Ebymect

Patient Information Leaflet

Ebymect 5 mg/850 mg film-coated tablets, 5 mg/1,000 mg film-coated tablets

dapagliflozin/metformin hydrochloride
Please 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 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 to them.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What Ebymect is and what it is used for

Ebymect contains two different active substances called dapagliflozin and metformin. Both belong to a class of medicines known as oral antidiabetic agents. These are medicines taken by mouth for diabetes.
Ebymect is used for a type of diabetes called "type 2 diabetes" in adult patients (18 years of age and older).
If you have type 2 diabetes, your pancreas does not produce enough insulin or your body is unable to use the insulin it produces effectively. This leads to high levels of sugar (glucose) in the blood.

• Dapagliflozin works by removing excess sugar from the body through the urine, thereby reducing the amount of sugar in the blood. This may also help prevent heart disease.
• Metformin primarily works by inhibiting glucose production in the liver.

To treat type 2 diabetes:

• This medicine must be taken in combination with diet and exercise.
• This medicine is used when diabetes cannot be controlled with other antidiabetic medicines.
• Your doctor may instruct you to take this medicine alone or together with other medicines for treating diabetes, which may include another oral medicine and/or an injectable medicine.
• If you are already taking dapagliflozin and metformin as separate tablets, your doctor may ask you to switch to this medicine. To avoid overdose, do not continue taking separate dapagliflozin and metformin tablets while taking Ebymect.

It is important to continue following your doctor’s, pharmacist’s or nurse’s advice regarding diet and exercise.

2. What you need to know before taking Ebymect

Do not take Ebymect

• if you are allergic to dapagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6).
• if you have recently had diabetic coma.
• if you have uncontrolled diabetes, associated, for example, with severe hyperglycaemia (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 deep breathing, drowsiness, and breath with an unusual fruity odour.
• if you have severely reduced kidney function.
• if you have conditions that could worsen kidney function such as:
  • loss of large amounts of body water (dehydration), for example due to prolonged or severe diarrhoea, or if you have repeatedly vomited
  • severe infection
  • serious problems with blood circulation (shock)
• if you have a disease that may cause problems in blood supply to organs such as:
  • Heart failure
  • breathing difficulties due to acute heart or lung disease
  • recent heart attack
  • serious problems with blood circulation (shock)
• if you have liver problems.
• if you drink alcohol excessively (either daily or occasionally) (see section “Ebymect and alcohol”).

Do not take this medicine if any of the above conditions apply to you.
Warnings and precautions
Risk of lactic acidosis
Ebymect may cause a very rare but very serious side effect called lactic acidosis,
particularly if the kidneys are not functioning properly. The risk of developing lactic acidosis is higher in
the presence 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 in cases of severe heart disease).
If you have any of the medical conditions described above, consult your doctor for further instructions.
Temporarily stop taking Ebymect 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 fluids than usual. Consult your doctor for further
instructions.
If you experience any of the symptoms of lactic acidosis, stop taking Ebymect and contact
your doctor or the nearest hospital immediately, because lactic acidosis can lead to coma.
Symptoms of lactic acidosis include:

• vomiting
• stomach ache (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.
Talk to your doctor, pharmacist, or nurse before taking Ebymect, and during
treatment:

• if you experience rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, rapid deep breathing, confusion, drowsiness or unusual tiredness, sweet-smelling breath, sweet or metallic taste in the mouth, or a different odour of urine or sweat, contact your doctor or the nearest hospital immediately. These symptoms may be a sign of diabetic ketoacidosis, a rare but serious condition which can sometimes be life-threatening, caused by diabetes due to increased levels of “ketone bodies” in urine or blood, detectable by laboratory tests. The risk of developing diabetic ketoacidosis may be increased by prolonged fasting, excessive alcohol intake, dehydration, sudden reduction in insulin dose, or increased insulin requirement due to major surgery or serious illness.
• if you have “type 1 diabetes” – you do not produce insulin. Ebymect must not be used to treat this medical condition.
• if you have very high blood glucose levels that may dehydrate you (excessive loss of body fluids). Possible signs of dehydration are listed in section 4. Inform your doctor before starting this medicine if you have any of these signs.
• if you are taking medicines to lower blood pressure (antihypertensives) and have previously had low blood pressure (hypotension). More information is provided below in section “Other medicines and Ebymect”.
• if you frequently get urinary tract infections. This medicine may cause urinary tract infections and your doctor may wish to monitor you more frequently. Your doctor may consider temporarily changing your treatment if you develop a serious infection.

