Sitagliptin and metformin Zentiva S.R.L.: detailed information

Patient Information Leaflet

Sitagliptin and Metformin Zentiva Srl 50 mg/850 mg film-coated tablets

Sitagliptin and Metformin Zentiva Srl 50 mg/1000 mg film-coated tablets
Equivalent medicine
Please read this leaflet carefully before taking this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Sitagliptin and Metformin Zentiva Srl is and what it is used for
What you need to know before taking Sitagliptin and Metformin Zentiva Srl
How to take Sitagliptin and Metformin Zentiva Srl
Possible side effects
How to store Sitagliptin and Metformin Zentiva Srl
Contents of the pack and other information

1. What is Sitagliptin and Metformin Zentiva Srl and what is it used for?

Sitagliptin and Metformin Zentiva Srl contains two different medicines called sitagliptin and
metformin.

Sitagliptin belongs to a class of medicines called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
Metformin belongs to a class of medicines called biguanides.

They work together to control blood sugar levels in adult patients with a form of diabetes called "type 2 diabetes mellitus". This medicine helps increase insulin levels produced after meals and reduces the amount of sugar produced by the body.
Together with diet and exercise, this medicine helps lower blood sugar levels. This medicine may be used alone or in combination with certain other diabetes medicines (insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?
Type 2 diabetes is a condition in which the body does not produce enough insulin and the insulin produced by the body does not work properly. Your body may also produce too much sugar. When this happens, sugar (glucose) accumulates in the blood. This can lead to serious medical problems such as heart disease, kidney disease, blindness, and amputation.

2. What you should know before taking Sitagliptin and Metformina Zentiva Srl

Do not take Sitagliptin and Metformina Zentiva Srl:

if you are allergic to sitagliptin, metformin or any of the other ingredients of this medicine (listed in section 6)
if you have severely reduced kidney function.
if you have uncontrolled diabetes associated, for example, with severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see below “Risk of lactic acidosis”) 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 stomach pain, rapid and deep breathing, drowsiness or breath with an unusually fruity odour.
if you have a severe infection or are dehydrated
if you are about to undergo radiographic imaging involving injection of a contrast agent. You will need to stop taking Sitagliptin and Metformina Zentiva at the time of the imaging procedure and for 2 or more days afterwards, as directed by your doctor, depending on how well your kidneys are functioning.
if you have recently had a heart attack or have serious circulatory problems, such as “shock” or breathing difficulties.
if you have liver problems.
if you drink excessive amounts of alcohol (either regularly or occasionally).
if you are breastfeeding.

Do not take Sitagliptin and Metformina Zentiva Srl if you have any of the conditions listed above and
speak with your doctor about other methods of managing diabetes. If you are unsure, consult your
doctor or pharmacist before taking Sitagliptin and Metformina Zentiva Srl.
Warnings and precautions
Cases of inflammation of the pancreas (pancreatitis) have been reported in patients treated with sitagliptin/metformina (see section 4).
If you develop blisters on your skin, this may be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop treatment with Sitagliptin and Metformina Zentiva Srl.
Risk of lactic acidosis
Sitagliptin and Metformina Zentiva Srl may cause a very rare but serious side effect called lactic acidosis, particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is also higher in the presence of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see below for further information), liver problems, or any other medical condition characterized by reduced oxygen supply to part of the body (such as in cases of severe acute heart disease).
If you have any of the medical conditions listed above, consult your doctor for further instructions.
Temporarily stop taking Sitagliptin and Metformina Zentiva Srl
if you have a medical condition that may be associated with dehydration (significant loss of body fluids), such as severe vomiting, diarrhoea, fever, heat exposure, or if you are drinking less fluid than normal. Consult your doctor for further instructions.
If you experience any of the symptoms of lactic acidosis, stop taking Sitagliptin and
Metformina Zentiva Srl and contact your doctor or go to the nearest hospital immediately, as this
condition may lead to coma.
Symptoms of lactic acidosis include:

vomiting,
stomach ache (abdominal pain),
muscle cramps,
a general feeling of discomfort associated with severe fatigue,
difficulty breathing,
low body temperature and slow heart rate.

Lactic acidosis is a medical emergency and must be treated in hospital. Consult your doctor or pharmacist before taking Sitagliptin and Metformina Zentiva Srl:

if you have or have had a disease of the pancreas (such as pancreatitis),
if you have or have had gallstones, alcohol dependence, or very high levels of triglycerides (a type of fat) in the blood. These medical conditions may increase your risk of developing pancreatitis (see section 4),
if you have type 1 diabetes. This is sometimes called insulin-dependent diabetes,
if you have or have had an allergic reaction to sitagliptin, metformin or Sitagliptin and Metformina Zentiva Srl (see section 4),
if you are taking a sulfonylurea or insulin, diabetes medicines, together with Sitagliptin and Metformina Zentiva Srl, as this may cause low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of sulfonylurea or insulin.

