SIOFOR 1000

Package leaflet: Information for the patient

SIOFOR 1000
1000 mg, coated tablets
For use in children over 10 years of age and in adults
Metformini hydrochloridum
Please read carefully the entire leaflet before taking the medicine, as it contains
important information for the patient.

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

Leaflet contents:

1. What Siofor 1000 is and what it is used for
2. Important information before taking Siofor 1000
3. How to take Siofor 1000
4. Possible side effects
5. How to store Siofor 1000
6. Contents of the pack and other information

1. What Siofor 1000 is and what it is used for

What Siofor 1000 is
Siofor 1000 contains metformin, a substance 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. Siofor 1000 helps lower blood glucose levels to values as close to normal as possible.
In overweight adults, long-term use of Siofor 1000 also reduces the risk of diabetes-related complications. Treatment with Siofor 1000 is associated with stabilization or moderate reduction in body weight.

What Siofor 1000 is used for
Siofor 1000 is used in the treatment of patients with type 2 diabetes (also known as non-insulin-dependent diabetes), in whom diet and physical exercise alone are insufficient to achieve adequate control of blood glucose levels. It is particularly used in patients who are overweight.
Adults may take Siofor 1000 as monotherapy or in combination with other antidiabetic medicines (oral medications or insulin).
In children over 10 years of age and adolescents, Siofor 1000 may be used as monotherapy or in combination with insulin.

2. Information before using Siofor 1000

When not to use Siofor 1000:

• if the patient is allergic to metformin hydrochloride or any of the other ingredients of this medicine (listed in section 6),
• if the patient has significantly reduced kidney function,
• in case of liver dysfunction,
• 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 a diabetic pre-coma state. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or an unusual fruity odour of the breath,
• in case of excessive fluid loss from the body (dehydration), e.g. due to prolonged or severe diarrhoea or repeated vomiting. Dehydration may lead to impaired kidney function, which in turn may increase the risk of lactic acidosis (see below "Warnings and precautions"),
• in case of severe infection, such as affecting the lungs, bronchi or kidneys. Severe infections may lead to impaired kidney function, 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 (such as 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, consult a doctor before using this medicine.

Warnings and precautions
Before starting treatment with Siofor 1000, discuss this with your doctor.
You must consult your doctor if:

• you need to undergo a radiological examination or any procedure requiring intravenous injection of an iodine-containing contrast agent,
• you need to undergo major surgery.

If you are undergoing major surgery, you must not take Siofor 1000 during the procedure
and for some time afterwards. Your doctor will decide when you should stop and restart treatment
with Siofor 1000. It is important to follow your doctor's instructions exactly.
Risk of lactic acidosis
Siofor 1000 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), liver dysfunction, 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 you, consult your doctor for further instructions.
You should temporarily stop taking Siofor 1000 if you develop any illness that may lead to dehydration (significant fluid loss from the body), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if you are drinking less fluid than usual. Consult your doctor for further instructions.
You should stop taking Siofor 1000 and contact your doctor or the nearest hospital immediately if you experience any symptoms of lactic acidosis, 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.

Contact your doctor immediately for further instructions if:

• you have 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 treatment, you experience any of the following symptoms: seizures, worsening cognitive function, movement difficulties, signs indicating nerve damage (e.g. pain or numbness), migraine or deafness.

During treatment with Siofor 1000, your doctor will monitor your kidney function at least once a year, or more frequently if you are elderly and/or have worsening kidney function.
Siofor 1000 alone does not cause hypoglycaemia (low blood glucose levels).
However, if Siofor 1000 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, vision disturbances or difficulty concentrating, eating or drinking something containing sugar usually helps.

