Metformin Mille

Patient Information Leaflet: Information for the User

Metforalmille

1000 mg film-coated tablets
For use in children aged 10 years and above and in adults
Metformin hydrochloride
Generic medicine
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 effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Metforalmille is and what it is used for

What Metforalmille is
Metforalmille contains metformin, a medicine used to treat diabetes. It belongs to a group of
medicines called biguanides.
Insulin is a hormone produced by the pancreas that enables the body to take 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 results in high levels of glucose in the blood. Metforalmille helps to reduce blood glucose levels to as near normal as possible.
If you are an overweight adult, taking Metforalmille over a long period of time also helps to reduce the
risk of diabetes-related complications. Metforalmille is associated with stabilization or modest weight loss.

What Metforalmille is used for
Metforalmille is used to treat patients with type 2 diabetes (also known as non-insulin-dependent
diabetes) when diet and exercise alone are not sufficient to control blood glucose levels. It is
particularly used in overweight patients.
Adults may take Metforalmille alone or in combination with other antidiabetic medicines (oral
medicines or insulin).
Children aged 10 years and older and adolescents may take Metforalmille alone or in combination with insulin.

2. What you need to know before taking Metforalmille

Do not take Metforalmille

• if you are allergic (hypersensitive) to metformin hydrochloride or to any of the other ingredients of this medicine (listed in section 6)
• if you have severely reduced kidney function
• if you have liver problems
• if you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see below “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, or breath with an unusually fruity odour
• if your body has lost too much water (dehydration), such as in case of persistent or severe diarrhoea, or if you have vomited several times in succession. Dehydration can lead to kidney problems which may put you at risk of lactic acidosis (see “Warnings and precautions” below)
• if you have a severe infection, for example an infection affecting the lung, bronchial system or kidney. Severe infections can lead to kidney problems which may put you at risk of lactic acidosis (see “Warnings and precautions” below)
• if you are being treated for acute heart failure or have recently had a heart attack, if you suffer from serious circulatory problems (such as shock) or have breathing difficulties. This may lead to inadequate oxygen supply to tissues, which may put you at risk of developing lactic acidosis (see “Warnings and precautions” below)
• if you consume significant amounts of alcohol

If any of the above conditions apply to you, talk to your doctor before starting to take this medicine.

Warnings and precautions

Talk to your doctor before taking Metforalmille.

Ask your doctor for advice if

• you need to undergo examinations such as X-rays or CT scans involving the injection into the bloodstream of iodinated contrast agents
• you are scheduled for major surgery.

You must stop taking Metforalmille during the procedure and for a certain period of time afterwards. Your doctor will decide when you should stop and when you should restart treatment with Metforalmille. It is important that you follow your doctor’s instructions exactly.

Risk of lactic acidosis

Metforalmille may cause a very rare but very serious side effect called lactic acidosis, particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterized by reduced oxygen supply to part of the body (such as in cases of severe acute heart disease).

If you have any of the medical conditions described above, consult your doctor for further information.

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

If you experience any symptoms of lactic acidosis, stop taking Metforalmille 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 malaise associated with severe fatigue,
• difficulty breathing,
• reduced body temperature and slower heartbeat.

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

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

Metforalmille alone does not cause hypoglycaemia (low blood glucose levels). However, if Metforalmille is taken 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, visual disturbances or difficulty concentrating, eating or drinking something containing sugar usually helps.

Other medicines and Metforalmille

If you need to receive an injection of an iodinated contrast agent into the bloodstream, for example for an X-ray or CT scan, you must stop taking Metforalmille before or during the injection. Your doctor will decide when you should stop and when you should restart treatment with Metforalmille (see section above “Ask your doctor for advice if”).

Tell your doctor if you are taking, have recently taken, or might take any other medicines. You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust your Metforalmille dose.

It is particularly important to mention the following:

• medicines that increase urine production (diuretics)
• medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• some medicines for treating 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)
• other medicines used in the treatment of diabetes
• medicines that may alter the amount of Metforalmille in the blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib)

Metforalmille and alcohol

Avoid excessive alcohol consumption during treatment with Metforalmille, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”), particularly if you have liver problems or are malnourished. This also applies to medicines containing alcohol.

Pregnancy and breastfeeding

During pregnancy, you will need insulin to treat diabetes.

If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine, so that your doctor can adjust your treatment.

This medicine is not recommended if you are breastfeeding.

Driving and using machines

Metforalmille alone does not cause hypoglycaemia (low blood glucose levels). This means it does not affect your ability to drive or use machines.

However, take particular care if you take Metforalmille together with other diabetes 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 you begin to experience any of these symptoms, do not drive or operate machinery.

3. How to take Metforalmille

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Metforalmille cannot replace the benefits of a healthy lifestyle. Continue to follow any dietary advice given by your doctor and maintain regular physical activity.

