Patient Information Leaflet

GLUCOPHAGE UNIDIE 500 mg prolonged-release tablets, 750 mg prolonged-release tablets, 1000 mg prolonged-release tablets

Metformin hydrochloride
Please read all of this 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, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, because it could 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 UNIDIE is and what it is used for
What you need to know before taking GLUCOPHAGE UNIDIE
How to take GLUCOPHAGE UNIDIE
Possible side effects
How to store GLUCOPHAGE UNIDIE
Contents of the pack and other information

1. What GLUCOPHAGE UNIDIE is and what it is used for

GLUCOPHAGE UNIDIE contains the active substance metformin hydrochloride and belongs to a group
of medicines called biguanides, used in the treatment of diabetes.
GLUCOPHAGE UNIDIE is specially formulated to release the active substance slowly (prolonged-release tablets) and is used to treat type 2 diabetes mellitus (non-insulin-dependent diabetes) when diet and physical exercise alone have not been sufficient to control blood sugar (glucose) levels, and when immediate-release metformin doses are not effective.
Insulin is a hormone that enables the body's tissues to take glucose from the blood and use it to produce energy or store it for future use. People with type 2 diabetes mellitus either do not produce enough insulin in the pancreas or their body does not respond properly to insulin.
This causes glucose to accumulate in the blood, which over time may lead to a number of serious complications.
GLUCOPHAGE UNIDIE makes the body more sensitive to insulin and helps normalize the way the body uses glucose. It is important to continue taking GLUCOPHAGE UNIDIE, even if you do not have any obvious symptoms.

2. What you need to know before taking GLUCOPHAGE UNIDIE

Do not take GLUCOPHAGE UNIDIE if:

you are allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
you have severely reduced kidney function;
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, deep and rapid breathing, drowsiness, and breath with an unusually fruity odour;
you have a serious condition that may cause kidney problems such as dehydration, severe infection, shock, or administration of a contrast agent into the bloodstream for X-ray examinations (iodinated contrast agents, see “Warnings and precautions”);
you have liver disease;
you have acute or chronic conditions that may cause reduced oxygen supply to body tissues (hypoxia), such as impaired heart function (unstable heart failure) or breathing difficulties, recent heart attack, or shock;
you are a heavy drinker of alcohol or have had a severe alcohol intoxication;
you are breastfeeding.

Warnings and precautions
After starting treatment with GLUCOPHAGE UNIDIE
If you have diabetes, you need to regularly monitor your blood or urine sugar levels.
During treatment with GLUCOPHAGE UNIDIE, your doctor will check your kidney function at least once a year, or more frequently if you are elderly and/or if kidney function worsens.
Risk of lactic acidosis
GLUCOPHAGE UNIDIE 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 severe heart disease).
If you have any of the medical conditions described above, consult your doctor for further instructions.
Temporarily stop taking GLUCOPHAGE UNIDIE if you have a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, heat exposure, or if you are drinking less fluid than normal. Consult your doctor for further instructions.
If you experience any of the symptoms of lactic acidosis, stop taking GLUCOPHAGE UNIDIE 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 and slower heart rate.

Lactic acidosis is a medical emergency and must be treated in hospital.
GLUCOPHAGE UNIDIE alone does not cause hypoglycaemia (blood glucose level too low). However, the risk of hypoglycaemia may occur if you take GLUCOPHAGE UNIDIE together with antidiabetic medicines (such as sulfonylureas, insulin, glinides) that can cause hypoglycaemia.
It is possible that parts of the tablet may appear in the faeces. Do not be concerned: this is normal for this type of tablet.
If you are undergoing major surgery, you must stop taking GLUCOPHAGE UNIDIE during the procedure and for a certain period afterwards. Your doctor will decide when you should stop and when you should restart treatment with GLUCOPHAGE UNIDIE.
Continue to follow any dietary advice given by your doctor; consume carbohydrates regularly throughout the day.
Do not stop taking this medicine without consulting your doctor.
Children
GLUCOPHAGE UNIDIE is not suitable for children.
Other medicines and GLUCOPHAGE UNIDIE
If you are due to receive an injection of an iodinated contrast agent into the bloodstream, for example for an X-ray examination, you must stop taking GLUCOPHAGE UNIDIE before or during the injection. Your doctor will decide when you should stop and when you should restart treatment with GLUCOPHAGE UNIDIE.
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 UNIDIE.
It is particularly important to mention the following:

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

GLUCOPHAGE UNIDIE and alcohol
Avoid excessive alcohol consumption during treatment with GLUCOPHAGE UNIDIE, 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.
Ask your doctor whether changes to your treatment or monitoring of blood glucose levels are needed.
The use of this medicine is not recommended during breastfeeding or if you intend to breastfeed your baby. Consult your doctor.
Driving and using machines
GLUCOPHAGE UNIDIE does not cause “hypoglycaemic attacks” (symptoms of hypoglycaemia, low blood sugar levels, are: weakness, confusion, and increased sweating) and therefore should not affect your ability to drive or use machines. However, you should be aware that taking GLUCOPHAGE UNIDIE together with other antidiabetic medicines may cause hypoglycaemia.
If you take GLUCOPHAGE UNIDIE together with other antidiabetic medicines, exercise particular caution when driving or using machines.
Glucophage Unidie contains:
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to take GLUCOPHAGE UNIDIE

