PIOGLITAZONE/METFORMIN ARISTO 15 mg/850 mg FILM-COATED TABLETS

2. What you need to know before taking Pioglitazone/Metformin Aristo

Do not take Pioglitazone/Metformin Aristo:

• if you are allergic to pioglitazone, metformin, or any of the other components of this medication (listed in section 6).
• if you have heart failure or have had it in the past.
• if you have recently had a heart attack, have severe circulation problems such as shock, or have breathing difficulties.
• if you have any liver disease.
• if you drink too much alcohol (daily or only occasionally).
• if you have uncontrolled diabetes, such as severe hyperglycemia (high blood sugar), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see section "Risk of Lactic Acidosis"), or ketoacidosis. Ketoacidosis is a disorder in which substances called "ketone bodies" accumulate in the blood, which can lead to a pre-diabetic coma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or unusual fruity breath odor.
• if you have or have had bladder cancer.
• if you have blood in your urine that has not been controlled by your doctor.
• if you have severe kidney function impairment.
• if you have a severe infection or are dehydrated.
• if you are to undergo a contrast radiology test (a specific type of diagnostic test with X-rays and an injectable contrast medium), consult your doctor, as you will need to stop taking this medication for a certain period before and after the test.
• if you are breastfeeding.

Warnings and Precautions

Consult your doctor or pharmacist before starting to take this medication (see also section 4).

• if you have heart problems. Some patients with long-standing type 2 diabetes mellitus and pre-existing heart disease or stroke who received pioglitazone and insulin concomitantly developed heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).
• if you have fluid retention or heart problems, particularly if you are over 75 years old. If you are taking anti-inflammatory medications that can also cause fluid retention and swelling, you should also consult your doctor.
• if you have a special type of diabetic eye disease called macular edema (inflammation of the back of the eye), consult your doctor if you notice changes in your vision.
• if you have cysts on the ovaries (polycystic ovary syndrome). You may be more likely to become pregnant, as taking pioglitazone/metformin can cause you to ovulate again. If this is the case, use appropriate contraceptive methods to avoid the possibility of an unplanned pregnancy.
• if you have liver problems. Before starting treatment with pioglitazone/metformin, you will undergo a blood test to check your liver function. These tests should be performed periodically. Inform your doctor as soon as possible if you develop symptoms suggesting a liver problem (such as unexplained nausea, vomiting, stomach pain, fatigue, loss of appetite, and/or dark urine), as your liver function should be checked.

You may also experience a reduction in blood cell count (anemia).

Risk of Lactic Acidosis

Pioglitazone/metformin may cause a very rare but very serious side effect called lactic acidosis, especially if your kidneys do not function properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, severe infections, prolonged fasting, or alcohol consumption, dehydration (see below), liver problems, and any medical condition in which a part of the body has a reduced oxygen supply (such as severe and acute heart disease).

If any of the above applies to you, consult your doctor for further instructions.

Stop taking Pioglitazone/Metformin Aristo for a short period if you have a disorder that may be associated with dehydration(significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you drink less fluid than usual. Consult your doctor for further instructions.

Stop taking Pioglitazone/Metformin Aristo and contact a doctor or the nearest hospital immediately if you experience any symptoms of lactic acidosis, as this condition can lead to a coma.

The symptoms of lactic acidosis include:

• Vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort, with intense fatigue
• difficulty breathing
• reduced body temperature and heart rate

Lactic acidosis is a medical emergency and should be treated in a hospital.

During treatment with pioglitazone/metformin, your doctor will check your kidney function at least once a year or more frequently if you are elderly and/or if your kidney function is deteriorating.

If you need to undergo major surgery, you should stop taking pioglitazone/metformin during the procedure and for a period after it. Your doctor will decide when to stop and restart treatment with pioglitazone/metformin.

Hypoglycemia

If you take pioglitazone/metformin with other diabetes medications, you are more likely to experience low blood sugar (hypoglycemia). If you experience symptoms of hypoglycemia, such as weakness, dizziness, increased sweating, rapid heartbeat, vision changes, or difficulty concentrating, take some sugar to raise your blood sugar levels. Consult your doctor or pharmacist if you are unsure how to recognize such symptoms. It is recommended that you carry sugar lumps, sweets, biscuits, or some sugary fruit juice with you.

Bone Fractures

A higher number of bone fractures has been observed in patients, particularly women, taking pioglitazone. Your doctor will take this into account when treating your diabetes.

Children and Adolescents

It is not recommended for children and adolescents under 18 years of age.

Other Medications and Pioglitazone/Metformin Aristo

If you need to be administered an injection of a contrast medium containing iodine into your bloodstream, for example, in the context of an X-ray or examination, you should stop taking pioglitazone/metformin before the injection or at the time of the injection. Your doctor will decide when to stop and restart treatment with pioglitazone/metformin.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medication. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of pioglitazone/metformin. It is especially important to mention the following:

• gemfibrozil (used to reduce cholesterol)
• rifampicin (used to treat tuberculosis and other infections)
• cimetidine (used to reduce stomach acidity)
• glucocorticoids (used to treat inflammation)
• beta-2 agonists (used to treat asthma)
• medications that increase urine production (diuretics)
• medications used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib)
• certain medications used to treat high blood pressure (angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists)

Taking Pioglitazone/Metformin Aristo with Alcohol

Avoid excessive alcohol consumption while taking pioglitazone/metformin, as this can increase the risk of lactic acidosis (see section "Risk of Lactic Acidosis").

Pregnancy and Breastfeeding

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor. Pioglitazone/metformin is not recommended during pregnancy. If you plan to become pregnant, your doctor will advise you to stop taking this medication.
• Do not take pioglitazone/metformin if you are breastfeeding or plan to breastfeed (see section "Do not take Pioglitazone/Metformin Aristo").

