Glyxambi

Package leaflet: Information for the patient

Glyxambi 10 mg/5 mg film-coated tablets, 25 mg/5 mg film-coated tablets

empagliflozin/linagliptin
Read this entire 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 they have the same symptoms as you, because it could be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Glyxambi is and what it is used for

What Glyxambi is
Glyxambi contains two active substances called empagliflozin and linagliptin, both belonging to a group of medicines known as "oral antidiabetics". These are medicines taken by mouth to treat type 2 diabetes.
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 may 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 sugar in the blood, which can cause health problems such as heart or kidney disease, blindness, and poor circulation in the limbs.
How Glyxambi 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, causing blood sugar (glucose) to be removed through the urine.
Linagliptin works differently, more specifically by enabling the pancreas to produce more insulin to reduce blood glucose levels. It does this by blocking a protein called DPP-4.
In this way, Glyxambi reduces the amount of sugar in the blood.
What Glyxambi is used for

• Glyxambi is added to metformin and/or sulphonylurea (SU) for the treatment of type 2 diabetes in adult patients aged 18 years and older in whom diabetes cannot be controlled with treatment using metformin and/or sulphonylurea in combination with empagliflozin or with treatment using metformin and/or sulphonylurea in combination with linagliptin.
• Glyxambi may also be used as an alternative to taking separate empagliflozin and linagliptin tablets. To avoid overdose, do not continue taking empagliflozin and linagliptin tablets separately if you are taking this medicine.

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

2. What you need to know before taking Glyxambi

Do not take Glyxambi

• if you are allergic to empagliflozin, linagliptin, any other SGLT2 inhibitor (e.g. dapagliflozin, canagliflozin), any other DPP-4 inhibitor (e.g. sitagliptin, vildagliptin), or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor 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 Glyxambi if you have type 1 diabetes.
• if you experience rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, rapid and deep breathing, confusion, unusual drowsiness or tiredness, sweet-smelling breath, a metallic or sweet taste in your mouth, or a different smell in your sweat or urine, contact your doctor or 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, sometimes life-threatening condition that can 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, or sudden reduction in insulin dose, or increased insulin requirement due to major surgery or serious illness.
• if you are taking other antidiabetic medicines known as “sulfonylureas” (e.g. glimepiride, glipizide) and/or using insulin. Your doctor may decide to reduce the dose of these medicines when taken together with Glyxambi, to avoid your blood sugar becoming too low (hypoglycaemia).
• if you have or have had a disease of the pancreas.
• 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 Glyxambi”).
• if you have severe liver problems. Your doctor may ask you to take a different medicine.
• if you may be at risk of dehydration, for example: if you have vomiting, diarrhoea or fever, or are unable to eat or drink, or if you are taking medicines that increase urine production [diuretics] or that lower blood pressure, or if you are over 75 years old. Possible signs are listed in section 4 under “Dehydration”. Your doctor may ask you not to take Glyxambi until the condition is resolved, to prevent excessive loss of body fluids. Ask how to prevent dehydration.
• if you have an increased proportion of red blood cells in the blood (haematocrit) detected by blood tests (see also section 4, “Possible side effects”).

Talk to your doctor if you experience any of the following symptoms during treatment with
Glyxambi:

• if you develop symptoms of acute pancreatitis, such as persistent and severe stomach pain (abdominal pain). Possible signs are listed in section 4 “Possible side effects”. Your doctor may consider it necessary to change your treatment.
• if you develop a severe infection of the kidneys or urinary tract, with fever. Your doctor may ask you to stop taking Glyxambi until the infection has healed.
• if blisters appear on the skin, which could be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop treatment with Glyxambi.

