Qtern

Patient Information Leaflet

Qtern 5 mg/10 mg film-coated tablets

saxagliptin/dapagliflozin
Please read all of this leaflet carefully before you start taking this medicine, as 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.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What is Qtern and what is it used for?

Qtern contains the active substances saxagliptin and dapagliflozin. Both belong to a class of
medicinal products called "oral antidiabetics". These medicines are taken orally for diabetes.
Qtern is used for a type of diabetes called "type 2 diabetes mellitus" in adult patients (aged 18 years and older). If you have type 2 diabetes, your pancreas does not produce enough insulin or your body cannot properly use the insulin it produces. This leads to high blood sugar levels.
The two active substances in Qtern work through different mechanisms that help control blood sugar levels and remove excess sugar from the body through the urine.
Qtern is used to treat type 2 diabetes when:

• saxagliptin or dapagliflozin alone, together with metformin and/or a sulphonylurea, cannot control diabetes.
• you are already being treated with saxagliptin and dapagliflozin as separate tablets. Your doctor may ask you to switch to this medicine.

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

2. What you should know before taking Qtern

Do not take Qtern:

• if you are allergic to saxagliptin, dapagliflozin, or any of the other ingredients of this medicine (listed in section 6).
• if you have previously had a severe allergic reaction to any similar medicine (for example, a DPP-4 inhibitor such as sitagliptin, linagliptin, alogliptin, or an SGLT2 inhibitor such as canagliflozin, empagliflozin) that you take to control blood sugar.

If any of the above conditions apply to you, do not take Qtern. If you are unsure, speak with your doctor,
pharmacist, or nurse before taking this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before starting Qtern and during treatment:

• if you have or have had a pancreatic disease called pancreatitis. Possible signs of pancreatitis are listed in section 4.
• if you are taking medicines to lower blood pressure (antihypertensives) and have previously experienced low blood pressure (hypotension). For further information, see the section “Other medicines and Qtern” below.
• if you have very high blood sugar levels that could dehydrate you (excessive loss of body fluids). Possible signs of dehydration are listed in section 4. Inform your doctor before starting Qtern if you have any of these signs.
• if you have, or develop, nausea (feeling sick), vomiting, or fever, or if you are unable to eat or drink. These conditions may lead to dehydration. Your doctor may ask you to stop taking Qtern until you recover to prevent dehydration.
• if you have moderate or severe liver problems.
• if you experience rapid weight loss, nausea or vomiting, stomach pain, excessive thirst, rapid and deep breathing, confusion, drowsiness, unusual tiredness, sweet-smelling breath, sweet or metallic taste in the mouth, or a different smell in urine or sweat, contact your doctor or the nearest hospital immediately. These symptoms may indicate “diabetic ketoacidosis”—a rare but serious, potentially life-threatening condition that can occur in diabetes due to increased levels of “ketone bodies” in the blood or urine, 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 need due to major surgery or serious illness.
• if you have "type 1 diabetes", in which your body does not produce insulin. Qtern must not be used to treat this condition.
• if you have had, have, or suspect you may have severe hypersensitivity (allergic) reactions. Signs of a severe allergic reaction are listed in section 4.
• if you frequently get urinary tract infections.
• if you have previously had a serious heart condition.
• if you have heart failure or other risk factors for developing heart failure, such as kidney problems. Your doctor will inform you about the signs and symptoms of heart failure. Symptoms may include, among others, increasing shortness of breath, rapid weight gain, and swelling of the feet (pedal edema). Contact your doctor, pharmacist, or nurse immediately if you notice any of these symptoms.
• if you suffer from severe joint pain.
• if you have a condition that reduces your body’s ability to fight infections, such as AIDS, or if you have had an organ transplant.
• if you are taking a medicine to lower blood sugar, for example, sulfonylureas (see “Other medicines and Qtern”).