Siofor 1000 and other medicines:
If you are to receive an intravenous iodine-containing contrast agent, for example for an X-ray examination or computed tomography, you must stop taking Siofor 1000 before or at the latest at the time of such injection. Your doctor will decide when you should stop and restart treatment with Siofor 1000 (see above: "You must consult your doctor if:").
Tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take. You may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Siofor 1000 by your doctor. It is particularly important to inform your 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),
• other medicines used to treat diabetes,
• medicines that may alter the blood concentration of Siofor 1000, especially if you have impaired kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).

Use of Siofor 1000 with alcohol:
Avoid consuming excessive amounts of alcohol while taking Siofor 1000, as this may increase the risk of lactic acidosis (see section "Warnings and precautions"), particularly in patients with liver impairment or in undernourished individuals.
This also applies to medicines containing alcohol.

Pregnancy and breastfeeding:
During pregnancy, diabetes treatment requires insulin therapy.
If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to have a baby, you should consult your doctor or pharmacist before using this medicine. In such cases, your doctor may adjust your treatment accordingly.
This medicine is not recommended during breastfeeding.

Driving and operating machinery:
Siofor 1000, when used as the sole antidiabetic medicine (monotherapy), does not cause hypoglycaemia.
This means it does not affect the ability to drive or operate machinery.
However, you should exercise particular caution if Siofor 1000 is used together with other antidiabetic medicines that may cause hypoglycaemia (such as: sulfonylurea derivatives, insulin, meglitinides). Symptoms of hypoglycaemia include: weakness, dizziness, increased sweating, rapid heartbeat, vision disturbances or difficulty concentrating.
If such symptoms occur, you should not drive or operate machinery.

3. How to use Siofor 1000

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor or pharmacist.
Siofor 1000 does not replace the benefits of a healthy lifestyle. You should continue to follow your doctor's advice regarding diet and regular physical exercise.

Recommended dose
In adults, the usual starting dose is half a coated tablet of Siofor 1000 (corresponding to 500 mg of metformin hydrochloride) taken two or three times daily, or 850 mg of metformin hydrochloride taken two or three times daily (this dose is not available when using Siofor 1000).
The maximum daily dose is one coated tablet of Siofor 1000 taken three times a day.
If the patient has impaired kidney function, the doctor may prescribe a lower dose.

Use in children and adolescents
In children over 10 years of age and adolescents, the usual starting dose is half a coated tablet of Siofor 1000 (corresponding to 500 mg of metformin hydrochloride) taken once daily, or 850 mg of metformin hydrochloride taken once daily (this dose is not available when using Siofor 1000).
The maximum daily dose is one coated tablet of Siofor 1000 taken twice daily.
Treatment of children aged 10 to 12 years is recommended by the doctor only in justified cases, as experience with the use of this medicine in this age group is limited.

If the patient is also using insulin, the doctor will advise how to start treatment with Siofor 1000.

Monitoring of treatment

• Your doctor will order regular blood glucose tests and adjust the dose of Siofor 1000 according to blood glucose levels. You should attend regular follow-up visits with your doctor. This is particularly important for children and adolescents or elderly patients.
• Your doctor will check your kidney function at least once a year. More frequent monitoring may be necessary in elderly patients or if the patient's kidneys are not functioning properly.

How to divide Siofor 1000 coated tablets
The tablet can be divided into equal doses. Due to its formulation, Siofor 1000 allows for easy and precise splitting of the coated tablet. The coated tablets can be broken in half with both hands or with the thumb by placing the tablet on a flat surface with the scored side facing down and applying pressure (see Figure 1, 2, 3).

How to take Siofor 1000 coated tablets
Take the tablets during or after a meal. This helps 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 it in the morning (with breakfast).
• If taking two divided doses per day, take them in the morning (with breakfast) and in the evening (with dinner).
• If taking three divided doses per day, take them in the morning (with breakfast), at midday (with lunch), and in the evening (with dinner).

If after some time the patient feels that the medicine's effect is too strong or too weak, they should consult their doctor or pharmacist.

