SYNJARDY 12.5 mg/1000 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Synjardy 5mg/850mg film-coated tablets

Synjardy 5mg/1,000mg film-coated tablets

Synjardy 12.5mg/850mgfilm-coated tablets

Synjardy 12.5mg/1,000mgfilm-coated tablets

empagliflozin/metformin hydrochloride

Read all of this leaflet carefully before you start 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 signs of illness 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 pack

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

1. What is Synjardy and what is it used for

What is Synjardy

Synjardy contains two active substances: empagliflozin and metformin. Both belong to a group of medicines called “oral antidiabetics”. These medicines are taken by mouth to treat type 2 diabetes.

What is type 2 diabetes?

Type 2 diabetes is a disease that comes from your genes and your lifestyle. If you have type 2 diabetes, your pancreas does not produce enough insulin to control the level of glucose in your blood, and your body is unable to use its own insulin effectively. This leads to high levels of glucose in your blood, which can cause medical problems such as heart disease, kidney disease, blindness, and poor circulation in your limbs.

How Synjardy works

Empagliflozin belongs to a group of medicines called sodium-glucose co-transporter-2 (SGLT2) inhibitors. It works by blocking the SGLT2 protein in the kidneys. This leads to the elimination of sugar (glucose) from the blood in the urine. Metformin works in a different way to reduce blood glucose levels, mainly by blocking glucose production in the liver.

As a result, Synjardy reduces the amount of sugar present in the blood. This medicine may help prevent heart disease.

What Synjardy is used for

• Synjardy is added to diet and exercise to treat type 2 diabetes in adult and pediatric patients aged 10 years and older who cannot be controlled on metformin alone or metformin with other diabetes medicines.

• Synjardy may also be used in combination with other diabetes medicines, including oral medicines or injectable medicines such as insulin.

• In addition, Synjardy may be used as an alternative to taking empagliflozin and metformin as separate tablets. To avoid overdose, do not continue taking separate empagliflozin and metformin tablets if you are taking this medicine.

It is important that you follow the diet and exercise plan that your doctor, pharmacist, or nurse has advised.

2. What you need to know before you take Synjardy

Do not take Synjardy

• if you are allergic to empagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6);
• if you have uncontrolled diabetes with, for example, severe hyperglycemia (very high blood sugar), nausea, vomiting, diarrhea, rapid 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, which can lead to diabetic precoma. The symptoms include stomach pain, rapid and deep breathing, drowsiness, or unusual fruity odor of the breath;
• if you have had diabetic precoma;
• if you have severe kidney problems. Your doctor may limit your daily dose or ask you to take another medicine (see also section 3, “How to take Synjardy”);
• if you have a severe infection such as an infection affecting the lung or bronchial system, or the kidney. Severe infections can lead to kidney problems, which can put you at risk of lactic acidosis (see “Warnings and precautions”);
• if you have lost a significant amount of body fluid (dehydration), for example, due to severe and prolonged diarrhea or vomiting, or if you have not been able to eat or drink. Dehydration can lead to kidney problems, which can put you at risk of lactic acidosis (see “Warnings and precautions”);
• if you are being treated for acute heart failure or have recently had a heart attack, have severe circulation problems (such as “shock”), or breathing difficulties. This can lead to a lack of oxygen supply to the tissues, which can put you at risk of lactic acidosis (see “Warnings and precautions”);
• if you have liver problems;
• if you drink large amounts of alcohol, either every day or only occasionally (see section “Taking Synjardy with alcohol”).

Warnings and precautions

Risk of lactic acidosis

Synjardy may cause a very rare but very serious side effect called lactic acidosis, especially if your kidneys are not working properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, severe infections, prolonged fasting, or alcohol intake, dehydration (see more information below), liver problems, and any medical condition in which a part of the body has a reduced oxygen supply (such as acute and severe heart disease).

If any of the above applies to you, consult your doctor for further instructions.

