SYNJARDY

Patient Information Leaflet

Synjardy 5 mg/850 mg film-coated tablets, 5 mg/1.000 mg film-coated tablets, 12.5 mg/850 mg film-coated tablets, 12.5 mg/1.000 mg film-coated tablets

empagliflozin/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, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Synjardy is and what it is used for

What is Synjardy
Synjardy contains two active substances, empagliflozin and metformin, which belong to a group of
medicines called “oral antidiabetics”. These are medicines taken by mouth to treat type 2 diabetes.
What is type 2 diabetes?
Type 2 diabetes is a condition linked to genetics and 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 cannot effectively use the insulin it produces. This leads to high levels of glucose in the
blood, which can cause health problems such as heart or kidney disease, blindness and circulation
problems in the limbs.
How Synjardy works
Empagliflozin belongs to a group of medicines called sodium-glucose co-transporter 2 (SGLT2)
inhibitors and works by blocking the SGLT2 protein in the kidneys. This causes sugar in the blood
(glucose) to be removed through the urine. Metformin works differently to reduce blood sugar levels,
mainly by blocking glucose production in the liver.
Therefore, Synjardy reduces the amount of sugar in the blood. This medicine may also help prevent
heart disease.
What Synjardy is used for

• Synjardy is used in addition to diet and exercise to treat type 2 diabetes in adults and children aged 10 years and older when diabetes cannot

be controlled with metformin alone or with metformin in combination with other antidiabetic medicines.

• Synjardy may be combined with other medicines for the treatment of diabetes. These may be medicines taken by mouth or administered by injection, such as insulin.
• Additionally, Synjardy may be used as an alternative to empagliflozin and metformin taken as separate tablets. To avoid overdose, do not continue taking separate empagliflozin and metformin tablets if you are taking Synjardy.

It is important that you continue with the diet and exercise programme recommended by your doctor,
pharmacist or nurse.

2. What you should know before taking 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 associated, for example, with severe hyperglycaemia (very 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, or breath with an unusually fruity odour.
• if you have had diabetic pre-coma.
• if you have severe kidney problems. Your doctor may reduce your daily dose or ask you to take a different medicine (see also section 3, “How to take Synjardy”).
• if you have a severe infection such as a lung, bronchial or kidney infection. Severe infections can cause kidney problems, which may increase your risk of lactic acidosis (see “Warnings and precautions”).
• if you have lost a lot of fluids (dehydration) due to severe or prolonged diarrhoea, or if you have vomited repeatedly. Dehydration can cause kidney problems, which may increase your risk of lactic acidosis (see “Warnings and precautions”).
• if you are being treated for acute heart failure or have recently had a heart attack, severe circulatory problems (such as “shock”), or breathing difficulties. These conditions may lead to insufficient oxygen supply to tissues, which may increase your risk of lactic acid游戏副本 (see “Warnings and precautions”).
• if you have liver problems.
• if you drink large amounts of alcohol daily or intermittently (see section “Synjardy and alcohol”).

Warnings and precautions
Risk of lactic acidosis
Synjardy 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 cases 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 listed above, consult your doctor for further
instructions.
Temporarily stop taking Synjardy if you develop a medical condition that may be associated with 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 of the symptoms of lactic acidosis, stop taking Synjardy immediately and contact your doctor or go to the nearest hospital, as this condition may lead to coma.
Symptoms of lactic acidosis include:

• vomiting
• stomach pain (abdominal pain)
• muscle cramps
• a general feeling of discomfort 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.
Consult your doctor, pharmacist, or nurse before taking this medicine, and during
treatment:

• if you experience rapid weight loss, feeling unwell or nauseous, stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness or unusual tiredness, breath with a sweet odour, a metallic or sweet taste in your mouth, or an unusual odour of your sweat or urine, contact your doctor or go to the nearest hospital immediately and stop taking this medicine until your doctor gives you further advice. These symptoms may indicate “diabetic ketoacidosis”, a rare but serious and potentially life-threatening condition that may occur in diabetes when levels of “ketone bodies” in the blood or urine increase, as shown by laboratory tests. The risk of developing diabetic ketoacidosis may increase with prolonged fasting, excessive alcohol consumption, dehydration, a sudden reduction in insulin dose, or an increased need for insulin due to major surgery or serious illness.
• if you have “type 1 diabetes”: this type of diabetes usually develops in younger people and means your body does not produce insulin. You must not take Synjardy if you have type 1 diabetes.
• if you may be at risk of dehydration, for example: if you are unwell, have diarrhoea or fever, cannot eat or drink, are taking medicines that increase urine production [diuretics] or lower blood pressure, or if you are 75 years of age or older. Possible signs are listed in section 4 under “dehydration”. Your doctor may ask you to stop taking Synjardy until you recover to prevent excessive fluid loss. Ask for advice on how to prevent dehydration.
• if you have a severe kidney or urinary tract infection with fever. Your doctor may ask you not to take Synjardy until the infection has resolved.
• if you are scheduled to undergo an imaging test using iodinated contrast agents (such as an X-ray). More information is provided in the section “Other medicines and Synjardy”.

