Dagraduo

Package leaflet: Information for the patient

Dagraduo, 100 mg + 10 mg, film-coated tablets
Sitagliptinum + Dapagliflozinum
Please read this leaflet carefully before using this medicine, as it contains
important information for you.

• 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. It 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.

Leaflet contents

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

1. What Dagraduo is and what it is used for

Dagraduo contains the active substances dapagliflozin and sitagliptin. Each of these belongs to a group of medicines called oral antidiabetic drugs.
Dapagliflozin belongs to a group of medicines known as sodium-glucose cotransporter 2 (SGLT2) inhibitors. These work by blocking the SGLT2 protein in the kidneys. By blocking this protein, sugar in the blood (glucose), salt (sodium), and water are removed from the body through urine.
Sitagliptin belongs to a class of drugs called DPP-4 inhibitors (dipeptidyl peptidase-4 inhibitors), which reduce blood sugar levels in adults with type 2 diabetes.
Type 2 diabetes is a condition in which the body does not produce enough insulin, and the insulin that is produced does not work as effectively as it should. This leads to elevated blood sugar levels, which can cause serious health problems.
The two active substances in Dagraduo work in different ways to help control blood sugar levels and remove excess sugar from the body via the urine.
Dagraduo is used in the treatment of type 2 diabetes in adults as an adjunct to diet and exercise, as replacement therapy in patients already treated with dapagliflozin and sitagliptin as separate tablets. Your doctor may recommend switching to this medicine.
It is important that while taking this medicine, you continue to follow the dietary and physical activity advice given by your doctor, pharmacist, or nurse.

2. Important information before using Dagraduo

When not to use Dagraduo

• if the patient is allergic to dapagliflozin, sitagliptin, or any of the other ingredients of this medicine (listed in section 6), or if the patient has ever experienced a severe allergic reaction to another medicine belonging to the group of DPP-4 inhibitors.

Warnings and precautions
Before starting treatment with Dagraduo and during therapy, discuss the following with your
doctor, pharmacist, or nurse:

• if the patient has kidney disease – the doctor may recommend using an additional or different medicine to control blood glucose levels.
• if the patient currently has or has previously had a disease of the pancreas called pancreatitis. Possible symptoms of pancreatitis are listed in section 4.
• if the patient is taking blood pressure-lowering medicines (antihypertensives) and has a history of low blood pressure (hypotension). More information is provided below under "Dagraduo with other medicines".
• if the patient currently has very high blood glucose levels, leading to dehydration (excessive fluid loss). Possible symptoms of excessive fluid loss are listed in section 4. Inform the doctor if any of these symptoms have occurred before starting Dagraduo.
• if the patient experiences nausea, vomiting, or fever, or is unable to eat or drink. This may lead to dehydration. The doctor may advise temporarily discontinuing Dagraduo until the patient's condition improves, to prevent dehydration.
• if the patient has moderate or severe liver impairment.
• 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 smell of urine or sweat, seek immediate medical attention from a doctor or the nearest hospital. These symptoms may indicate "diabetic ketoacidosis" – a rare but serious, sometimes life-threatening complication of diabetes caused by increased levels of "ketone bodies" in 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. Diabetic ketoacidosis may occur even when blood glucose levels are within the normal range.
• if the patient has type 1 diabetes, in which the body does not produce insulin. Dagraduo must not be used to treat this condition.
• if the patient currently has or has previously experienced, or has suspected (or previously suspected) a severe hypersensitivity reaction (allergy). Symptoms of severe allergic reactions are listed in section 4.
• if the patient frequently experiences urinary tract infections.
• if the patient has a history of severe heart disease.
• if the patient has heart failure or risk factors for developing heart failure, such as kidney disease. The doctor will inform the patient about the symptoms of heart failure. These may include, but are not limited to, worsening shortness of breath, rapid weight gain, and swelling around the ankles. Any of these symptoms should be reported immediately to the doctor, pharmacist, or nurse.
• if the patient experiences severe joint pain.
• if the body's ability to fight infections is reduced, for example, due to a condition such as AIDS or following organ transplantation.
• if the patient is taking a medicine that lowers blood glucose, such as a sulfonylurea (see "Dagraduo with other medicines").

