Sitagliptin + metformin hydrochloride apc

Package leaflet: Information for the user

Sitagliptin + Metformin hydrochloride APC, 50 mg + 500 mg,
modified-release tablets
Sitagliptin + Metformin hydrochloride APC, 50 mg + 1000 mg,
modified-release tablets
Sitagliptin + Metformin hydrochloride APC, 100 mg + 1000 mg,
modified-release 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, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Sitagliptin + Metformin hydrochloride APC is and what it is used for
Sitagliptin + Metformin hydrochloride APC contains two different active substances called
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 medicines helps to control blood sugar levels in adult patients
with diabetes known as "type 2 diabetes". This medicine helps to increase the amount of
insulin released after a meal and reduces the amount of sugar produced by the body.
Used together with diet and exercise, this medicine helps lower blood sugar levels.
This medicine may be used alone or in combination with certain other antidiabetic medicines
(insulin, sulfonylureas, or glitazones).

What is type 2 diabetes?
In type 2 diabetes, the body does not produce enough insulin, and the insulin produced does not
work properly. The body may also produce too much sugar. When this happens, sugar (glucose)
builds up in the blood. This may lead to serious conditions such as heart disease, kidney disease,
loss of vision, and limb amputations.

2. What you need to know before you take Sitagliptin + Metformin hydrochloride APC

Do not take Sitagliptin + Metformin hydrochloride APC:

• if you are allergic to sitagliptin or metformin or any of the other ingredients of this medicine (listed in section 6).
• if you have significantly reduced kidney function,
• if you have uncontrolled diabetes, e.g. 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 may lead to a diabetic pre-coma state. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness, or an unusual fruity odour on the breath.
• if you have a severe infection or dehydration,
• if you are scheduled to have a radiological examination with intravascular iodinated contrast medium. You must stop taking Sitagliptin + Metformin hydrochloride APC for the examination and for 2 or more days afterwards, as directed by your doctor, depending on your kidney function.
• if you recently had a heart attack or have severe circulatory problems such as shock or breathing difficulties,
• if you have liver disease,
• if you consume excessive amounts of alcohol (daily or occasionally),
• if you are breastfeeding.

Do not take Sitagliptin + Metformin hydrochloride APC if any of the above apply to you.
Talk to your doctor about other ways to manage your diabetes. If you are unsure, discuss this with your
doctor, pharmacist, or nurse before taking Sitagliptin + Metformin hydrochloride APC.

Warnings and precautions
Talk to your doctor or pharmacist before taking Sitagliptin + Metformin hydrochloride APC.
Cases of pancreatitis (inflammation of the pancreas) have been reported in patients taking
Sitagliptin + Metformin hydrochloride APC (see section 4).
If you develop blisters on your skin, this may be a sign of a condition called bullous pemphigoid.
Your doctor may advise you to stop taking Sitagliptin + Metformin hydrochloride APC.

Risk of lactic acidosis
Sitagliptin + Metformin hydrochloride APC may cause a very rare but serious side effect called
lactic acidosis, especially if you have impaired kidney function. The risk of lactic acidosis is also
increased in cases of uncontrolled diabetes, severe infections, prolonged fasting or alcohol use,
dehydration (see additional information below), liver dysfunction, and any condition in which any
part of the body is inadequately supplied with oxygen (such as acute severe heart disease).
If any of the above situations apply to you, talk to your doctor for further instructions.

Contact your doctor immediately for further instructions if:

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

Temporarily stop taking Sitagliptin + Metformin hydrochloride APC if you have an illness that may
involve dehydration (significant loss of water from the body), such as severe vomiting, diarrhoea,
fever, exposure to high temperatures, or if you are drinking less fluid than usual. Talk to your doctor
for further instructions.

Stop taking Sitagliptin + Metformin hydrochloride APC and contact your doctor or the nearest
hospital immediately if you experience any symptoms of lactic acidosis, as this condition may lead
to coma.
Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of being unwell with severe tiredness
• difficulty breathing
• low body temperature and slow heart rate

Lactic acidosis is an acute, life-threatening condition requiring hospital treatment.

Before starting Sitagliptin + Metformin hydrochloride APC, talk to your doctor or pharmacist:

• if you have or have had pancreas disease (e.g. pancreatitis)
• if you have or have had gallstones, alcohol dependence, or very high levels of triglycerides (a type of fat) in your blood. In such cases, the risk of pancreatitis may be increased (see section 4)
• if you have been diagnosed with type 1 diabetes. This is sometimes called insulin-dependent diabetes
• if you currently have or have had an allergic reaction to sitagliptin, metformin, or Sitagliptin + Metformin hydrochloride APC (see section 4)
• if you are taking a sulfonylurea or insulin, antidiabetic medicines together with Sitagliptin + Metformin hydrochloride APC, as this may lead to excessively low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of the sulfonylurea or insulin

If you are undergoing major surgery, you must stop taking Sitagliptin + Metformin hydrochloride APC during the procedure and for some time afterwards. Your doctor will decide when you should stop and restart treatment with Sitagliptin + Metformin hydrochloride APC.
If you are unsure whether any of the above situations apply to you, discuss this with your doctor or
pharmacist before taking Sitagliptin + Metformin hydrochloride APC.