Taking more than the recommended dose of SIOFOR 1000
If a patient takes more Siofor 1000 than prescribed, lactic acidosis may occur.
Symptoms of lactic acidosis include: vomiting, abdominal pain (abdominal discomfort) with muscle cramps, general malaise accompanied by severe fatigue and difficulty breathing. Other symptoms include lowered body temperature and slowed heart rate. If these symptoms occur, the patient may require immediate hospital treatment, as lactic acidosis can lead to coma.
Contact a doctor immediately or go to the nearest hospital.

Missed dose of Siofor 1000
Do not take a double dose to make up for a missed dose. Take the next dose according to the prescribed dosing schedule.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody gets them.
The following adverse reactions may occur:
Siofor 1000 may very rarely cause (may affect up to 1 in
10,000 people) a very serious adverse reaction known as lactic acidosis
(see section “Warnings and precautions”). If this occurs in a patient, treatment with Siofor 1000 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 (may affect more than 1 in 10 people)

• Gastrointestinal disorders such as nausea, vomiting, diarrhoea, abdominal pain (pain in the abdominal cavity), loss of appetite. These adverse reactions most commonly occur at the beginning of Siofor 1000 treatment. Splitting the daily dose and taking Siofor 1000 with or immediately after meals may be helpful. If symptoms do not resolve, Siofor 1000 should be discontinued and the doctor informed.

Common adverse reactions (may affect up to 1 in 10 people)

• Taste disturbances.
• Reduced or low blood levels of vitamin B_(12) (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling sensations (paraesthesiae), or pale or yellowish skin). The 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 (may affect up to 1 in 10,000 people)

• Skin reactions such as skin redness (erythema), itching, or itchy rash (urticaria),
• Abnormal liver function test results or hepatitis (liver inflammation, which may cause fatigue, loss of appetite, weight loss, with or without yellowing of the skin and whites of the eyes). If such symptoms occur, this medicine should be discontinued and the doctor informed.

Children and adolescents
Limited data in children and adolescents have shown that adverse reactions were similar in type and severity to those reported in adults.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform a doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Reactions of Medicinal Products at 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 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 Siofor 1000

Keep this medicine out of sight and reach of children.
If a child is being treated with Siofor 1000, parents and caregivers should supervise how the medicine is used.
Do not use this medicine after the expiry date stated on the blister pack and the outer cardboard box following the abbreviation EXP. The expiry date refers to the last day of the stated month.
No special storage conditions are required.
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 Siofor 1000 contains
The active substance is metformin hydrochloride.
Each film-coated tablet contains 1000 mg of metformin hydrochloride (equivalent to 780 mg of metformin).
The other ingredients are: hypromellose, povidone K 25, magnesium stearate, macrogol 6000, titanium dioxide (E 171).

What Siofor 1000 looks like and contents of the pack
Siofor 1000 is a white, biconvex, elongated film-coated tablet with a score line on one side and a dividing groove on the other.
The tablet can be divided into two equal doses (see section 3 of the splitting instructions).
Pack contents: 30, 60, 90 or 120 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
Berlin-Chemie AG
Glienicker Weg 125
D-12489 Berlin
Germany

Manufacturer
Berlin-Chemie AG
Glienicker Weg 125
D-12489 Berlin
Germany
Menarini - Von Heyden GmbH
Leipziger Str. 7 - 13
D-01097 Dresden
Germany

For further information, contact the representative of the Marketing Authorisation Holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
tel. (22) 566 21 00
fax. (22) 566 21 01

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium Metformax 1000 mg film-coated tablets
Czech Republic Siofor
Estonia Metforal 1000 mg
Lithuania Metforal 1000 mg plėvele dengtos tabletės
Luxembourg Metformax 1000 mg comprimés pelliculés
Latvia Metforal 1000
Germany Siofor 1000
Poland Siofor 1000
Slovakia Siofor 1000
Slovenia Siofor 1000 mg
Hungary Meforal 1000 mg
Italy Metforalmille