SIOFOR 1000 mg Tablets

Contents of the leaflet

1. Leaflet accompanying the packaging: patient information
2. Siofor XR 500 mg, 500 mg, prolonged-release tablets
3. Siofor XR 750 mg, 750 mg, prolonged-release tablets
4. Siofor XR 1000 mg, 1000 mg, prolonged-release tablets
   1. Read the leaflet carefully before taking the medicine, as it contains important information for the patient.
   2. Table of contents of the leaflet:
5. What is Siofor XR and what is it used for
6. Important information before taking Siofor XR
   1. When not to take Siofor XR:
   2. Warnings and precautions
   3. Risk of lactic acidosis
   4. The patient should temporarily stop taking Siofor XR if they have a condition that may lead to dehydration
   5. The patient should stop taking Siofor XR and immediately contact their doctor or go to the nearest hospital if they experience any symptoms of lactic acidosis
   6. The patient should immediately contact their doctor for further instructions if:
   7. Siofor XR and other medicines:
   8. Taking Siofor XR with alcohol
   9. Pregnancy, breastfeeding, and fertility
   10. Driving and using machines
   11. Siofor XR contains sodium
7. How to take Siofor XR
   1. Recommended dose
   2. Taking a higher dose of Siofor XR than recommended
   3. Missing a dose of Siofor XR
8. Possible side effects
   1. The following side effects may occur:
   2. Other possible side effects, which have been reported with the following frequencies:
   3. Reporting side effects
9. How to store Siofor XR
10. Package contents and other information
    1. What Siofor XR contains
    2. What Siofor XR looks like and contents of the pack
    3. Marketing authorization holder and manufacturer:
    4. This medicine is authorized in the Member States of the European Economic Area under the following names:
    5. Date of last revision of the leaflet: 03/2025

Leaflet accompanying the packaging: patient information

Siofor XR 500 mg, 500 mg, prolonged-release tablets

Siofor XR 750 mg, 750 mg, prolonged-release tablets

Siofor XR 1000 mg, 1000 mg, prolonged-release tablets

Metformin hydrochloride

Read the leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this leaflet, so you can read it again if you need to.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Siofor XR and what is it used for
• 2. Important information before taking Siofor XR
• 3. How to take Siofor XR
• 4. Possible side effects
• 5. How to store Siofor XR
• 6.Package contents and other information

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

Siofor XR contains the active substance metformin hydrochloride, which belongs to a group of medicines called biguanides and is used to treat type 2 diabetes (non-insulin-dependent).
Siofor XR is used to treat patients with type 2 diabetes (also called non-insulin-dependent diabetes) who are not adequately controlled by diet and exercise alone. Insulin is a hormone that allows the body's cells to take up glucose from the blood to produce energy or store it for later use. In patients with type 2 diabetes, the pancreas does not produce enough insulin or the body does not respond properly to the insulin produced. This leads to a buildup of glucose in the blood, which can cause a range of serious, long-term complications. Therefore, it is essential for the patient to continue taking the medicine, even if they do not feel any visible symptoms.
Siofor XR makes the body more sensitive to insulin and helps restore the normal way the body uses glucose.
Taking Siofor XR is associated with both weight stabilization and moderate weight loss.
Siofor XR is designed to release the active substance slowly in the body and is therefore different from many other types of tablets containing metformin hydrochloride.

2. Important information before taking Siofor XR

When not to take Siofor XR:

• if the patient is allergic to metformin hydrochloride or any of the other ingredients of this medicine (listed in section 6). An allergic reaction may cause a rash, itching, or shortness of breath,
• in case of liver dysfunction,
• if the patient has significantly reduced kidney function,
• if the patient has uncontrolled diabetes, such as severe hyperglycemia (high blood sugar levels), nausea, vomiting, diarrhea, sudden weight loss, lactic acidosis (see "Risk of lactic acidosis" below) or diabetic ketoacidosis. Diabetic ketoacidosis is a condition in which substances called ketone bodies accumulate in the blood and can lead to diabetic pre-coma. Its symptoms include abdominal pain, rapid and deep breathing, drowsiness or an unusual fruity odor from the mouth,
• in case of excessive fluid loss from the body (dehydration), which may occur in case of prolonged or severe diarrhea or repeated vomiting. Dehydration can lead to kidney dysfunction, which can increase the risk of lactic acidosis (see "Warnings and precautions" below),
• in case of severe infection, such as one affecting the lungs, bronchi, or kidneys. Severe infections can lead to kidney dysfunction, which can increase the risk of lactic acidosis (see "Warnings and precautions" below),
• in case of treatment for acute heart failure or recent myocardial infarction, severe circulatory disorders, or breathing difficulties. This may cause tissue hypoxia, which can increase the risk of lactic acidosis (see "Warnings and precautions" below),
• in case of alcohol abuse.
• if the patient is under 18 years old.

Warnings and precautions

Before starting Siofor XR, the patient should discuss it with their doctor or pharmacist.

