Mexdagry

Package leaflet: Information for the patient

Mexdagry, 5 mg + 850 mg, film-coated tablets
Mexdagry, 5 mg + 1000 mg, film-coated tablets
Dapagliflozin + Metformin hydrochloride
Please read the entire leaflet carefully before using this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Mexdagry is and what it is used for

This medicine contains two different active substances: dapagliflozin and metformin. Both belong to a group of medicines known as oral antidiabetic agents. These are medicines taken by mouth for the treatment of diabetes.
Mexdagry is used in the treatment of a type of diabetes called type 2 diabetes in adult patients (aged 18 years and older), which usually occurs in older patients. In patients with type 2 diabetes, the pancreas does not produce enough insulin, or the body cannot respond properly to the insulin produced in adequate amounts. This leads to high levels of sugar (glucose) in the blood.

• Dapagliflozin works mainly by removing excess sugar from the body through urine and lowering blood sugar levels. It may also help prevent heart disease.
• Metformin works mainly by reducing glucose production in the liver.

In the treatment of diabetes:

• This medicine should be taken together with the recommended diet and exercise program.
• This medicine is used when adequate control of diabetes cannot be achieved with other antidiabetic medicines.
• Your doctor may prescribe this medicine alone or in combination with other medicines used to treat diabetes. These may include other oral medicines and/or injectable medicines such as insulin or a GLP-1 receptor agonist (which helps the body increase insulin production when blood sugar levels are high).
• If you are currently taking dapagliflozin and metformin as separate tablets, your doctor may recommend switching your treatment to this medicine. To avoid overdose, do not continue taking dapagliflozin and metformin as separate tablets once you start taking Mexdagry.

It is important to continue following the dietary and exercise advice provided by your doctor, pharmacist, or nurse.

2. Important information before using Mexdagry

When not to use Mexdagry

• if the patient is allergic (hypersensitive) to dapagliflozin, metformin, or any of the other ingredients of this medicine (listed in section 6);
• if the patient has ever experienced diabetic coma;
• if the patient has uncontrolled diabetes, for example severe hyperglycaemia (high blood glucose levels), nausea, vomiting, diarrhoea, sudden weight loss, lactic acidosis (see "Risk of lactic acidosis" below), or ketoacidosis. Ketoacidosis is a condition in which substances called ketone bodies accumulate in the blood and may lead to a diabetic pre-coma state. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness, or an unusual fruity odour of the breath;
• if the patient has significantly reduced kidney function;
• if the patient has a severe infection;
• if the patient has lost a significant amount of body fluid (is dehydrated), for example due to prolonged or severe diarrhoea, or due to repeated vomiting occurring in quick succession;
• if the patient has recently had a heart attack, or has heart failure/circulatory failure, serious circulatory disorders, or breathing difficulties;
• if the patient has liver diseases or impaired liver function;
• if the patient consumes large amounts of alcohol, either daily or occasionally (see section "Mexdagry and alcohol").

Do not take this medicine if any of the above conditions apply to the patient.
Warnings and precautions
Risk of lactic acidosis
Mexdagry may cause a very rare but serious adverse effect called lactic acidosis, especially if the patient has impaired kidney function. The risk of lactic acidosis is also increased in cases of uncontrolled diabetes, severe infection, prolonged fasting or alcohol consumption, dehydration (see more detailed information below), impaired liver function, and any medical conditions in which part of the body is inadequately supplied with oxygen (e.g. acute severe heart disease).
If any of the above conditions apply to the patient, consult a doctor for further instructions.
Temporarily discontinue Mexdagry if the patient develops a medical condition that may involve dehydration (significant loss of body water), such as severe vomiting, diarrhoea, fever, exposure to high temperatures, or if the patient drinks less fluid than usual. Consult a doctor for further instructions.
Discontinue Mexdagry and immediately contact a doctor or the nearest hospital if the patient experiences any symptoms of lactic acidosis, as this condition may lead to coma.
Symptoms of lactic acidosis include:

• vomiting,
• abdominal pain,
• muscle cramps,
• general feeling of being unwell combined with severe fatigue,
• difficulty breathing,
• decreased body temperature and slowed heart rate.

