Jardiance

Patient Information Leaflet

Jardiance 10 mg film-coated tablets, 25 mg film-coated tablets

empagliflozin
Please read all of this leaflet carefully before you start taking this medicine as 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 pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Jardiance and what is it used for

What is Jardiance
Jardiance contains the active substance empagliflozin.
Jardiance belongs to a group of medicines called sodium-glucose co-transporter 2 (SGLT2) inhibitors.

What Jardiance is used for
Type 2 diabetes

• Jardiance is used to treat type 2 diabetes in adults and children aged 10 years and older whose diabetes cannot be controlled by diet and exercise.
• Jardiance can be used without other diabetes medicines in patients who cannot take metformin (another diabetes medicine).
• Jardiance can also be used together with other medicines for the treatment of diabetes. These may be medicines taken by mouth or given by injection, such as insulin.

Jardiance blocks the SGLT2 protein in the kidneys, causing the removal of blood sugar (glucose) through the urine. This way, Jardiance reduces the amount of sugar in the blood.
This medicine may also help prevent heart disease in patients with type 2 diabetes mellitus.
It is important that you continue with the diet and exercise programme recommended by your doctor, pharmacist, or nurse.

Heart failure

• Jardiance is used to treat heart failure in adult patients with symptoms due to reduced heart function.

Chronic kidney disease

• Jardiance is used to treat chronic kidney disease in adult patients.

What is type 2 diabetes?
Type 2 diabetes is a condition caused by both genetic and lifestyle factors. If you have type 2 diabetes, your pancreas does not produce enough insulin to control your blood glucose level, 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.

What is heart failure?
Heart failure occurs when the heart is too weak or too stiff and cannot function properly. This can lead to serious medical problems and the need for hospital treatment. The most common symptoms of heart failure are shortness of breath, persistent or severe tiredness, and swelling of the ankles.
Jardiance helps protect the heart from weakening and improves symptoms.

What is chronic kidney disease?
Chronic kidney disease is a long-term condition. It can be caused by other diseases, such as diabetes and high blood pressure, or by the body's own immune system attacking the kidneys. When you have chronic kidney disease, the kidneys may gradually lose their ability to clean and filter the blood as they should. This can lead to serious medical problems, such as swelling of the legs or heart failure, or the need for hospital treatment.
Jardiance helps protect the kidneys from losing their function.

2. What you need to know before taking Jardiance

Do not take Jardiance

• if you are allergic to empagliflozin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Contact your doctor or the nearest hospital immediately:
Ketoacidosis

• if you experience rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, rapid and deep breathing, confusion, unusual drowsiness or fatigue, breath with a sweet or fruity odour, a sweet or metallic taste in your mouth, or a different odour of your sweat or urine, contact your doctor or the nearest hospital immediately. These symptoms may indicate the presence of "ketoacidosis", a serious and sometimes potentially life-threatening condition that can occur when levels of "ketone bodies" increase in the blood or urine, as detected in laboratory tests. The risk of developing ketoacidosis may increase with prolonged fasting, excessive alcohol consumption, dehydration, a sudden reduction in insulin dose, or an increased insulin requirement due to major surgery or serious illness. If you suspect you have ketoacidosis, contact your doctor or the nearest hospital immediately and stop taking this medicine until your doctor gives you further advice.

Talk to your doctor, pharmacist, or nurse before taking this medicine, and
during treatment:

• if you have "type 1 diabetes". This type of diabetes usually develops at a young age and means your body does not produce insulin. You must not take Jardiance if you have type 1 diabetes.
• if you have severe kidney problems – your doctor may limit your dose to 10 mg once daily or advise you to take a different medicine (see also section 3, “How to take Jardiance”).
• if you have severe liver problems – your doctor may advise you to take a different medicine.
• if you may be at risk of dehydration, for example: if you have vomiting, diarrhoea, or fever, or if you are unable to eat or drink, or if you 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 not to take Jardiance until the condition is resolved, to prevent excessive loss of body fluids. Ask how to prevent dehydration.
• if you have a severe infection of the kidneys or urinary tract accompanied by fever. Your doctor may ask you not to take Jardiance until the infection has resolved.

