Metsunix

Patient Information Leaflet

Metsunix 50 mg/500 mg modified-release tablets, 50 mg/1000 mg modified-release tablets, 100 mg/1000 mg modified-release tablets

sitagliptin/metformin hydrochloride
Please read 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Metsunix is and what it is used for

Metsunix 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.

These work together to control blood sugar levels in adult patients with a type 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 the body produces does not work properly. Your body may also produce too much sugar. When this happens, sugar (glucose) builds up in the blood. This can lead to serious medical problems such as heart disease, kidney disease, blindness and limb amputation.

2. What you need to know before taking Metsunix

Do not take Metsunix:

• if you are allergic to sitagliptin, metformin, or any of the excipients 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 precoma. Symptoms
include stomach pain, rapid and deep breathing, drowsiness, and breath with an unusual fruity odour.

• if you have a severe infection or are dehydrated.
• if you are about to undergo an X-ray procedure involving the use of a contrast agent. You will need to stop taking Metsunix at the time of the X-ray 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 difficulty breathing.
• if you have liver problems.
• if you drink excessive amounts of alcohol (either regularly or occasionally).
• if you are breastfeeding.

Do not take Metsunix if you have any of the conditions listed above. Speak with your doctor about other methods of managing diabetes. If you are unsure, speak with your doctor, pharmacist, or nurse before taking Metsunix.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Metsunix.
Cases of inflammation of the pancreas (pancreatitis) have been reported in patients treated with Metsunix (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 Metsunix.
Risk of lactic acidosis
Metsunix may cause a very rare but serious side effect called lactic acidosis, particularly if your kidneys are not functioning properly. The risk of developing lactic acidosis is 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 severe heart disease).
If you have any of the medical conditions described above, consult your doctor for further instructions. Contact your doctor immediately for further instructions if:

• you know you have a hereditary genetic mitochondrial disease (components that produce energy within cells), such as MELAS syndrome (Mitochondrial Encephalopathy, myopathy, Lactic Acidosis and Stroke-like episodes, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD, Maternal Inherited Diabetes and Deafness);
• you experience any of the following symptoms after starting metformin: seizures, reduced cognitive ability, movement difficulties, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Temporarily stop taking Metsunix if you have a medical condition that may lead to dehydration (significant loss of body fluids), such as severe vomiting,
diarrhoea, fever, heat exposure, or if you are drinking less fluid than usual. Consult your doctor for further instructions.
If you experience any symptoms of lactic acidosis, stop taking Metsunix and contact your doctor or the nearest hospital immediately, because lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

• vomiting,
• stomach ache (abdominal pain),
• muscle cramps,
• a general feeling of illness associated with extreme tiredness,
• difficulty breathing,
• reduced body temperature and slower heart rate.

Lactic acidosis is a medical emergency and must be treated in hospital.
Talk to your doctor or pharmacist before taking Metsunix:

• if you have or have had a pancreatic disease (such as pancreatitis).
• if you have or have had gallstones, alcohol dependence, or very high levels of triglycerides (a type of fat) in your 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 Metsunix (see section 4).
• if you are taking a sulfonylurea or insulin, diabetes medicines, together with Metsunix, as this may cause excessively low blood sugar levels (hypoglycaemia). Your doctor may reduce the dose of sulfonylurea or insulin.

If you are undergoing major surgery, you must stop taking Metsunix during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Metsunix.
If you are unsure whether any of the conditions listed above apply to you, consult your doctor or pharmacist before taking Metsunix.
During treatment with Metsunix, your doctor will monitor your kidney function at least once a year, or more frequently if you are elderly and/or if your 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 Metsunix
If you are due to receive an injection of iodinated contrast medium into your bloodstream, for example for an X-ray procedure, you must stop taking Metsunix before or at the time of the injection. Your doctor will decide when to stop and when to restart treatment with Metsunix.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine. You may need to check your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Metsunix. 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 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 treating irregular heartbeat and other heart problems). It may be necessary to monitor digoxin blood levels if taken with Metsunix.

Metsunix and alcohol
Avoid excessive alcohol consumption while taking Metsunix, 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, are 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 Metsunix.
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 or 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 machines, or work without protective barriers.
Metsunix contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially “sodium-free”.