While being treated with Sitagliptin + Metformin hydrochloride APC, your doctor will monitor your
kidney function at least once a year, or more frequently if you are elderly and/or have worsening
kidney function.

Children and adolescents
Do not use this medicine 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 not known whether this medicine is
safe and effective in children under 10 years of age.

Sitagliptin + Metformin hydrochloride APC with other medicines
If you are to receive an intravascular iodinated contrast medium, for example for an X-ray or CT
scan, you must stop taking Sitagliptin + Metformin hydrochloride APC before or at the latest at the
time of the injection. Your doctor will decide when you should stop and restart treatment with
Sitagliptin + Metformin hydrochloride APC.

Tell your doctor or pharmacist about all medicines you are currently taking, have recently taken,
or might take in the future. You may need more frequent monitoring of your blood glucose levels and
kidney function, or your doctor may need to adjust your dose of Sitagliptin + Metformin hydrochloride
APC. It is especially important to inform your doctor about the following medicines:

• 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 used to treat asthma (β-sympathomimetics)
• iodinated contrast media 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 (used to treat heart rhythm disorders and other heart conditions). Blood levels of digoxin should be monitored when taken with Sitagliptin + Metformin hydrochloride APC.

Sitagliptin + Metformin hydrochloride APC and alcohol
Avoid consuming excessive amounts of alcohol while taking Sitagliptin + Metformin hydrochloride
APC, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby,
you should consult your doctor or pharmacist before taking this medicine. Do not use this medicine
during pregnancy or while breastfeeding. See section 2 "Do not take Sitagliptin + Metformin hydrochloride
APC".

Driving and using machines
This medicine has no effect or a negligible effect on the ability to drive and use machines.
However, dizziness and drowsiness have been reported during treatment with sitagliptin, which
may affect the ability to drive and use machines.
Taking this medicine together with medicines called sulfonylureas or insulin may lead to
hypoglycaemia, which may affect the ability to drive and use machines or work without secure
footing.

Sitagliptin + Metformin hydrochloride APC contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, meaning it is considered
"sodium-free".

3. How to take Sitagliptin + Metformin hydrochloride APC

This medicine should always be taken exactly as prescribed by your doctor. If you have any doubts,
consult your doctor or pharmacist. Your doctor will inform you how many tablets of Sitagliptin +
Metformin hydrochloride APC to take and when to take them.
The maximum daily dose is 100 milligrams of sitagliptin and 2000 milligrams of metformin.
Usually, the tablets should be taken once daily with the evening meal.
In some cases, your doctor may advise taking the tablets twice daily.
The tablets should always be taken with food to reduce the risk of stomach upset.
Swallow the tablets whole with a glass of water; do not chew them.
Your doctor may increase the dose of this medicine to help control your blood sugar levels.
If you have reduced kidney function, your doctor may prescribe a lower dose.
While taking this medicine, continue to follow the diet recommended by your doctor and pay attention to
consuming carbohydrates evenly 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 or insulin – in such cases,
your doctor may reduce the dose of the sulphonylurea or insulin.

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

If you forget to take Sitagliptin + Metformin hydrochloride APC
If you miss a dose, take it as soon as you remember. However, if you do not remember until it is time for your
next dose, skip the missed dose and return to your regular dosing schedule. Do not take a double dose to
make up for a missed dose.

Stopping Sitagliptin + Metformin hydrochloride APC
Continue taking this medicine for as long as your doctor recommends to maintain control of your blood sugar levels.
Do not stop taking this medicine without first consulting your doctor. Stopping treatment with Sitagliptin +
Metformin hydrochloride APC may cause your blood sugar levels to rise again.

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 hydrochloride APC and immediately contact your doctor if any of the following serious adverse reactions occur:

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

Sitagliptin + Metformin hydrochloride APC may very rarely (in no more than 1 in 10,000 people) cause a very serious adverse reaction known as lactic acidosis (see section "Warnings and precautions"). If this occurs, treatment with Sitagliptin + Metformin hydrochloride APC must be stopped immediately and you should contact your doctor or nearest hospital without delay, as lactic acidosis may lead to coma.