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 a sign 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.
Foot care
As with all diabetic patients, it is important to regularly check your feet and follow any other foot care advice provided by healthcare professionals.
Kidney function
Your kidney function should be monitored before starting and during treatment with this medicine.
Glucose in urine
Due to the mechanism of action of this medicine, your urine will test positive for sugar while you are taking this medicine.
Children and adolescents
Jardiance can be used in children aged 10 years and older for the treatment of type 2 diabetes. There is no available data in children under 10 years of age.
Jardiance is not recommended in children and adolescents under 18 years of age for the treatment of heart failure or chronic kidney disease, as it has not been studied in these patient groups.
Other medicines and Jardiance
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
It is important to inform your doctor:

• if you are taking medicines that increase urine production (diuretics). Your doctor may ask you to stop taking Jardiance. Possible signs of excessive fluid loss are listed in section 4.
• if you are taking other medicines that lower blood sugar levels, such as insulin or a medicine containing "sulphonylurea". Your doctor may reduce the dose of these medicines to prevent blood sugar levels from dropping too much (hypoglycaemia).
• if you are taking lithium, because Jardiance may reduce the amount of lithium in your blood.

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 Jardiance if you are pregnant. It is not known whether Jardiance is harmful to the unborn baby. Do not use Jardiance if you are breastfeeding. It is not known whether Jardiance passes into breast milk.
Driving and using machines
Jardiance has a minor influence on the ability to drive and use machines.
Taking this medicine in combination with medicines called sulphonylureas and/or insulin may lower blood sugar levels too much (hypoglycaemia), which can cause symptoms such as trembling, sweating, and blurred vision, thereby affecting your ability to drive and use machines. Do not drive or operate tools or machinery if you experience dizziness while taking Jardiance.
Jardiance contains lactose
Jardiance contains lactose (milk sugar). If your doctor has diagnosed you with an intolerance to certain sugars, contact them before taking this medicine.
Jardiance contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is essentially 'sodium-free'.

3. How to take Jardiance

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
How much medicine to take

• The recommended dose of Jardiance is one 10 mg tablet once daily. If you have type 2 diabetes mellitus, your doctor may decide to increase your dose to 25 mg once daily, if necessary, to help control your blood sugar levels.
• Your doctor may limit your dose to 10 mg once daily if you have kidney problems.
• Your doctor will prescribe the appropriate dose for you. Do not change the dose unless your doctor tells you to do so.

How to take this medicine

• Swallow the tablet whole with water.
• You may take the tablet with or without food.
• You may take the tablet at any time of day. However, try to take it at the same time each day. This will help you remember to take it.

If you have type 2 diabetes mellitus, your doctor may prescribe Jardiance together with another antidiabetic medicine. Remember to take all your medicines as prescribed by your doctor to achieve the best possible health outcomes.
An appropriate diet and physical exercise can help your body use blood sugar more effectively. It is important to continue following the diet and exercise plan recommended by your doctor while taking Jardiance.
If you take more Jardiance than you should
If you take more Jardiance than you should, contact your doctor immediately or go to the hospital straight away.
Take the medicine pack with you.
If you forget to take Jardiance
What to do if you forget to take a tablet (depends on how long it is until your next dose):

• If there are 12 hours or more until your next dose, take Jardiance as soon as you remember. Then take your next dose at the usual time.
• If there are less than 12 hours until your next dose, skip the dose you forgot. Then take your next dose at the usual time.
• Do not take a double dose of Jardiance to make up for a forgotten dose.