3. How to take Metsunix

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist. Your doctor will tell you how many Metsunix tablets to take and when to take them.
The maximum daily dose is 100 mg of sitagliptin and 2000 mg of metformin.
Normally, you should take the tablets once daily with your evening meal.
In some cases, your doctor may advise you to take two tablets per day.
Always take the tablets with food to reduce the likelihood of stomach problems.
Swallow the tablets whole with a glass of water; do not chew them.
Your doctor may need to increase your dose to help control your blood sugar levels.
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 Metsunix 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 Metsunix
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 usual time. Do not take a double dose of this medicine to make up for a forgotten dose.

If you stop taking Metsunix
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 taking this medicine without first talking to your doctor. If you stop taking Metsunix, 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 everyone experiences them.
STOP taking Metsunix and contact your doctor immediately if you notice any of the following serious side effects:

• Severe and persistent pain in the abdomen (stomach area), which may spread to the back, with or without nausea and vomiting, as these may be signs of inflammation of the pancreas (pancreatitis).

Metsunix 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 Metsunix and seek immediate medical attention at the nearest doctor’s office or hospital, because lactic acidosis can lead to coma.
If you experience a severe allergic reaction (frequency not known, as it cannot be estimated from the available data), including rash, hives, skin blisters/skin peeling, and swelling of the face, lips, tongue, or throat, which may cause difficulty breathing or swallowing, stop treatment with this medicine and contact your doctor immediately. Your doctor may prescribe a medicine to treat the 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 people): low blood sugar levels, nausea, flatulence, vomiting.
Uncommon (may affect up to 1 in 100 people): stomach ache, diarrhoea, constipation, drowsiness.
Some patients have experienced diarrhoea, nausea, flatulence, constipation, stomach ache, or vomiting when starting combination therapy with sitagliptin and metformina together (frequency is common).
Some patients have experienced the following side effects while taking this medicine with a sulphonylurea such as glimepiride:
Very common (may affect more than 1 in 10 people): 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 while taking sitagliptin alone (one of the medicines contained in Metsunix) or during post-marketing use of Metsunix or sitagliptin alone or in combination with other diabetes medicines:
Common: low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose and sore throat, osteoarthritis, pain in arms or legs.
Uncommon: dizziness, constipation, itching sensation.
Rare (may affect up to 1 in 1,000 people): 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 blister).
Some patients taking metformin alone have experienced the following side effects:
Very common: nausea, vomiting, diarrhoea, stomach ache, and loss of appetite. These symptoms may occur when you first start taking metformin and usually resolve over time.
Common: metallic taste.
Very rare: decreased vitamin B12 levels, 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 or pharmacist. You can also report side effects directly via the national reporting system at: 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 Metsunix

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and carton after Exp.
The expiry date refers to the last day of that month.
Do not store above 25°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Metsunix contains
The active substances are sitagliptin and metformin.
Metsunix 50 mg/500 mg: Each tablet contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 500 mg of metformin hydrochloride.
Metsunix 50 mg/1000 mg: Each tablet contains sitagliptin monohydrochloride monohydrate equivalent to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
Metsunix 100 mg/1000 mg: Each tablet contains sitagliptin monohydrochloride monohydrate equivalent to 100 mg of sitagliptin and 1000 mg of metformin hydrochloride.

The other components are:

• Metformin extended-release layer: hypromellose, magnesium stearate.
• Sitagliptin immediate-release layer: calcium hydrogen phosphate, microcrystalline cellulose, sodium stearyl fumarate, sodium croscarmellose (see section 2 “Metsunix contains sodium”).
• Additionally, the film coating contains:
  • for the 100 mg/1000 mg and 50 mg/500 mg strengths: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), red iron oxide (E172).
  • for the 50 mg/1000 mg strength: polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc.

Description of the appearance of Metsunix and contents of the pack
Metsunix 50 mg/500 mg: orange, oblong, biconvex, film-coated tablets of size 17.2 mm / 8.4 mm.
Metsunix 50 mg/1000 mg: white, oblong, biconvex, film-coated tablets of size 22.2 mm / 10.8 mm, with “50” printed on one side and “1000” on the other side.
Metsunix 100 mg/1000 mg: orange, oblong, biconvex, film-coated tablets of size 22.2 mm / 10.8 mm, with “100” printed on one side and “1000” on the other side.
Packs containing 28, 30, 56 or 60 modified-release tablets in PVC/PVDC/Alu blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Adamed s.r.l.,
Via G. Mazzini, 20
20123 Milano (Italy)
Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice
Poland

This medicinal product is authorised in the European Economic Area Member States under the following names:
Poland: Depepsit Met
Germany: Metsunix
Latvia: TIXULDA
Italy: Metsunix
Spain: Metsunix