Package Insert: Information for the Patient

Pioglitazona/Metformina Aristo 15 mg/850 mg Film-Coated Tablets EFG

pioglitazone/hydrochloride of metformin

Read this package insert carefully before starting to take this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

This medication contains pioglitazone and metformin. It is an antidiabetic medication used in adult patients to treat type 2 diabetes mellitus (non-insulin dependent) when treatment with metformin alone is not sufficient. This type of type 2 diabetes typically presents in adults, primarily as a result of overweight and if the body either does not produce enough insulin (a hormone that controls blood sugar levels) or is unable to effectively use the insulin produced. Your doctor will monitor the effect this medication is having on you between 3 and 6 months since treatment began.

This medication helps control blood sugar levels if you have type 2 diabetes, allowing your body to use insulin more effectively that it produces.

Do not take Pioglitazona/Metformina 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 difficulty breathing.
• if you have any liver disease.
• if you drink too much alcohol (daily or occasionally).
• if you have uncontrolled diabetes with, for example, severe hyperglycemia (high blood sugar), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see section “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called “ketone bodies” accumulate in the blood, which can lead to diabetic precoma. Symptoms include stomach pain, rapid and deep breathing, drowsiness, or an unusual fruity odor in your breath.
• if you have or have had bladder cancer.
• if you have uncontrolled blood in your urine that has not been controlled by your doctor.
• if you have severe kidney function reduction.
• if you have a severe infection or are dehydrated.
• if you are undergoing a radiology contrast study (a specific type of diagnostic test using X-rays and an injectable contrast medium), consult your doctor as you will need to stop taking this medication for a certain period of time before and after the test.
• if you are breastfeeding.

Warnings and precautions

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

• if you have heart problems. Some patients with type 2 diabetes mellitus of long duration and heart disease or previous stroke who received pioglitazone and insulin together 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 take 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 polycystic ovary syndrome (PCOS). You may be more likely to become pregnant, as taking pioglitazone/metformin may cause you to ovulate again. If this is your case, use suitable contraceptive methods to avoid the possibility of unplanned pregnancy.
• if you have liver problems. Before starting treatment with pioglitazone/metformin, you will have a blood test to check your liver function. These tests should be done periodically. Inform your doctor as soon as possible if you develop symptoms that suggest liver problems (such as inexplicable nausea, vomiting, stomach pain, fatigue, loss of appetite, and/or dark urine) as your liver function should be checked.

You may also show a reduction in the count of blood cells (anemia).

Risk of lactic acidosis

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

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

Stop taking Pioglitazona/Metformina Aristo for a short period of time if you have a condition that may be associated with dehydration(significant loss of body fluids), such as intense vomiting, diarrhea, fever, exposure to heat, or if you drink less liquid than normal. Consult your doctor for further instructions.

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

The symptoms of lactic acidosis include:

• Vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of discomfort, with intense fatigue
• difficulty breathing
• reduction in 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 an older person and/or if your kidney function is worsening.

If you need to undergo major surgery, you should stop taking pioglitazone/metformin while the procedure is being performed and for a period of time after it. Your doctor will decide when to interrupt treatment with pioglitazone/metformin and when to restart it.

Hypoglycemia

If you take pioglitazone/metformin with other diabetes medications, you are more likely to have your blood sugar level drop below the normal limit (hypoglycemia). If you experience hypoglycemia symptoms, such as weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances, or difficulty concentrating, take something sweet to raise your blood sugar levels. Consult your doctor or pharmacist if you are unsure how to recognize these symptoms. It is recommended that you carry sugar cubes, candies, cookies, or fruit juice with you.

Fractures

There has been an observed increase in bone fractures in patients, particularly in women who took pioglitazone. Your doctor will take this into account when treating your diabetes.

Children and adolescents

Not recommended for children and adolescents under 18 years old.

Other medications and Pioglitazona/Metformina Aristo

If you need to receive an injection of a contrast medium containing iodine, such as in the context of a radiography or examination, you should stop taking pioglitazone/metformin before the injection or at the time of the injection. Your doctor will decide when to interrupt treatment with pioglitazone/metformin and when to restart it.

