heart failure or recent myocardial infarction, severe circulatory disorders (e.g. shock) or breathing difficulties. These conditions may cause tissue hypoxia, which may increase the risk of lactic acidosis (see below "Warnings and precautions"),
• in case of alcohol abuse.

If any of the above situations apply, the patient should consult a doctor before using this medicine.
It is essential to consult a doctor if:

• a radiological examination or a procedure requiring intravenous injection of an iodine-containing contrast agent is required,
• a major surgical procedure is planned.

Glucophage must be discontinued for a certain period before and after such an examination or surgical procedure. The doctor will decide whether alternative treatment is necessary during this time. It is important to strictly follow the doctor's instructions.

Warnings and precautions
Risk of lactic acidosis
Glucophage may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has impaired kidney function. The risk of lactic acidosis increases in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), liver dysfunction, and any medical conditions in which part of the body is inadequately supplied with oxygen (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, medical advice should be sought for further instructions.

Glucophage should be temporarily discontinued if the patient develops a medical condition associated with dehydration (significant fluid loss from the body), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. Medical advice should be sought.

Glucophage should be discontinued and the patient should immediately contact a doctor or the nearest hospital if any symptoms of lactic acidosis occur, as this condition may lead to coma.

Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general malaise associated with profound fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.

Immediate medical advice should be sought if:

• the patient has a genetically inherited disease affecting mitochondria (cellular energy-producing structures), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD),
• after starting metformin, the patient develops any of the following symptoms: seizures, worsening cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

If the patient is undergoing a major surgical procedure, Glucophage must not be taken during the procedure and for some time afterwards. The doctor will decide when the patient should stop and restart treatment with Glucophage.

Glucophage does not cause hypoglycaemia (low blood glucose levels).
However, if Glucophage is used in combination with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylureas, insulin, or meglitinides), there is a risk of hypoglycaemia. If symptoms of hypoglycaemia occur, such as weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances or difficulty concentrating, eating or drinking a sugary food or drink usually helps.

During treatment with Glucophage, the doctor will monitor kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.

Glucophage and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example during an X-ray or CT scan, Glucophage must be discontinued before or at the latest at the time of injection. The doctor will decide when the patient should stop and restart treatment with Glucophage.

Inform the doctor about all medicines currently taken, recently taken, or planned for use. The patient may require more frequent monitoring of blood glucose levels and kidney function, or a dose adjustment of Glucophage. It is especially important to inform the doctor about the following medicines:

• diuretics (medicines that increase urine production),
• 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 adrenergic receptor agonists, such as salbutamol or terbutaline (used in the treatment of asthma),
• corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma),
• medicines that may alter Glucophage blood levels, especially if the patient has impaired kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib),
• other medicines used in the treatment of diabetes.

Glucophage and alcohol
Excessive alcohol consumption should be avoided during treatment with Glucophage, as it may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult her doctor regarding any necessary changes in treatment or monitoring of blood glucose levels.
This medicine is not recommended for patients who are breastfeeding or planning to breastfeed.

Driving and operating machinery
Glucophage does not cause hypoglycaemia (low blood glucose levels). This means that it does not affect the patient's ability to drive or operate machinery.
However, particular caution is required if Glucophage is used together with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylureas, insulin, meglitinides). Symptoms of hypoglycaemia include: weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances or difficulty concentrating. If such symptoms occur, the patient should not drive or operate machinery.

3. How to take Glucophage

This medicine should always be taken exactly as prescribed by your doctor. If you are unsure, you should
consult your doctor or pharmacist.
Glucophage does not replace the benefits of a healthy lifestyle. You should continue to follow all your
doctor's advice regarding diet and regular physical activity.
Recommended dose
Children aged 10 years and adolescents: treatment usually starts with a dose of 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 10 to 12 years should only be undertaken on special recommendation by a doctor, as
experience with Glucophage in this age group is limited.
Adults: treatment usually starts with a dose of 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 impaired kidney function, your doctor may prescribe a lower dose.
If you are also taking insulin, your doctor will advise you on how to start treatment with Glucophage.
Monitoring of treatment

• Your doctor will order regular blood glucose tests and adjust the dose of Glucophage according to your blood glucose levels. You should attend regular check-up appointments with your doctor. This is particularly important for children, adolescents, and elderly patients.
• Your doctor will check your kidney function at least once a year. More frequent monitoring may be necessary for elderly patients or if your kidneys are not functioning properly.