Contact your doctor immediately 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, with fever or a general
feeling of being unwell. These symptoms could indicate a rare but serious and potentially life-threatening
infection called necrotising fasciitis of the perineum or Fournier’s gangrene, which destroys subcutaneous
tissue. Fournier’s gangrene must be treated immediately.
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 doctor will check your kidney function before starting treatment with Glyxambi and at regular
intervals during treatment.
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
This medicine is not recommended for children and adolescents under 18 years of age, because
linagliptin is not effective in children and adolescents aged 10 to 17 years. It is not known whether
this medicine is safe and effective when used in children under 10 years of age.
Other medicines and Glyxambi
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicine. In particular, you must inform your doctor if you are taking the following
medicines:

• other antidiabetic medicines, such as insulin or sulfonylureas. Your doctor may reduce the dose of these medicines to avoid your blood sugar becoming too low.
• medicines used to remove water from the body (diuretics). Your doctor may ask you not to take Glyxambi.
• medicines that may affect the breakdown of empagliflozin or linagliptin in the body, such as rifampicin (an antibiotic used to treat tuberculosis) or certain medicines used to treat epileptic seizures (such as carbamazepine, phenobarbital or phenytoin). The effect of Glyxambi may be reduced.
• lithium, because Glyxambi may reduce the amount of lithium in the blood.

Pregnancy, breast-feeding and fertility
If you are pregnant, think you may be pregnant, or are planning to become pregnant, ask your doctor
or pharmacist for advice before taking this medicine.
It is not known whether Glyxambi is harmful to the unborn baby. As a precaution, it is preferable to
avoid using this medicine during pregnancy.
It is not known whether the active substances of Glyxambi pass into breast milk. Do not use this
medicine if you are breast-feeding.
It is not known whether Glyxambi has an effect on human fertility.
Driving and using machines
Glyxambi has a minor influence on the ability to drive and use machines.
Taking this medicine together with sulfonylureas or insulin may lower your blood sugar too much
(hypoglycaemia), which can cause symptoms such as trembling, sweating and altered vision, affecting
your ability to drive and use machines. Do not drive or operate tools or machinery if you experience
these symptoms while taking Glyxambi.

3. How to take Glyxambi

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 starting dose is one film-coated tablet of Glyxambi 10 mg/5 mg (10 mg of empagliflozin and 5 mg of linagliptin) once daily.

Your doctor may decide whether it is necessary to increase the dose to one film-coated tablet of Glyxambi 25 mg/5 mg (25 mg of empagliflozin and 5 mg of linagliptin) once daily. If you are already taking 25 mg of empagliflozin and 5 mg of linagliptin as separate tablets and are switching to Glyxambi, you may start directly with Glyxambi 25 mg/5 mg.

Renal impairment

Talk to your doctor if you have kidney problems. Your doctor may limit the dose or decide to use another medicine.

Hepatic impairment

Talk to your doctor if you have severe liver impairment. Glyxambi is not recommended, and your doctor may decide to use another medicine.

How to take this medicine

• Swallow the tablet whole with water.
• You may take Glyxambi 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.

Your doctor may prescribe Glyxambi in combination with another antidiabetic medicine. Remember to take all your medicines as prescribed by your doctor to achieve the best possible health outcomes.

Appropriate diet and physical 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 Glyxambi.

If you take more Glyxambi than you should

If you take more Glyxambi than you should, contact your doctor immediately or go to hospital straight away. Take the medicine pack with you.

If you forget to take Glyxambi

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 Glyxambi 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 missed dose. Then take your next dose at the usual time.
• Do not take a double dose of this medicine to make up for a forgotten dose.

If you stop taking Glyxambi

Do not stop taking this medicine without first consulting your doctor, unless you suspect you have diabetic ketoacidosis (see section 2, "Warnings and precautions"). Blood sugar levels may rise when you stop treatment with Glyxambi.

