Depepsit met

Package leaflet: Information for the patient

Depepsit Met, 50 mg + 500 mg, modified-release tablets
Depepsit Met, 50 mg + 1000 mg, modified-release tablets
Depepsit Met, 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 further questions, 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 them, even if their symptoms are the same.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents

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

1. What Depepsit Met is and what it is used for

Depepsit Met 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 two medicines helps regulate blood glucose levels in adults with diabetes known as "type 2 diabetes". This medicine helps increase insulin release 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 as an antidiabetic treatment or in combination with certain other antidiabetic medicines (insulin, sulfonylurea derivatives, or glitazones).

What is type 2 diabetes?
In type 2 diabetes, 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, sugar (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 Depepsit Met

When not to use Depepsit Met:

• if the patient is allergic to sitagliptin or metformin or 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. Diabetic ketoacidosis is a condition in which substances called ketones 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 the patient has a severe infection or dehydration,
• if the patient is scheduled to undergo a radiological examination with intravascular iodinated contrast medium. Treatment with Depepsit Met must be discontinued before or at the latest during the radiological examination and for a period of 2 or more days, according to the physician's instructions, depending on the patient's kidney function,
• if the patient has recently experienced a heart attack or has severe circulatory disorders such as shock or breathing difficulties,
• if the patient has liver disease,
• if the patient consumes excessive amounts of alcohol (daily or even occasionally),
• if the patient is breastfeeding.

Do not take Depepsit Met if any of the above contraindications apply.
Consult your doctor to determine alternative methods of diabetes control. If in doubt, discuss this with your doctor, pharmacist or nurse before taking Depepsit Met.
Warnings and precautions
Discuss with your doctor or pharmacist before starting treatment with Depepsit Met.
Cases of pancreatitis have been reported in patients taking Depepsit Met (see section 4).
If the patient develops skin blisters, this may be a symptom of a disease called bullous pemphigoid. Your doctor may advise discontinuation of Depepsit Met.
Risk of lactic acidosis
Depepsit Met may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has impaired kidney function. The risk of lactic acidosis is also increased in cases of uncontrolled diabetes, severe infections, prolonged fasting or alcohol consumption, dehydration (see additional information below), liver dysfunction, and any medical conditions in which any part of the body is inadequately supplied with oxygen (such as acute severe heart disease).
If any of the above conditions apply to the patient, consult a doctor for further instructions.
Contact your doctor immediately for further instructions if:

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

Temporarily discontinue Depepsit Met if the patient develops a medical condition that may involve
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 doctor for further instructions.
Stop taking Depepsit Met and contact your doctor or the nearest hospital immediately if the
patient experiences 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 malaise with severe fatigue,
• difficulty breathing,
• low body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring hospital treatment.
Discuss with your doctor or pharmacist before starting Depepsit Met:

• 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 levels of triglycerides (a type of fat) in the blood. In such cases, the risk of developing pancreatitis may increase (see section 4),
• if the patient has been diagnosed with type 1 diabetes. This is sometimes referred to as insulin-dependent diabetes,
• if the patient currently has or has previously experienced an allergic reaction to sitagliptin, metformin or Depepsit Met (see section 4),
• if the patient is taking a sulfonylurea derivative or insulin together with Depepsit Met, as this may cause excessively low blood sugar levels (hypoglycaemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is scheduled for major surgery, treatment with Depepsit Met must be discontinued during the procedure and for some time afterwards. The doctor will decide when to stop and restart treatment with Depepsit Met.
If in doubt whether any of the above situations apply, discuss this with your doctor or pharmacist before taking Depepsit Met.
While being treated with Depepsit Met, your doctor will monitor kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening 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 not known whether this medicine is safe and effective in children under 10 years of age.
Depepsit Met and other medicines
If the patient is to receive an intravenous iodine-containing contrast agent, for example during an X-ray or CT scan, treatment with Depepsit Met must be stopped before or at the latest at the time of injection. The doctor will decide when to stop and restart treatment with Depepsit Met.
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function, or the doctor may need to adjust the dose of Depepsit Met. It is especially important to inform 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 bronchial asthma (β-sympathomimetics),
• iodine-containing contrast agents or medicines containing alcohol,
• certain medicines used to treat stomach problems, such as cimetidine,
• ranolazine, a medicine used to treat angina pectoris,
• 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 Depepsit Met is taken concomitantly with digoxin.