Lactic acidosis is an acute, life-threatening condition requiring immediate hospital treatment.
Contact a doctor immediately for further instructions if:

• the patient has a genetically inherited mitochondrial disorder (energy-producing structures in cells), such as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes) or maternally inherited diabetes and deafness (MIDD).
• the patient experiences any of the following symptoms after starting metformin: seizures, worsening cognitive function, difficulty moving, symptoms indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

Before starting and while taking Mexdagry, inform the doctor,
pharmacist, or nurse:

• if the patient has type 1 diabetes – a type of diabetes that usually begins in young people, in which the patient's body does not produce insulin. Mexdagry should not be used to treat this condition.
• if the patient experiences rapid weight loss, nausea or vomiting, abdominal pain, excessive thirst, rapid and deep breathing, confusion, unusual drowsiness or fatigue, sweet-smelling breath, sweet or metallic taste in the mouth, or a change in the smell of urine or sweat, contact a doctor or the nearest hospital immediately. These symptoms may indicate "diabetic ketoacidosis" – a rare but serious, sometimes life-threatening complication of diabetes resulting from increased levels of "ketone bodies" in the blood or urine, as confirmed by laboratory tests. The risk of diabetic ketoacidosis may increase during prolonged fasting, excessive alcohol consumption, dehydration, sudden reduction in insulin dose, or increased insulin requirements due to major surgery or serious illness.
• if the patient has kidney disease. The doctor will monitor the patient's kidney function.
• if the patient has very high blood glucose levels, which may lead to dehydration (excessive fluid loss). Possible symptoms of dehydration are listed in section 4. Inform the doctor before starting this medicine if the patient has experienced any of these symptoms.
• if the patient is taking antihypertensive medicines (blood pressure-lowering drugs) and has a history of low blood pressure (hypotension). More information is provided below in section "Mexdagry and other medicines".
• if the patient frequently suffers from urinary tract infections. This medicine may contribute to the development of urinary tract infections, and therefore the doctor may recommend more frequent check-ups to monitor the patient's health. If the patient develops a serious infection, the doctor may consider temporarily changing the treatment.

If the patient is scheduled for major surgery, Mexdagry must not be used during and for some time after the procedure. The doctor will decide when the patient should stop and restart treatment with Mexdagry.
It is important to regularly check the condition of the feet and to follow all foot care advice provided by the doctor.
If any of the above warnings apply to the patient (or if the patient is unsure), consult a doctor, pharmacist, or nurse before using this medicine.
If the patient develops a combination of symptoms such as pain, tenderness, redness, or swelling of the external genital organs or the area between the genitals and the anus, accompanied by fever or general malaise, seek medical attention immediately.
These may be symptoms of a rare but severe or even life-threatening infection called necrotizing fasciitis of the perineum or Fournier's gangrene, which leads to damage of subcutaneous tissue. Immediate treatment of Fournier's gangrene is essential.
Kidney function
While being treated with Mexdagry, the doctor will monitor the patient's kidney function at least once a year, or more frequently if the patient is elderly and/or has worsening kidney function.
Glucose in urine
Due to the mechanism of action of this medicine, laboratory tests will show the presence of sugar (glucose) in the urine during treatment.
Children and adolescents
This medicine should not be used in children and adolescents under 18 years of age, as it has not been studied in this patient group.
Mexdagry and other medicines
If the patient is to receive an iodine-containing contrast agent injected into the bloodstream, for example for an X-ray or CT scan, treatment with Mexdagry must be stopped before or at the latest at the time of injection. The doctor will decide when the patient should stop and restart treatment with Mexdagry.
Inform the doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take. The patient may require more frequent monitoring of blood glucose levels and kidney function assessments, or dose adjustments of Mexdagry by the doctor. It is particularly important to inform the doctor about the following medicines:

• diuretics (medicines that increase urine production);
• other medicines that lower blood sugar levels, such as insulin or sulfonylurea derivatives. The doctor may recommend reducing the doses of these other medicines to prevent low blood sugar levels (hypoglycaemia);
• lithium, because Mexdagry may reduce blood lithium levels;
• cimetidine, a medicine used to treat stomach disorders and conditions;
• bronchodilators (beta-2 adrenergic receptor agonists) used in the treatment of asthma;
• corticosteroids (used to treat inflammatory conditions in diseases such as asthma and arthritis, administered orally, by injection, or by inhalation);
• 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).