If any of the above conditions apply to you (or you are unsure), inform your doctor, pharmacist, or nurse
before taking this medicine.
Seek immediate medical attention 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
malaise. These symptoms may indicate 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 must be treated immediately.
Surgery
If you are undergoing major surgery, you must stop taking Ebymect during the procedure and for a certain period afterwards. Your doctor will decide when to stop and when to restart treatment with Ebymect.
Kidney function
Your kidneys must be checked before starting Ebymect. During treatment with this
medicine, your doctor will monitor your kidney function once a year, or more frequently if you are elderly and/or if kidney function worsens.
Foot care
It is important to regularly check your feet and follow any other foot care advice provided by healthcare professionals.
Glucose in urine
Due to the mechanism of action of this medicine, urine tests will show the presence of
sugar during treatment with this medicine.
Elderly (≥ 65 years and older)
If you are elderly, there may be an increased risk of reduced kidney function and of concomitant use of
other medicines (see also “Kidney function” above and “Other medicines and Ebymect” below).
Children and adolescents
This medicine is not recommended for children and adolescents under 18 years of age, as it has not been studied in these patients.
Other medicines and Ebymect
If you are due to receive an iodinated contrast agent injected into the bloodstream, for example
for an X-ray procedure, you must stop taking Ebymect before or during the injection. Your
doctor will decide when to stop and when to restart treatment with Ebymect.
Inform your doctor if you are taking, have recently taken, or might take any other
medicines. You may need to have more frequent blood glucose and kidney function tests, or your doctor may decide to adjust the dose of Ebymect. It is particularly
important to mention the following:

• if you are taking medicines that increase urine production (diuretics).
• if you are taking other medicines that lower blood sugar levels, such as insulin or a “sulfonylurea” medicine. Your doctor may consider reducing the dose of these other medicines to prevent excessively low blood sugar levels (hypoglycaemia);
• if you are taking lithium, because Ebymect may reduce the amount of lithium in the blood.
• if you are taking cimetidine, a medicine used to treat stomach problems;
• if you are taking bronchodilators (beta-2 agonists) used to treat asthma;
• if you are taking corticosteroids (used to treat inflammatory diseases such as asthma and arthritis) administered orally, by injection, or by inhalation.
• if you are taking medicines used to treat pain and inflammation (NSAIDs and COX-2 inhibitors, such as ibuprofen and celecoxib);
• if you are taking certain medicines for high blood pressure (ACE inhibitors and angiotensin II receptor antagonists).

Ebymect and alcohol
Avoid excessive alcohol consumption while taking Ebymect, as this may increase the
risk of lactic acidosis (see section “Warnings and precautions”).
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine. You must stop taking this medicine if you become pregnant, as Ebymect is not recommended during
the second and third trimesters of pregnancy (last six months). Ask your doctor how best to manage blood sugar control during pregnancy.
Inform your doctor if you intend to breastfeed or are currently breastfeeding before taking this medicine. Do not use this medicine if you are breastfeeding. Metformin passes into breast milk in small amounts. It is not known whether dapagliflozin passes into breast milk.
Driving and use of machines
This medicine does not affect or has negligible effect on the ability to drive or use
machinery. However, taking this medicine together with other medicines that lower blood sugar levels, such as insulin or a “sulfonylurea” medicine, may cause excessively low blood sugar (hypoglycaemia), which can cause symptoms such as weakness, dizziness, increased sweating, tachycardia, visual disturbances, or difficulty concentrating, and may impair the ability to drive and use machinery. Do not drive or operate tools or machinery if you begin to experience these symptoms.
Ebymect contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially ‘sodium-free’.

3. How to take Ebymect

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

How much to take

• The dose of this medicine you should take depends on your condition and the doses of metformin and/or separate dapagliflozin and metformin tablets you are currently taking. Your doctor will tell you exactly what dose of this medicine you should take.
• The recommended dose is one tablet twice daily.

How to take Ebymect

• Swallow the tablet whole with half a glass of water.
• Take the tablet with food. This helps reduce the risk of stomach-related side effects.
• Take the tablet twice daily: one in the morning (breakfast) and one in the evening (dinner).

Your doctor may prescribe this medicine together with other medicines to lower your blood sugar levels. These may be oral medicines or injectable treatments, such as insulin or a GLP-1 receptor agonist. Remember to take these other medicines exactly as your doctor has instructed. This will help you achieve the best possible health outcomes.

Diet and exercise

Even while taking this medicine, a healthy diet and regular physical activity are essential for managing diabetes. It is therefore important to follow the advice of your doctor, pharmacist, or nurse regarding diet and exercise. In particular, if you are already following a diabetic or weight-control diet, continue it while taking this medicine.