Driving and Using Machines

This medication does not affect your ability to drive or use machines, but you should be cautious if you experience vision changes.

This medication contains less than 23 mg of sodium (1 mmol) per tablet; it is essentially "sodium-free".

3. How to Take Pioglitazone/Metformin Aristo

Follow the administration instructions for this medication exactly as indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose is one tablet twice a day. If necessary, your doctor may prescribe a different dose. If you have reduced kidney function, your doctor may prescribe a lower dose that may need to be administered through separate tablets of pioglitazone and metformin.

Take the tablets with a glass of water. You should take the tablets with meals or immediately after meals to reduce the risk of digestive discomfort.

If you are following a special diet for diabetics, maintain it while taking this medication.

You should regularly check your weight; if you gain weight, inform your doctor.

Your doctor will regularly request blood tests during treatment with pioglitazone/metformin to check the proper functioning of your liver.

At least once a year (more frequently if you are elderly or have kidney problems), your doctor will check the proper functioning of your kidneys.

If you take more Pioglitazone/Metformin Aristo than you should

If you accidentally take too many tablets, or if a child or another person takes your medication, inform your doctor or pharmacist immediately. Your blood sugar level may drop below normal, but you can increase it by taking sugar. It is recommended that you carry sugar lumps, sweets, biscuits, or some sugary fruit juice with you.

If you have taken more pioglitazone/metformin than you should, you may experience lactic acidosis (see section "Warnings and Precautions")

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Pioglitazone/Metformin Aristo

Take Pioglitazone/Metformin Aristo every day, as prescribed. However, if you forget to take a dose, omit the missed dose and continue with your treatment as usual. Do not take a double dose to make up for missed doses.

If you stop taking Pioglitazone/Metformin Aristo

Take pioglitazone/metformin every day, as prescribed. If you stop taking pioglitazone/metformin, your blood sugar level may increase. Consult your doctor before stopping treatment.

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

4. Possible Side Effects

Like all medications, this medication can cause side effects, although not everyone will experience them.

Pioglitazone/metformin may cause a very rare but very serious side effect called lactic acidosis (see section "Warnings and Precautions"), which can lead to a coma.

Uncommonly (may affect up to 1 in 100 people), bladder cancer has been developed in patients taking pioglitazone/metformin. The signs and symptoms include blood in the urine, pain when urinating, or urgent need to urinate. If you experience any of these symptoms, consult your doctor immediately.

Bone fractures: frequently (may affect up to 1 in 10 people) reported in both women and men taking pioglitazone/metformin (frequency cannot be estimated from the available data). Consult your doctor as soon as possible if you experience this side effect.

Blurred vision due to swelling (or fluid) in the back of the eye (macular edema) has been reported (frequency cannot be estimated from the available data). If you experience these symptoms for the first time, inform your doctor as soon as possible. If you have already experienced blurred vision and the symptoms worsen, consult your doctor as soon as possible.

Allergic reactions have been reported with an unknown frequency (cannot be estimated from the available data) in patients treated with pioglitazone/metformin. If you have a severe allergic reaction, including hives and swelling of the face, lips, tongue, or throat that can cause difficulty breathing or swallowing, stop taking this medication and consult your doctor immediately.

Some patients have experienced the following side effects when taking pioglitazone/metformin:

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

• stomach pain
• nausea
• vomiting
• diarrhea
• loss of appetite

Common (may affect up to 1 in 10 people)

• localized swelling (edema)
• weight gain
• headache
• respiratory infection
• vision disorders
• joint pain
• impotence
• blood in the urine
• reduced red blood cell count (anemia)
• numbness
• taste disturbance

Uncommon (may affect up to 1 in 100 people)

• nasal passage inflammation (sinusitis)
• gas
• difficulty sleeping (insomnia)

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

• reduced vitamin B12 levels in the blood
• skin redness
• skin itching
• hives

Frequency not known (cannot be estimated from the available data)

• liver inflammation (hepatitis)
• liver dysfunction (changes in liver enzymes)

5. Storage of Pioglitazone/Metformin Aristo

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date stated on the carton and blister after "EXP". The expiration date is the last day of the month indicated.

Store in the original packaging to protect from light.

Medications should not be disposed of via wastewater or household waste. Return the packaging and any unused medication to the pharmacy's SIGRE Point. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Pioglitazone/Metformin Aristo

The active ingredients are pioglitazone and metformin hydrochloride. Each tablet contains 15 mg of pioglitazone (as hydrochloride) and 850 mg of metformin hydrochloride.

The other ingredients are microcrystalline cellulose, povidone (K 30), sodium croscarmellose, magnesium stearate, hypromellose, macrogol 8000, talc, and titanium dioxide (E171).

Appearance of the Product and Package Contents

The film-coated tablets (tablets) are white, oblong, biconvex, and engraved with '15 / 850' on one side and smooth on the other.

They are available in packs of 56 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Aristo Pharma GmbH

Wallenroder Str. 8-10

13435 Berlin

Germany

Manufacturer

Genepham S.A

Marathonos Avenue 18 km

Pallini, Attiki

15351 Greece

Or

RONTIS HELLAS MEDICAL AND PHARMACEUTICAL PRODUCTS S.A.

P.O. BOX 3012 Larissa Industrial Area,

Larissa, 41500, Greece

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Aristo Pharma Iberia, S.L.

C/ Solana, 26

28850, Torrejón de Ardoz

Madrid, Spain

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

Italy Pioglitazone/Metformin hydrochloride Aristo

Spain Pioglitazona/Metformina Aristo 15 mg/850 mg film-coated tablets EFG

Date of the last revision of this leaflet: January 2020

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/