Juzimette

Package leaflet: Information for the patient
JUZIMETTE, 50 mg + 850 mg, film-coated tablets
sitagliptin + metformin hydrochloride
Please read carefully all the information in this leaflet before taking this medicine, because it contains important information for you.

• Keep this leaflet as 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 personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents

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

1. What Juzimette is and what it is used for

Juzimette 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 adult patients with diabetes known as "type 2 diabetes." This medicine helps increase the amount of insulin released after a meal and reduces the amount of glucose produced by the body.
When used together with diet and exercise, this medicine helps lower blood glucose levels.
It may be used as the only antidiabetic medicine 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 taking Juzimette

When not to take Juzimette:

• 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 unusual fruity odour of breath;

• if the patient has severe infection or dehydration;

• if the patient is scheduled for a radiological procedure involving intravascular administration of contrast medium. The use of Juzimette should be temporarily discontinued during the radiological examination and for 2 or more days afterwards, as advised by the physician, depending on the patient's kidney function;

• if the patient has recently suffered a heart attack or has experienced 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 take Juzimette 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 Juzimette.
Warnings and precautions
Cases of pancreatitis have been reported in patients taking Juzimette (see section 4).
If the patient develops blisters on the skin, this may be a sign of a condition known as bullous pemphigoid. The doctor may advise discontinuation of Juzimette.

Risk of lactic acidosis
Juzimette 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 increases in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information 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 doctor for further instructions.
Temporarily discontinue use of Juzimette if the patient develops a medical condition associated with dehydration (significant loss of body fluids), 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.
Discontinue use of Juzimette and contact a 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;
• abdominal pain;
• muscle cramps;
• general feeling of 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 medical advice immediately 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).
• after starting metformin, the patient developed any of the following symptoms: seizures, worsening of cognitive function, difficulty moving, signs indicating nerve damage (e.g. pain or tingling), migraine, or deafness.

Before starting Juzimette, discuss the following with your doctor 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, sometimes referred to as insulin-dependent diabetes;
• if the patient currently has or has previously experienced allergic reactions to sitagliptin, metformin, or Juzimette (see section 4);
• if the patient is taking a sulfonylurea derivative or insulin together with Juzimette, as this may lead to excessively low blood sugar levels (hypoglycaemia). The doctor may reduce the dose of the sulfonylurea derivative or insulin.

If the patient is undergoing major surgery, Juzimette must not be used during the procedure and for some time afterwards. The doctor will decide when the patient should stop and restart treatment with Juzimette.
If the patient is unsure whether any of the above statements apply, they should discuss this with their doctor or pharmacist before taking Juzimette.
While being treated with Juzimette, the 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 should not be used in children and adolescents under 18 years of age. The medicine is not effective in children and adolescents aged 10 to 17 years. It is unknown whether this medicine is safe and effective for use in children under 10 years of age.

Juzimette and other medicines
If the patient is to receive an iodine-containing contrast agent injected into the bloodstream, for example during an X-ray or CT scan, they must stop taking Juzimette before or at the latest at the time of injection. The doctor will decide when the patient should stop and restart treatment with Juzimette.
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines they plan to take. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Juzimette by the doctor. It is especially important to inform about the following medicines:

• medicines (taken orally, by inhalation, or injection) used to treat inflammatory conditions such as asthma or arthritis (corticosteroids);
• diuretics (medicines that increase urine production);
• 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 Juzimette with digoxin.

Juzimette and alcohol
Avoid consuming excessive amounts of alcohol while taking Juzimette, 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 have a child, she should consult her doctor or pharmacist before taking this medicine. This medicine should not be used during pregnancy. This medicine should not be taken during breastfeeding.
See section 2, When not to take Juzimette.

Driving and operating machinery
This medicine has no effect or negligible effect on the ability to drive and operate machinery. However, dizziness and drowsiness have been reported during treatment with sitagliptin, which may affect the ability to drive and operate machinery.
Taking this medicine together with medicines known as sulfonylurea derivatives or insulin may lead to hypoglycaemia, which in turn may affect the ability to drive and operate machinery or work without secure foot support.

Juzimette 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 take Juzimette

This medicine should always be taken according to the doctor's instructions. 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 glucose levels, your doctor may increase the dose of this medicine.
• If the patient has impaired kidney function, the doctor may prescribe a lower dose.

While taking this medicine, continue the diet recommended by your doctor and pay attention to
consuming carbohydrates evenly throughout the day.
It is unlikely that this medicine, when used alone, would cause abnormally low blood glucose levels (hypoglycaemia). Low blood glucose levels may occur when this medicine is taken together with a sulfonylurea derivative or insulin – in such cases, your doctor may reduce the dose of the sulfonylurea derivative or insulin.
Taking more Juzimette than recommended
If you take more than the recommended dose of this medicine, contact your doctor immediately.
Go to hospital if symptoms of lactic acidosis occur, such as feeling cold or discomfort, severe nausea or vomiting, stomach pain, unexplained weight loss, muscle cramps or rapid breathing (see section "Warnings and precautions").
If you forget to take Juzimette
If you miss a dose, take it as soon as possible. If it is almost time for the next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose of this medicine.
Stopping Juzimette
To maintain control of blood glucose levels, take this medicine for as long as your doctor recommends. Do not stop taking this medicine without first consulting your doctor.
Stopping treatment with Juzimette may lead to increased blood glucose levels.
If you have any further doubts about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine may cause side effects, although not everyone gets them.