Mexdagry and alcohol
Avoid consuming excessive amounts of alcohol while taking Mexdagry, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine. If the patient becomes pregnant, she should stop taking Mexdagry, as its use is not recommended during the second and third trimesters (i.e. the last 6 months) of pregnancy. Consult a doctor to determine the best way to manage blood glucose control during pregnancy.
If the patient is breastfeeding or intends to breastfeed, she should inform the doctor before starting this medicine. This medicine should not be used during breastfeeding. Metformin passes into breast milk in small amounts. It is unknown whether dapagliflozin passes into breast milk.
Driving and operating machinery
Mexdagry has no effect or negligible effect on the ability to drive and operate machinery. However, using this medicine together with other medicines that lower blood sugar levels, such as insulin or sulfonylurea derivatives, may cause excessive lowering of blood sugar (hypoglycaemia), manifesting as weakness, dizziness, increased sweating, rapid heartbeat, visual disturbances, or difficulty concentrating, which may affect the ability to drive and operate machinery.
Do not drive or use tools or operate machinery if the patient begins to experience these symptoms.
Mexdagry contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".

3. How to use Mexdagry

This medicine should always be used exactly as your doctor has told you. If you are unsure,
you should consult your doctor or pharmacist.

What dose to take

• The dose of this medicine will vary depending on the patient's condition and the current doses of metformin and (or) separately taken dapagliflozin and metformin tablets. Your doctor will clearly inform you which strength of tablet you should take.
• The recommended dose is one tablet twice daily.

How to take the medicine

• Swallow the tablet whole with half a glass of water.
• The tablets may be taken with food. This is intended to reduce the risk of gastrointestinal side effects.
• Take the tablets twice daily—one in the morning (with breakfast) and one in the evening (with dinner). The symbols on the blister pack will help you remember which dose has already been taken. The sun ( ) indicates the morning dose, and the moon ( ) indicates the evening dose.

Your doctor may prescribe this medicine together with other medicines to lower blood sugar levels. These may be oral medicines or injections such as insulin or a GLP-1 receptor agonist. Always take these other medicines as directed by your doctor. This will help achieve the best treatment results.

Diet and physical activity
To properly manage diabetes, you should continue to follow a proper diet and engage in physical activity, even while taking this medicine. It is important to continue following the advice of your doctor, pharmacist, or nurse regarding diet and exercise. In particular, if you are on a diabetic diet aimed at maintaining a healthy body weight, you should continue this diet while taking this medicine.

Taking more Mexdagry than prescribed
If you take more Mexdagry than prescribed, you may develop lactic acidosis. Symptoms of lactic acidosis include severe nausea or vomiting, abdominal pain, muscle cramps, extreme fatigue, or difficulty breathing. If you develop lactic acidosis, you may require immediate hospitalization, as lactic acidosis can lead to coma. In such a case, stop taking this medicine immediately and contact your doctor or the nearest hospital without delay (see section 2). Take the medicine package with you.

Missing a dose of Mexdagry
If you miss a dose, take it as soon as you remember. However, 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 to make up for a missed dose.

Stopping Mexdagry
Do not stop taking this medicine without consulting your doctor. Blood sugar levels may increase after stopping the medicine.

If you have any further questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Treatment with Mexdagry must be discontinued and immediate medical advice sought if
the patient experiences any of the following severe or potentially severe adverse reactions:

• Lactic acidosis, very rare (may occur in up to 1 in 10,000 people). Mexdagry may very rarely cause a very serious adverse reaction known as lactic acidosis (see section 2, "Warnings and precautions"). If lactic acidosis occurs, Mexdagry must be stopped immediately and the patient must contact a doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.

Immediate medical advice should be sought from a doctor or the nearest hospital if the patient
experiences any of the following adverse reactions:

• Diabetic ketoacidosis, observed rarely (may occur in up to 1 in 1,000 people). Symptoms of ketoacidosis include (see also section 2, "Warnings and precautions"):
• increased concentration of "ketone bodies" in urine or blood,
• rapid weight loss,
• nausea or vomiting,
• abdominal pain,
• excessive thirst,
• rapid and deep breathing,
• confusion,
• unusual drowsiness or fatigue,
• sweet-smelling breath, sweet or metallic taste in the mouth, or change in the smell of urine or sweat. This may occur regardless of blood glucose levels. The doctor may decide to discontinue or stop treatment with Mexdagry.
• Necrotizing fasciitis of the perineum, also known as Fournier's gangrene, a severe infection of the soft tissues of the external genital organs or the area between the genitals and the anus, observed very rarely.

Treatment with Mexdagry must be discontinued and medical advice sought as soon as possible if
the patient experiences any of the following severe or potentially severe adverse reactions:

• 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 during urination,
• back or flank pain. Blood in the urine may occasionally occur; in such cases, immediate medical advice should be sought.