How to take Glucophage
Glucophage should be taken during or immediately after a meal. This helps to avoid gastrointestinal
side effects.
Do not crush or chew the tablets. Swallow the tablet whole with a glass of water.

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

If at any time you feel that the effect of the medicine is too strong or too weak, you should consult your
doctor or pharmacist.
Taking more Glucophage than you should
If you take more Glucophage than prescribed, lactic acidosis may occur. Symptoms of lactic acidosis
are non-specific and include vomiting, abdominal pain (pain in the abdominal cavity) with muscle
cramps, general malaise accompanied by severe fatigue and difficulty breathing. Other symptoms include
lowered body temperature and slowed heart rate. If any of these symptoms occur, you must seek
immediate medical help, as lactic acidosis can lead to coma. You must stop taking Glucophage
immediately and contact your doctor or go to the nearest hospital.
If you forget to take Glucophage
Do not take a double dose to make up for a missed dose. Take the next dose at the usual time.
If you have any further 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 everyone will experience them.
The side effects that may occur are listed below.
Glucophage may very rarely cause (may occur in up to 1 patient in 10,000) a very serious side effect known as lactic acidosis (see section “Warnings and precautions”). If this occurs in a patient, treatment with Glucophage must be stopped and immediate contact must be made with a doctor or the nearest hospital, as lactic acidosis may lead to coma.

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

• Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain (pain in the abdominal cavity), loss of appetite. These side effects most commonly occur at the beginning of Glucophage treatment. It may help to divide the daily dose into several smaller doses taken throughout the day and to take Glucophage with a meal or immediately after a meal. If symptoms do not resolve, Glucophage should be discontinued and the doctor informed.

Common side effects (may affect less than 1 in 10 people)

• Taste disturbances.
• Reduced or low blood levels of vitamin B_{12} (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling sensations (paraesthesiae), or pale or yellow skin). Your doctor may order several tests to determine the cause of symptoms, as some of them may also be caused by diabetes or other health problems unrelated to diabetes.

Very rare side effects (may affect less than 1 in 10,000 people)

• Lactic acidosis. This is a very rare but serious complication, particularly when kidneys are not functioning properly. Symptoms of lactic acidosis are non-specific (see section “Warnings and precautions”).
• Abnormal liver function test results or symptoms of hepatitis (associated with fatigue, loss of appetite and weight loss, with or without yellowing of the skin and whites of the eyes). If such symptoms occur, Glucophage should be discontinued and the doctor informed.
• Skin reactions such as skin redness (erythema), itching or itchy rash (urticaria).

Children and adolescents
Limited data in children and adolescents indicate that the side effects experienced are of similar nature and severity to those observed in adults.

Reporting of side effects
If any side effects occur, including any unlisted side effects, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products,
Al. Jerozolimskie 181C
02-222 Warszawa
Tel.: +48 22 49 21 301
Fax: +48 22 4921 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Glucophage

Keep this medicine out of sight and reach of children. If Glucophage is being used in a child,
it is recommended that parents or caregivers supervise the treatment.
No special storage instructions apply for this medicine.
Do not use this medicine after the expiry date stated on the carton after the word "EXP".
The expiry date refers to the last day of the stated month.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist
how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack 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.
• The other ingredients are: povidone K 30, magnesium stearate, and components of the coating (Opadry clear YS-1-7472): hypromellose, polyethylene glycol 400 and polyethylene glycol 8000.

What Glucophage looks like and contents of the pack
Glucophage 1000 mg film-coated tablets are white, oval, biconvex, with a breakline on both sides of the tablet and engraved with "1000" on one side.
The tablet can be divided into halves.
Each pack contains 30, 60 or 120 film-coated tablets.
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Merck Sante s.a.s.
37, rue Saint-Romain
69008 Lyon
France
(logo of the marketing authorisation holder)
Manufacturer
Merck Sante s.a.s.
2, rue du Pressoir Vert
45400 Semoy
France
Merck S.L.
Poligono Merck
Mollet Del Vallés 08100 Barcelona
Spain
(for Greece only)
Petsiavas S.A
Agion Anargiron 21, Kaliftaki
Kato Kifisia Attiki 14564
Greece
This medicinal product is authorised in the European Economic Area member states 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