If any of the above conditions apply to you (or if you are unsure), speak with your doctor, pharmacist,
or nurse before taking Qtern.
Skin lesions (skin damage such as sores or ulcers) are a common complication of diabetes. Skin rash has been observed with both saxagliptin and dapagliflozin when administered separately (see section 4). We recommend that you follow the skin care advice provided by your doctor or nurse.
Contact your doctor immediately if blisters appear on your skin, as this could be a sign of a condition called bullous pemphigoid. Your doctor may ask you to stop taking Qtern.
As with all diabetic patients, it is important to regularly check your feet and follow any foot care advice given by healthcare professionals.
Immediately inform your doctor 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, accompanied by fever or a general feeling of being unwell. These symptoms could 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 requires immediate treatment.
Kidney function
Your kidneys should be checked before starting Qtern. During treatment with this medicine, your doctor will monitor your kidney function at least once a year, or more frequently if you have worsening kidney function.
Urine tests
Due to the mechanism of action of Qtern, urine tests will show the presence of sugar during treatment with this medicine.
Children and adolescents
Qtern is not recommended for children and adolescents under 18 years of age, as it has not been studied in these patients.
Other medicines and Qtern
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor:

• if you are taking a medicine to increase the amount of water eliminated from the body (diuretics).
• if you are taking another medicine that lowers blood sugar, such as a sulfonylurea (e.g., glimepiride). Your doctor may want to reduce the dose of this other medicine to avoid low blood sugar levels (hypoglycaemia).
• if you are taking lithium, because Qtern may reduce the amount of lithium in your blood.
• if you are taking medicines containing any of the following active substances, as they may affect how Qtern is distributed in your body. Your doctor may ask you to monitor your blood sugar levels more frequently while taking these medicines:
• Carbamazepine, phenobarbital, or phenytoin. These medicines may be taken to control epileptic seizures or chronic pain.
• Desamethasone – a steroid medicine. This medicine may be used to treat inflammation in different organs and body parts.
• Rifampicin. This is an antibiotic used to treat infections such as tuberculosis.
• Ketoconazole. This medicine may be used to treat fungal infections.
• Diltiazem. This medicine is used to treat angina (chest pain) and to lower blood pressure. If any of the above conditions apply to you (or if you are unsure), speak with your doctor, pharmacist, or nurse before taking Qtern.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine. Qtern is not recommended during pregnancy, and your doctor will ask you to stop taking this medicine if you become pregnant. Ask your doctor how best to control your blood sugar during pregnancy.
You must not use Qtern if you are breastfeeding. It is not known whether this medicine passes into breast milk. Inform your doctor if you intend to breastfeed or are currently breastfeeding before taking this medicine.
Driving and using machines
Qtern is not expected to affect your ability to drive or use tools or machines. However, if you feel dizzy when taking this medicine, you should not drive or use tools or machines. Taking this medicine together with another medicine that lowers blood sugar, such as a sulfonylurea, may cause blood sugar to drop too low (hypoglycaemia).
This may cause symptoms such as trembling, sweating, and vision disturbances, and may impair your ability to drive or use machinery.
Qtern contains lactose
Qtern contains lactose (milk sugar). If your doctor has diagnosed you with an intolerance to certain sugars, consult your doctor before taking this medicine.
Qtern contains sodium
Qtern contains less than 1 mmol of sodium (23 mg) per dose, i.e., essentially “sodium-free”.

3. How to take Qtern

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor, pharmacist or nurse.
How much to take

• The recommended dose is one tablet daily.

How to take this medicine

• Swallow the tablet whole with half a glass of water.
• You may take the tablet with or without food.
• You may take the tablet at any time of day. However, try to take the tablet at the same time each day. This will help you remember to take it.

Your doctor may prescribe other medicines to reduce blood sugar levels. Remember to take these other medicines as directed by your doctor. This will help you achieve the best health outcomes.
Diet and exercise
To control diabetes, diet and exercise are still necessary even while taking this medicine. It is therefore important to follow your doctor's, pharmacist's or nurse's advice regarding diet and physical activity. In particular, if you are already following a diabetic diet or a diet for weight control, continue it while taking Qtern.
If you take more Qtern than you should
If you take more Qtern tablets than prescribed, contact your doctor immediately or go to hospital straight away. Take the medicine pack with you.
If you forget to take Qtern
What to do if you forget to take a tablet.

• If less than 12 hours have passed since you should have taken your dose, take a dose of Qtern as soon as you remember. Then take your next dose at the usual time.
• If more than 12 hours have passed since you should have taken your dose, skip the missed dose. Then take your next dose at the usual time.
• Do not take a double dose of Qtern to make up for a forgotten dose.