If you take more Ebymect than you should

If you take more Ebymect tablets than prescribed, you may develop lactic acidosis. Symptoms of lactic acidosis include feeling unwell or generally unwell, vomiting, stomach pain, severe muscle pain, extreme tiredness, or difficulty breathing. If this occurs, immediate hospital treatment may be necessary, as lactic acidosis can lead to coma. Stop taking this medicine immediately and contact your doctor or go to the nearest hospital straight away (see section 2). Take the medicine with you.

If you forget to take Ebymect

If you forget a dose, take it as soon as you remember. If you do not remember until it is time for your next dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose of this medicine to make up for a forgotten dose.

If you stop taking Ebymect

Do not stop taking this medicine without first talking to your doctor. Without this medicine, your blood sugar levels may rise.

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 will get them.
Stop taking Ebymect and contact your doctor immediately if you experience any of the following
serious or potentially serious side effects:

• Lactic acidosis, very rarely observed (may affect up to 1 in 10,000 people): Ebymect can cause a very rare but very serious side effect called lactic acidosis (see section 2, “Warnings and precautions”). If this occurs, you must stop taking Ebymect and seek immediate medical attention at the nearest doctor’s office or hospital, as lactic acidosis can lead to coma.

Contact your doctor or the nearest hospital immediately if you experience any of the following side effects:

• Diabetic ketoacidosis, which occurs rarely (may affect up to 1 in 1,000 people). Symptoms of diabetic ketoacidosis include (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 breath odour, sweet or metallic taste in the mouth, or a different odour of urine or sweat.

This may occur regardless of blood sugar levels. Your doctor may decide to temporarily or permanently discontinue treatment with Ebymect.

• Necrotizing 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, observed very rarely.

Stop taking Ebymect and contact your doctor as soon as possible if you experience any of the following
serious or potentially serious adverse events:

• Urinary tract infections, commonly observed (may affect up to 1 in 10 people). Symptoms of severe urinary tract infection include:
  • fever and/or chills
  • burning sensation when urinating
  • back or side pain. Although uncommon, if you notice blood in your urine, contact your doctor immediately.

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

• Low blood sugar levels (hypoglycaemia), very commonly observed (may affect more than 1 in 10 people) – when taking this medicine with a sulphonylurea or other medicines that lower blood sugar levels, such as insulin. Symptoms of low blood sugar include:
  • trembling, sweating, strong feeling of anxiety, rapid heartbeat
  • feeling of hunger, headache, vision changes
  • mood changes or feeling confused. Your doctor will advise you on how to treat low blood sugar levels and what to do if any of the symptoms listed above occur. If you have symptoms of low blood sugar, eat sugar cubes, a sugary snack, or drink a fruit juice. If possible, check your blood sugar level and rest.

Other side effects include:
Very common

• nausea, vomiting
• diarrhoea or stomach ache
• loss of appetite

Common

• genital infections (thrush) of the penis or vagina (signs may include irritation, itching, abnormal discharge or unusual odour)
• back pain
• difficulty urinating, increased amount of urine, or increased urge to urinate more frequently
• changes in blood cholesterol or fat levels (observed in blood tests)
• increase in haematocrit (the percentage of blood volume occupied by cells) (observed in blood tests)
• decrease in creatinine renal clearance (observed in blood tests) at the beginning of treatment
• changes in taste
• dizziness
• skin rash
• low or reduced vitamin B levels in the blood: symptoms may include extreme tiredness (fatigue), sore and red tongue (glossitis), tingling (paraesthesia), or pale or yellowish skin. Your doctor may prescribe certain tests to determine the cause of symptoms, as some of these may also be caused by diabetes or other unrelated health conditions.

Uncommon (may affect up to 1 in 100 people)

• excessive loss of body fluids (dehydration, signs may include very dry or sticky mouth, little or no urine, or rapid heartbeat)
• fungal infection
• thirst
• constipation
• waking up during the night to urinate
• dry mouth
• weight loss
• increased creatinine (observed in blood tests) at the beginning of treatment
• increased urea (observed in laboratory tests)

Very rare

• abnormalities in liver function tests, inflammation of the liver (hepatitis)
• skin redness (erythema), itching, or itchy rash (urticaria)
• 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 listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Ebymect

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister 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 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 Ebymect contains

• The active substances are dapagliflozin and metformin hydrochloride (metformin HCl). Each film-coated tablet (tablet) of Ebymect 5 mg/850 mg contains dapagliflozin propanediol monohydrate, equivalent to 5 mg of dapagliflozin, and 850 mg of metformin hydrochloride. Each film-coated tablet (tablet) of Ebymect 5 mg/1,000 mg contains dapagliflozin propanediol monohydrate, equivalent to 5 mg of dapagliflozin, and 1,000 mg of metformin hydrochloride.
• The other components are:
  • tablet core: hydroxypropylcellulose (E463), microcrystalline cellulose (E460(i)), magnesium stearate (E470b), sodium starch glycolate (type A)
  • film coating: poly(vinyl alcohol) (E1203), macrogol (3350) (E1521), talc (E553b), titanium dioxide (E171), yellow iron oxide (E172), red iron oxide (E172) (only in Ebymect 5 mg/850 mg).

