GOBEMICINA 500 mg INJECTABLE

Introduction

Package Leaflet: Information for the Patient

Glyxambi 10mg/5mg film-coated tablets

Glyxambi 25mg/5mg film-coated tablets

empagliflozin/linagliptin

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

1. What is Glyxambi and what is it used for

What is Glyxambi

Glyxambi contains two active substances called empagliflozin and linagliptin. Each one belongs 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 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 glucose in your blood, which can cause medical problems such as heart disease, kidney disease, blindness, and poor circulation in your limbs.

How Glyxambi works

Empagliflozin belongs to a group of medicines called sodium-glucose cotransporter 2 (SGLT2) inhibitors. It works by blocking the SGLT2 protein in the kidneys. This makes the glucose (sugar) in the blood be eliminated with the urine.

Linagliptin works in a different way, specifically by making the pancreas produce more insulin to reduce blood glucose levels. This is achieved by blocking a protein called DPP-4.

Therefore, Glyxambi reduces the amount of glucose in the blood.

What Glyxambi is used for

• Glyxambi is added to metformin and/or a sulfonylurea (SU) to treat type 2 diabetes in adult patients aged 18 years or older, whose diabetes cannot be controlled when treated with metformin and/or a sulfonylurea in combination with empagliflozin, or when treated with metformin and/or a sulfonylurea in combination with linagliptin.

• Glyxambi can also be used as an alternative to taking empagliflozin and linagliptin as separate tablets. To avoid overdose, if you are taking this medicine, do not continue to take empagliflozin and linagliptin tablets separately.

It is important that you follow the diet and exercise plan recommended by your doctor, pharmacist, or nurse while taking Glyxambi.

2. What you need to know before you take Glyxambi

Do not take Glyxambi

• if you are allergic to empagliflozin, linagliptin, any other SGLT2 inhibitor (e.g., dapagliflozin, canagliflozina), 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

Consult your doctor before starting to take this medicine and during treatment:

• 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 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, drowsiness, or unusual fatigue, sweet breath odor, sweet or metallic taste in the mouth, or a distinct 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, 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 increase with prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin dose, or increased need for insulin due to major surgery or severe illness.
• if you are taking other antidiabetic medicines known as “sulfonylureas” (e.g., glimepiride, glipizide) or using insulin. Your doctor may want to reduce your dose of these medicines when taken with Glyxambi to avoid low blood sugar levels (hypoglycemia).
• if you have or have had a pancreatic disease.
• 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 Glyxambi”).

• if you have severe liver problems. Your doctor may ask you to take another medicine.

• if you may be at risk of dehydration, for example:
• • if you have nausea or vomiting, diarrhea, or fever, or if you are unable to eat or drink
  • if you are taking medicines that increase urine production [diuretics] or that lower blood pressure
  • if you are over 75 years old

The possible signs are listed in section 4 under “dehydration”. Your doctor may ask you to stop taking Glyxambi until you recover to prevent excessive fluid loss. Ask about ways to avoid dehydration.

• if you have an increase in the proportion of red blood cells in the blood (hematocrit), observed in clinical blood tests (see also section 4, "Possible side effects").

Contact your doctor if you experience any of the following during treatment with Glyxambi:

• if you develop symptoms of acute pancreatitis, such as severe and persistent stomach pain (abdominal pain). The possible signs are listed in section 4, “Possible side effects”. Your doctor may need to change your treatment.
• if you have a severe infection in the kidney or urinary tract with fever. Your doctor may ask you to stop taking Glyxambi until you recover.

• if you find a blister on the skin, it could be a sign of a disease called bullous pemphigoid. Your doctor may indicate that you interrupt Glyxambi.

Consult your doctor immediately if you present a combination of symptoms of pain, pain on palpation, redness, or inflammation of the genitals or the area between the genitals and the anus, with fever or general malaise. 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 should be treated immediately.

Foot care

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

Kidney function

Before starting treatment with Glyxambi, and regularly during treatment, your doctor will check how well your kidneys are working.

Glucose in urine

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

Children and adolescents

This medicine is not recommended in children and adolescents under 18 years of age because linagliptin is not effective in children and adolescents between 10 and 17 years of age. It is not known if 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 using, have recently used, or might use any other medicines. In particular, you should tell your doctor if you are using the following medicines:

• other antidiabetic medicines, 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.
• medicines used to remove water from your body (diuretics). Your doctor may ask you to stop taking Glyxambi.
• medicines that may affect the breakdown of empagliflozin or linagliptin in your body, such as rifampicin (an antibiotic used to treat tuberculosis) or certain medicines used to treat seizures (such as carbamazepine, phenobarbital, or phenytoin). The effect of Glyxambi may be reduced.
• lithium, as Glyxambi may reduce the amount of lithium in your blood.

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before using this medicine.

It is not known if Glyxambi is harmful to the fetus. As a precaution, it is preferable to avoid the use of this medicine during pregnancy.

It is not known if the active substances of Glyxambi pass into breast milk. Do not use this medicine if you are breastfeeding.

It is not known if Glyxambi has effects on fertility in humans.

Driving and using machines

The influence of Glyxambi on the ability to drive and use machines is small.

Taking this medicine in combination with sulfonylureas or insulin may cause your blood glucose levels to become too low (hypoglycemia), which can cause symptoms such as tremors, 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 experience any of these symptoms while taking Glyxambi.