Immediately inform your doctor if you notice a combination of symptoms such as pain, tenderness,
redness, or swelling of the genitals or the area between the genitals and the anus, accompanied by fever or a general feeling of being unwell. These symptoms could be signs of a rare but serious and potentially life-threatening infection called necrotizing fasciitis of the perineum or Fournier’s gangrene, which destroys subcutaneous tissue. Fournier’s gangrene requires immediate treatment.
Surgery
If you are scheduled for major surgery, you must stop taking Synjardy during the procedure and for a certain period afterwards. Your doctor will decide when you should stop and when you should resume treatment with Synjardy.
Kidney function
During treatment with Synjardy, 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.
Foot care
As with all diabetic patients, it is important to regularly check your feet and follow any foot care advice provided by healthcare professionals.
Glucose in urine
Due to the mechanism of action of this medicine, your urine will test positive for glucose while you are taking this medicine.
Children and adolescents
Synjardy can 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 this medicine in children aged between 10 and 12 years.
No data are available for children under 10 years of age.
Other medicines and Synjardy
If you are scheduled to receive an injection of an iodinated contrast agent into your bloodstream, for
example for an X-ray, you must stop taking Synjardy before or during the injection. Your doctor will decide when you should stop and when you should resume treatment with
Synjardy.
Inform your doctor if you are taking, have recently taken, or might take any other
medicine. You may need to monitor your blood glucose and kidney function more frequently, or your doctor may decide to adjust the dose of Synjardy.
It is particularly important to mention the following:

• medicines that increase urine production (diuretics), because Synjardy may increase the risk of excessive fluid loss. Your doctor may ask you to stop taking Synjardy. Possible symptoms of excessive fluid loss are listed in section 4.
• other medicines that lower blood sugar levels, such as insulin or medicines containing “sulphonylureas”. Your doctor may reduce the dose of these medicines to prevent blood sugar levels from becoming too low (hypoglycaemia).
• medicines that may alter the amount 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 (oral, injected, or inhaled) used to treat inflammation in conditions 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 “Synjardy and alcohol”).
• iodinated contrast agents (medicines used during X-rays, see section “Warnings and precautions”).
• if you are taking lithium, because Synjardy may reduce the amount of lithium in the blood.

Synjardy and alcohol
Avoid excessive alcohol consumption while taking Synjardy, 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.
Do not use Synjardy if you are pregnant. It is not known whether this medicine is harmful to the
unborn baby.
Metformin passes into breast milk in small amounts. It is not known whether empagliflozin passes into breast milk. Do not use Synjardy if you are breastfeeding.
Driving and using machines
Synjardy has a minor effect on the ability to drive and use machines.
Taking this medicine in combination with medicines called sulphonylureas or with insulin
may lower your blood sugar levels too much (hypoglycaemia), which may cause symptoms such as
trembling, sweating, and blurred vision, affecting your ability to drive and use
machines. Do not drive or operate tools or machinery if you feel dizzy while taking
Synjardy.

3. How to take Synjardy

Take this medicine exactly as your doctor has told you. If you have any doubts, consult your doctor or pharmacist.
How much medicine to take
The dose of Synjardy varies depending on your medical condition and the doses of antidiabetic medicines you are taking. Your doctor will adjust the dose according to your needs and will tell you exactly how much medicine you should take.
The recommended dose is one tablet twice daily.
Usually, your doctor will start your treatment with Synjardy using tablets containing the same metformin dose (850 mg or 1,000 mg twice daily) you are already taking, combined with the lowest dose of empagliflozin (5 mg twice daily). If you are already taking the two medicines separately, your doctor will prescribe as initial treatment the Synjardy tablets containing the same amounts of these medicines. If you have reduced kidney function, your doctor may prescribe a lower dose or decide to use another medicine.
How to take this medicine

• Swallow the tablet whole with water.
• Take the tablets after meals to reduce the possibility of stomach problems.
• Take the tablet twice daily by mouth.