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.
If you experience any of these symptoms, contact your doctor or go to the nearest hospital immediately:
Diabetic ketoacidosis, observed rarely (may occur in up to 1 in 1,000 people)
Signs of diabetic 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 tiredness
• breath with a sweet, fruity odour, 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 this medicine.
Contact your doctor immediately if you notice any of the following side effects:
Allergic reactions, uncommon frequency (may affect up to 1 in 100 people)
This medicine may cause allergic reactions, which could be severe, including hives and swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing (angioedema).
Inflammation of the pancreas (pancreatitis), uncommon frequency
This medicine may cause pancreatitis, which generally presents as severe and persistent abdominal (stomach) pain that may extend to the back, often accompanied by feeling unwell or nausea and vomiting. Your doctor may consider it necessary to change your treatment.
Low blood sugar levels (hypoglycaemia), common frequency (may occur in up to 1 in 10 people)
If you take Glyxambi with another medicine that can lower blood sugar, such as a sulphonylurea or insulin, you are at risk of developing blood sugar levels that are too low (hypoglycaemia). 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 sugary snack, or drink a glass of fruit juice. If possible, measure your blood glucose and rest.
Urinary tract infections, common frequency
Signs of a urinary tract infection include:

• 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 urgency to urinate may be due to how this medicine works; however, since it may also indicate a urinary tract infection, you should contact your doctor if you notice an increase in these symptoms.
Loss of body fluids (dehydration), uncommon frequency
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 Glyxambi:
Common frequency

• genital yeast infection such as candidiasis
• inflammation of the nose or throat (nasopharyngitis)
• cough
• increased amount of urine or increased urge to urinate
• itching
• skin rash
• increased blood levels of amylase enzyme
• increased blood levels of pancreatic lipase enzyme
• thirst
• constipation

Uncommon frequency

• difficulty or pain when emptying the bladder
• blood tests may show changes in blood fat levels, an increase in the number of red blood cells (increased haematocrit), and changes related to kidney function (reduced filtration rate and increased blood creatinine)

Rare frequency

• mouth ulcers
• 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 frequency

• inflammation of the kidneys (tubulo-interstitial nephritis)

Frequency not known (frequency cannot be estimated from the available data)

• development of blisters on the skin (bullous pemphigoid)

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

5. How to store Glyxambi

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister after EXP and on the carton after Exp. 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 Glyxambi contains
Glyxambi 10 mg/5 mg film-coated tablets

• The active substances are empagliflozin and linagliptin. Each film-coated tablet contains 10 mg of empagliflozin and 5 mg of linagliptin.
• Other components are:
  Tablet core: mannitol (E421), pregelatinized starch (maize), maize starch, copovidone, crospovidone, talc, and magnesium stearate.
  Film coating: hypromellose, mannitol (E421), talc, titanium dioxide (E171), macrogol 6000, and yellow iron oxide (E172).

Glyxambi 25 mg/5 mg film-coated tablets

• The active substances are empagliflozin and linagliptin. Each film-coated tablet contains 25 mg of empagliflozin and 5 mg of linagliptin.
• Other components are:
  Tablet core: mannitol (E421), pregelatinized starch (maize), maize starch, copovidone, crospovidone, talc, and magnesium stearate.
  Film coating: hypromellose, mannitol (E421), talc, titanium dioxide (E171), macrogol 6000, and red iron oxide (E172).

Description of the appearance of Glyxambi and contents of the pack
Glyxambi 10 mg/5 mg film-coated tablets (tablets) are light yellow, rounded triangular in shape, flat-faced, with rounded edges. "10/5" is printed on one side and the Boehringer Ingelheim logo on the other side. Each side of the tablet measures 8 mm in length.
Glyxambi 25 mg/5 mg film-coated tablets (tablets) are light pink, curved rounded triangular in shape, flat-faced, with rounded edges. "25/5" is printed on one side and the Boehringer Ingelheim logo on the other side. Each side of the tablet measures 8 mm in length.
Glyxambi is available in unit-dose perforated blister packs made of PVC/PVDC/aluminum.
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 Authorization Holder
Boehringer Ingelheim International GmbH
Binger Str. 173
55216 Ingelheim am Rhein
Germany

Manufacturer
Boehringer Ingelheim Pharma GmbH & Co. KG
Binger Strasse 173
55216 Ingelheim am Rhein
Germany
Rottendorf Pharma GmbH
Ostenfelder Strasse 51 – 61
59320 Ennigerloh
Germany

For further information on this medicinal product, please contact the local representative of the Marketing Authorization 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. z o.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 05 5425 71

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