Package leaflet: Information for the user

Gliptivil Combo, 50 mg + 850 mg, film-coated tablets
Gliptivil Combo, 50 mg + 1000 mg, film-coated tablets
Vildagliptinum + Metformini hydrochloridum
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet so that you can read it again if necessary.
If you have any further questions, please ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

What Gliptivil Combo is and what it is used for
Important information before taking Gliptivil Combo
How to take Gliptivil Combo
Possible side effects
How to store Gliptivil Combo
Contents of the pack and other information

1. What Gliptivil Combo is and what it is used for

The active substances in Gliptivil Combo are vildagliptin and metformin hydrochloride, which belong to a group of medicines called "oral antidiabetic agents".
Gliptivil Combo is used in the treatment of adult patients with type 2 diabetes. This type of diabetes is also known as insulin-independent diabetes. Gliptivil Combo is used when diabetes cannot be controlled by diet and exercise alone, and/or when it is administered together with other antidiabetic medicines (insulin or sulfonylurea derivatives).
Type 2 diabetes develops when the body does not produce enough insulin or when the insulin produced by the body does not work as well as it should. It may also develop when the body produces too much glucagon.
Both insulin and glucagon are produced in the pancreas. Insulin helps lower blood sugar levels, especially after meals. Glucagon stimulates the liver to produce sugar, leading to an increase in blood sugar levels.

How Gliptivil Combo works
Both active substances, vildagliptin and metformin, help control blood sugar levels.
Vildagliptin works by stimulating the pancreas to produce insulin and by reducing the production of glucagon. Metformin helps the body make better use of insulin.
This medicine has been shown to lower blood sugar levels, which may help prevent complications associated with diabetes.

2. Important information before taking Gliptivil Combo

When not to take Gliptivil Combo

If the patient is allergic to vildagliptin, metformin, or any of the other ingredients of this medicine (listed in section 6). If the patient thinks they may be allergic to any of these ingredients, they should inform their doctor before taking Gliptivil Combo.
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, 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.
If the patient has recently had a heart attack, or has heart failure, severe circulatory problems, or breathing difficulties that may be signs of heart problems.
If the patient has significantly reduced kidney function.
If the patient has a severe infection or is severely dehydrated (has lost a large amount of body fluid).
If the patient is scheduled for a contrast radiological examination (a special type of imaging requiring injection of a contrast agent). For further information on this, see section "Warnings and precautions".
If the patient has liver disease.
If the patient consumes excessive amounts of alcohol (either regularly or occasionally).
If the patient is breastfeeding (see also section "Pregnancy, breastfeeding and fertility").

Warnings and precautions
Risk of lactic acidosis
Gliptivil Combo may cause a very rare but serious adverse effect called lactic acidosis, particularly if the patient has impaired kidney function. The risk of developing lactic acidosis is also increased in cases of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see further information below), impaired liver function, and any medical conditions in which a part of the body receives reduced oxygen supply (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, they should consult their doctor for further instructions.
Treatment with Gliptivil Combo should be temporarily discontinued if the patient develops a medical condition that may involve dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. The patient should consult their doctor for further guidance.
If any symptoms of lactic acidosis occur, the patient must stop taking Gliptivil Combo and contact their doctor or nearest hospital immediately, as this condition may lead to coma.
Symptoms of lactic acidosis include:

vomiting
stomach pain (abdominal pain)
muscle cramps
general malaise associated with profound fatigue
difficulty breathing
lowered body temperature and slowed heart rate.

Lactic acidosis is an acute condition requiring hospital treatment.
The patient should contact their doctor immediately for further instructions if:

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

Gliptivil Combo does not replace insulin. Therefore, Gliptivil Combo must not be used in the treatment of type 1 diabetes.
Before starting treatment with Gliptivil Combo, the patient should discuss this with their doctor, pharmacist, or nurse if they have or have had pancreatic disorders.
Before starting treatment with Gliptivil Combo, the patient should consult their doctor, pharmacist, or nurse if they are taking an antidiabetic medicine called a sulfonylurea.
The doctor may wish to reduce the dose of the sulfonylurea taken together with Gliptivil Combo to avoid low blood glucose levels (hypoglycaemia).
If the patient previously took vildagliptin but had to stop due to liver disease, they should not take this medicine again.
Diabetic skin changes are a common complication of diabetes. The patient should follow the advice of their doctor or nurse regarding skin and foot care. The patient should also pay particular attention to the development of new blisters or ulcers while taking Gliptivil Combo. If these occur, the patient should speak to their doctor promptly.
If major surgery is required, the patient must stop taking Gliptivil Combo during and for some time after the procedure. The doctor will decide when the patient should stop and restart treatment with Gliptivil Combo.
Before starting treatment with Gliptivil Combo and every three months during the first year of treatment, and periodically thereafter, liver function tests should be performed. This allows early detection of signs of increased liver enzyme activity.
During treatment with Gliptivil Combo, the doctor will monitor the patient's kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.
The doctor will regularly monitor blood and urine glucose levels.

