Sitagliptin + metformin medreg

Package leaflet: Information for the patient

Sitagliptin + Metformin Medreg, 50 mg + 1000 mg, film-coated tablets
Sitagliptinum + Metformini hydrochloridum
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Sitagliptin + Metformin Medreg is and what it is used for
2. What you need to know before taking Sitagliptin + Metformin Medreg
3. How to take Sitagliptin + Metformin Medreg
4. Possible side effects
5. How to store Sitagliptin + Metformin Medreg
6. Contents of the pack and other information

1. What Sitagliptin + Metformin Medreg is and what it is used for

Sitagliptin + Metformin Medreg contains two different active substances: sitagliptin and metformin.

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

The combined action of these substances helps control blood glucose levels in adult patients with diabetes known as "type 2 diabetes". This medicine helps increase insulin levels released after meals and reduces the amount of glucose produced by the body. When used together with diet and physical exercise, it helps lower blood glucose levels. This medicine may be used alone or in combination with certain other antidiabetic medicines (insulin, sulfonylurea derivatives, 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 that is produced does not work properly. The body may also produce too much glucose. When this happens, glucose accumulates in the blood. This may lead to serious health problems such as heart disease, kidney disease, vision loss, and limb amputations.

2. Important information before using Sitagliptin + Metformin Medreg

When not to use Sitagliptin + Metformin Medreg

• if the patient is allergic to sitagliptin or metformin, or to any of the other ingredients of this medicine (listed in section 6)
• if the patient has significantly reduced kidney function
• 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 which may lead to diabetic pre-coma.
Symptoms include abdominal pain, rapid and deep breathing, drowsiness, or an unusual fruity
odour of the breath.

• if the patient has severe infection or dehydration
• if the patient is scheduled for a radiological examination with intravascular administration of contrast medium. Treatment with Sitagliptin + Metformin Medreg must be discontinued during the radiological examination and for 2 or more days afterwards, according to the physician's instructions, depending on the patient's kidney function.
• if the patient has recently experienced a heart attack or has developed severe circulatory disorders, such as shock or breathing difficulties
• if the patient has liver disease
• if the patient consumes excessive amounts of alcohol (either daily or occasionally)
• if the patient is breastfeeding

Do not use Sitagliptin + Metformin Medreg if any of the
above contraindications apply. Consult a physician to determine alternative methods
of diabetes control. If in doubt, discuss this with your doctor or pharmacist before using Sitagliptin + Metformin
Medreg.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking Sitagliptin + Metformin Medreg (see section 4).
If the patient develops blisters on the skin, this may be a symptom of a disease known as bullous pemphigoid. The physician may advise the patient to discontinue treatment with Sitagliptin + Metformin
Medreg.
Risk of lactic acidosis
Sitagliptin + Metformin Medreg may cause a very rare but serious adverse effect called lactic acidosis, particularly 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 further
details 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, consult a physician for additional instructions.
Treatment with Sitagliptin + Metformin Medreg should be temporarily discontinued if the
patient develops a medical condition that may lead to dehydration (significant loss of water
from the body), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if
the patient drinks less fluid than usual. Consult a physician for additional instructions.
Treatment with Sitagliptin + Metformin Medreg should be discontinued and the patient should immediately contact a physician 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.
Seek immediate medical advice 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).
• the patient develops any of the following symptoms after starting metformin: seizures, worsening of cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Before starting treatment with Sitagliptin + Metformin Medreg, discuss with a physician
or pharmacist:

• if the patient has or has had pancreatic disease (e.g. pancreatitis)
• if the patient has or has had gallstones, alcohol dependence, or very high blood triglyceride levels (a type of fat). In such cases, the risk of pancreatitis may increase (see section 4).
• if the patient has type 1 diabetes. This is sometimes referred to as insulin-dependent diabetes.
• if the patient currently has or has previously experienced allergic reactions to sitagliptin, metformin, or Sitagliptin + Metformin Medreg (see section 4)
• if the patient is taking a sulfonylurea derivative or insulin, antidiabetic medicines together with Sitagliptin + Metformin Medreg, as this may lead to excessively low blood glucose levels (hypoglycaemia). The physician may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Sitagliptin + Metformin
Medreg must not be used during the procedure and for a certain period afterwards. The physician will decide when the patient should stop and resume treatment with Sitagliptin + Metformin Medreg.
If in doubt whether any of the above situations apply, discuss this with a physician or pharmacist before using Sitagliptin + Metformin Medreg.
During treatment with Sitagliptin + Metformin Medreg, the physician will monitor the patient's kidney function at least once a year, or more frequently if the patient is elderly and/or has deteriorating kidney function.
Children and adolescents
This medicine must not be used in children and adolescents under 18 years of age. This medicine is not effective in children and adolescents aged 10 to 17 years. It is unknown whether this medicine is safe and effective when used in children under 10 years of age.
Sitagliptin + Metformin Medreg and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example for an X-ray or CT scan, treatment with Sitagliptin + Metformin Medreg must be discontinued before or at the latest at the time of administration. The physician will decide when the patient should stop and resume treatment with Sitagliptin + Metformin Medreg.
Inform the physician or pharmacist about all medicines currently used, recently used, or planned for use. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Sitagliptin + Metformin Medreg by the physician. It is particularly important to inform about the following medicines:

• medicines (taken orally, by inhalation, or by injection) used to treat inflammatory conditions such as asthma or 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 used to treat bronchial asthma (β-sympathomimetics)
• iodine-containing contrast agents or medicines containing alcohol
• some medicines used to treat gastrointestinal disorders, 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 (used to treat heart rhythm disorders and other heart conditions). Blood digoxin levels should be monitored when taking Sitagliptin + Metformin Medreg with digoxin.

Use of Sitagliptin + Metformin Medreg with alcohol
Avoid consuming excessive amounts of alcohol while taking Sitagliptin +
Metformin Medreg, as this may increase the risk of lactic acidosis (see section
"Warnings and precautions").
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a
child, she should consult a physician or pharmacist before using this medicine. This medicine must not be used during pregnancy. This medicine must not be used during breastfeeding. See
section 2, "When not to use Sitagliptin + Metformin Medreg".
Driving and operating machinery
This medicine has no effect or a negligible effect on the ability to drive and operate machinery. However, dizziness and drowsiness have been reported, which may affect the ability to drive or operate machinery.
Taking this medicine together with medicines called sulfonylurea derivatives or
with insulin may lead to hypoglycaemia, which in turn may affect the ability to drive
and operate machinery or work without secure foot support.
Sitagliptin + Metformin Medreg contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Sitagliptin + Metformin Medreg

This medicine should always be taken exactly as instructed by your doctor. If in doubt, consult your doctor or pharmacist.

Take one tablet:

• twice daily, orally
• with meals to reduce the likelihood of gastrointestinal upset.

To control blood sugar levels, your doctor may increase the dose of this medicine.
If you have impaired kidney function, your doctor may prescribe a lower dose of this medicine.
While taking this medicine, continue to follow the diet recommended by your doctor and pay attention to evenly distributing carbohydrate intake throughout the day.
It is unlikely that taking this medicine alone will lead to abnormally low blood sugar levels (hypoglycaemia). Low blood sugar may occur if this medicine is taken together with a sulphonylurea derivative or insulin – in such a case, your doctor may reduce the dose of the sulphonylurea derivative or insulin.

Taking more Sitagliptin + Metformin Medreg than prescribed
If you take more of this medicine than prescribed, contact your doctor immediately. Go to hospital if symptoms of lactic acidosis occur, 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").

Missing a dose of Sitagliptin + Metformin Medreg
If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed dose.

Stopping Sitagliptin + Metformin Medreg
To maintain control of blood sugar levels, take this medicine for as long as your doctor recommends. Do not stop taking this medicine without first consulting your doctor.
Discontinuing treatment with Sitagliptin + Metformin Medreg may result in increased blood sugar levels.

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 will experience them.
You should STOP taking Sitagliptin + Metformin Medreg and contact your doctor immediately if you experience any of the following serious adverse reactions:

• Severe and persistent abdominal pain (in the stomach area), possibly radiating to the back, with or without nausea and vomiting, as these may be symptoms of pancreatitis.

