Metformin

Package leaflet: Information for the patient

Metcrean, 500 mg, film-coated tablets
Metcrean, 850 mg, film-coated tablets
Metcrean, 1000 mg, film-coated tablets
Metformini hydrochloridum
Please read the entire leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet for future reference.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Metcrean is and what it is used for

Metcrean 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. Metcrean helps reduce blood glucose levels to values as close as possible to normal.
In overweight adults, long-term use of Metcrean reduces the risk of diabetes-related complications. Treatment with Metcrean is associated with stabilization or moderate reduction in body weight.
Metcrean is used to treat 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 exercise alone. It is particularly used in patients who are overweight.
Adults may take Metcrean either as monotherapy or in combination with other antidiabetic medicines (oral medications or insulin).
Children aged 10 years and adolescents may take Metcrean either as monotherapy or in combination with insulin.

2. Information before using Metcrean

When not to use Metcrean:

• if the patient is allergic to metformin or any of the other ingredients of this medicine (listed in section 6),
• in case of liver function disorders,
• 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 loss of body water (dehydration), e.g. due to prolonged or severe diarrhoea or repeated vomiting. Dehydration may lead to kidney function disorders, which in turn 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 kidney function disorders, 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 necessary,
• a major surgical procedure is to be performed.

Metcrean 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 follow the doctor's instructions exactly.

Warnings and precautions

Risk of lactic acidosis
Metcrean may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has kidney function disorders. 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 function disorders, and any medical conditions in which a part of the body is inadequately oxygenated (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, the patient should consult a doctor for further instructions.

Metcrean should be temporarily discontinued if the patient develops a medical condition that may involve dehydration (significant loss of body water), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. The patient should consult a doctor for further instructions.

Metcrean 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 severe fatigue,
• breathing difficulties,
• decreased body temperature and slowed heart rate.

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

If the patient is to undergo a major surgical procedure, Metcrean must not be used during and for some time after the procedure. The doctor will decide when the patient should stop and restart treatment with Metcrean.

Metcrean does not cause hypoglycaemia (low blood glucose levels).
However, if Metcrean 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, consuming or drinking a sugary food or beverage usually helps.

During treatment with Metcrean, 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.

Metcrean and other medicines
If an iodine-containing contrast agent is to be injected into the bloodstream, for example for an X-ray or CT scan, the patient must stop taking Metcrean before or at the latest at the time of injection. The doctor will decide when the patient should stop and resume treatment with Metcrean.

The patient should inform the doctor about all medicines currently used or recently used, as well as any medicines planned for future use. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Metcrean by the doctor. 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 Metcrean 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.

Taking Metcrean with food and drink
The patient should avoid consuming excessive amounts of alcohol while taking Metcrean, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
During pregnancy, diabetes treatment requires the use of insulin.
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should inform her doctor so that treatment can be adjusted accordingly.
This medicine is not recommended for patients who are breastfeeding or planning to breastfeed.

Driving and operating machinery
Metcrean does not cause hypoglycaemia (low blood glucose levels). This means it does not affect the patient's ability to drive or operate machinery. However, particular caution should be exercised if Metcrean 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.

Metcrean contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered "sodium-free".

Metcrean contains propylene glycol
Metcrean 500 mg contains 0.385 mg of propylene glycol in each tablet.
Metcrean 850 mg contains 0.652 mg of propylene glycol in each tablet.
Metcrean 1000 mg contains 0.77 mg of propylene glycol in each tablet.

3. How to use Metcrean

Metcrean must always be used exactly as directed by the physician. If in doubt, consult the doctor or pharmacist again.
Treatment with Metcrean does not replace the benefits of a healthy lifestyle. Patients should continue to follow the doctor’s recommendations regarding diet and maintain regular physical activity.

Recommended dose
Children aged 10 years and adolescents: treatment usually begins with a dose of 500 mg or 850 mg of Metcrean 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 initiated upon specific physician recommendation, as experience with Metcrean in this age group is limited.
Adults: treatment usually begins with a dose of 500 mg or 850 mg of Metcrean, taken two or three times daily. The maximum daily dose is 3000 mg, administered in 3 divided doses.
If the patient has impaired kidney function, the physician may prescribe a lower dose.
If the patient is also using insulin, the physician will provide instructions on how to initiate Metcrean treatment.