Take this medicine exactly as prescribed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
Your doctor may prescribe GLUCOPHAGE UNIDIE alone or in combination with other oral antidiabetic
medicines or insulin; they will also tell you how many tablets to take and when to take them.
If you have reduced kidney function, your doctor may prescribe you a lower dose.
The usual starting dose is 1 tablet of GLUCOPHAGE UNIDIE 500 mg per day.
After approximately 2 weeks of treatment, your doctor will assess your blood sugar levels and, if necessary,
adjust the dose.
The maximum daily dose is 4 tablets of GLUCOPHAGE UNIDIE 500 mg.
Dose increases should be by 500 mg every 10–15 days, up to a maximum of 2000 mg once daily with the
evening meal. If blood glucose control is not achieved with GLUCOPHAGE UNIDIE 2000 mg administered
as a single daily dose, your doctor may consider treatment with GLUCOPHAGE UNIDIE 1000 mg twice
daily, taken with food. If blood glucose control is still not achieved, your doctor may prescribe standard
metformin tablets, up to the maximum dose of 3000 mg per day.
If you are already being treated with metformin tablets, the starting dose of GLUCOPHAGE UNIDIE should
be equivalent to your daily dose of immediate-release metformin. Switching to
GLUCOPHAGE UNIDIE is not recommended if you are already taking metformin at doses exceeding
2000 mg per day.
If switching from another antidiabetic agent to GLUCOPHAGE UNIDIE:
discontinue the other agent and start taking GLUCOPHAGE UNIDIE at the doses indicated above.
GLUCOPHAGE UNIDIE 750 mg and 1000 mg should be used if you are already being treated with metformin
(either prolonged- or immediate-release).
The dose of GLUCOPHAGE UNIDIE 750 mg or 1000 mg should correspond to your daily dose of
metformin (prolonged- or immediate-release), up to a maximum dose of 1500 mg or 2000 mg, respectively, taken with the evening meal.
Combination with insulin
Metformin hydrochloride and insulin may be used together to improve glycaemic control (blood glucose levels). Metformin hydrochloride is administered at the usual starting dose of GLUCOPHAGE UNIDIE 500 mg tablets once daily, while the insulin dose is adjusted based on blood glucose levels.
If you are already being treated with metformin and insulin in combination, the dose of GLUCOPHAGE UNIDIE 750 mg or 1000 mg should be equivalent to your daily dose of metformin tablets, up to a maximum of 1500 mg or 2000 mg, respectively, taken with the evening meal, while the insulin dose is adjusted based on blood glucose levels.
Elderly
Due to the potential reduction in kidney function in elderly patients, the dosage of metformin hydrochloride should be adjusted according to renal function. Regular monitoring of kidney function is necessary (see section 4.4).
Children
GLUCOPHAGE UNIDIE should not be used in children.
If you take more GLUCOPHAGE UNIDIE than you should, consult your doctor or go to the nearest
hospital immediately.
If you forget to take GLUCOPHAGE UNIDIE
If you forget to take a tablet, you may take it as soon as you remember, unless it is almost time for your next
dose. Do not take a double dose to make up for a forgotten tablet. Take the remaining doses at the usual times.
Always take the tablets with some food.
If you stop taking GLUCOPHAGE UNIDIE
If you stop treatment with GLUCOPHAGE UNIDIE without consulting your doctor, you should be aware
that uncontrolled increases in blood sugar levels may occur. Late complications of diabetes such as eye, kidney, and vascular damage may develop.
If you visit another doctor or go to hospital, inform the doctor or hospital staff about the medicines you are taking.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
GLUCOPHAGE UNIDIE 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 UNIDIE and must immediately contact your doctor or go to the nearest hospital, because lactic acidosis can lead to coma.
Inform your doctor or pharmacist if, during treatment with GLUCOPHAGE UNIDIE, you notice:

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

diarrhoea, nausea, vomiting, abdominal pain and loss of appetite. These side effects usually occur at the beginning of treatment and resolve spontaneously in most cases.

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 (paraesthesiae), or pale or yellowish skin). Your doctor may prescribe some 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)

skin rashes (such as erythema, itching and urticaria);
changes in liver function tests and hepatitis (inflammation of the liver).

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 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 UNIDIE

Keep this medicine out of the sight and reach of children.
This medicine requires no special storage conditions.
Do not use this medicine after the expiry date stated on the packaging. 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 UNIDIE Contains
The active substance is: metformin hydrochloride.
GLUCOPHAGE UNIDIE 500 mg
One prolonged-release tablet of GLUCOPHAGE UNIDIE 500 contains: 500 mg of metformin
hydrochloride, equivalent to 390 mg of metformin base.
The other components are: sodium carmellose, hypromellose 100,000 cP, hypromellose 5 cP, microcrystalline
cellulose, magnesium stearate, purified water.
GLUCOPHAGE UNIDIE 750 mg
One prolonged-release tablet of GLUCOPHAGE UNIDIE 750 mg contains: 750 mg of
metformin hydrochloride, equivalent to 585 mg of metformin base.
The other components are: sodium carmellose, hypromellose 100,000 cP, magnesium stearate, purified water.
GLUCOPHAGE UNIDIE 1000 mg
One prolonged-release tablet of GLUCOPHAGE UNIDIE 1000 mg contains: 1000 mg of
metformin hydrochloride, equivalent to 780 mg of metformin base.
The other components are: sodium carmellose, hypromellose 100,000 cP, magnesium stearate, purified water.
Description of the Appearance of GLUCOPHAGE UNIDIE and Package Contents
GLUCOPHAGE UNIDIE is available in packages containing 30 or 60 prolonged-release tablets.
Marketing Authorization Holder
Bruno Farmaceutici S.p.A., Via delle Ande, 15 – 00144 Rome, Italy
Manufacturer
Savio Industrial S.r.l., Via Emilia, 21 – 27100 Pavia – Italy
Special Product’s Line SpA, via Fratta Rotonda Vado Largo 1-03012 Anagni-Italy