Xuvelex xr

Package leaflet: Information for the user

Xuvelex XR, 500 mg, prolonged-release tablets
Xuvelex XR, 750 mg, prolonged-release tablets
Xuvelex XR, 1000 mg, prolonged-release tablets
Metformini hydrochloridum
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for you personally. Do not share it with others. This medicine may harm others, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents

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

1. What Xuvelex XR is and what it is used for

Xuvelex XR contains metformin hydrochloride as the active substance and belongs to a group of medicines called biguanides, used in the treatment of patients with type 2 diabetes (also known as insulin-independent diabetes).
Xuvelex XR is used in the treatment of type 2 diabetes when normal blood glucose (sugar) levels cannot be achieved through diet and physical exercise alone. It is particularly used in patients who are overweight. Insulin is a hormone that enables the body to take up glucose from the blood and use it for energy or store it for later use. In patients with type 2 diabetes, the pancreas does not produce enough insulin or the body cannot properly use the insulin it produces. This leads to abnormally high blood glucose levels, which may cause a range of serious, long-term complications. Therefore, it is important to continue taking the medicine even if no obvious symptoms are present.
Xuvelex XR increases the body's sensitivity to insulin and helps restore normal glucose utilization.
If you are overweight, long-term use of Xuvelex XR also reduces the risk of diabetes-related complications. Treatment with Xuvelex XR is associated with maintenance of body weight or moderate weight reduction.
Polycystic ovary syndrome (PCOS) is a health condition that affects hormone levels in women, menstrual cycles, and fertility. Xuvelex XR is used in women with PCOS to stimulate ovulation (release of an egg from the ovaries) and thereby increase the chance of becoming pregnant, either alone or in combination with other treatment options.
Xuvelex XR tablets are prolonged-release tablets specially formulated to slowly release the medicine in the body, and therefore differ from many other types of tablets containing metformin.

2. Important information before taking Xuvelex XR

When not to use Xuvelex XR:

• if the patient is allergic to metformin or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may cause rash, itching or shortness of breath.
• if the patient has 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 unusual fruity odour of breath.
• in case of excessive fluid loss from the body (dehydration). Dehydration may lead to kidney function disorders, 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 kidney function disorders, which may increase the risk of lactic acidosis (see below "Warnings and precautions").
• in case of treatment of acute heart failure or recent myocardial infarction, severe circulatory disorders or breathing difficulties. This may cause tissue hypoxia, which may increase the risk of lactic acidosis (see "Warnings and precautions").
• if the patient abuses alcohol.

If any of the above conditions apply, 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 required. The use of Xuvelex XR should be temporarily discontinued before and after the examination or surgical procedure. The doctor will decide whether alternative treatment is necessary during this period. It is important to strictly follow the doctor's instructions.

Warnings and precautions
Before taking Xuvelex XR, talk to your doctor.
Risk of lactic acidosis
Xuvelex XR 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 is also increased in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more details 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, consult a doctor for further instructions.
Contact a doctor immediately for further instructions if:

• the patient has a genetically inherited mitochondrial disease (energy-producing structures in cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• the patient experiences any of the following symptoms after starting metformin: seizures, worsening cognitive function, difficulty moving the body, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness. The use of Xuvelex XR should be temporarily discontinued if a condition occurs that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, exposure to high temperature, or if the patient drinks less fluids than usual. Consult a doctor for further instructions.

The use of Xuvelex XR should be discontinued and immediate contact should be made with 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,
• stomach pain (abdominal pain),
• muscle cramps,
• general malaise combined with severe fatigue,
• difficulty breathing,
• 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, they must stop taking Xuvelex XR during the procedure and for some time afterwards. The doctor will decide when the patient should stop and resume treatment with Xuvelex XR.
Xuvelex XR does not cause hypoglycaemia (low blood glucose levels).
However, if Xuvelex XR is used in combination with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylurea derivatives, 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, eating or drinking something containing sugar usually helps.
During treatment with Xuvelex XR, the doctor will monitor the patient's kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.
Undigested tablet residues may be visible in the stool. This is normal with this type of tablet and should not be a cause for concern.
Follow all dietary recommendations provided by the doctor and ensure that the recommended amount of carbohydrates is evenly distributed throughout the day.
Do not discontinue this medicine without consulting a doctor.
Children and adolescents
Due to lack of data, Xuvelex XR should not be used in children and adolescents.
Xuvelex XR and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example for an X-ray examination or computed tomography, they must stop taking Xuvelex XR before or at the latest at the time of such injection. The doctor will decide when the patient should stop and resume treatment with Xuvelex XR.
Tell your doctor or pharmacist 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 assessments, or dose adjustments of Xuvelex XR by the doctor. It is especially important to inform about the following medicines:

• diuretics (water tablets) such as furosemide.
• 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, allergic reactions or asthma), such as prednisolone, mometasone, beclomethasone.
• other medicines used to treat diabetes.
• sympathomimetic medicines, including epinephrine and dopamine, used in the treatment of heart attacks and low blood pressure. Epinephrine is also part of some dental anaesthetic medicines.
• medicines that may alter metformin blood levels, especially if the patient has reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).

Taking Xuvelex XR with alcohol
Avoid excessive alcohol consumption while taking Xuvelex XR, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy, breastfeeding and effects on fertility
If the patient is pregnant, suspects she may be pregnant, or is planning to have a child, she should consult a doctor before taking this medicine.
If the patient is pregnant, suspects she may be pregnant, or is planning to have a child, she should consult a doctor in case any changes in treatment or blood glucose monitoring are required.
This medicine is not recommended if the patient is breastfeeding or planning to breastfeed.
Women of childbearing potential:
Xuvelex XR may stimulate ovulation (release of an egg from the ovaries) in women who do not ovulate properly. Increased risk of pregnancy should be considered during treatment with Xuvelex XR.
Driving and operating machinery
Xuvelex XR taken alone does not cause hypoglycaemia (symptoms of low blood sugar or hypoglycaemia, such as fainting, confusion and excessive sweating), and therefore should not affect the ability to drive or operate machinery.
However, it should be noted that Xuvelex XR taken in combination with other antidiabetic medicines (such as sulfonylurea derivatives, insulin, meglitinides) may cause hypoglycaemia; therefore, particular caution should be exercised when driving or operating machinery in such cases.
Xuvelex XR contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per prolonged-release tablet, meaning the medicine is considered "sodium-free".

3. How to use Xuvelex XR

Your doctor may prescribe Xuvelex XR to be taken alone or in combination with other oral antidiabetic medicines or insulin.
This medicine should always be taken as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Xuvelex XR does not replace the benefits of a healthy lifestyle. You should continue to follow all dietary advice given by your doctor and maintain regular physical exercise.

Recommended dose in adults
Treatment is usually initiated with 500 mg of Xuvelex XR once daily. After approximately 2 weeks of treatment with Xuvelex XR, based on blood glucose measurements, your doctor may adjust the dose. The maximum daily dose of Xuvelex XR is 2,000 mg.
If you have impaired kidney function, your doctor may prescribe a lower dose.
If you are also using insulin, your doctor will advise you on how to start treatment with Xuvelex XR.

Monitoring of treatment

• Your doctor will order regular blood glucose tests and adjust the dose of Xuvelex XR according to your blood glucose levels. You should ensure regular contact with your doctor. This is particularly important if you are elderly.
• Your doctor will also check at least once a year how well your kidneys are functioning. More frequent monitoring may be necessary if you are elderly or if your kidneys are not working properly.

How to take Xuvelex XR
Tablets are usually taken once daily with the evening meal. This helps to avoid gastrointestinal side effects.
In some cases, your doctor may advise taking the tablets twice daily. Tablets should always be taken with food.

Polycystic ovary syndrome (PCOS)
The usual dose is 1500–2000 mg of metformin hydrochloride taken once daily with the evening meal. Consult your doctor or pharmacist regarding when to discontinue the medicine.
Swallow the tablets whole with a glass of water. Do not crush or chew them.

Taking more Xuvelex XR than prescribed
If you take more Xuvelex XR than prescribed, lactic acidosis may occur. Symptoms of lactic acidosis are nonspecific and include vomiting, stomach pain (abdominal pain) with muscle cramps, general malaise with severe fatigue, and difficulty breathing. Other symptoms include lowered body temperature and slowed heart rate. If any of these symptoms occur, seek immediate medical help, as lactic acidosis can lead to coma. Immediately stop taking Xuvelex XR and contact your doctor or the nearest hospital immediately.