Risk of lactic acidosis

Siofor XR may cause a very rare but very serious side effect called lactic acidosis, especially if the patient has kidney dysfunction. The risk of lactic acidosis also increases in case of uncontrolled diabetes, severe infection, prolonged fasting, or alcohol consumption, dehydration (see more information below), liver dysfunction, and any conditions in which a part of the body is not adequately supplied with oxygen (e.g., acute severe heart disease).
If any of the above conditions apply to the patient, they should consult their doctor for more detailed instructions.

The patient should temporarily stop taking Siofor XR if they have a condition that may lead to dehydration

(excessive fluid loss from the body), such as severe vomiting, diarrhea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. The patient should consult their doctor for more detailed instructions.

The patient should stop taking Siofor XR and immediately contact their doctor or go to the nearest hospital if they experience any symptoms of lactic acidosis

because this condition can lead to coma.
Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain (pain in the abdominal cavity),
• muscle cramps,
• general poor condition with severe fatigue,
• breathing difficulties,
• decreased body temperature and slowed heart rate.

Lactic acidosis is a life-threatening condition that requires hospital treatment.

The patient should immediately contact their doctor for further instructions if:

• they have a genetically inherited disease affecting the mitochondria (energy-producing structures in cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness.
• they experience any of the following symptoms after starting metformin: seizures, impaired cognitive function, difficulty moving, signs of nerve damage (e.g., pain or numbness), migraine, or hearing loss.

If the patient is to undergo a major surgical procedure, THEY MUST STOPtaking Siofor XR during the procedure and for some time after it. The doctor will decide when the patient should stop and resume treatment with Siofor XR.
During treatment with Siofor XR, the doctor will monitor the patient's kidney function at least once a year or more often if the patient is elderly and/or has impaired kidney function.
Tablet residues may appear in the stool. The patient should not be concerned, as this is normal when taking this type of tablet.
The patient should continue to follow the dietary recommendations given by their doctor and ensure that carbohydrates are consumed regularly throughout the day.
The patient should not stop taking this medicine without consulting their doctor.

Siofor XR and other medicines:

If the patient is to receive an iodine-containing contrast agent intravenously, for example, for an X-ray examination or computed tomography, THEY MUST STOPtaking Siofor XR before or at the latest at the time of such administration. The doctor will decide when the patient should stop and resume treatment with Siofor XR.
The patient should tell their doctor or pharmacist about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
The patient may require more frequent monitoring of blood glucose levels and kidney function or dose adjustment of Siofor XR by their doctor. It is particularly important to inform about the following medicines:

• diuretics (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),
• steroids such as prednisolone, mometasone, beclometasone,
• sympathomimetic medicines, including epinephrine and dopamine used to treat myocardial infarction and low blood pressure. Epinephrine is also contained in some dental anesthetics.
• medicines that may change the level of Siofor XR in the blood, especially if the patient has impaired kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).

Taking Siofor XR with alcohol

The patient should avoid consuming excessive amounts of alcohol while taking Siofor XR, as this may increase the risk of lactic acidosis (see "Warnings and precautions").

Pregnancy, breastfeeding, and fertility

If the patient is pregnant, thinks they may be pregnant, or plans to have a baby, they should consult their doctor, as changes in treatment or blood glucose monitoring may be necessary.
This medicine is not recommended for breastfeeding women or those planning to breastfeed.
Before taking any medicine, the patient should consult their doctor or pharmacist.

Driving and using machines

Siofor XR used as the only antidiabetic medicine does not cause hypoglycemia (symptoms of low blood sugar levels, such as fainting, disorientation, and increased sweating). This means it does not affect the patient's ability to drive or operate machinery.
However, the patient should be aware that taking Siofor XR with other antidiabetic medicines may cause hypoglycemia. In such cases, the patient should be particularly careful while driving or operating machinery.

Siofor XR contains sodium

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

3. How to take Siofor XR

The doctor may prescribe Siofor XR as the only antidiabetic medicine (monotherapy) or in combination with other oral antidiabetic medicines or insulin.
This medicine should always be taken exactly as prescribed by the doctor or pharmacist.
If the patient has any doubts, they should consult their doctor or pharmacist.

Recommended dose

The usual starting dose is 500 mg of Siofor XR per day. After about 2 weeks of taking Siofor XR, the doctor will order a blood sugar test and adjust the dose of the medicine.
The maximum daily dose is 2000 mg of Siofor XR.
If the patient has impaired kidney function, the doctor may prescribe a lower dose.
Usually, the patient should take one tablet once a day during the evening meal.
In some cases, the doctor may recommend taking the tablet twice a day. The patient should always take the tablet with a meal.
The tablet should be swallowed whole with a glass of water, without chewing.

Taking a higher dose of Siofor XR than recommended

Accidentally taking more tablets than recommended should not be a cause for concern, but if unusual symptoms occur, the patient should contact their doctor. In case of significant overdose, lactic acidosis may occur. The symptoms of lactic acidosis are non-specific and include vomiting, abdominal pain (pain in the abdominal cavity) with muscle cramps, poor general condition with severe fatigue, and breathing difficulties. Further symptoms include decreased body temperature and slowed heart rate.
If any of these symptoms occur, the patient should immediately stop taking Siofor XR and contact their doctor or go to the nearest hospital, as lactic acidosis can lead to coma.