If you are scheduled to undergo major surgery, you must stop taking Sitagliptin and Metformina Zentiva Srl during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Sitagliptin and Metformina Zentiva Srl.
If you are unsure whether any of the conditions listed above apply to you, consult your doctor or pharmacist before taking Sitagliptin and Metformina Zentiva Srl.
During treatment with Sitagliptin and Metformina Zentiva Srl, your doctor will check your kidney function at least once a year, or more frequently if you are elderly and/or if kidney function worsens.
Children and adolescents
Children and adolescents under 18 years of age must not use this medicine. It is not effective in children and adolescents aged between 10 and 17 years. It is not known whether this medicine is safe and effective when used in children under 10 years of age.
Other medicines and Sitagliptin and Metformina Zentiva Srl
If you are scheduled to receive an injection of iodinated contrast medium into the bloodstream, for example for radiographic imaging, you must stop taking Sitagliptin and Metformina Zentiva Srl before or at the time of the injection. Your doctor will decide when to stop and when to restart treatment with Sitagliptin and Metformina Zentiva Srl.
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Sitagliptin and Metformina Zentiva Srl. It is particularly important to mention the following:

medicines (taken orally, inhaled or injected) used to treat inflammatory conditions, such as asthma and arthritis (corticosteroids),
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),
specific medicines for the treatment of bronchial asthma (β-sympathomimetics),
iodinated contrast agents or medicines containing alcohol,
certain medicines used to treat stomach problems such as cimetidine,
ranolazine, a medicine used to treat angina,
dolutegravir, a medicine used to treat HIV infection,
vandetanib, a medicine used to treat a specific type of thyroid cancer (medullary thyroid cancer),
digoxin (for the treatment of irregular heartbeat and other heart-related problems). It may be necessary to monitor digoxin blood levels if taken together with Sitagliptin and Metformina Zentiva Srl.

Sitagliptin and Metformina Zentiva Srl and alcohol
Avoid excessive alcohol consumption during treatment with Sitagliptin and Metformina Zentiva Srl, as this may increase the risk of lactic acidosis (see section “Warnings and precautions”).
Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before taking this medicine.
You must not take this medicine during pregnancy or while breastfeeding. See section 2 “Do not take Sitagliptin and Metformina Zentiva Srl”.
Driving and using machines
This medicine has no effect or has a negligible effect on the ability to drive and use machines. However, dizziness and drowsiness have been reported with sitagliptin, which may affect your ability to drive and use machines.
Taking this medicine together with other medicines called sulfonylureas or with insulin may cause hypoglycaemia, which may affect your ability to drive, use machinery or work without protective barriers.
Sitagliptin and Metformina Zentiva Srl contains sodium, sulfite and sunset yellow aluminium lake
only for Sitagliptin and Metformina Zentiva Srl 50 mg/1000 mg
Sodium: This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.
Sulfite: may rarely cause severe hypersensitivity reactions and bronchospasm.
Only for Sitagliptin and Metformina Zentiva Srl 50 mg/1000 mg
Sunset yellow aluminium lake: may cause allergic reactions.

3. How to take Sitagliptin and Metformin Zentiva Srl

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

Take one tablet:
- twice daily by mouth,
- with meals to reduce the likelihood of stomach problems.
Your doctor may need to increase your dose to control the level of sugar in your blood.
If you have reduced kidney function, your doctor may prescribe you a lower dose.

You must continue the diet recommended by your doctor during treatment with this medicine and ensure that carbohydrate intake is evenly distributed throughout the day.
It is unlikely that this medicine alone will cause abnormally low blood sugar levels (hypoglycaemia). However, when this medicine is used together with a sulphonylurea or insulin, low blood sugar may occur, and your doctor may reduce your dose of sulphonylurea or insulin.

If you take more Sitagliptin and Metformin Zentiva Srl than you should
If you take more of this medicine than prescribed, contact your doctor immediately. Go to hospital if you experience symptoms of lactic acidosis such as feeling cold or unwell, severe nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps, or rapid breathing (see section “Warnings and precautions”).

If you forget to take Sitagliptin and Metformin Zentiva Srl
If you miss a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and take your next dose at the regular time. Do not take a double dose of this medicine.

If you stop taking Sitagliptin and Metformin Zentiva Srl
Continue taking this medicine for as long as your doctor prescribes it, so that you can keep controlling your blood sugar levels. Do not stop treatment with this medicine without first talking to your doctor. If you stop taking Sitagliptin and Metformin Zentiva Srl, your blood sugar levels may rise again.

If you have any questions about how to use this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
STOP taking Sitagliptin and Metformina Zentiva Srl and contact a doctor immediately if you experience any of the following serious side effects:

Severe and persistent pain in the stomach area (abdomen), which may extend to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (pancreatitis). Sitagliptin and Metformina Zentiva Srl may cause a very rare (may affect up to 1 in 10,000 people), but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this occurs, you must stop taking Sitagliptin and Metformina Zentiva Srl and seek immediate medical attention at the nearest doctor or hospital, as lactic acidosis can lead to coma.

If you have a severe allergic reaction (frequency not known), including rash, hives, blistering or peeling of the skin, and swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop taking this medicine and contact a doctor immediately. Your doctor may prescribe a medicine to treat your allergic reaction and a different medicine for your diabetes.