Your doctor may prescribe Synjardy in combination with another antidiabetic medicine. Remember to take all your medicines as prescribed by your doctor to achieve the best results for your health. Your doctor may need to adjust your dose to control your blood sugar levels.
Appropriate diet and exercise help your body use blood sugar more effectively. It is important to continue the diet and exercise programme recommended by your doctor while taking Synjardy.
If you take more Synjardy than you should
If you take more Synjardy tablets than prescribed, you may develop lactic acidosis. Symptoms of lactic acidosis are not specific and may include severe nausea, vomiting, stomach pain associated with muscle cramps, a general feeling of discomfort associated with extreme tiredness and difficulty breathing. Other symptoms include a drop in body temperature and heart rate. If you have these symptoms, immediate hospital treatment may be necessary, because lactic acidosis can lead to coma. Stop taking this medicine immediately and contact a doctor or go to the nearest hospital (see section 2). Take the medicine pack with you.
If you forget to take Synjardy
If you forget a dose, take it as soon as you remember. If you realize you have missed a dose when it is already time for your next dose, skip the missed dose and continue with your regular schedule. Do not take a double dose of this medicine.
If you stop taking Synjardy
Do not stop taking Synjardy without first consulting your doctor, unless you suspect you have diabetic ketoacidosis or lactic acidosis, or if you develop a medical condition that may be associated with dehydration (see section 2, "Warnings and precautions"). Blood sugar levels may rise when you stop treatment with Synjardy.
If you have any questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor or the nearest hospital immediately if you notice any of the following
side effects:
Severe allergic reaction, seen with uncommon frequency (may occur in 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 may make it difficult to breathe or swallow

Lactic acidosis, seen very rarely (may occur in up to 1 in 10,000 people)
Synjardy may cause a very rare but serious side effect called lactic acidosis (see section 2). If this occurs, you must stop taking Synjardy and contact your doctor or the nearest hospital immediately, because lactic acidosis can lead to coma.
Diabetic ketoacidosis, seen rarely (may occur in up to 1 in 1,000 people)
Signs of diabetic ketoacidosis are (see section 2):

• increased levels of ketones in the urine or blood
• rapid weight loss
• feeling unwell or nausea
• stomach pain
• excessive thirst
• rapid and deep breathing
• confusion
• unusual drowsiness or fatigue
• breath with a sweet smell, a sweet or metallic taste in the mouth, or a different odour of sweat or urine.

These symptoms may occur regardless of blood sugar levels. Your doctor may decide to temporarily or permanently discontinue treatment with Synjardy.
Contact your doctor as soon as possible if you notice the following side effects:
Low blood sugar levels (hypoglycaemia), very common frequency (may occur in more than 1 in 10 people)
If you take Synjardy with another medicine that can cause low blood sugar (hypoglycaemia), such as a sulphonylurea or insulin, your risk of developing low blood sugar is increased. Symptoms of low blood sugar may include:

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

Your doctor will explain how to treat low blood sugar levels and what to do if you experience any of the signs described above. If you have symptoms of low blood sugar, eat some sugar, a sugary snack, or drink a glass of fruit juice. If possible, measure your blood glucose and rest.
Urinary tract infection, common frequency (may occur in up to 1 in 10 people)
Symptoms of a urinary tract infection are:

• burning sensation when passing urine
• cloudy-looking urine
• pelvic pain, or pain in the middle of the back (in case of kidney infection)

An increased urge or need to urinate more frequently may be due to the way Synjardy works, but it may also indicate a urinary tract infection. If you notice an increase in these symptoms, contact your doctor.
Dehydration, uncommon frequency (may occur in up to 1 in 100 people)
Symptoms of dehydration are not specific but may include:

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

Other side effects of Synjardy:
Very common

• feeling unwell (nausea), vomiting
• diarrhoea or stomach pain
• loss of appetite

Common

• genital yeast infection (candidiasis)
• increased amount of urine or increased need to urinate
• itching
• skin rash or redness of the skin which may cause itching and may include bumps, oozing or blisters
• changes in taste
• thirst
• blood tests may show increased levels of fat in the blood (cholesterol)
• constipation
• reduced or low levels of vitamin B12 in the blood (symptoms may include extreme tiredness (fatigue), inflammation and redness of the tongue (glossitis), tingling (paraesthesia), paleness or yellowing of the skin). Your doctor may carry out some tests to determine the cause of the symptoms, as some of these may also be caused by diabetes or other unrelated health problems.