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to 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 acid)
• glucocorticoids (used to treat inflammation)
• beta-2 agonists (used to treat asthma)
• diuretics (used to treat high blood pressure)
• nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors, such as ibuprofen and celecoxib (used to treat pain and inflammation)
• some medications used to treat high blood pressure (ACE inhibitors and angiotensin II receptor antagonists)

Taking Pioglitazona/Metformina 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, or if you think you may be 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 do so (see section “Do not take Pioglitazona/Metformina Aristo”).

Driving and operating machinery

This medication does not affect your ability to drive or operate machinery, but you should be cautious if you experience visual disturbances.

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

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of 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 renal function, your doctor may prescribe a lower dose that may need to be administered in separate tablets of pioglitazone and metformin.

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

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

You will need to control your weight regularly; if you gain weight, inform your doctor.

Your doctor will ask you to have blood tests regularly during treatment with pioglitazone/metformin to check the correct functioning of your liver.

At least once a year (more often if you are advanced in age or have kidney problems), your doctor will check the correct 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 decrease below normal, but you can increase it by taking sugar. It is recommended that you carry some sugar cubes, candies, cookies, or some fruit juice.

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

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

If you forgot 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 compensate for the missed doses.

If you interrupt treatment with Pioglitazone/Metformin Aristo

Take pioglitazone/metformin every day, as prescribed. If you interrupt treatment with pioglitazone/metformin, your blood sugar level may increase. Consult with your doctor before interrupting treatment.

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

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

Pioglitazona/metformina may cause a very rare but serious side effect called lactic acidosis (see "Warnings and Precautions" section), which can lead to coma. If this occurs, stop taking pioglitazona/metformina and contact a doctor or the nearest hospital immediately.

Infrequently (may affect up to 1 in 100 people), bladder cancer has developed in patients taking pioglitazona/metformina. Symptoms include blood in the urine, pain while urinating, or a sudden urge to urinate. If you experience any of these symptoms, consult your doctor immediately.

Bone fractures: frequent reports (may affect up to 1 in 10 people) have been made in both men and women taking pioglitazona/metformina (frequency cannot be estimated from available data). Consult your doctor as soon as possible if you experience this side effect.

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

Unknown frequency (cannot be estimated from available data) allergic reactions have been reported in patients treated with pioglitazona/metformina. If you experience a severe allergic reaction, including hives, facial swelling, lip, tongue, or throat swelling that may cause difficulty breathing or swallowing, stop taking this medication and consult your doctor immediately.

Some patients have experienced the following side effects when taking pioglitazona/metformina:

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

• Stomach pain
• Nausea
• Vomiting
• Diarrhea
• Loss of appetite

Frequent (may affect up to 1 in 10 people)

• Localized swelling (edema)
• Weight gain
• Headache
• Respiratory infection
• Vision disturbances
• Joint pain
• Impotence
• Blood in the urine
• Reduction in red blood cell count (anemia)
• Numbness
• Altered taste

Poorly frequent (may affect up to 1 in 100 people)

• Nasal sinusitis (inflammation of the nasal sinuses)
• Gas
• Difficulty sleeping (insomnia)

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

• Decreased vitamin B12 levels in the blood
• Skin redness
• Itching skin
• Hives

Unknown frequency (cannot be estimated from available data)

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

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

Do not use this medication after the expiration date that appears on the box and in the blister after “CAD”. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from light.

Medications should not be disposed of through drains or in the trash. Dispose of packaging and medications you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Pioglitazona/Metformina Aristo

The active principles are pioglitazona and hydrochloride of metformina. Each tablet contains 15 mg of pioglitazona (as hydrochloride) and 850 mg of hydrochloride of metformina.

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

Appearance of the product and contents of the packaging

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

They are presented in packaging with 56 tablets.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Aristo Pharma GmbH

Wallenroder Str. 8-10

13435 Berlin

Germany

Responsible for manufacturing

Genepham S.A

Marathonos Avenue 18 km

Pallini, Attiki

15351 Greece

O

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 by contacting the local representative of the holder of the marketing authorization:

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 with the following names:

ItalyPioglitazone/Metformin hydrochloride Aristo

SpainPioglitazona/Metformina Aristo 15 mg/850 mg film-coated tablets EFG

Last review date of this leaflet: January 2020

Detailed and updated information about this medicinal product is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/