Description of the appearance of Ebymect and package contents

• Ebymect 5 mg/850 mg are brown, oval-shaped film-coated tablets (9.5 x 20 mm). They are marked with “5/850” on one side and “1067” on the other side.
• Ebymect 5 mg/1,000 mg are yellow, oval-shaped film-coated tablets (10.5 x 21.5 mm). They are marked with “5/1000” on one side and “1069” on the other side.

Ebymect 5 mg/850 mg film-coated tablets and Ebymect 5 mg/1,000 mg film-coated tablets are available in PVC/PCTFE/Alu blisters. Packs contain 14, 28, 56, and 196 (2 packs of 98) non-perforated film-coated tablets in calendarized blisters of 14 tablets, 60 film-coated tablets in non-perforated blisters of 10 tablets, and 60x1 film-coated tablets in perforated blisters as single doses.
Not all pack sizes may be marketed.

Marketing Authorization Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
AstraZeneca AB
Gärtunavägen
SE-152 57 Södertälje
Sweden

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

België/Belgique/Belgien Lietuva
AstraZeneca S.A./N.V. UAB AstraZeneca Lietuva
Tel: +32 2 370 48 11 Tel: +370 5 2660550

България Luxembourg/Luxemburg
АстраЗенека България ЕООД AstraZeneca S.A./N.V.
Тел.: +359 (2) 44 55 000 Tél/Tel: +32 2 370 48 11

Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500

Danmark Malta
AstraZeneca A/S Associated Drug Co. Ltd
Tlf.: +45 43 66 64 62 Tel: +356 2277 8000

Deutschland Nederland
AstraZeneca GmbH AstraZeneca BV
Tel: +49 40 809034100 Tel: +31 85 808 9900

Eesti Norge
AstraZeneca AstraZeneca AS
Tel: +372 6549 600 Tlf: +47 21 00 64 00

Ελλάδα Österreich
AstraZeneca A.E. AstraZeneca Österreich GmbH
Τηλ: +30 2 106871500 Tel: +43 1 711 31 0

España Polska
Esteve Pharmaceuticals, S.A. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 93 446 60 00 Tel.: +48 22 874 35 00
Laboratorio Tau, S. A.
Tel: +34 91 301 91 00

France Portugal
AstraZeneca BIAL-Portela & Cª., S.A.
Tél: +33 1 41 29 40 00 Tel.: +351 22 986 61 00

Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41

Ireland Slovenija
AstraZeneca Pharmaceuticals (Ireland) DAC AstraZeneca UK Limited
Tel: +353 1609 7100 Tel: +386 1 51 35 600

Ísland Slovenská republika
Vistor hf. AstraZeneca AB, o.z.
Sími: +354 535 7000 Tel: +421 2 5737 7777

Italia Suomi/Finland
AstraZeneca S.p.A. AstraZeneca Oy
Tel: +39 02 00704500 Puh/Tel: +358 10 23 010

Κύπρος Sverige
Αλέκτωρ Φαρµακευτική Λτδ AstraZeneca AB
Τηλ: +357 22490305 Tel: +46 8 553 26 000

Latvija United Kingdom (Northern Ireland)
SIA AstraZeneca Latvija AstraZeneca UK Ltd
Tel: +371 67377100 Tel: +44 1582 836 836

This information leaflet was last updated

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

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

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for dapagliflozin/metformin, the PRAC's scientific conclusions are as follows:
Based on available data on polycythaemia from the literature and spontaneous reports, and considering a plausible mechanism of action, the PRAC considers that there is sufficient evidence to justify a causal relationship between dapagliflozin and increased haematocrit. The PRAC has concluded that the product information for medicinal products containing dapagliflozin/metformin should be updated accordingly.

Having reviewed the PRAC's recommendation, the Committee for Human Medicinal Products (CHMP) agrees with its general conclusions and the rationale behind the recommendation.

Reasons for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on dapagliflozin/metformin, the CHMP considers that the benefit-risk balance of medicinal products containing dapagliflozin/metformin remains favourable, subject to the proposed changes to the product information.
The CHMP recommends a variation to the terms of the marketing authorisation.