Zenofor

Package leaflet: Information for the user

Zenofor, 500 mg, film-coated tablets
Zenofor, 850 mg, film-coated tablets
Zenofor, 1000 mg, film-coated tablets
Metformini hydrochloridum
Please read this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Zenofor is and what it is used for

Zenofor 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. Zenofor helps reduce blood glucose levels to values as close to normal as possible.
In overweight adults, long-term use of Zenofor also reduces the risk of diabetes-related complications. Treatment with Zenofor is associated with stable body weight or modest weight reduction.
Zenofor is used in the treatment of patients with type 2 diabetes (also known as non-insulin-dependent diabetes), in whom adequate blood glucose control cannot be achieved by diet and physical exercise alone. It is particularly used in overweight patients.
Adults may take Zenofor either as monotherapy or in combination with other antidiabetic medicines (oral agents or insulin).
Children aged 10 years and adolescents may take Zenofor either as monotherapy or in combination with insulin.

2. Important information before taking Zenofor

When not to take Zenofor:

• if the patient is allergic to metformin or any of the other ingredients of this medicine
  (listed in section 6).
• if the patient has impaired liver function.
• 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 may lead to diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or unusual fruity odour of the breath.
• in case of excessive loss of body water (dehydration), for example 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 "Warnings and precautions").
• in case of severe infection, e.g. pneumonia, bronchitis or kidney infection. Severe infections may impair kidney function, increasing the risk of lactic acidosis (see "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, increasing the risk of lactic acidosis (see "Warnings and precautions").
• in case of alcohol abuse.

If any of the above conditions apply, the patient should consult a doctor before taking 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 planned.

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

Warnings and precautions
Risk of lactic acidosis
Zenofor 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), impaired liver function, 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.

Zenofor should be temporarily discontinued if the patient develops any illness that may lead to dehydration (significant loss of body water), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient is drinking less fluid than usual. Medical advice should be sought.

Zenofor should be discontinued and the patient should contact a doctor or the nearest hospital immediately 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 accompanied by profound fatigue,
• breathing difficulties,
• decreased body temperature and slowed heart rate.

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

Contact a doctor immediately for further instructions 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 experiences any of the following symptoms: seizures, worsening cognitive function, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

If the patient is to undergo major surgery, Zenofor 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 Zenofor.

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

During treatment with Zenofor, 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.

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

Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function, or the doctor may need to adjust the dose of Zenofor.

It is especially important to inform the doctor about the use of 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 asthma treatment),
• corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma),
• medicines that may alter Zenofor 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 diabetes treatment.

Zenofor and alcohol
Avoid excessive alcohol consumption while taking Zenofor, as this 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 to become pregnant, she should consult her doctor regarding any necessary changes in treatment or blood glucose monitoring.

This medicine is not recommended for patients who are breastfeeding or planning to breastfeed.

Driving and operating machinery
Zenofor 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 advised if Zenofor 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, blurred vision or difficulty concentrating. If such symptoms occur, the patient should not drive or operate machinery.

Zenofor contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose and is therefore considered "sodium-free".

3. How to take Zenofor

Always take this medicine exactly as prescribed by your doctor. If you are unsure,
consult your doctor or pharmacist.
Zenofor does not replace the benefits of a healthy lifestyle.
You should continue to follow all your doctor's recommendations 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 Zenofor 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 on special recommendation by the doctor, as experience with Zenofor in this age group is limited.
Adults: treatment usually starts with a dose of 500 mg or 850 mg of Zenofor, 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 doctor may prescribe a lower dose.
If the patient is also taking insulin, the doctor will advise on how to start treatment with Zenofor.

Monitoring of treatment

• Your doctor will order regular blood glucose tests and adjust the dose of Zenofor according to blood glucose levels. You must attend regular check-up visits 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 the patient's kidneys are not functioning properly.

How to take Zenofor
Zenofor 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 in the morning (with breakfast) and in the evening (with dinner).
• If taking three doses per day, take in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If at any time the patient feels that the effect of Zenofor is too strong or too weak, they should consult their doctor or pharmacist.