Stop taking Synjardy for a short period if you have a condition that may be associated with dehydration(significant loss of body fluids), such as severe vomiting, diarrhea, fever, heat exposure, or if you drink less fluid than usual. Consult your doctor for further instructions.

Stop taking Synjardy and contact a doctor or the nearest hospital immediately if you experience any of the symptoms that lactic acidosis can cause, as this condition can lead to coma.

The symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• general feeling of being unwell, with intense tiredness
• difficulty breathing
• reduced body temperature and heart rate

Consult your doctor promptly to advise you on what to do

• if you know you have a genetic disease that affects the mitochondria (the energy-producing components within cells), such as MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• if you experience any of the following symptoms after starting treatment with metformin: seizure, cognitive impairment, difficulty with body movements, symptoms indicating nerve damage (e.g., pain or numbness), migraine, and hearing loss.

Lactic acidosis is a medical emergency and must be treated in a hospital.

Consult your doctor, pharmacist, or nurse before you start taking this medicine and during treatment:

• if you experience rapid weight loss, nausea, or vomiting, stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness, or unusual tiredness, sweet smell of the breath, sweet or metallic taste in the mouth, or unusual odor in the urine or sweat, contact a doctor or the nearest hospital immediately and stop taking this medicine until you talk to your doctor. These symptoms may be a sign of “diabetic ketoacidosis”, a rare but serious and potentially life-threatening problem that can occur with diabetes due to increased levels of “ketone bodies” in your urine or blood, detected by laboratory tests. The risk of developing diabetic ketoacidosis may be increased with prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin dose, or increased need for insulin due to major surgery or serious illness;
• if you have “type 1 diabetes”: this type of diabetes usually starts when you are young and your body does not produce any insulin. You should not take Synjardy if you have type 1 diabetes;
• if you may be at risk of dehydration, for example:

• if you have vomiting, diarrhea, or fever, or if you are unable to eat or drink
• if you are taking medicines that increase urine production (diuretics) or lower blood pressure
• if you are 75 years of age or older

The possible signs are indicated in section 4 under the heading “dehydration”. Your doctor may advise you to stop taking Synjardy until you recover to avoid losing too much body fluid. Ask your doctor about ways to prevent dehydration.

• if you have a severe kidney or urinary tract infection with fever. Your doctor may ask you to stop taking Synjardy until you recover;
• if you need to have an examination with iodine-containing contrast agents (e.g., an X-ray or scan). More information is provided below in the section “Other medicines and Synjardy”.

Consult your doctor immediately if you experience a combination of symptoms of pain, pain on palpation, redness, or swelling of the genitals or the area between the genitals and the anus, with fever or general feeling of being unwell. These symptoms could be a sign of a rare but serious, potentially life-threatening infection called necrotizing fasciitis of the perineum or Fournier's gangrene, which destroys tissue under the skin. Fournier's gangrene must be treated immediately.

Surgery

If you need to have major surgery, you should stop taking Synjardy during the procedure and for some time after. Your doctor will decide when you should stop taking Synjardy and when you can start taking it again.

Kidney function

During treatment with Synjardy, your doctor will check your kidney function at least once a year or more frequently if you are an elderly person and/or if your kidney function is worsening.

Foot care

As with all diabetic patients, it is important that you regularly check your feet and follow any other foot care advice given by your healthcare professional.

Glucose in urine

Due to the way this medicine works, your urine will test positive for glucose while you are taking this medicine.

Children and adolescents

Synjardy may be used in children aged 10 years and older for the treatment of type 2 diabetes mellitus.

Due to limited data, caution is recommended when using the medicine in children between 10 and 12 years of age.

No data are available in children under 10 years of age.

Other medicines and Synjardy

If you need to be given an injection of a contrast agent containing iodine into your bloodstream, for example, in the context of an X-ray or scan, you should stop taking Synjardy before or at the time of the injection. Your doctor will decide when you should stop taking Synjardy and when you can start taking it again.