3. How to take Glyxambi

Follow exactly the administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

How much to take

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

Your doctor will decide if you need to increase your dose to one film-coated tablet of Glyxambi 25 mg/5 mg (25 mg of empagliflozin and 5 mg of linagliptin) once a day. If you are already taking 25 mg of empagliflozin and 5 mg of linagliptin as separate tablets and switch to Glyxambi, you can start directly with Glyxambi 25 mg/5 mg.

Kidney impairment

Consult your doctor if you have kidney problems. Your doctor may limit your dose or decide to use an alternative medicine.

Liver impairment

Consult your doctor if you have severe liver impairment. The use of Glyxambi is not recommended, and your doctor may decide to use an alternative medicine.

Taking this medicine

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

Your doctor may prescribe Glyxambi together with another antidiabetic medicine. Remember to take all the medicines as your doctor has indicated to achieve the best results for your health.

A suitable diet and exercise help your body use blood glucose better. It is important to follow the diet and exercise plan recommended by your doctor while taking Glyxambi.

If you take more Glyxambi than you should

If you take more of this medicine than you should, consult a doctor immediately or go to a hospital. Take the medicine pack with you.

If you forget to take Glyxambi

If you forget to take a tablet, what you should do depends on the time until your next dose:

• If it is 12 hours or more until your next dose, take Glyxambi as soon as you remember. Then, take the next dose at the usual time.
• If it is less than 12 hours until your next dose, skip the missed dose. Then, take the next dose at the usual time.
• Do not take a double dose of this medicine to make up for missed doses.

If you stop taking Glyxambi

Do not stop taking this medicine without consulting your doctor first, unless you suspect you have diabetic ketoacidosis (see section 2 “Warnings and precautions”). Your blood glucose levels may increase if you stop taking Glyxambi.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

Contact a doctor or the nearest hospital immediately if you experience any of the following adverse effects:

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

These are the signs of diabetic ketoacidosis (see also section 2 "Warnings and Precautions"):

• 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 drowsiness 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 glucose level. Your doctor may decide to temporarily or permanently discontinue treatment with this medicine.

Contact your doctor immediately if you notice any of the following adverse effects:

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

This medicine may cause allergic reactions, which can be severe, including hives (urticaria) and swelling of the face, lips, tongue, and throat, which can cause difficulty breathing or swallowing (angioedema).

Pancreatitis (inflammation of the pancreas), infrequently observed

This medicine may cause pancreatitis, which is usually presented as persistent and severe abdominal pain (in the stomach) that can radiate to the back, often accompanied by nausea or vomiting. Your doctor will need to change your treatment.

Low blood sugar (hypoglycemia), frequently observed (may affect up to 1 in 10 people)

If you take Glyxambi with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin, you are at risk of having too low blood sugar (hypoglycemia). The signs of low blood sugar include:

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

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

Urinary tract infections, frequently observed

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 this medicine works, but it can also be a sign of a urinary tract infection. If you experience an increase in these symptoms, contact your doctor.

Loss of body fluids (dehydration), infrequently observed

The signs of dehydration are not specific, but may include:

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

Other Adverse Effects While Taking Glyxambi:

Frequently Observed

• fungal genital infections, such as candidiasis
• inflammation of the nose or throat (nasopharyngitis)
• cough
• urinating more than usual or needing to urinate more frequently
• itching (pruritus)
• skin rash
• increased amylase enzyme in blood
• increased pancreatic lipase enzyme
• • thirst
  • constipation

Infrequently Observed

• difficulty or pain when emptying the bladder
• clinical blood tests may show changes in blood fat levels, an increase in red blood cell count (increase in hematocrit), and changes related to kidney function (decrease in glomerular filtration rate and increase in blood creatinine)

Rarely Observed

• mouth pain
• 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 Rarely Observed

• kidney inflammation (tubulointerstitial nephritis)

Frequency Not Known (Cannot be Estimated from Available Data)

• skin blisters (bullous pemphigoid)

Reporting Adverse Effects

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

5. Storage of Glyxambi

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the blister 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 medicine if you notice that the packaging is damaged or shows visible signs of tampering.

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

6. Package Contents and Additional Information

Composition of Glyxambi

Glyxambi 10 mg/5 mg film-coated tablets

• The active ingredients are empagliflozin and linagliptin. Each film-coated tablet contains 10 mg of empagliflozin and 5 mg of linagliptin.
• The other ingredients are:

Tablet core: mannitol (E421), pregelatinized starch (from corn), corn starch, copovidone, crospovidone, talc, and magnesium stearate.

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 ingredients are empagliflozin and linagliptin. Each film-coated tablet contains 25 mg of empagliflozin and 5 mg of linagliptin.
• The other ingredients are: Tablet core: mannitol (E421), pregelatinized starch (from corn), corn starch, copovidone, crospovidone, talc, and magnesium stearate. Coating: hypromellose, mannitol (E421), talc, titanium dioxide (E171), macrogol 6000, and red iron oxide (E172).

Appearance of the Product and Package Contents

The Glyxambi 10 mg/5 mg film-coated tablets are pale yellow, triangular, and have a flat face with a beveled edge. They are engraved with "10/5" on one side and the Boehringer Ingelheim logo on the other. Each side of the tablet measures 8 mm in length.

The Glyxambi 25 mg/5 mg film-coated tablets are pale pink, triangular, and have a flat face with a beveled edge. They are engraved with "25/5" on one side and the Boehringer Ingelheim logo on the other. Each side of the tablet measures 8 mm in length.

Glyxambi is available in perforated unit dose blisters of PVC/PVDC/aluminum.

The pack sizes are 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

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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