In case of a severe allergic reaction (frequency unknown, cannot be estimated from available data), including rash, urticaria, skin blisters and/or skin peeling, and swelling of the face, lips, tongue, and throat, which may cause difficulty in breathing or swallowing, you must stop taking this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat the allergic reaction and another medicine (a different medicine) for the treatment of diabetes.

The following adverse reactions have been reported in some patients taking metformin after starting sitagliptin:

Common (may affect up to 1 in 10 people): low blood sugar levels, nausea, bloating, vomiting
Uncommon (may affect up to 1 in 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).

Some patients taking this medicine in combination with a sulfonylurea derivative such as glimepiride experienced the following adverse reactions:

Very common (may affect more than 1 in 10 people): low blood sugar levels
Common: constipation

Some patients taking this medicine in combination with pioglitazone experienced the following adverse reactions:

Common: swelling of hands or feet

Some patients taking this medicine in combination with insulin experienced the following adverse reactions:

Very common: low blood sugar levels
Uncommon: dry mouth, headache

During clinical studies and post-marketing use of Sitagliptin + Metformin hydrochloride APC, sitagliptin alone (one of the active substances in Sitagliptin + Metformin hydrochloride APC), or in combination with other antidiabetic medicines, the following adverse reactions have been reported:

Common: low blood sugar levels, headache, upper respiratory tract infection, stuffy or runny nose and sore throat, bone and joint pain, pain in hands or feet
Uncommon: dizziness, constipation, itching
Rare (may affect up to 1 in 1,000 people): 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)

The following adverse reactions have been reported in some patients taking metformin alone:

Very common: nausea, vomiting, diarrhoea, stomach pain, and loss of appetite. These symptoms may occur at the beginning of metformin treatment and usually resolve over time.
Common: metallic taste in the mouth, reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), numbness and tingling sensations (paresthesia), or pale or yellowish skin). Your doctor may order certain tests to identify 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 adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring of 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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Sitagliptin + Metformin hydrochloride APC
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton following the abbreviation "EXP". The expiry date refers to the last day of the specified month.
Do not store above 25°C.
Medicines should not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Sitagliptin + Metformin hydrochloride APC contains
The active substances are sitagliptin and metformin.
Sitagliptin + Metformin hydrochloride APC, 50 mg + 500 mg: Each tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 500 mg of metformin hydrochloride.
Sitagliptin + Metformin hydrochloride APC, 50 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
Sitagliptin + Metformin hydrochloride APC, 100 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate equivalent to 100 mg of sitagliptin and 1000 mg of metformin hydrochloride.
The other ingredients are:

• Metformin extended-release layer: hypromellose K100M CR, hypromellose E50, magnesium stearate
• Sitagliptin immediate-release layer: calcium hydrogen phosphate, microcrystalline cellulose, sodium stearyl fumarate, sodium croscarmellose (see section 2: "Sitagliptin + Metformin hydrochloride APC contains sodium")
• Additionally, the coating contains:
  • For strengths 100 mg + 1000 mg and 50 mg + 500 mg: partially hydrolysed polyvinyl alcohol, titanium dioxide (E 171), macrogol 4000, talc, yellow iron oxide (E 172), red iron oxide (E 172)
  • For strength 50 mg + 1000 mg: partially hydrolysed polyvinyl alcohol, titanium dioxide (E 171), macrogol 4000, talc

What Sitagliptin + Metformin hydrochloride APC looks like and contents of the pack
Sitagliptin + Metformin hydrochloride APC, 50 mg + 500 mg: Orange, elongated, biconvex coated tablets with dimensions of 17.2 mm x 8.4 mm.
Sitagliptin + Metformin hydrochloride APC, 50 mg + 1000 mg: White, elongated, biconvex coated tablets with dimensions of 22.2 mm x 10.8 mm, engraved with "50" on one side and "1000" on the other side.
Sitagliptin + Metformin hydrochloride APC, 100 mg + 1000 mg: Orange, elongated, biconvex coated tablets with dimensions of 22.2 mm x 10.8 mm, engraved with "100" on one side and "1000" on the other side.
Packs: PVC/PVDC/Aluminium foil blisters in cardboard boxes. Pack sizes of 10, 14, 28, 30, 56, 60, 98, 100, 112, 160, 168, 180, 196 or 200 modified-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
APC Instytut Sp. z o.o.
Al. Jerozolimskie 146C
02-305 Warszawa
Poland
Tel. +48 22 668 68 23

Manufacturer:
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland

This medicinal product is authorised in the European Economic Area countries under the following trade names:
Bulgaria: Sophamet Duo XR
Croatia: Sitagliptin/metformin chloride APC
Cyprus: Sitagliptin+Metformin APC
Greece: Sitagliptin+Metformin APC
Poland: Sitagliptin + Metformin hydrochloride APC
Portugal: Mesiglic
Italy: Diesmit