Inform your doctor if you are taking, have recently taken, or might take any other medicines. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of Synjardy. It is especially important to mention the following:

• medicines that increase urine production (diuretics), as Synjardy may increase the risk of losing too much fluid. Your doctor may ask you to stop taking Synjardy. The possible signs of excessive fluid loss from your body are included in section 4.
• other medicines that lower the amount of glucose in your blood, such as insulin or a “sulfonylurea”. Your doctor may decide to reduce the dose of these other medicines to prevent your blood glucose levels from becoming too low (hypoglycemia).
• medicines that may change the levels of metformin in the blood, especially if you have reduced kidney function (such as verapamil, rifampicin, cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole, crizotinib, olaparib).
• bronchodilators (beta-2 agonists) used to treat asthma.
• corticosteroids (taken by mouth, injected, or inhaled) used to treat inflammation in diseases such as asthma and arthritis.
• 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).
• medicines containing alcohol (see section “Taking Synjardy with alcohol”).
• iodine-containing contrast agents (medicines used during an X-ray; see section 2, “Warnings and precautions”).
• if you are taking lithium, as Synjardy may reduce the amount of lithium in your blood.

Taking Synjardy with alcohol

Avoid excessive alcohol intake while taking Synjardy, as this can 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, ask your doctor or pharmacist for advice before taking this medicine.

Do not take Synjardy if you are pregnant. It is not known if this medicine is harmful to the unborn baby.

Metformin passes into breast milk in small amounts. It is not known if empagliflozin passes into breast milk. Do not take Synjardy if you are breastfeeding.

Driving and using machines

Synjardy has a minor influence on the ability to drive and use machines.

Taking this medicine in combination with medicines called sulfonylureas or with insulin may cause your blood glucose levels to become too low (hypoglycemia), which can cause symptoms such as trembling, sweating, and changes in vision that can affect your ability to drive and use machines. Do not drive or use tools or machines if you feel dizzy while taking Synjardy.

3. How to take Synjardy

Follow your doctor's instructions for taking this medication exactly. If you are unsure, consult your doctor or pharmacist again.

What dose to take

The dose of Synjardy varies depending on your condition and the doses of diabetes medications you are currently taking. Your doctor will adjust the dose as needed and tell you exactly what concentration of the medication to take.

The recommended dose is one tablet twice a day. Normally, your doctor will start treatment with Synjardy by prescribing the tablet strength that provides the same dose of metformin you are already taking (850 mg or 1,000 mg twice a day), and the lowest dose of empagliflozin (5 mg twice a day). If you are already taking both medications separately, your doctor will start treatment with Synjardy tablets that provide the same amount of both. If you have reduced kidney function, your doctor may prescribe a lower dose or decide to use an alternative medication.

Taking this medication

• Swallow the tablet whole with water.
• Take the tablets with food to reduce the likelihood of stomach upset.
• Take the tablet twice a day by mouth.

Your doctor may prescribe Synjardy along with another diabetes medication. Remember to take all medications as your doctor has instructed to get the best results for your health. Your doctor may need to adjust your doses to control your blood sugar levels.

A suitable diet and exercise help your body use blood sugar better. It is essential to follow the diet and exercise plan recommended by your doctor while taking Synjardy.

If you take more Synjardy than you should

If you take more Synjardy tablets than you should, you may experience lactic acidosis. The symptoms of lactic acidosis are non-specific, such as nausea, vomiting, stomach pain with muscle cramps, a feeling of general discomfort with intense fatigue, and difficulty breathing. Other symptoms include decreased body temperature and heart rate. If this happens, you may need immediate hospital treatment, as lactic acidosis can lead to coma. Stop taking this medication immediately and contact a doctor or the nearest hospital right away(see section 2). Bring the medication packaging with you.