Recommended dose
The usual initial dose in adults is ½ tablet of Metforalmille (equivalent to 500 mg of metformin hydrochloride) 2–3 times daily, or 850 mg of metformin hydrochloride 2–3 times daily (this dosage is not available with Metforalmille).
The maximum daily dose is 1 tablet of Metforalmille taken 3 times a day.
If you have reduced kidney function, your doctor may prescribe a lower dose.

Use in children and adolescents
The usual initial dose in children aged 10 years and older and in adolescents is ½ tablet of Metforalmille (equivalent to 500 mg of metformin hydrochloride) once daily, or 850 mg of metformin hydrochloride once daily (this dosage is not available with Metforalmille).
The maximum daily dose is 1 tablet of Metforalmille twice daily. Treatment in children aged between 10 and 12 years is recommended only on the specific advice of your doctor, as experience in this age group is limited.
If you are also taking insulin, your doctor will advise you on how to start taking Metforalmille.

Monitoring

• Your doctor will regularly measure your blood glucose levels and adjust the dose of Metforalmille accordingly. Talk to your doctor regularly. This is particularly important for children, adolescents, and elderly patients.
• Your doctor will also check your kidney function at least once a year. More frequent monitoring may be needed if you are elderly or if your kidneys do not function properly.

How to split the Metforalmille film-coated tablet
The tablet can be divided into equal parts.
Due to its shape, the Metforalmille film-coated tablet can be easily and accurately split. The film-coated tablet may be divided either by hand, or by placing the tablet with the score line facing downwards on a flat, rigid surface and pressing with the thumb (see figure).

How to take the Metforalmille film-coated tablets
Take the tablets during or after a meal. This helps to avoid unwanted effects on digestion.
Do not break or chew the tablets. Swallow each tablet with a glass of water.

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

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

If you take more Metforalmille than you should
If you have taken more Metforalmille than you should, lactic acidosis may occur. Symptoms of lactic acidosis include vomiting, abdominal pain with muscle cramps, general feeling of malaise with profound fatigue and difficulty breathing. If any of these symptoms occur, you may require immediate medical treatment in a hospital, as lactic acidosis can lead to coma. Contact a doctor or the nearest hospital immediately.

If you forget to take Metforalmille
Do not take a double dose to make up for a missed dose. Take the next dose at your usual 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:
Metforalmille may cause a very rare (may affect up to 1 in 10,000 people) but serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking METFORALMILLE and seek immediate medical attention at the nearest doctor or hospital, because lactic acidosis can lead to coma.

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

• Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain, and loss of appetite. These side effects often occur at the beginning of treatment with Metforalmille. They can usually be relieved by spreading the doses throughout the day and taking the tablets during or immediately after meals. If symptoms persist, stop taking Metforalmille and consult your doctor.

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

• Altered taste.

Rare side effects (may affect up to 1 in 10,000 patients)

• Skin reactions such as redness (erythema), itching, or itchy rash (urticaria).
• Low levels of vitamin B12 in the blood.
• Abnormal liver function tests or hepatitis (liver inflammation; this may cause fatigue, loss of appetite, weight loss with or without yellowing of the skin or whites of the eyes). If you notice any of these effects, stop taking this medicine and consult your doctor.

Children and adolescents
Limited data in children and adolescents have shown that the nature and severity of side effects were similar to those reported in adults.

Reporting of side effects
If you experience any side effect, 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 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 Metforalmille

Keep this medicine out of the sight and reach of children. If Metforalmille is administered to children, parents and caregivers must supervise the use of this medicine.
Do not use this medicine after the expiry date which is stated on the blister pack and carton after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
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 Metforalmille contains
The active substance is metformin hydrochloride.
Each coated tablet contains 1000 mg of metformin hydrochloride (equivalent to 780 mg of
metformin).
The other components are: hypromellose, povidone K 25, magnesium stearate (Ph. Eur.) [vegetable],
macrogol 6000, titanium dioxide (E 171).

Description of the appearance of Metforalmille and the contents of the pack
White, oblong, biconvex tablets, with a break line on one side and a score line on the other side.
The tablet can be divided into two equal doses (for instructions on how to split the tablet, see section 3).
Metforalmille is available in packs of 10, 30, 60 and 120 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
LABORATORI GUIDOTTI S.p.A.
Via Livornese, 897
Pisa – La Vettola
Italy

Manufacturer
BERLIN-CHEMIE AG
Glienicker Weg 125
12489 Berlin
Germany
MENARINI - VON HEYDEN GmbH
Leipziger Strasse, 7-13
Dresden
Germany

This medicinal product is authorized in the European Economic Area countries under the following names:
Belgium Metformax 1000 mg film-coated tablets
Germany Siofor 1000
Estonia Metforal 1000 mg
Italy Metforalmille
Latvia Metforal 1000
Lithuania Metforal 1000 mg plėvele dengtos tabletės
Luxembourg Metformax 1000 mg comprimés pelliculés 1000 mg
Poland Siofor 1000
Slovakia Siofor 1000
Slovenia Siofor 1000 mg
Czech Republic Siofor
Hungary Meforal 1000