Siofor 850

Package leaflet: information for the patient

SIOFOR 850, 850 mg, film-coated tablets
Metformini hydrochloridum
For use in children over 10 years of age and in adults
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• 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.
• The medicine may harm another person, 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.

Table of contents:

1. What Siofor 850 is and what it is used for
2. Important information before taking Siofor 850
3. How to take Siofor 850
4. Possible side effects
5. How to store Siofor 850
6. Contents of the pack and other information

1. What Siofor 850 is and what it is used for

Siofor 850 contains metformin, an active 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 850 helps lower blood glucose levels to values as close to normal as possible.
In overweight adults, long-term use of Siofor 850 also reduces the risk of complications associated with type 2 diabetes. Treatment with Siofor 850 is associated with stabilization or moderate reduction in body weight.
For what purpose is Siofor 850 used?
Siofor 850 is a medicine used in:

• the treatment of type 2 diabetes, especially in overweight patients, to achieve proper control of blood glucose levels;
• prevention of type 2 diabetes in patients with prediabetes.

Adults with type 2 diabetes may take Siofor 850 as monotherapy or in combination with other antidiabetic medicines (oral medications or insulin).
Children over 10 years of age and adolescents with type 2 diabetes may take Siofor 850 as monotherapy or in combination with insulin.
During treatment with Siofor 850, a proper diet and regular physical activity should be maintained.

2. Important information before using Siofor 850

When not to use Siofor 850:

• if the patient is allergic to metformin 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 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 impaired kidney function, which may increase the risk of lactic acidosis (see below "Warnings and precautions")
• in case of severe infection affecting the lungs, bronchi or kidneys. Severe infections may impair 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.

Warnings and precautions
Before starting treatment with Siofor 850, discuss this with your doctor.
You must consult your doctor if:

• a radiological examination or a procedure requiring intravenous injection of an iodine-containing contrast agent is planned
• a major surgical procedure is planned. If the patient is to undergo surgery, Siofor 850 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 Siofor 850. It is important to strictly follow the doctor's instructions.

Risk of lactic acidosis
Siofor 850 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 a 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.
Siofor 850 should be temporarily discontinued if the patient develops a medical condition that may be associated with 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. Consult your doctor for further instructions.
Siofor 850 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 accompanied by profound fatigue
• difficulty breathing
• 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:

• the patient has a genetically inherited mitochondrial disorder (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)
• after starting metformin, the patient experiences any of the following symptoms: seizures, worsening cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine or deafness.

During treatment with Siofor 850, 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.
Siofor 850 itself does not cause hypoglycaemia (low blood glucose levels).
However, there is a risk of hypoglycaemia when Siofor 850 is used in combination with other antidiabetic medicines that may cause hypoglycaemia (such as sulfonylurea derivatives, insulin, meglitinides). 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.

Siofor 850 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, the patient must stop taking Siofor 850 before or at the latest at the time of such injection. The doctor will decide when the patient should stop and restart treatment with Siofor 850 (see above: "You must consult your doctor if necessary:").
Tell your doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take together with Siofor 850.
The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Siofor 850 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 asthma treatment)
• corticosteroids (used to treat various conditions, such as severe skin inflammation or asthma)
• other medicines used in diabetes treatment
• medicines that may alter the blood concentration of Siofor 850, especially if the patient has impaired kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib)

Siofor 850 and alcohol
Avoid consuming excessive amounts of alcohol while taking Siofor 850, as this may increase the risk of lactic acidosis (see section "Warnings and precautions"), particularly in patients with liver dysfunction or in malnourished individuals.
This also applies to medicines containing alcohol.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor before using this medicine.

Pregnancy
During pregnancy, diabetes treatment requires insulin therapy.

Breastfeeding
This medicine is not recommended during breastfeeding.

Driving and operating machinery
Siofor 850, when used alone as an antidiabetic medicine, does not cause hypoglycaemia (symptoms of low blood glucose levels). This means it does not affect the ability to drive or operate machinery.
However, special caution is required when Siofor 850 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, blurred vision or difficulty concentrating.
If such symptoms occur, the patient should not drive or operate machinery.