Children and adolescents
Gliptivil Combo is not recommended for use in children and adolescents under 18 years of age.

Gliptivil Combo 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 (CT scan), they must stop taking Gliptivil Combo before or at the latest at the time of administration. The doctor will decide when the patient should stop and restart treatment with Gliptivil Combo.
The patient should inform their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take. More frequent monitoring of blood glucose levels and kidney function or dose adjustment of Gliptivil Combo may be necessary. It is especially important to inform the doctor about the following medicines:

glucocorticoids commonly used to treat inflammatory conditions
beta-2 adrenergic receptor agonists, usually used in the treatment of respiratory disorders
other medicines used to treat diabetes
medicines that increase urine production (diuretics)
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)
certain medicines affecting the thyroid gland
certain medicines affecting the nervous system
certain medicines used to treat angina pectoris (e.g. ranolazine)
certain medicines used to treat HIV infection (e.g. dolutegravir)
certain medicines used to treat a specific type of thyroid cancer (medullary thyroid cancer) (e.g. vandetanib)
certain medicines used to treat heartburn and peptic ulcers (e.g. cimetidine).

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

Pregnancy, breastfeeding and fertility

If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should consult her doctor before taking this medicine. The doctor will discuss with the patient the possible risks associated with taking Gliptivil Combo during pregnancy.
Gliptivil Combo must not be used if the patient is pregnant or breastfeeding (see also "When not to take Gliptivil Combo").

Before taking any medicine, consult a doctor or pharmacist.
Driving and using machines
If the patient experiences dizziness while taking Gliptivil Combo, they should not drive or operate machinery.

3. How to use Gliptivil Combo

The dose of Gliptivil Combo that a patient should take varies depending on their condition. The doctor
will precisely determine the appropriate dose of Gliptivil Combo to take.
This medicine should always be used exactly as directed by the doctor or pharmacist. If in doubt,
consult the doctor or pharmacist.
The recommended dose is one 50 mg + 850 mg or 50 mg + 1000 mg film-coated tablet taken twice
daily.
If the patient has impaired kidney function, the doctor may prescribe a lower dose. If the patient is
taking a diabetes medicine called a sulfonylurea, the doctor may also prescribe a lower dose.
The doctor may prescribe this medicine to be taken alone (as monotherapy) or together with certain
other medicines that lower blood sugar levels.
When and how to take Gliptivil Combo

Swallow the tablets whole with a glass of water.
Take one tablet in the morning and one in the evening, with a meal or immediately after a meal. Taking the tablet right after a meal may help reduce the risk of gastrointestinal disturbances.

Continue to follow all dietary advice given by the doctor. In particular, if the patient is on a diabetic
diet for weight control, this diet should be continued during treatment with Gliptivil Combo.
Taking more Gliptivil Combo than recommended
If too many tablets of Gliptivil Combo are accidentally taken or if someone else takes the tablets,
inform the doctor or pharmacist immediately. Medical care may be necessary. If it is necessary to
see a doctor or go to hospital, bring the medicine pack and the leaflet with you.
If you miss a dose of Gliptivil Combo
If the patient forgets to take a tablet, take it with the next meal, unless it is almost time for the next
dose.
Do not take a double dose (two tablets at the same time) to make up for a missed tablet.
Stopping Gliptivil Combo treatment
Continue taking this medicine for as long as the doctor recommends, to maintain control of blood
sugar levels. Do not stop taking Gliptivil Combo unless instructed by the doctor. If there are any
questions about how long to take Gliptivil Combo, consult the doctor.
If there are any further doubts about the use of this medicine, consult the doctor, pharmacist, or
nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You should stop taking Gliptivil Combo and immediately contact your doctor if any of the following adverse reactions occur:

Lactic acidosis (very rare: may occur in no more than 1 in 10,000 people): Gliptivil Combo may cause a very rare but serious adverse reaction called lactic acidosis (see section "Warnings and precautions"). In such a case, you must stop taking Gliptivil Combo and immediately contact your doctor or the nearest hospital, as lactic acidosis may lead to coma.
Angioedema (rare: may occur in no more than 1 in 1,000 people): Symptoms include swelling of the face, tongue or throat, difficulty swallowing, difficulty breathing, sudden onset of rash or hives, which may indicate a reaction called "angioedema".
Liver disease (hepatitis) (uncommon: may occur in no more than 1 in 100 people): Symptoms include yellowing of the skin and whites of the eyes, nausea, loss of appetite, or dark urine, which may indicate liver disease (hepatitis).
Pancreatitis (uncommon: may occur in no more than 1 in 100 people): Symptoms include severe and persistent abdominal pain (in the stomach area), which may radiate to the back, as well as nausea and vomiting.

Other adverse reactions
The following adverse reactions have been reported in some patients taking Gliptivil Combo:

Common (may occur in up to 1 in 10 people): sore throat, nasal congestion, fever, itchy rash, excessive sweating, joint pain, dizziness, headache, uncontrollable trembling, constipation, nausea, vomiting, diarrhoea, bloating, heartburn, stomach and perigastric pain (abdominal pain).
Uncommon (may occur in up to 1 in 100 people): fatigue, weakness, metallic taste in the mouth, low blood glucose levels, loss of appetite, swelling of hands, ankles or feet (oedema), chills, pancreatitis, muscle pain.
Very rare (may occur in up to 1 in 10,000 people): symptoms of high blood lactic acid levels (called lactic acidosis), such as drowsiness or dizziness, severe nausea or vomiting, abdominal pain, irregular heartbeat or deep, rapid breathing; skin redness, itching; decreased vitamin B12 levels (pallor, fatigue, psychiatric symptoms such as confusion or memory disorders).

After the introduction of this medicine into the market, the following adverse reactions have also been reported:

Frequency unknown (frequency cannot be estimated from available data): localised skin peeling or blistering, vasculitis which may cause skin rash or small, flat, red, round spots under the skin surface or bruising.

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of 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 authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Gliptivil Combo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister or carton:
EXP. The expiry date refers to the last day of the stated month.
Do not store above 30°C.
Store in the original packaging to protect from moisture.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Gliptivil Combo contains
The active substances are vildagliptin and metformin hydrochloride.
Each film-coated tablet contains 50 mg of vildagliptin and 850 mg of metformin hydrochloride (equivalent to 660 mg of metformin).
Each film-coated tablet contains 50 mg of vildagliptin and 1000 mg of metformin hydrochloride (equivalent to 780 mg of metformin).
Other ingredients include: copovidone (K-28), anhydrous colloidal silica, magnesium stearate, hypromellose 2910 (E 464), polydextrose (E 1200), titanium dioxide (E 171), talc (E 553b), yellow iron oxide (E 172), maltodextrin, and medium-chain triglycerides.

What Gliptivil Combo looks like and contents of the pack
Film-coated tablet.
Gliptivil Combo 50 mg + 850 mg film-coated tablets are yellow, oval-shaped, with bevelled edges, embossed with the number "50" on one side and "850" on the other.
Gliptivil Combo 50 mg + 1000 mg film-coated tablets are yellow, oval-shaped, with bevelled edges, embossed with the number "50" on one side and "1000" on the other.
Gliptivil Combo, film-coated tablets, are packed in blisters.
Pack sizes: 10, 30, 60, 90, and 120 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Aurovitas Pharma Polska Sp. z o.o.
ul. Sokratesa 13D, lokal 27
01-909 Warsaw
e-mail: [email protected]

Manufacturer:
PHARMATHEN INTERNATIONAL S.A.
Industrial Park Sapes, Rodopi Prefecture, Block No 5
69300 Rodopi
Greece
PHARMATHEN S.A.
Dervenakion 6
15351 Pallini Attiki
Greece

This medicinal product is authorised in the European Economic Area under the following names:
Poland: Gliptivil Combo
Portugal: Metformina + Vildagliptina Generis Phar