Sitagliptin + Metformin Medreg may very rarely (may occur in 1 out of 10,000 people) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs, STOP taking Sitagliptin + Metformin Medreg and contact your doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.
In case of a severe allergic reaction (frequency unknown), including rash, hives, skin blisters or peeling, and swelling of the face, lips, tongue or throat, which may cause difficulty in breathing or swallowing, you must stop taking the medicine and contact your doctor immediately. Your doctor may prescribe medication to treat the allergic reaction and another medicine to treat diabetes.
In some patients taking metformin, the following adverse reactions occurred after starting sitagliptin:

Common (may occur in 1 out of 10 people): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may occur in 1 out of 100 people): stomach pain, diarrhoea, constipation, drowsiness

Some patients experienced diarrhoea, nausea, bloating, constipation, stomach pain or vomiting after starting treatment with sitagliptin in combination with metformin (common).

In some patients taking this medicine together with a sulfonylurea derivative, such as glimepiride, the following adverse reactions occurred:
Very common (may occur in more than 1 out of 10 people): low blood sugar levels
Common: constipation

In some patients taking this medicine together with pioglitazone, the following adverse reactions occurred:
Common: swelling of hands or feet

In some patients taking this medicine together with insulin, the following adverse reactions occurred:
Very common: low blood sugar levels
Uncommon: dry mouth, headache

In clinical studies, in some patients taking sitagliptin alone (one of the active substances in Sitagliptin + Metformin Medreg), or after marketing authorization of Sitagliptin + Metformin Medreg, or sitagliptin alone, or in combination with other antidiabetic medicines, the following adverse reactions were observed:
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
Rare: decreased platelet count
Frequency not known: kidney disorders (sometimes requiring dialysis), vomiting, joint pain, muscle pain, back pain, interstitial lung disease, bullous pemphigoid (a type of blistering skin condition)

In some patients taking metformin alone, the following adverse reactions occurred:
Very common: nausea, vomiting, diarrhoea, stomach pain and loss of appetite. These symptoms may occur when starting metformin and usually resolve over time.
Common: metallic taste, reduced or low blood levels of vitamin B12 (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling or numbness (paresthesia), or paleness or yellowing of the skin). Your doctor may order certain tests to determine the cause of symptoms, as some of them may also be caused by diabetes or other unrelated health problems.
Very rare: hepatitis (liver disease), urticaria, skin redness (rash) or itching

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

5. How to store Sitagliptin + Metformin Medreg

Keep this medicine out of the sight and reach of children.
No special storage precautions apply.
Do not use this medicine after the expiry date stated on the carton, blister pack, or label after EXP. The expiry date refers to the last day of the specified month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the packaging and other information

What Sitagliptin + Metformin Medreg contains

• The active substances are sitagliptin and metformin hydrochloride. Each film-coated tablet contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
• Other ingredients are:
  Tablet core: microcrystalline cellulose, sodium lauryl sulfate, povidone K-90, sodium stearyl fumarate
  Tablet coating: polyvinyl alcohol (E 1203), titanium dioxide (E 171), macrogol (E 1521), talc (E 553b), and yellow iron oxide (E 172)

What Sitagliptin + Metformin Medreg looks like and contents of the pack
Yellow, capsule-shaped film-coated tablets, approximately 21.4 x 10.4 mm in size, with a thickness of 7.0 ± 0.4 mm, imprinted with the code "S19" and a breakline on one side and "H" on the other side. The breakline on the tablet is intended only to facilitate breaking for easier swallowing and does not ensure division into equal doses.
Film-coated tablets are supplied in PVC/Aluminium/OPA/Aluminium blister packs in cardboard cartons.
Pack sizes: 20, 28, 30, 56, 60, 98, 100, 196 or 200 film-coated tablets.
Not all pack sizes may be available on the market.
Film-coated tablets are also supplied in HDPE bottles with a polypropylene child-resistant closure and a sealing liner, packed in a cardboard carton.
Pack sizes: 30 or 60 film-coated tablets.
Not all pack sizes may be available on the market.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Medreg s.r.o.
Na Florenci 2116/15
Nové Město
110 00 Prague 1
Czech Republic
Tel.: (+420) 516 770 199

Manufacturer/Importer:
Medis International a.s.
Průmyslová 961/16
747 23 Bolatice
Czech Republic
Dr. Max Pharma s.r.o.
Na Florenci 2116/15
Nové Město
110 00 Prague 1
Czech Republic

This medicinal product is authorised in the European Economic Area under the following names:
Czech Republic: Sitagliptin/Metformin Medreg
Poland: Sitagliptin + Metformin Medreg
Slovakia: Sitagliptin/Metformin Medreg
Romania: Sitagliptin/Metformin Gemax Pharma 50 mg/1000 mg film-coated tablets