If any of these warnings apply to the patient (or if the patient is unsure), consult a
doctor, pharmacist, or nurse before using Dagraduo.
Diabetic skin complications (skin damage, such as ulcers) are common complications
of diabetes. Skin rashes have been observed during treatment with both sitagliptin and dapagliflozin
when administered separately (see section 4). Follow the skin care advice provided by the
doctor or nurse. Contact the doctor immediately if blisters appear on the skin, as this may be a sign of a condition called bullous pemphigoid. The doctor may recommend discontinuing Dagraduo. For all patients with diabetes, it is important to regularly check the condition of the feet and to follow all foot care advice given by the doctor.
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 immediate medical attention.
These may be symptoms of a rare but serious or even life-threatening infection called necrotizing fasciitis of the perineum, also known as Fournier's gangrene, which leads to damage of subcutaneous tissue. Immediate treatment of Fournier's gangrene is essential.
Due to the mechanism of action of Dagraduo, laboratory tests will show the presence of glucose in the urine during treatment.

Children and adolescents
Dagraduo must not be used in children and adolescents under 18 years of age, as studies have not been conducted in this age group.

Dagraduo with other medicines
Inform your doctor or pharmacist about all medicines currently used, recently taken, or planned for use.
In particular, inform the doctor:

• if the patient is taking medicines that help remove water from the body (diuretics).
• if the patient is taking other medicines that lower blood glucose, such as insulin or a sulfonylurea. The doctor may recommend reducing the dose of other medicines to prevent low blood glucose (hypoglycaemia).
• if the patient is taking lithium, as dapagliflozin may reduce lithium levels in the blood.
• if the patient is taking digoxin (a medicine used to treat heart rhythm disorders and other heart conditions). When taking sitagliptin and digoxin together, digoxin blood levels should be monitored.

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.
This medicine must not be used during pregnancy. Consult the doctor to determine the best way to manage blood glucose control during pregnancy.
Dagraduo must not be used during breastfeeding. It is not known whether the medicine passes into human milk. If the patient is breastfeeding or intends to breastfeed, she should inform the doctor before starting Dagraduo.

Driving and operating machinery
Dagraduo has no effect or a negligible effect on the ability to drive and operate machinery. However, bear in mind that dizziness and drowsiness have been reported. Using this medicine together with other medicines such as sulfonylureas or insulin may cause excessively low blood glucose (hypoglycaemia), manifesting as muscle tremors, excessive sweating, and visual disturbances, which may affect the ability to drive and operate machinery.

3. How to use Dagraduo

This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your doctor, pharmacist, or nurse.
What dose to take

• The recommended dose is one tablet once daily.

How to take the medicine

• Swallow the tablet whole with half a glass of water.
• The tablets may be taken during or between meals.
• The tablet may be taken at any time of day. However, it is advisable to take it at approximately the same time each day to help remember to take it.

Your doctor may recommend taking Dagraduo together with other medicines that lower blood sugar levels. It is important to take these medicines exactly as directed by your doctor. This will help achieve the best possible treatment results.
Diet and physical exercise may help your body use blood sugar more effectively. For patients with diabetes, it is important to follow all dietary and exercise recommendations provided by the treating doctor while taking Dagraduo.
Taking more Dagraduo than recommended
If you take more Dagraduo than recommended, contact your doctor immediately or go to the nearest hospital. Take the medicine packaging with you.
If you forget to take Dagraduo
The action to take if a dose is missed depends on the time remaining until the next dose.

• If 12 hours or more remain before the next dose is due, take Dagraduo as soon as you remember. Then take the next dose at the usual time.
• If less than 12 hours remain before the next dose is due, skip the missed dose. Take the next dose at the usual time.
• Do not take a double dose of Dagraduo to make up for a missed dose.

Stopping Dagraduo
Do not stop taking Dagraduo without consulting your doctor. In patients with diabetes, blood sugar levels may increase 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 may cause adverse reactions, although not everyone will experience them.
You should consult a doctor immediately if the patient experiences any of the
following adverse reactions:

• Symptoms of a severe allergic reaction (anaphylactic reaction, angioedema), observed rarely (may affect up to 1 in 1,000 people), which may include:
• rash,
• raised red skin patches (urticaria),
• skin blistering or peeling,
• swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing.

The doctor may prescribe a medicine to treat the allergic reaction and another medicine to treat
diabetes.

• Pancreatitis (frequency unknown): severe and prolonged abdominal pain (in the stomach area), which may radiate to the back, as well as nausea and vomiting, which may be signs of inflammation of the pancreas.
• Urinary tract infections, observed frequently (may affect up to 1 in 10 people). Symptoms of a severe urinary tract infection include:
• fever and (or) chills,
• burning sensation during urination,
• back or side pain.

Blood in the urine may occur not very frequently; if this occurs, immediate consultation with a doctor is required.