Depepsit Met and alcohol
Avoid consuming excessive amounts of alcohol while taking Depepsit Met, 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 plans to become pregnant, she should consult her doctor or pharmacist before using this medicine. This medicine must not be used during pregnancy or breastfeeding. See section 2 "When not to use Depepsit Met".
Driving and using machines
This medicine has no or 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 in combination with medicines called sulfonylurea derivatives or insulin may lead to hypoglycaemia, which in turn may affect the ability to drive and use machines or work without secure foot support.
Depepsit Met contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to use Depepsit Met

This medicine should always be taken as instructed by your doctor. If in doubt, consult your doctor or pharmacist. Your doctor will inform you how many tablets of Depepsit Met 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 following 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 Depepsit Met than recommended
If you take more Depepsit Met than recommended, 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 Depepsit Met
If you miss a dose, take it as soon as possible. If you do not remember the missed dose 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 Depepsit Met
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 Depepsit Met 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 Depepsit Met and contact your doctor immediately if you experience any of the following serious adverse reactions:

• 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.

Depepsit Met may very rarely (not more often than 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 in a patient, treatment with Depepsit Met must be discontinued immediately and medical advice must be sought immediately from a doctor or the nearest hospital, as lactic acidosis may lead to coma.

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

In some patients taking metformin, the following adverse reactions occurred after starting treatment with sitagliptin:

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

In some patients taking this medicine in combination with a sulfonylurea derivative such as glimepiride, the following adverse reactions occurred:

Very frequent (may occur in more than 1 in 10 people): low blood sugar levels
Frequent: constipation

In some patients taking this medicine in combination with pioglitazone, the following adverse reactions occurred:

Frequent: swelling of hands or feet

In some patients taking this medicine in combination with insulin, the following adverse reactions occurred:

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

During clinical trials and post-marketing use, the following adverse reactions occurred in some patients taking sitagliptin alone (one of the active substances in Depepsit Met), or when using Depepsit Met or sitagliptin alone or in combination with other antidiabetic medicines:

Frequent: low blood sugar levels, headache, upper respiratory tract infection, stuffy or runny nose, sore throat, bone and joint pain, pain in hands or feet
Uncommon: dizziness, constipation, itching
Rare (may occur in 1 out of 1,000 people): decreased platelet count
Frequency unknown: 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 frequent: nausea, vomiting, diarrhoea, stomach pain and loss of appetite. These symptoms may occur at the beginning of metformin treatment and usually resolve over time.
Frequent: metallic taste in the mouth
Very rare: decreased vitamin B12 levels, 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 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 this medicine.

5. How to store Depepsit Met
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 carton after the abbreviation "EXP". The expiry date refers to the last day of the stated month.
Do not store above 25°C.
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 pack and other information

What Depepsit Met contains
The active substances in this medicine are sitagliptin and metformin.
Depepsit Met, 50 mg + 500 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 50 mg of sitagliptin and 500 mg of metformin hydrochloride.
Depepsit Met, 50 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 50 mg of sitagliptin and 1000 mg of metformin hydrochloride.
Depepsit Met, 100 mg + 1000 mg: Each tablet contains sitagliptin hydrochloride monohydrate, corresponding to 100 mg of sitagliptin and 1000 mg of metformin hydrochloride.

Other components 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, "Depepsit Met contains sodium")
• Additionally, the film coating contains:
  • For 100 mg + 1000 mg and 50 mg + 500 mg doses: partially hydrolysed polyvinyl alcohol, titanium dioxide (E 171), macrogol 4000, talc, yellow iron oxide (E 172), red iron oxide (E 172)
  • For 50 mg + 1000 mg dose: partially hydrolysed polyvinyl alcohol, titanium dioxide (E 171), macrogol 4000, talc

What Depepsit Met looks like and contents of the pack
Depepsit Met, 50 mg + 500 mg: Orange, elongated, biconvex film-coated tablets, 17.2 mm x 8.4 mm in size.
Depepsit Met, 50 mg + 1000 mg: White, elongated, biconvex film-coated tablets, 22.2 mm x 10.8 mm in size, with the imprint "50" on one side and "1000" on the other.
Depepsit Met, 100 mg + 1000 mg: Orange, elongated, biconvex film-coated tablets, 22.2 mm x 10.8 mm in size, with the imprint "100" on one side and "1000" on the other.

Blister packs made of PVC/PVDC/Aluminium in cardboard cartons. Pack sizes of 28, 30, 56, and 60 modified-release tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Adamed Pharma S.A.
Pieńków, ul. M. Adamkiewicza 6A
05-152 Czosnów
Tel: +48 22 732 77 00

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

This medicine is authorised in the European Economic Area under the following brand names:
Spain: Metsunix
Latvia: TIXULDA
Germany: Metsunix
Poland: Depepsit Met
Italy: Metsunix