If you forget to take Synjardy

If you forget a dose, take it as soon as you remember. If you don't remember until it's time for your next dose, skip the missed dose and return to your regular schedule. Do not take a double dose of this medication.

If you stop taking Synjardy

Do not stop taking Synjardy without consulting your doctor first, unless you suspect you have diabetic ketoacidosis, lactic acidosis, or a disorder that can be associated with dehydration (see section 2 "Warnings and precautions"). Your blood sugar levels may increase if you stop taking Synjardy.

If you have any further questions about using this medication, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medications, this medication can cause side effects, although not everyone gets them.

Contact a doctor or the nearest hospital immediately if you have any of the following side effects:

Severe allergic reaction, observed rarely (may affect up to 1 in 100 people)

Possible signs of a severe allergic reaction may include:

• swelling of the face, lips, mouth, tongue, or throat, which can cause difficulty breathing or swallowing

Lactic acidosis, observed very rarely (may affect up to 1 in 10,000 people)

Synjardy may cause a very rare but severe side effect called lactic acidosis (see section 2). If this happens, you must stop taking Synjardy and contact a doctor or the nearest hospital immediately, as lactic acidosis can lead to coma.

Diabetic ketoacidosis, observed rarely (may affect up to 1 in 1,000 people)

These are the signs of diabetic ketoacidosis (see section 2):

• increase in "ketone bodies" in your urine or blood
• rapid weight loss
• nausea or vomiting
• stomach pain
• excessive thirst
• rapid and deep breathing
• confusion
• unusual sleepiness or fatigue
• sweet breath odor, sweet taste or metallic taste in the mouth, or distinct odor in urine or sweat

This can occur regardless of your blood sugar level. Your doctor may decide to temporarily or permanently stop treatment with Synjardy.

Contact your doctor as soon as possible if you experience the following side effects:

Low blood sugar (hypoglycemia), observed very frequently (may affect more than 1 in 10 people)

If you take Synjardy with another medication that can cause low blood sugar, such as a sulfonylurea or insulin, the risk of having low blood sugar is higher. The signs of low blood sugar include:

• shaking, sweating, feeling anxious or confused, or rapid heartbeat
• excessive hunger, headache

Your doctor will tell you how to treat low blood sugar and what to do if you have any of the above symptoms. If you have symptoms of low blood sugar, take glucose tablets, have a snack with high glucose content, or drink fruit juice. Measure your blood sugar levels if possible and rest.

Urinary tract infection, observed frequently (may affect up to 1 in 10 people)

The signs of a urinary tract infection are:

• burning sensation when urinating
• cloudy urine
• pain in the pelvis or middle back (when the kidneys are infected)

The need to urinate urgently or frequently may be due to the way Synjardy works, but it can also be a sign of a urinary tract infection. If you experience an increase in these symptoms, contact your doctor.

Dehydration, observed infrequently (may affect up to 1 in 100 people)

The signs of dehydration are non-specific but may include:

• unusual thirst
• dizziness or fainting when standing up
• fainting or loss of consciousness

Other side effects while taking Synjardy:

Very common

• feeling sick (nausea), vomiting
• diarrhea or stomach pain
• loss of appetite

Common

• genital fungal infection (candidiasis)
• urinating more than usual or needing to urinate more frequently
• itching (pruritus)
• rash or skin redness that can cause itching and include bumps, fluid discharge, or blisters
• changes in taste
• thirst
• blood tests may show increased levels of fats in the blood (cholesterol)
• constipation
• decreased or low vitamin B12 levels in the blood (symptoms may include extreme fatigue, inflamed and reddened tongue, tingling sensation, or pale or yellowish skin). It is possible that your doctor may request certain tests to identify the cause of your symptoms, as some of them can also be caused by diabetes or other unrelated health problems.