• Diabetic ketoacidosis, observed rarely (may occur in no more than 1 in 1,000 people). Symptoms of ketoacidosis include:
• increased concentration of "ketone bodies" in urine or blood,
• rapid weight loss,
• nausea or vomiting,
• abdominal pain,
• intense thirst,
• rapid and deep breathing,
• confusion,
• unusual drowsiness or fatigue,
• sweet breath odor, sweet or metallic taste in the mouth, or change in the odor of urine or sweat.

It may occur regardless of blood sugar levels. The doctor may decide to suspend or discontinue treatment with Dagraduo.

• 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 (may affect up to 1 in 10,000 people).

Treatment with Dagraduo should be discontinued and immediate medical advice sought if the patient experiences any of the above adverse reactions.
You should consult a doctor immediately if the patient experiences any of the
following adverse reactions:

• Low blood sugar (hypoglycaemia), observed very commonly (may occur in more than 1 in 10 people), when this medicine is used with other antidiabetic medicines causing hypoglycaemia. 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 how to treat low blood sugar and what to do if any of the above adverse reactions occur.
Other adverse reactions during treatment with this medicine:
Frequent (may affect up to 1 in 10 people):

• fungal infections of the penis or vagina (e.g. irritation, itching, unusual discharge or unpleasant odour),
• dizziness,
• headache,
• rash,
• back pain,
• excessive urination or increased need to urinate,
• increase in red blood cell count (detected in laboratory tests),
• decreased renal creatinine clearance (detected in laboratory tests) at the beginning of treatment,
• changes in cholesterol or fat levels in the blood (detected in laboratory tests).

Not very common (may affect up to 1 in 100 people):

• fungal infections,
• 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, or rapid heartbeat),
• thirst,
• constipation,
• dry mouth,
• skin rash which may appear as raised lumps, skin irritation or unpleasant skin itching,
• getting up at night to pass urine,
• itching in the genital area (genital itching, vulvar and vaginal itching) or discomfort during urination,
• increased creatinine concentration (detected in blood laboratory tests) at the beginning of treatment,
• increased urea concentration (detected in blood laboratory tests),
• weight loss.

Rare (may affect up to 1 in 1,000 people):

• decreased number of platelets (thrombocytopenia).

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

• kidney inflammation (tubulointerstitial nephritis).

Unknown (frequency cannot be estimated from available data):

• conditions causing lung inflammation and scarring (interstitial lung disease),
• vomiting,
• skin vasculitis,
• bullous pemphigoid (a type of blistering skin condition),
• muscle pain and myalgia,
• joint disorders (arthropathy), including joint stiffness (arthralgia),
• worsening of kidney function (including kidney dysfunction and acute kidney failure).

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed
in this leaflet, you should inform your 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 authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Dagraduo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and the outer carton
after 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 storage temperature requirements for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Dagraduo contains

• The active substances are sitagliptin and dapagliflozin. Each coated tablet contains 100 mg sitagliptin (as sitagliptin phosphate monohydrate) and 10 mg dapagliflozin (as dapagliflozin propanediol monohydrate).
• Other ingredients are:
• tablet core: microcrystalline cellulose, mannitol, hydroxypropylcellulose, crospovidone (type A), colloidal anhydrous silica, and magnesium stearate.
• tablet coating: polyvinyl alcohol, macrogol 3350, titanium dioxide (E 171), talc, iron oxide yellow (E 172).

What Dagraduo looks like and contents of the pack
Brownish-yellow, oval, biconvex, coated tablets. The tablet diameter is approximately 15 x 7 mm.
Dagraduo is available in packs containing:

• 10, 14, 28, 30, 56, 60, 84, 90, 98, 100 coated tablets in blister packs in a cardboard carton.
• 14, 28, 56, 84 or 98 coated tablets in calendar blister packs in a cardboard carton.
• 10 x 1, 14 x 1, 28 x 1, 30 x 1, 56 x 1, 60 x 1, 84 x 1, 90 x 1, 98 x 1 or 100 x 1 coated tablet in perforated single-dose blisters in a cardboard carton.
• 14 x 1, 28 x 1, 56 x 1, 84 x 1 or 98 x 1 coated tablet in perforated single-dose calendar blister packs in a cardboard carton.

Not all pack sizes may be marketed.
Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann - Straße 5, 27472 Cuxhaven, Germany
This medicinal product is authorised in the European Economic Area countries under the following names:

For more detailed information about this medicinal product, please contact the local representative of the marketing authorization holder:
KRKA-POLSKA Sp. z o.o.
Równoległa 5 Street
02-235 Warsaw
Tel. 22 57 37 500