Diaflix combo

Package leaflet: Information for the patient

Diaflix Combo, 5 mg + 850 mg, film-coated tablets
Diaflix Combo, 5 mg + 1000 mg, film-coated tablets
Dapagliflozinum + Metformini hydrochloridum
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific person only. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What Diaflix Combo is and what it is used for

This medicine contains two different substances: dapagliflozin and metformin. Both belong to a group of medicines known as oral antidiabetic agents. These are medicines taken by mouth for diabetes.
Diaflix Combo is used in the treatment of a type of diabetes called type 2 diabetes in adults (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 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 inhibiting glucose production in the liver.
In the treatment of diabetes:
This medicine should be used together with a 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 in the treatment of 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 when you are taking Diaflix Combo.
It is important to continue following the dietary and exercise advice given to you by your doctor, pharmacist, or nurse.

2. Important information before taking Diaflix Combo

When not to use Diaflix Combo

• 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 diabetic pre-coma. Symptoms include: abdominal pain, rapid and deep breathing, drowsiness or unusual fruity odour of 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, or serious circulatory disorders or breathing difficulties;
• if the patient has liver disease or impaired liver function;
• if the patient consumes large amounts of alcohol, either daily or occasionally (please refer to the section "Diaflix Combo and alcohol"). Do not take this medicine if any of the above conditions apply to the patient.

Warnings and precautions
Risk of lactic acidosis
Diaflix Combo 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 use of Diaflix Combo if the patient develops a medical condition that may lead to 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.
Stop taking Diaflix Combo and contact a doctor or the nearest hospital immediately 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 malaise combined with profound fatigue, difficulty breathing, lowered 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 disease (energy-producing structures in cells), such as MELAS (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, signs indicating nerve damage (e.g. pain or numbness), migraine, or deafness.

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

• if the patient has type 1 diabetes – a type of diabetes that usually begins in young people whose bodies do not produce insulin. Diaflix Combo 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 changes in the odour 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 urine or blood, 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 requirement due to major surgery or severe illness.
• if the patient has kidney disease; the doctor will monitor kidney function.
• if the patient has very high blood glucose levels, which may lead to dehydration (loss of excessive amounts of fluid). Possible symptoms of dehydration are listed at the beginning of section 4. Inform the doctor before starting this medicine if any of these symptoms occur.
• 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 the section "Diaflix Combo and other medicines".
• if the patient frequently experiences urinary tract infections; this medicine may contribute to the development of urinary tract infections, so 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, Diaflix Combo must not be taken during and for some time after the procedure. The doctor will decide when the patient should stop and resume treatment with Diaflix Combo.

It is important to regularly check the condition of the feet and follow all foot care advice given by healthcare professionals.
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 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 necrotising fasciitis of the perineum or Fournier's gangrene, leading to damage of subcutaneous tissue. Immediate treatment of Fournier's gangrene is essential.
Kidney function
During treatment with Diaflix Combo, 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 must not be used in children and adolescents under 18 years of age, as it has not been studied in this patient group.
Diaflix Combo 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, the patient must stop taking Diaflix Combo before or at the latest at the time of injection. The doctor will decide when the patient should stop and resume treatment with Diaflix Combo.
Inform the doctor about all medicines the patient is currently taking or has 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 Diaflix Combo by the doctor.
It is especially important to inform about the following medicines:

• diuretics (medicines that increase urine production);
• other medicines that reduce blood sugar levels, such as insulin or sulfonylurea derivatives; the doctor may recommend reducing the dose of these other medicines to prevent low blood sugar levels (hypoglycaemia);
• cimetidine, a medicine used to treat stomach disorders;
• bronchodilators (beta-2 adrenergic receptor agonists) used in the treatment of asthma;
• corticosteroids (used to treat inflammatory conditions 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).

Diaflix Combo and alcohol
Avoid consuming excessive amounts of alcohol while taking Diaflix Combo, as this may increase the risk of lactic acidosis (see section "Warnings and precautions").
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult a doctor or pharmacist before using this medicine.
If the patient becomes pregnant, she should stop taking Diaflix Combo, as its use is not recommended during the second and third trimesters (the last six months) of pregnancy. Consult a doctor to determine the best way to control glycaemia during pregnancy.
If the patient is breastfeeding or intends to breastfeed, she should inform the doctor before starting Diaflix Combo. Diaflix Combo must not be used during breastfeeding.
Metformin passes into human milk in small amounts. It is not known whether dapagliflozin passes into human milk.
Driving and operating machinery
This medicine has no effect or a 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 excessively low blood sugar levels (hypoglycaemia), manifesting as weakness, dizziness, increased sweating, rapid heartbeat, blurred vision 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.

3. How to take Diaflix Combo

Diaflix Combo should always be taken as directed by your doctor. If you have any doubts, consult your doctor or pharmacist.

What dose to take
The dose of this medicine varies depending on the patient's condition and the current doses of metformin and/or separate dapagliflozin and metformin tablets being taken. Your doctor will inform you exactly 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.
Take the tablet during a meal. 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).
Your doctor may recommend taking 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 outcomes.

Diet and physical exercise
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 your doctor’s, pharmacist’s, or nurse’s advice 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 Diaflix Combo than recommended
If you take more Diaflix Combo than recommended, you may develop lactic acidosis. Symptoms of lactic acidosis include severe nausea or vomiting, abdominal pain, muscle cramps, extreme fatigue, or difficulty breathing. If lactic acidosis occurs, you may require immediate hospitalization, as it 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 packaging with you.

Missing a dose of Diaflix Combo
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 of this medicine to make up for a missed dose.