Uncommon

• hives
• straining or pain when urinating
• blood tests may show decreased kidney function (creatinine or urea)
• blood tests may show an increase in the number of red blood cells in your blood (hematocrit)

Rare

• necrotizing fasciitis of the perineum or Fournier's gangrene, a severe infection of the soft tissues of the genitals or the area between the genitals and the anus

Very rare

• abnormalities in liver function tests, liver inflammation (hepatitis)
• skin redness (erythema)
• kidney inflammation (tubulointerstitial nephritis)

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if it is possible side effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Synjardy

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date stated on the blister pack and carton after "EXP". The expiration date is the last day of the month indicated.

No special storage conditions are required.

Do not use this medication if you notice that the packaging is damaged or shows visible signs of tampering.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package contents and additional information

Synjardy composition

The active ingredients are empagliflozin and metformin.

Each film-coated tablet (tablet) of Synjardy 5 mg/850 mg contains 5 mg of empagliflozin and 850 mg of metformin hydrochloride.

Each film-coated tablet (tablet) of Synjardy 5 mg/1,000 mg contains 5 mg of empagliflozin and 1,000 mg of metformin hydrochloride.

Each film-coated tablet (tablet) of Synjardy 12.5 mg/850 mg contains 12.5 mg of empagliflozin and 850 mg of metformin hydrochloride.

Each film-coated tablet (tablet) of Synjardy 12.5 mg/1,000 mg contains 12.5 mg of empagliflozin and 1,000 mg of metformin hydrochloride.

The other ingredients are:

• Tablet core: corn starch, copovidone, colloidal anhydrous silica, magnesium stearate.
• Film coating: hypromellose, macrogol 400, titanium dioxide (E171), talc.

Synjardy 5 mg/850 mg and Synjardy 5 mg/1,000 mg tablets also contain yellow iron oxide (E172). Synjardy 12.5 mg/850 mg and Synjardy 12.5 mg/1,000 mg tablets also contain black iron oxide (E172) and red iron oxide (E172).

Appearance of the product and package contents

Synjardy 5 mg/850 mg film-coated tablets are white-yellowish, oval, and biconvex. They are engraved with "S5" and the Boehringer Ingelheim logo on one side and "850" on the other. The tablet measures 19.2 mm in length and 9.4 mm in width.

Synjardy 5 mg/1,000 mg film-coated tablets are yellow-brown, oval, and biconvex. They are engraved with "S5" and the Boehringer Ingelheim logo on one side and "1,000" on the other. The tablet measures 21.1 mm in length and 9.7 mm in width.

Synjardy 12.5 mg/850 mg film-coated tablets are pink-white, oval, and biconvex. They are engraved with "S12" and the Boehringer Ingelheim logo on one side and "850" on the other. The tablet measures 19.2 mm in length and 9.4 mm in width.

Synjardy 12.5 mg/1,000 mg film-coated tablets are dark brown-purple, oval, and biconvex. They are engraved with "S12" and the Boehringer Ingelheim logo on one side and "1,000" on the other. The tablet measures 21.1 mm in length and 9.7 mm in width.

The tablets are available in single-dose perforated PVC/PVDC/aluminum blisters. The pack sizes are 10 x 1, 14 x 1, 30 x 1, 56 x 1, 60 x 1, 90 x 1, and 100 x 1 film-coated tablets, and multiple packs containing 120 (2 packs of 60 x 1), 180 (2 packs of 90 x 1), and 200 (2 packs of 100 x 1) film-coated tablets.

Not all pack sizes may be marketed in your country.

Marketing authorization holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Boehringer Ingelheim Hellas Single Member S.A.

5th km Paiania – Markopoulo

Koropi Attiki, 19441

Greece

Patheon France

40 boulevard de Champaret

Bourgoin Jallieu, 38300

France

Boehringer Ingelheim France

100-104 Avenue de France

75013 Paris

France

You can obtain further information on this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

Detailed information on this medication is available on the European Medicines Agency website: https://www.ema.europa.eu.