Diesmit

Package leaflet: Information for the patient

DIESMIT 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 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What DIESMIT is and what it is used for

DIESMIT contains two different medicines called sitagliptin and metformin.

• Sitagliptin belongs to a class of medicines known as DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors).
• Metformin belongs to a class of medicines known as 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 as it should. 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 amputation.

2. What you need to know before taking DIESMIT

Do not take DIESMIT:

• 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 pre-coma. 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 undergoing radiographic imaging involving the use of a contrast agent. You must stop taking DIESMIT at the time of the imaging procedure and for 2 or more days afterwards, as directed by your doctor, depending on your kidney function
• 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 DIESMIT if you have any of the above conditions and speak with your doctor about other methods of managing diabetes. If you are unsure, talk to your doctor, pharmacist, or nurse before taking DIESMIT.

Warnings and precautions

Cases of inflammation of the pancreas (pancreatitis) have been reported in patients treated with DIESMIT (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 DIESMIT.

Risk of lactic acidosis
DIESMIT 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 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.

Temporarily stop taking DIESMIT if you develop 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 normal. Consult your doctor for further instructions.

If you experience any of the symptoms of lactic acidosis, stop taking DIESMIT and contact your doctor or go to the nearest hospital immediately, as lactic acidosis can lead to coma. Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• a general feeling of being unwell associated with severe fatigue
• 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 DIESMIT:

• 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 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 DIESMIT (see section 4)
• if you are taking a sulphonylurea or insulin, diabetes medicines, together with DIESMIT, as excessively low blood sugar levels (hypoglycaemia) may occur. Your doctor may reduce the dose of the sulphonylurea or insulin.

If you are scheduled for major surgery, you must stop taking DIESMIT during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with DIESMIT.

If you are unsure whether any of the conditions listed above apply to you, consult your doctor or pharmacist before taking DIESMIT.

During treatment with DIESMIT, your doctor will monitor 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 10 to 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 DIESMIT
If you are to receive an injection of an iodinated contrast agent into the bloodstream, for example for a radiograph or another examination, you must stop taking DIESMIT before or during the injection. Your doctor will decide when to stop and when to restart treatment with DIESMIT.

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. You may need to check your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of DIESMIT. It is particularly important to mention the following:

• medicines (taken orally, by inhalation, or by injection) 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 (used to treat irregular heartbeat and other heart-related problems). It may be necessary to monitor digoxin blood levels if taken together with DIESMIT.

DIESMIT and alcohol
Avoid excessive alcohol consumption during treatment with DIESMIT, 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 a pregnancy, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine. You must not take this medicine during pregnancy or while breastfeeding. See section 2, Do not take DIESMIT.

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 sulphonylureas or with insulin may cause hypoglycaemia, which may affect your ability to drive, use machines, or work without protective barriers.

DIESMIT contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e., essentially “sodium-free”.

3. How to take DIESMIT

Take this medicine exactly as your doctor has told you. If you are not sure, consult your doctor or pharmacist. Your doctor will tell you how many DIESMIT tablets to take and when to take them.
The maximum daily dose is 100 milligrams of sitagliptin and 2,000 milligrams of metformin.
The tablets are usually taken once daily with the evening meal.
In some cases, your doctor may advise you to take the tablets twice daily.
Always take the tablets with food to reduce the likelihood of stomach problems.
The tablets must be swallowed whole with a glass of water, without chewing.
Your doctor may need to increase your dose to control the sugar level 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 DIESMIT 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 DIESMIT
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 continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten dose.

If you stop taking DIESMIT
Continue taking this medicine for as long as your doctor prescribes it, so that you can keep your blood sugar level under control. Do not stop treatment with this medicine without first talking to your doctor. If you stop treatment with DIESMIT, your blood sugar level 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 DIESMIT 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).

DIESMIT 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 DIESMIT and seek immediate medical attention at the nearest doctor 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 blistering/desquamation, or 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 your allergic reaction and a different medicine for your diabetes.

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

Some patients experienced diarrhoea, nausea, flatulence, constipation, stomach ache, or vomiting when starting combination therapy with sitagliptin and metformin (frequency is common).

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

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

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

During clinical studies, some patients experienced the following side effects while taking sitagliptin alone (one of the medicines contained in DIESMIT) or after the marketing of DIESMIT or sitagliptin alone or in combination with other diabetes medicines:
Common: low blood sugar level, headache, upper respiratory tract infection, nasal congestion or runny nose, 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 blister)

Some patients, while taking metformin alone, 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 metformin and usually resolve over time
Common: metallic taste
Very rare: decreased levels of vitamin B12, hepatitis (a liver problem), hives, skin redness (rash), or itching

Reporting of side effects
If you experience any side effect, 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 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 DIESMIT

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 outer packaging after
"EXP". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

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

The other components are:

• Metformin prolonged-release layer: hypromellose, magnesium stearate

• Sitagliptin immediate-release layer: calcium hydrogen phosphate, microcrystalline cellulose, sodium stearyl fumarate, sodium croscarmellose (see section 2 “contains sodium”)

• The film coating additionally contains:

  • for strengths 100 mg/1000 mg and 50 mg/500 mg: partially hydrolysed polyvinyl alcohol, titanium dioxide (E171), macrogol 4000, talc, yellow iron oxide (E172), red iron oxide (E172)
  • for strength 50 mg/1000 mg: poly(vinyl alcohol), titanium dioxide (E171), macrogol 4000, talc

Description of the appearance of DIESMIT and contents of the pack
DIESMIT 50 mg/500 mg: Orange, film-coated, oblong, biconvex tablets, 17.2 mm x 8.4 mm in size.
DIESMIT 50 mg/1000 mg: White, film-coated, oblong, biconvex tablets, 22.2 mm x 10.8 mm in size, with "50" printed on one side and "1000" on the other.
DIESMIT 100 mg/1000 mg: Orange, film-coated, oblong, biconvex tablets, 22.2 mm x 10.8 mm in size, with "100" printed on one side and "1000" on the other.

Packs of 10, 14, 28, 30, 56, 60, 98, 100, 112, 160, 168, 180, 196 or 200 modified-release tablets in PVC/PVDC/Aluminium blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Bruno Farmaceutici Spa
Via delle Ande 15,
00144 Roma, 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 countries under the following names:
Austria, Croatia: Sitagliptin/Metformin APC
Bulgaria, Cyprus, Greece: Sitagliptin+Metformin APC
Poland: Sitagliptin + Metformin hydrochloride APC
Portugal: Mesiglic
Italy: Diesmit