If you stop taking Jardiance
Do not stop treatment with Jardiance without first consulting your doctor, unless you suspect you have ketoacidosis (see “Ketoacidosis” under “Warnings and precautions”). If you have type 2 diabetes mellitus, your blood sugar levels may rise when you stop treatment with Jardiance.
If you have any questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
If you experience any of these symptoms, contact your doctor or go to the nearest hospital immediately.
Severe allergic reaction, observed uncommonly (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 may make breathing or swallowing difficult

Ketoacidosis, observed uncommonly (may affect up to 1 in 100 people).
Signs of ketoacidosis are (see also section 2, “Warnings and precautions”):

• increased levels of “ketone bodies” in the urine or blood
• rapid weight loss
• nausea or vomiting
• stomach pain
• excessive thirst
• rapid and deep breathing
• confusion
• unusual drowsiness or fatigue
• sweet-smelling breath, 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 Jardiance.
Contact your doctor as soon as possible if you notice the following side effects:
Low blood sugar (hypoglycaemia), very common (may affect more than 1 in 10 people)
If you take Jardiance together with another medicine that can cause low blood sugar (hypoglycaemia), such as a sulphonylurea or insulin, your risk of experiencing low blood sugar is higher. Signs 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 symptoms described above. If you have symptoms of low blood sugar, eat some sugar, a snack high in sugar, or drink a glass of fruit juice. If possible, check your blood glucose and rest.
Urinary tract infection, common (may affect up to 1 in 10 people)
Signs of a urinary tract infection include:

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

An increased need to urinate or a more urgent need to urinate may be due to the action of Jardiance; however, it may also indicate a urinary tract infection. If you notice an increase in these symptoms, contact your doctor.
Dehydration, very common (may affect more than 1 in 10 people)
Signs 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 Jardiance:
Common

• genital yeast infection (candidiasis)
• increased amount of urine or increased need to urinate more frequently
• itching
• skin rash or redness of the skin which may cause itching and may include bumps, oozing or blisters
• thirst
• blood tests may show increased levels of blood fats (cholesterol)
• constipation

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 tissues of the genitals or the area between the genitals and the anus

Very rare

• inflammation of the kidneys (tubulo-interstitial nephritis)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, contact 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 Jardiance

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 does not require any 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 Jardiance contains

• The active substance is empagliflozin.
• Each tablet contains 10 mg or 25 mg of empagliflozin.
• The other components are:
• tablet core: lactose monohydrate (see the end of section 2 under “Jardiance contains lactose”), microcrystalline cellulose, hydroxypropylcellulose, croscarmellose sodium (see the end of section 2 under “Jardiance contains sodium”), anhydrous colloidal silica, magnesium stearate
• tablet coating: hypromellose, titanium dioxide (E171), talc, macrogol (400), yellow iron oxide (E172)

Description of the appearance of Jardiance and the contents of the pack
Jardiance 10 mg film-coated tablets are round, biconvex, bevelled-edge, light yellow tablets.
“S10” is imprinted on one side and the Boehringer Ingelheim logo is imprinted on the other side.
The tablets have a diameter of 9.1 mm.
Jardiance 25 mg film-coated tablets are oval, biconvex, light yellow tablets. “S25” is imprinted on
one side and the Boehringer Ingelheim logo is imprinted on the other side. The tablet is 11.1 mm in
length and 5.6 mm in width.
Jardiance tablets are supplied in perforated, divisible unit-dose blisters made of PVC/aluminium.
Pack sizes contain 7 x 1, 10 x 1, 14 x 1, 28 x 1, 30 x 1, 60 x 1, 70 x 1, 90 x 1 and 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
Rottendorf Pharma GmbH
Ostenfelder Strasse 51 – 61
59320 Ennigerloh
Germany
Boehringer Ingelheim France
100-104 Avenue de France
75013 Paris
France

For further information about 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 S.A.S. 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 European Medicines Agency website: http://www.ema.europa.eu.

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

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Report(s) (PSUR) for empagliflozin and empagliflozin/metformin, the scientific conclusions of the PRAC 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 non-diabetic populations, and in view of a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a change in 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 emerging from spontaneous reports, and in view of a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a change in 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 emerging 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 an amendment to 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 emerging from the literature and spontaneous reports, the PRAC considers that there is sufficient evidence to justify an amendment to 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 respective general conclusions and the reasoning of the recommendation.

Reasons 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 unchanged, subject to the proposed amendments to the product information.
The CHMP recommends the variation of the terms of the marketing authorisation(s).