Missing a dose of Xuvelex XR
If you miss a dose, take it as soon as you remember, or take the next dose at the usual time with food. Do not take a double dose to make up for a missed dose.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects may occur:
Xuvelex XR may very rarely (may affect up to 1 in 10,000 patients)
cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs in a patient, treatment with Xuvelex XR must be discontinued immediately and the patient should contact a doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.
Xuvelex XR may cause abnormalities in liver function tests and hepatitis, which may lead to jaundice (may affect up to 1 in 10,000 patients). If yellowing of the eyes and/or skin occurs in a patient, treatment with Xuvelex XR must be discontinued and the patient should contact a doctor immediately.
Other possible adverse effects are listed below according to their frequency of occurrence as follows:
Very common (may affect more than 1 in 10 people):

• Diarrhoea, nausea, vomiting, abdominal pain, loss of appetite. If these symptoms occur, do not stop taking the tablets, as these symptoms usually resolve after about 2 weeks. It may help to take the tablets with food or immediately after a meal.

Common (may affect less than 1 in 10 people):

• Taste disturbances.
• Reduced or low blood levels of vitamin B12 (symptoms may include: extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling (paresthesia), or pale or yellowish skin). Your doctor may order several tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other health problems unrelated to diabetes.

Very rare (may affect no more than 1 in 10,000 people):

• Skin rash, including redness, itching and urticaria.

Reporting of adverse effects
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department for Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: + 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 authorisation holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Xuvelex XR

Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton after "EXP".
The expiry date refers to the last day of the specified month.
Store below 25°C.
Medicines should 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 Xuvelex XR contains
The active substance is metformin hydrochloride.
Xuvelex XR 500 mg prolonged-release tablets:
each prolonged-release tablet contains 500 mg of metformin hydrochloride, equivalent to
389.938 mg of metformin.
Xuvelex XR 750 mg prolonged-release tablets:
each prolonged-release tablet contains 750 mg of metformin hydrochloride, equivalent to
584.907 mg of metformin.
Xuvelex XR 1000 mg prolonged-release tablets:
each prolonged-release tablet contains 1000 mg of metformin hydrochloride, equivalent to
779.876 mg of metformin.
The other ingredients are: povidone K-90F, anhydrous colloidal silicon dioxide, sodium carboxymethylcellulose 2 500–3 500 mPa·s, hypromellose 10 000 cps, microcrystalline cellulose, magnesium stearate.

What Xuvelex XR looks like and contents of the pack
Description
Xuvelex XR 500 mg prolonged-release tablets: white or almost white, rounded, biconvex tablets with "500" embossed on one side and smooth on the other. Tablets have a diameter of approximately 12.15 mm.
Xuvelex XR 750 mg prolonged-release tablets: white or almost white, biconvex capsule-shaped tablets with "750" embossed on one side and smooth on the other. Tablets are approximately 20.0 mm in length and 9.6 mm in width.
Xuvelex XR 1000 mg prolonged-release tablets: white or almost white, biconvex capsule-shaped tablets with "1000" embossed on one side and smooth on the other. Tablets are approximately 22.6 mm in length and 10.6 mm in width.

Pack contents
Xuvelex XR 500 mg prolonged-release tablets: tablets are available in PVC/PVDC/Aluminium foil blisters containing 20, 30, 60 and 90 tablets.
Xuvelex XR 750 mg prolonged-release tablets: tablets are available in PVC/PVDC/Aluminium foil blisters containing 20, 30, 60 and 90 tablets.
Xuvelex XR 1000 mg prolonged-release tablets: tablets are available in PVC/PVDC/Aluminium foil blisters containing 10, 30, 60 and 90 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Importer
PharOS MT Ltd.
HF62X, Hal Far Industrial Estate
Birzebbugia, BBG3000, Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Hungary: Xuvelex XR 500mg, 750mg & 1000mg, Retard tabletta
Czech Republic: Xuvelex
Poland: Xuvelex XR
Romania: Xuvelex XR 500mg, 750mg & 1000mg, Comprimat cu eliberare prelungită

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00