Some patients taking metformin have experienced the following side effects after starting therapy with sitagliptin:
Common (may affect up to 1 in 10): low blood sugar levels, nausea, flatulence, vomiting.
Uncommon (may affect up to 1 in 100): stomach discomfort, diarrhoea, constipation, drowsiness.

Some patients have experienced diarrhoea, nausea, flatulence, constipation, stomach discomfort, or vomiting when starting combination treatment with sitagliptin and metformina (frequency is common).

Some patients have experienced the following side effects while taking this medicine with a sulfonylurea such as glimepiride:
Very common (may affect more than 1 in 10): low blood sugar levels
Common: constipation.

Some patients have experienced the following side effects while taking this medicine in combination with pioglitazone:
Common: swelling of the hands or legs.

Some patients have experienced the following side effects while taking this medicine in combination with insulin:
Very common: low blood sugar levels.
Uncommon: dry mouth, headache.

During clinical studies, some patients experienced the following side effects when taking sitagliptin alone (one of the medicines contained in Sitagliptin and Metformina Zentiva Srl) or during post-marketing use of Sitagliptin and Metformina Zentiva Srl or sitagliptin alone or in combination with other diabetes medicines:
Common: low blood sugar levels, headache, upper respiratory tract infection, stuffy or runny nose and sore throat, osteoarthritis, pain in arms or legs.
Uncommon: dizziness, constipation, itching sensation.
Rare: reduced platelet count.
Frequency not known: kidney problems (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of skin blistering).

Some patients taking metformina alone have experienced the following side effects:
Very common: nausea, vomiting, diarrhoea, stomach discomfort, and loss of appetite. These symptoms may occur when you first start taking metformina and usually go away over time.
Common: metallic taste, low or decreased blood levels of vitamin B12 (symptoms may include extreme tiredness (fatigue), sore and red tongue (glossitis), tingling sensations (paraesthesia), or yellowish or pale skin). Your doctor may carry out some tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.
Very rare: hepatitis (a liver problem), urticaria, skin redness (rash), or itching sensation.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the following website:
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Sitagliptin and Metformin Zentiva Srl

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the carton after "Exp.". The expiry date refers to the last day of that month.
Store below 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Sitagliptin and Metformin Zentiva Srl contains

Sitagliptin and Metformin Zentiva Srl 50 mg/850 mg: The active substances are sitagliptin and metformin. Each film-coated tablet contains sitagliptin phosphate monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride.
Sitagliptin and Metformin Zentiva Srl 50 mg/1000 mg: The active substances are sitagliptin and metformin. Each film-coated tablet contains sitagliptin phosphate monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.

The other components are:
Tablet core – microcrystalline cellulose (E 460i), povidone, sodium sulfite (E221),
sodium lauryl sulfate and sodium stearyl fumarate (E485);
Tablet coating – graft copolymer of polyvinyl alcohol-polyethylene glycol (PEG) (E1209), talc (E553b), titanium dioxide (E171), mono- and diglycerides of fatty acids (E471), polyvinyl alcohol (E1203), red iron oxide (E172);
Tablet coating – poly(vinyl alcohol) (E1203), titanium dioxide (E171), macrogol (E1521), talc (E553b).
Additionally, for Sitagliptin and Metformin Zentiva Srl 50 mg/1000 mg: aluminium lake of sunset yellow FCF (E110), yellow iron oxide (E172), red iron oxide (E172).

Description of the appearance of Sitagliptin and Metformin Zentiva Srl and contents of the pack

Sitagliptin and Metformin Zentiva Srl 50 mg/850 mg film-coated tablets (tablets) are oblong, white or almost white tablets with a score line on both sides, approximately 21 x 10 mm in size. The score line is intended only to facilitate breaking the tablet for ease of swallowing and is not intended to divide the tablet into equal doses.

Sitagliptin and Metformin Zentiva Srl 50 mg/1000 mg film-coated tablets (tablets) are oblong, light pink tablets with a score line on both sides, approximately 21 x 10 mm in size. The score line is intended only to facilitate breaking the tablet for ease of swallowing and is not intended to divide the tablet into equal doses.

PVC/PVDC/Al blisters
Pack sizes: 28, 56, 60 and 196 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Zentiva Italia S.r.l.
Via Pietro Paleocapa, 7
20121 Milano
Italy

Manufacturer
Zentiva k.s
U kabelovny 130
Prague 10, 102 37
Czech Republic

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Estonia, Hungary, Latvia, Lithuania - Sitagliptin/Metformin Zentiva
Denmark, Finland, Iceland, Norway - Sitagliptin/Metformin Zentiva ApS
Austria, Czech Republic, France, Sweden - Sitagliptin/Metformin Zentiva k.s.
Germany - Sitagliptin Metformin Zentiva k.s.
France - Sitagliptine/Metformines Zentiva k.s.
Italy - Sitagliptin e Metformina Zentiva Srl
Portugal - Metformina + Sitagliptina ZenPrime