Overdose of Zenofor
If a dose higher than recommended 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 can lead to coma. Zenofor must be stopped immediately and the patient should contact their doctor or go to the nearest hospital.

Missed dose of Zenofor
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 doubts about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur:
The medicine Zenofor may very rarely (may occur in up to 1 patient in 10,000) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs in a patient, treatment with Zenofor must be discontinued and immediate contact must be made with a doctor or the nearest hospital, as lactic acidosis may lead to coma.

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

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

Common adverse reactions (occurring in fewer than 1 in 10 people)

• Taste disturbances.
• Decreased or low blood levels of vitamin B12 (symptoms may include extreme fatigue, pain and redness of the tongue (glossitis), tingling sensations (paraesthesiae), or pale or yellowish 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 adverse reactions (occurring in fewer 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, Zenofor 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 adverse reactions occurring in these populations are of similar nature and severity to those observed in adults.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Zenofor

Keep this medicine out of sight and reach of children. If a child is being treated with Zenofor, parents and caregivers are advised to supervise the use of this medicine.
There are no special storage conditions required.
Do not use this medicine after the expiry date stated on the carton after "EXP".
The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Zenofor contains
The active substance is metformin hydrochloride.
Each Zenofor 500 mg film-coated tablet contains 500 mg of metformin hydrochloride, equivalent to
390 mg of metformin.
Each Zenofor 850 mg film-coated tablet contains 850 mg of metformin hydrochloride, equivalent to
662.9 mg of metformin.
Each Zenofor 1000 mg film-coated tablet contains 1000 mg of metformin hydrochloride, equivalent to
780 mg of metformin.
The other ingredients are:
Tablet core: hypromellose 615, sodium carbonate anhydrous, povidone K 25, magnesium stearate
Tablet coating: hypromellose 606, macrogol 6000, titanium dioxide (E 171)

What Zenofor looks like and contents of the pack
Zenofor 500 mg, film-coated tablets:
White, round, biconvex film-coated tablets. One side of the tablet is engraved with a V-shaped break line. The tablet diameter is approximately 12 mm. The break line on the tablet is intended only to facilitate breaking the tablet for easier swallowing and does not ensure division into equal doses.

Zenofor 850 mg, film-coated tablets:
White, oblong film-coated tablets. A V-shaped break line is present on both sides of the tablet. The tablet dimensions are approximately 19 x 8.7 mm. The break line on the tablet is intended only to facilitate breaking the tablet for easier swallowing and does not ensure division into equal doses.

Zenofor 1000 mg, film-coated tablets:
White, oblong film-coated tablets. Break lines are engraved on both sides of the tablet, with a V-shaped line on one side. The tablet dimensions are approximately 19 x 10 mm. The tablet can be divided into equal doses.

Packs: PVC/Aluminium blisters in cardboard cartons.
Pack sizes:
Zenofor 500 mg: 20, 28, 30, 50, 56, 60, 84, 90, 100, 120, 180, 300, 400, 500 film-coated tablets
Zenofor 850 mg: 30, 40, 50, 56, 60, 80, 90, 100, 120, 180, 200, 500 film-coated tablets
Zenofor 1000 mg: 28, 30, 50, 56, 60, 80, 90, 100, 120, 180 film-coated tablets
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic
(logo of the Marketing Authorisation Holder)

Importer
S.C. ZENTIVA S.A.
B-dul Theodor Pallady no. 50, sector 3
032266 Bucharest
Romania

This medicinal product has been authorised in the European Economic Area countries under the following names:
Czech Republic: Mulado
Denmark, Estonia, Germany, Latvia, Norway: Metformin Zentiva
France: Metformine Zentiva
Finland, Sweden: Metformin Zentiva
Poland, Romania: Zenofor
Lithuania: Metformin hydrochloride Zentiva
Slovakia: Mirovian

For further information about this medicinal product, please contact the representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.
ul. Bonifraterska 17
00-203 Warsaw
tel.: +48 22 375 92 00