You must STOP taking Juzimette and contact your doctor immediately if any of the following serious side effects occur:

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

Juzimette may very rarely (may occur in less than 1 in 10,000 patients) cause a very serious side effect known as lactic acidosis (see section "Warnings and precautions"). If lactic acidosis occurs in a patient, treatment with Juzimette must be STOPPED and the patient should immediately contact a doctor or the nearest hospital, as lactic acid In case of a severe allergic reaction (frequency unknown), including rash, hives, skin blisters or skin 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 treatment for the allergic reaction and switch you to another medicine (change of medicine) for diabetes management.

In some patients taking metformin, the following side effects occurred after starting sitagliptin:

Common (may occur in less than 1 in 10 patients): low blood sugar levels, nausea, flatulence, vomiting
Uncommon (may occur in less than 1 in 100 patients): stomach pain, diarrhoea, constipation, drowsiness.

Some patients experienced diarrhoea, nausea, flatulence, 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 side effects occurred:

Very common (may occur in more than 1 in 10 patients): low blood sugar levels
Common (may occur in less than 1 in 10 patients): constipation.

In some patients taking this medicine in combination with pioglitazone, the following side effects occurred:

Common (may occur in less than 1 in 10 patients): swelling of hands or legs.

In some patients taking this medicine in combination with insulin, the following side effects occurred:

Very common (may occur in more than 1 in 10 patients): low blood sugar levels
Uncommon (may occur in less than 1 in 100 patients): dry mouth, headache.

In clinical trials and post-marketing experience with sitagliptin alone (one of the active substances in Juzimette) or with Juzimette or sitagliptin alone or in combination with other antidiabetic medicines, the following side effects were observed:

Common (may occur in less than 1 in 10 patients): low blood sugar levels, headache, upper respiratory tract infection, nasal congestion or runny nose, sore throat, bone fracture, joint pain, pain in arms or legs
Uncommon (may occur in less than 1 in 100 patients): dizziness, constipation, itching
Rare (may occur in less than 1 in 1000 patients): decreased platelet count
Frequency not known (frequency cannot be estimated from available data): 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 side effects occurred:

Very common (may occur in more than 1 in 10 patients): nausea, vomiting, diarrhoea, stomach pain and loss of appetite. These symptoms may occur after starting metformin and usually resolve over time.
Common (may occur in less than 1 in 10 patients): metallic taste, reduced or low levels of vitamin B in the blood (symptoms may include extreme tiredness (fatigue), pain and redness of the tongue (glossitis), tingling (paraesthesiae), or pale or yellowish skin). Your doctor may order tests to determine the cause of these symptoms, as some of them may also be caused by diabetes or other unrelated health problems.
Very rare (may occur in less than 1 in 10,000 patients): hepatitis (liver disease), urticaria, skin redness (rash) or itching.

Reporting of side effects

If you experience any adverse effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. Side effects can also 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
Side effects can also be reported directly to the marketing authorisation holder.

By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store Juzimette

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the cardboard box after "EXP". The expiry date refers to the last day of the stated month.
Store below 30°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Juzimette contains
The active substances are sitagliptin and metformin.
Each film-coated tablet contains sitagliptin hydrochloride monohydrate equivalent to 50 mg of sitagliptin and 850 mg of metformin hydrochloride (equivalent to 660 mg of metformin).
The other ingredients are:
Tablet core:
Microcrystalline cellulose type 101
Povidone K29/32
Sodium stearyl fumarate
Sodium lauryl sulfate
Coating:
Polyvinyl alcohol, partially hydrolysed
Macrogol 3350
Talc
Titanium dioxide (E 171)
Red iron oxide (E 172)
Black iron oxide (E 172)

What Juzimette looks like and contents of the pack
Pink (white or almost white film-coated tablet, pink in colour), oblong (approximately 17.7 mm in length, 10.0 mm in width), biconvex. The tablet is debossed with "AE3" on one side and has no marking on the other side.
The film-coated tablets are packed in white, opaque blisters made of PVC/PE/PVDC/Aluminium.
The blisters are placed in a cardboard box containing the patient leaflet.
The cardboard boxes contain 28, 30, 56, 60, 98 or 120 film-coated tablets. The multi-pack contains 196 film-coated tablets (2 packs of 98 tablets).
Not all pack sizes may be marketed.

Marketing Authorisation Holder
GEDEON RICHTER POLSKA Sp. z o.o.
ul. Ks. J. Poniatowskiego 5,
05-825 Grodzisk Mazowiecki
Poland

Manufacturer
Gedeon Richter România S.A.
Str. Cuza-Vodă nr. 99-105
540306 Târgu-Mureș
Romania
Gedeon Richter Plc.
Gyömrői út 19-21
1103 Budapest
Hungary

This medicinal product is authorised in the member countries of the European Economic Area under the following names:
Bulgaria Juzimette 50 mg/850 mg, film-coated tablets
Czech Republic Juzimette
Estonia Juzimette
Hungary Juzimette 50 mg/850 mg, filmtabletta
Latvia Juzimette 50 mg/850 mg, apvalkotas tabletes
Poland Juzimette
Romania Juzimette 50 mg/850 mg, comprimate filmate
Slovakia Juzimette 50 mg/850 mg, filmom obalené tablety