Monitoring of treatment

• The physician will order regular blood glucose measurements and adjust the dose of Metcrean according to blood glucose levels. Patients must attend regular follow-up visits. This is particularly important for children, adolescents, and elderly patients.
• The physician will check kidney function at least once a year. More frequent monitoring may be necessary for elderly patients or if kidney function is impaired.

How to use Metcrean
Metcrean should be taken during or immediately after a meal to minimize gastrointestinal side effects.
Do not crush or chew the tablets. Swallow the tablet whole with a glass of water.

• If taking once daily, take the dose in the morning (with breakfast).
• If taking twice daily, take the doses in the morning (with breakfast) and in the evening (with dinner).
• If taking three times daily, take the doses in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If the patient feels that the effect of the medicine is too strong or too weak, they should consult the doctor or pharmacist.

Overdose of Metcrean
If a larger than recommended dose of Metcrean is taken, 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, the patient must seek immediate medical help, as lactic acidosis may lead to coma. The patient must immediately stop taking Metcrean and contact a doctor or go to the nearest hospital.

If a dose of Metcrean is missed
Do not take a double dose to make up for the missed dose. Take the next dose at the usual time.
For any further questions about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse effects

The medicine Metcrean may very rarely (may occur in up to 1 in 10,000 patients) cause a very serious adverse effect known as lactic acidosis (see section "Warnings and precautions"). If this occurs in a patient, treatment with Metcrean must be discontinued and immediate contact must be made with a doctor or the nearest hospital, as lactic acidosis may lead to coma.

Like all medicines, this medicine may cause adverse effects, although not everybody gets them. The possible adverse effects are listed below.

Very common adverse effects (occurring in more than 1 in 10 people):

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

Common adverse effects (occurring in less than 1 in 10 people):

• Taste disturbances.

Very rare adverse effects (occurring in less than 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 test results or symptoms of hepatitis (associated with fatigue, loss of appetite, weight loss, and with or without yellowing of the skin and whites of the eyes). If such symptoms occur, treatment with Metcrean must be discontinued and the doctor should be informed;
• Skin reactions such as skin redness (erythema), itching, or itchy rash (urticaria);
• Low blood levels of vitamin B₁₂.

Children and adolescents
Limited data in children and adolescents indicate that adverse effects observed in these populations are of similar nature and severity to those observed in adults.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse 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 Warsaw, telephone: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Metcrean

Keep this medicine out of sight and reach of children. If Metcrean is being used in children,
it is recommended that parents or caregivers supervise the treatment.
No special storage conditions required.
Do not use this medicine after the expiry date stated on the carton and blister pack after
"Expiry date (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 in use. This will help protect
the environment.

6. Contents of the pack and other information

What Metcrean contains

• The active substance is metformin hydrochloride. One Metcrean 500 mg coated tablet contains 500 mg of metformin hydrochloride, equivalent to 390 mg of metformin. One Metcrean 850 mg coated tablet contains 850 mg of metformin hydrochloride, equivalent to 662.9 mg of metformin. One Metcrean 1000 mg coated tablet contains 1000 mg of metformin hydrochloride, equivalent to 780 mg of metformin.
• Other components are:
  Tablet core: sodium carboxymethyl starch (Type A), povidone K-30, maize starch, colloidal anhydrous silica, magnesium stearate.
  Coating: hypromellose, titanium dioxide (E171), talc, macrogol 6000, propylene glycol.

What Metcrean looks like and contents of the pack
Metcrean 500 mg: white, round, biconvex coated tablets, embossed with the number "500" on one side and smooth on the other side.
Metcrean 850 mg: white, round, biconvex coated tablets, embossed with the number "850" on one side and smooth on the other side.
Metcrean 1000 mg: white or almost white, oval, biconvex coated tablets, embossed with "10" and "00" separated by a groove on one side and a dividing line on the other side. The tablets can be divided into halves.
Packs of PVC/PVDC/Aluminium blisters containing 30, 60 or 90 coated tablets, placed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Synoptis Pharma Sp. z o.o.
ul. Krakowiaków 65
02-255 Warsaw, Poland

Manufacturer/Importer
Synoptis Industrial Sp. z o.o.
ul. Rabowicka 15
62-020 Swarzędz, Poland