Uncommon

• hives (urticaria)
• difficulty or pain when emptying the bladder
• blood tests may show reduced kidney function (creatinine or urea)
• blood tests may show increased number of red blood cells in the blood (haematocrit)

Rare

• necrotising fasciitis of the perineum or Fournier’s gangrene, a serious infection of the soft tissue of the genitals or the area between the genitals and the anus

Very rare

• abnormalities in liver function tests, inflammation of the liver (hepatitis)
• redness of the skin (erythema)
• inflammation of the kidneys (tubulo-interstitial nephritis)

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 referred to in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Synjardy

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister after "EXP" and on the carton after "Scad.". The expiry date refers to the last day of that month.
This medicine requires no special storage conditions.
Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
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. Package contents and other information

What Synjardy contains
The active substances are empagliflozin and metformin.
Each film-coated tablet of Synjardy 5 mg/850 mg contains 5 mg of empagliflozin and 850 mg of metformin hydrochloride.
Each film-coated tablet of Synjardy 5 mg/1,000 mg contains 5 mg of empagliflozin and 1,000 mg of metformin hydrochloride.
Each film-coated tablet of Synjardy 12.5 mg/850 mg contains 12.5 mg of empagliflozin and 850 mg of metformin hydrochloride.
Each film-coated tablet of Synjardy 12.5 mg/1,000 mg contains 12.5 mg of empagliflozin and 1,000 mg of metformin hydrochloride.
The other components are:

• Tablet core: maize 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).

Description of the appearance of Synjardy and contents of the pack
Synjardy 5 mg/850 mg film-coated tablets are white-yellowish, oval, biconvex tablets. On one side, “S5” and the Boehringer Ingelheim logo are imprinted; on the other side, the number “850” is imprinted. The tablet is 19.2 mm long and 9.4 mm wide.
Synjardy 5 mg/1,000 mg film-coated tablets are yellowish-brown, oval, biconvex tablets. On one side, “S5” and the Boehringer Ingelheim logo are imprinted; on the other side, the number “1000” is imprinted. The tablet is 21.1 mm long and 9.7 mm wide.
Synjardy 12.5 mg/850 mg film-coated tablets are white-pinkish, oval, biconvex tablets. On one side, “S12” and the Boehringer Ingelheim logo are imprinted; on the other side, the number “850” is imprinted. The tablet is 19.2 mm long and 9.4 mm wide.
Synjardy 12.5 mg/1,000 mg film-coated tablets are dark brown-purple, oval, biconvex tablets. On one side, “S12” and the Boehringer Ingelheim logo are imprinted; on the other side, the number “1000” is imprinted. The tablet is 21.1 mm long and 9.7 mm wide.
The tablets are available in perforated unit-dose blisters made of PVC/PVDC/aluminum, in packs of 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 in 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 Authorisation 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

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Boehringer Ingelheim SComm Boehringer Ingelheim RCV GmbH & Co KG
Tél/Tel: +32 2 773 33 11 Lietuvos filialas
Tel.: +370 5 2595942

България Luxembourg/Luxemburg
Бьорингер Ингелхайм РЦВ ГмбХ и Ко КГ - Boehringer Ingelheim SComm
клон България Tél/Tel: +32 2 773 33 11
Тел: +359 2 958 79 98

Česká republika Magyarország
Boehringer Ingelheim spol. s r.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +420 234 655 111 Magyarországi Fióktelepe
Tel.: +36 1 299 89 00

Danmark Malta
Boehringer Ingelheim Danmark A/S Boehringer Ingelheim Ireland Ltd.
Tlf: +45 39 15 88 88 Tel: +353 1 295 9620

Deutschland Nederland
Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim B.V.
Tel: +49 (0) 800 77 90 900 Tel: +31 (0) 800 22 55 889
Lilly Deutschland GmbH
Tel. +49 (0) 6172 273 2222