Missing a dose of Siofor XR

The patient should take the next dose as soon as possible during a meal. They should not take a double dose to make up for the missed dose.
If the patient has any further doubts about taking this medicine, they should consult their doctor or pharmacist.

4. Possible side effects

Like all medicines, Siofor XR can cause side effects, although not everybody gets them.

The following side effects may occur:

Siofor XR may very rarely cause (may affect up to 1 in 10,000 people) a very serious side effect called lactic acidosis (see "Warnings and precautions"). If this occurs, the patient should stop taking Siofor XR and immediately contact their doctor or the nearest hospital, as lactic acidosis can lead to coma.
Siofor XR may cause abnormal liver function test results and liver inflammation, which may result in jaundice (may affect up to 1 in 10,000 people). If the patient experiences yellowing of the eyes and/or skin, they should immediately contact their doctor.

Other possible side effects, which have been reported with the following frequencies:

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

• Diarrhea, nausea, vomiting, abdominal pain, or loss of appetite. If these symptoms occur, the patient should not stop taking the tablets, as they usually resolve within about 2 weeks. Taking Siofor XR with a meal or immediately after a meal may be helpful.

Common (may affect up to 1 in 10 people)

• Taste disturbances.
• Decreased or low levels of vitamin B in the blood (symptoms may include extreme fatigue, pain, and redness of the tongue, or numbness). The doctor may order several tests to find the cause of the symptoms, as some of them may also be caused by diabetes or other unrelated health problems.

Very rare (may affect up to 1 in 10,000 people)

• Skin rashes, including redness of the skin, itching, and hives.

Reporting side effects

If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor or pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Siofor XR

The medicine should be stored 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 month.
There are no special storage instructions for the medicinal product.
Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines they no longer use. This will help protect the environment.

6. Package contents and other information

What Siofor XR contains

The active substance of Siofor XR is metformin hydrochloride.
Each prolonged-release tablet of Siofor XR 500 mg contains 500 mg of metformin hydrochloride (equivalent to 390 mg of metformin).
Each prolonged-release tablet of Siofor XR 750 mg contains 750 mg of metformin hydrochloride (equivalent to 585 mg of metformin).
Each prolonged-release tablet of Siofor XR 1000 mg contains 1000 mg of metformin hydrochloride (equivalent to 780 mg of metformin).
The other ingredients are magnesium stearate, colloidal anhydrous silica, sodium carmellose, and hypromellose.

What Siofor XR looks like and contents of the pack

The prolonged-release tablets of Siofor XR 500 mg are white or almost white, capsule-shaped with the inscription "SR 500" on one side and smooth on the other. The dimensions of the tablet are: length 16.5 mm, width 8.2 mm, thickness 6.1 mm.
The prolonged-release tablets of Siofor XR 750 mg are white or almost white, capsule-shaped with the inscription "SR 750" on one side and smooth on the other. The dimensions of the tablet are: length 19.6 mm, width 9.3 mm, thickness 6.9 mm.
The prolonged-release tablets of Siofor XR 1000 mg are white or almost white, oval with the inscription "SR 1000" on one side and smooth on the other. The dimensions of the tablet are: length 22 mm, width 10.5 mm, thickness 8.9 mm.
Siofor XR is available in pack sizes of 15, 30, 60, 90, or 120 prolonged-release tablets in a carton.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer:

Berlin-Chemie AG
Glienicker Weg 125
12489 Berlin
Germany
For more information about this medicine, the patient should contact their local representative of the marketing authorization holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
phone: (22) 566 21 00
fax: (22) 566 21 01

This medicine is authorized in the Member States of the European Economic Area under the following names:

Bulgaria:
Сиофор SR 500 mg, 750 mg, 1000 mg таблетки с удължено освобождаване
Croatia:
Siofor SR 500 mg, 750 mg, 1000 mg tablete s produljenim oslobađanjem
Czech Republic:
Siofor Prolong
Estonia:
Metforal XR
Germany:
Siofor XR 500 mg, 750 mg, 1000 mg Retardtabletten
Hungary:
Meforal XR 500 mg, 750 mg, 1000 mg retard tabletta
Latvia:
Metforal 500 mg, 750 mg, 1000 mg ilgstošās darbības tabletes
Lithuania:
Tivulin 500 mg, 750 mg, 1000 mg pailginto atpalaidavimo tabletės
Poland:
Siofor XR 500 mg, 750 mg, 1000 mg
Portugal:
Romania:
Slovakia:
Siofor XR 500 mg, 750 mg, 1000 mg comprimidos de libertação prolongada
Siofor 500 mg, 750 mg, 1000 mg comprimate cu eliberare prelungită
Siofor SR 500 mg, 750 mg, 1000 mg tablety s predĺženým uvoľňovaním
Slovenia:
Siofor SR 500 mg, 750 mg, 1000 mg tablete s podaljšanim sproščanjem

Date of last revision of the leaflet: 03/2025