Stopping Diaflix Combo
Do not stop taking Diaflix Combo without consulting your doctor. If you have diabetes, your blood sugar levels may rise after stopping the medicine.
If you have any further questions about the use of 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.
You must stop taking Diaflix Combo and contact a doctor immediately if the patient experiences any of the following severe or potentially severe adverse reactions:

• Lactic acidosis, observed very rarely (may occur in less than 1 in 10,000 people). Diaflix Combo may very rarely cause a very serious adverse reaction known as lactic acidosis (see section 2 "Warnings and precautions"). If this occurs in a patient, the patient must stop taking Diaflix Combo immediately and contact a doctor or the nearest hospital without delay, as lactic acidosis may lead to coma.

Contact a doctor or the nearest hospital immediately if the patient experiences any of the following adverse reactions:

• Diabetic ketoacidosis, observed rarely (may occur in less than 1 in 1,000 people). Symptoms of ketoacidosis (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 Diaflix Combo.

Necrotizing fasciitis of the perineum, also known as Fournier's gangrene, a serious infection of the soft tissues of the external genital organs or the area between the genitals and the anus, observed very rarely.
You must stop taking Diaflix Combo and consult a doctor as quickly as possible if the patient experiences any of the following severe or potentially severe adverse reactions:
Urinary tract infections, observed frequently (may occur in less than 1 in 10 people). Signs and symptoms of serious urinary tract infection:

• fever and (or) chills, burning sensation during urination, back or flank pain. Blood in the urine may occasionally occur; if so, consult a doctor immediately.

Contact a doctor immediately if the patient experiences any of the following adverse reactions:
Low blood sugar (hypoglycaemia), observed very frequently (may occur in more than 1 in 10 people) when this medicine is taken with sulfonylurea derivatives or with other medicines that lower blood sugar levels, such as insulin.

• Symptoms of low blood sugar: trembling, sweating, feeling anxious, rapid heartbeat, feeling hungry, headache, vision disturbances, mood changes, or feeling confused. The doctor will advise on how to manage low blood sugar and what to do if any of the above symptoms occur. If symptoms of low blood sugar occur, the patient should consume glucose tablets, a sugary snack, or drink fruit juice. Blood sugar should be measured and the patient should rest.

Other adverse reactions include:
Very common: nausea, vomiting, diarrhoea or abdominal pain, loss of appetite.
Common: genital infections (candidiasis) of the penis or vagina (e.g. irritation, itching, unusual discharge or unpleasant odour), back pain, discomfort when urinating, passing larger than usual amounts of urine or needing to urinate more often, changes in cholesterol or blood lipid levels (detected in laboratory tests), increased red blood cell count (detected in laboratory tests), decreased renal creatinine clearance (detected in laboratory tests) at the beginning of treatment, taste disturbances, dizziness, rash.
Uncommon (may occur in no more than 1 in 100 people): excessive fluid loss from the body (dehydration, symptoms of which may include extreme dryness or stickiness in the mouth, passing small amounts of urine or no urine, or rapid heartbeat), thirst, constipation, getting up at night to pass urine, dry mouth, weight loss, increased creatinine levels (detected in blood laboratory tests) at the beginning of treatment, increased urea levels (detected in blood laboratory tests).
Very rare: decreased vitamin B12 levels in the blood, abnormal liver function test results, hepatitis, skin redness (erythema), itching or itchy rash (urticaria).
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department for Monitoring Adverse Reactions to Medicinal Products, 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 authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Diaflix Combo

Keep this medicine out of sight and reach of children.
There are no special storage instructions for this medicine.
Do not use this medicine after the expiry date stated on the blister pack and carton.
The expiry date follows the abbreviation EXP. The expiry date refers to the last day of the stated month.
The packaging label shows the expiry date after the abbreviation EXP, and the batch number after the abbreviation Lot/LOT.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Diaflix Combo contains
Diaflix Combo, 5 mg + 850 mg, film-coated tablets

• The active substances are dapagliflozin and metformin hydrochloride. Each film-coated tablet contains 5 mg of dapagliflozin and 850 mg of metformin hydrochloride.
• Other ingredients:
• tablet core: microcrystalline cellulose (PH102); microcrystalline cellulose (PH101); mannitol; copovidone K28; colloidal silicon dioxide, anhydrous; magnesium stearate;
• tablet coating: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide yellow (E172), iron oxide red (E172).

Diaflix Combo, 5 mg + 1000 mg, film-coated tablets

• The active substances are dapagliflozin and metformin hydrochloride. Each film-coated tablet contains 5 mg of dapagliflozin and 1000 mg of metformin hydrochloride.
• Other ingredients:
• tablet core: microcrystalline cellulose (PH102); microcrystalline cellulose (PH101); mannitol; copovidone K28; colloidal silicon dioxide, anhydrous; magnesium stearate;
• tablet coating: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, iron oxide yellow (E172).

What Diaflix Combo looks like and contents of the pack
Diaflix Combo, 5 mg + 850 mg, film-coated tablets
Oval, biconvex, light orange film-coated tablets with "850" embossed on one side.
Tablet dimensions: length 20.2 mm ± 0.2 mm, width 10.0 mm ± 0.2 mm.

Diaflix Combo, 5 mg + 1000 mg, film-coated tablets
Oval, biconvex, yellow film-coated tablets with "1000" embossed on one side.
Tablet dimensions: length 21.5 mm ± 0.2 mm, width 10.6 mm ± 0.2 mm.

Diaflix Combo, 5 mg + 850 mg, film-coated tablets and Diaflix Combo, 5 mg + 1000 mg, film-coated tablets are available in aluminum/PVC/PCTFE blisters in cardboard boxes.
Pack sizes: 10, 14, 28, 30, 56, 60, 90, 120, 180 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. +48 22 364 61 01