Immediate contact with a doctor is required if the patient experiences any of the
following adverse reactions:

• Low blood sugar (hypoglycaemia), very commonly observed (may occur in more than 1 in 10 people), when this medicine is used in combination with sulfonylurea derivatives or other medicines that lower blood glucose levels, such as insulin. Symptoms of low blood sugar include:
• trembling, sweating, feeling anxious, rapid heartbeat,
• feeling of hunger, headache, visual disturbances,
• mood changes or feeling confused. The doctor will advise on how to treat low blood sugar and what to do if any of the above adverse reactions occur. If symptoms of low blood sugar occur, the patient should consume glucose tablets, a high-sugar snack, or fruit juice. Blood glucose should be measured and the patient should rest.

Other adverse reactions include:
Very common (may affect more than 1 in 10 people):

• nausea, vomiting,
• diarrhoea or abdominal pain,
• loss of appetite.

Common (may affect up to 1 in 10 people):

• genital infections (fungal infections) of the penis or vagina (e.g. irritation, itching, unusual discharge or unpleasant odour),
• back pain,
• discomfort during urination, increased volume of urine passed, or increased frequency of urination,
• changes in blood levels of cholesterol or lipids (detected in laboratory tests),
• increased number of red blood cells (detected in laboratory tests),
• reduced renal creatinine clearance (detected in laboratory tests) at the beginning of treatment,
• taste disturbances,
• dizziness,
• rash,
• decreased or low blood levels of vitamin B (symptoms may include extreme fatigue, pain and redness of the tongue (glossitis), tingling sensations (paraesthesiae), or pale or yellowish skin). The doctor may order certain tests to identify the cause of symptoms, as some of them may also be caused by diabetes or other health problems unrelated to treatment.

Uncommon (may affect up to 1 in 100 people):

• excessive loss of body fluids (dehydration, symptoms of which may include extreme dryness or stickiness in the mouth, passing small amounts of urine or no urine at all, or rapid heartbeat),
• thirst,
• constipation,
• nocturia (waking up at night to pass urine),
• dry mouth,
• weight loss,
• increased blood creatinine levels (detected in laboratory blood tests) at the beginning of treatment,
• increased blood urea levels (detected in laboratory blood tests).

Very rare (may affect up to 1 in 10,000 people):

• abnormal liver function tests, hepatitis,
• skin redness (erythema), itching or itchy rash (urticaria),
• kidney inflammation (tubulointerstitial nephritis).

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, patients should inform their doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorisation holder.
Reporting adverse reactions helps provide more information on the safety of the medicine.

5. How to store Mexdagry

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 the outer carton
following the abbreviation "EXP". The expiry date refers to the last day of the stated month.
Store in the original packaging to protect from moisture.
There are no special requirements for the storage temperature of this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your
pharmacist how to dispose of medicines no longer required. This will help protect
the environment.

6. Contents of the pack and other information

What Mexdagry contains

• The active substances in this medicine are dapagliflozin and metformin hydrochloride.
  Mexdagry 5 mg + 850 mg, film-coated tablets
  Each film-coated tablet contains 5 mg dapagliflozin (as dapagliflozin propanediol monohydrate) and 850 mg metformin hydrochloride.
  Mexdagry 5 mg + 1000 mg, film-coated tablets
  Each film-coated tablet contains 5 mg dapagliflozin (as dapagliflozin propanediol monohydrate) and 1000 mg metformin hydrochloride.

• The other ingredients (excipients) are:
  Tablet core: copovidone, sodium croscarmellose, microcrystalline cellulose, magnesium stearate.
  Tablet coating: polyvinyl alcohol, calcium carbonate, macrogol, talc, yellow iron oxide (E 172), red iron oxide (E 172) – only for the 5 mg + 850 mg strength.

See section 2 "Mexdagry contains sodium".
What Mexdagry looks like and contents of the pack
5 mg + 850 mg: Orange, oval, biconvex film-coated tablets marked with
K1 on one side of the tablet. Tablet dimensions: 20 x 10 mm.
5 mg + 1000 mg: Yellow, oval, biconvex film-coated tablets marked with
K2 on one side of the tablet. Tablet dimensions: 22 x 11 mm.
Mexdagry is available in packs containing:

• 14, 28, 30, 56, 60, 90 or 196 film-coated tablets in blister packs, packed in a cardboard carton.

Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
KRKA-POLSKA Sp. z o.o.
ul. Równoległa 5
02-235 Warszawa, Poland
tel. 22 57 37 500