Eesti Norge
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Danmark
Eesti filiaal Norwegian branch
Tel: +372 612 8000 Tlf: +47 66 76 13 00

Ελλάδα Österreich
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim RCV GmbH & Co KG
Tηλ: +30 2 10 89 06 300 Tel: +43 1 80 105-7870

España Polska
Boehringer Ingelheim España S.A. Boehringer Ingelheim Sp.zo.o.
Tel: +34 93 404 51 00 Tel.: +48 22 699 0 699
Lilly S.A.
Tel: +34 91 663 50 00

France Portugal
Boehringer Ingelheim France Boehringer Ingelheim Portugal, Lda.
Tél: +33 3 26 50 45 33 Tel: +351 21 313 53 00
Lilly France Lilly Portugal Produtos Farmacêuticos, Lda
Tél: +33-(0) 1 55 49 34 34 Tel: +351 21 412 66 00

Hrvatska România
Boehringer Ingelheim Zagreb d.o.o. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +385 1 2444 600 Viena - Sucursala Bucureşti
Tel: +40 21 302 28 00

Ireland Slovenija
Boehringer Ingelheim Ireland Ltd. Boehringer Ingelheim RCV GmbH & Co KG
Tel: +353 1 295 9620 Podružnica Ljubljana
Tel: +386 1 586 40 00
Eli Lilly and Company (Ireland) Limited
Tel: +353-(0) 1 661 4377

Ísland Slovenská republika
Vistor ehf. Boehringer Ingelheim RCV GmbH & Co KG
Sími: +354 535 7000 organizačná zložka
Tel: +421 2 5810 1211

Italia Suomi/Finland
Boehringer Ingelheim Italia S.p.A. Boehringer Ingelheim Finland Ky
Tel: +39 02 5355 1 Puh/Tel: +358 10 3102 800
Eli Lilly Italia S.p.A.
Tel: +39 055 42571

Κύπρος Sverige
Boehringer Ingelheim Ελλάς Μονοπρόσωπη A.E. Boehringer Ingelheim AB
Tηλ: +30 2 10 89 06 300 Tel: +46 8 721 21 00

Latvija United Kingdom (Northern Ireland)
Boehringer Ingelheim RCV GmbH & Co KG Boehringer Ingelheim Ireland Ltd.
Latvijas filiāle Tel: +353 1 295 9620
Tel: +371 67 240 011
Eli Lilly and Company (Ireland) Limited
Tel: +353-(0) 1 661 4377

More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/

ANNEX IV
SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION OF THE TERMS OF THE MARKETING AUTHORISATION(S)

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for empagliflozin and empagliflozin/metformin, the PRAC's scientific conclusions are as follows:

• In view of the available data on the risk of necrotizing fasciitis of the perineum (Fournier’s gangrene) emerging from the literature and spontaneous reports of Fournier’s gangrene in the non-diabetic population, and in view of a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a modification of the product information to indicate that this adverse drug reaction may occur regardless of the indication. The PRAC concluded that the product information for medicinal products containing empagliflozin should be amended accordingly.
• In view of the available data on phimosis from spontaneous reports, and in view of a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a modification of the product information to highlight that genital infections may lead to phimosis, resulting in the need for circumcision. The PRAC concluded that the product information for medicinal products containing empagliflozin should be amended accordingly.
• In view of the available data on increased haematocrit/polycythaemia from the literature and spontaneous reports, and in view of a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a modification of section 4.4 of the SmPC to include that patients with marked increases in haematocrit should be monitored and investigated for underlying haematological disorders. The PRAC concluded that the product information for medicinal products containing empagliflozin should be amended accordingly.
• In view of the available data on prolonged ketoacidosis and prolonged glucosuria from the literature and spontaneous reports, the PRAC considers that there is sufficient evidence to justify a modification of section 4.4 of the SmPC regarding the warning on ketoacidosis, to indicate that in some patients, ketoacidosis may persist even after discontinuation of empagliflozin treatment. The PRAC concluded that the product information for medicinal products containing empagliflozin should be amended accordingly.

Having reviewed the PRAC recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and reasoning of the recommendation.

Grounds for the variation of the terms of the marketing authorisation(s)
Based on the scientific conclusions for empagliflozin and empagliflozin/metformin, the CHMP considers that the benefit-risk balance of the medicinal product(s) containing empagliflozin and empagliflozin/metformin remains favourable, subject to the proposed changes to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation(s).