3. How to use Siofor 850

This medicine should always be taken as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Siofor 850 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 dosage:
For adults, the usual starting dose is 1 Siofor 850 coated tablet two to three times daily
(corresponding to 1700 mg or 2550 mg of metformin hydrochloride per day), or 500 mg of
metformin hydrochloride two to three times daily (this dose cannot be achieved when using
Siofor 850).
The maximum daily dose is 3000 mg, divided into three doses.
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 1 coated tablet of
Siofor 850 once daily (corresponding to 850 mg of metformin hydrochloride per day), or
500 mg of metformin hydrochloride once daily (this dose cannot be achieved when using
Siofor 850).
The maximum daily dose is 2000 mg, administered in 2 or 3 divided doses.
Treatment of children aged over 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 on how to initiate treatment with
Siofor 850.

Prediabetes (monotherapy in adults with normal kidney function)
The recommended starting dose for patients with prediabetes is 1 coated tablet (500 mg or
850 mg) once daily, taken during or after a meal.
The usual dose for patients with prediabetes is 1 coated tablet (500 mg or 850 mg) twice
daily, taken during or after a meal.
Gradual dose escalation may improve gastrointestinal tolerance.
The doctor will assess whether treatment should be continued based on regular monitoring
of blood glucose levels and risk factors.

Monitoring of treatment

• The doctor will order regular blood glucose tests and adjust the dose of Siofor 850 according to blood glucose levels. Regular follow-up visits to the doctor are necessary. This is particularly important for children, adolescents, and elderly patients.
• The doctor will check kidney function at least once a year during treatment with Siofor 850. More frequent monitoring may be necessary in elderly patients or if the patient's kidneys are not functioning properly.

How to take Siofor 850 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).

The score line on the tablet is only intended to facilitate breaking the tablet for easier swallowing.
If after some time the patient feels that the effect of Siofor 850 is too strong or too weak, they should consult a doctor or pharmacist.

Taking more Siofor 850 than recommended
If more Siofor 850 is taken than recommended, lactic acidosis may occur.
Symptoms of lactic acidosis 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 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 850
Do not take a double dose to make up for a missed dose. Take the next dose according to the scheduled dosing regimen.
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 everyone experiences them.
The following adverse reactions may occur:
Important adverse reactions or symptoms that patients should be aware of, and precautions to be taken if they occur:
Siofor 850 may very rarely cause (in up to 1 in 10,000 patients) a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If a patient experiences this, Siofor 850 must be discontinued immediately and the patient should contact a doctor or go to the nearest hospital, as lactic acidosis may lead to coma.
Other possible adverse reactions
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), and loss of appetite. These adverse reactions occur most frequently at the beginning of treatment with Siofor 850. It may help to divide the daily dose into several smaller doses taken throughout the day and to take the tablets with or immediately after meals. If symptoms do not resolve, Siofor 850 should be discontinued and the doctor informed.

Common adverse reactions (may affect less than 1 in 10 people)

• Taste disturbances
• Decreased 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 these symptoms, as some of them may also be caused by diabetes or other health problems unrelated to diabetes.
Very rare adverse reactions (may affect less than 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, Siofor 850 should be discontinued and the doctor informed.

Additional adverse reactions in 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, patients should inform their 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 850

Keep the medicine out of the sight and reach of children. If a child is being treated with Siofor 850, parents and caregivers should supervise how the medicine is used.
Do not use this medicine after the expiry date stated on the outer packaging and blister after the abbreviation "EXP". The expiry date refers to the last day of the stated month.
No special storage conditions apply.
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 package and other information

What Siofor 850 contains

• The active substance is metformin hydrochloride.
• One coated tablet contains 850 mg of metformin hydrochloride, equivalent to 662.9 mg of metformin.
• Other components are:
  Tablet core: hypromellose, povidone, magnesium stearate.
  Tablet coating: hypromellose, polyethylene glycol 6000, titanium dioxide (E 171).

What Siofor 850 looks like and contents of the pack
White, elongated coated tablets with a score line on both sides, in blisters made of transparent PVC foil and aluminium foil.
Siofor 850 is available in packs containing: 15, 30, 60, 90 or 120 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
BERLIN – CHEMIE AG
(Menarini Group)
Glienicker Weg 125
12489 Berlin, Germany

Manufacturer:
BERLIN – CHEMIE AG
Glienicker Weg 125
12489 Berlin, Germany
Menarini - Von Heyden GmbH
Leipziger Str. 7 – 13
D-01097 Dresden
Germany

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Berlin-Chemie/Menarini Polska Sp. z o.o.
Tel.: + 48 22 566 21 00
Fax: + 48 22 566 21 01