If you stop taking Qtern
Do not stop taking Qtern 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 everyone gets them.
Stop taking Qtern and contact a doctor immediately if you experience any of the following serious
side effects:

• Symptoms of a severe allergic reaction (anaphylactic reaction, angioedema), which are rare (may affect up to 1 in 1,000 people), and may include:
• rash
• raised red spots on the skin (urticaria)
• swelling of the face, lips, tongue, and throat, which may cause difficulty breathing or swallowing. Your doctor may prescribe a medicine to treat the allergic reaction and a different medicine for diabetes.
• Pancreatitis, uncommon (may affect up to 1 in 100 people): severe and persistent pain in the abdomen (stomach area), possibly radiating to the back, along with nausea and vomiting, as these may be signs of inflammation of the pancreas.
• Urinary tract infection, common (may affect up to 1 in 10 people). These are symptoms of a severe urinary tract infection:
• fever and/or chills
• burning sensation when urinating
• pain in the back or side. Although uncommon, if you notice blood in your urine, contact your doctor immediately.
• Low blood sugar levels (hypoglycaemia), very common (may affect more than 1 in 10 people), when used in combination with other antidiabetic medicines known to cause hypoglycaemia. These are symptoms of low blood sugar:
• trembling, sweating, strong feeling of anxiety, rapid heartbeat
• feeling hungry, headache, blurred vision
• 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.
• Diabetic ketoacidosis, which is rare. These are symptoms of diabetic ketoacidosis (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
• fast and deep breathing
• confusion
• unusual drowsiness or tiredness
• sweet odour of breath, sweet or metallic taste in the mouth, or a different odour of urine or sweat. This may occur regardless of blood glucose levels. Your doctor may decide to temporarily or permanently discontinue treatment with Qtern.
• Necrotising 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, which is very rare (may affect up to 1 in 10,000 people).

If you notice any of the serious side effects listed above, stop taking Qtern and contact your doctor or nurse immediately.
Other side effects when taking Qtern alone or in combination with metformin:
Very common

• upper respiratory tract infection including:
• infection of the upper chest or lungs,
• sinus infection with a feeling of pain and fullness behind the cheeks and eyes (sinusitis),
• inflamed nose or throat (nasopharyngitis) (signs may include cold symptoms or sore throat).

Common

• genital infections (candidiasis) of the penis or vagina (signs may include irritation, itching, abnormal discharge, or unusual odour)
• back pain
• increased amount of urine or increased urge to urinate more frequently
• changes in cholesterol or blood fat levels (confirmed by blood tests)
• increase in haematocrit (the percentage of blood volume occupied by blood cells) (confirmed by blood tests)
• decrease in creatinine renal clearance (confirmed by blood tests) at the beginning of treatment
• dizziness
• fatigue
• severe joint pain (arthralgia)
• stomach ache and indigestion (dyspepsia)
• nausea
• diarrhoea
• inflammation of the stomach or intestine, usually caused by infection (gastroenteritis)
• headache, muscle pain (myalgia)
• vomiting, inflammation of the stomach (gastritis)
• rash.

Uncommon

• excessive loss of body fluids (dehydration, signs may include very dry or sticky mouth, reduced or no urine output, or rapid heartbeat)
• thirst
• constipation
• waking up during the night to urinate
• dry mouth
• weight loss
• increases in creatinine (confirmed by blood tests) at the beginning of treatment
• increases in urea (confirmed by blood tests)
• rash which may include swelling, skin irritation, or troublesome itching
• difficulty in getting or maintaining an erection (erectile dysfunction)
• fungal infection
• hypersensitivity reactions
• itching in the genital area (genital or vulvovaginal pruritus) or discomfort when urinating.

Very rare

• inflammation of the kidneys (tubulo-interstitial nephritis).

Not known (frequency cannot be estimated from the available data)

• blisters on the skin (bullous pemphigoid).

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system referred to in Annex V. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Qtern

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 carton after
"Exp./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 Qtern contains

• The active substances are saxagliptin and dapagliflozin. Each tablet contains saxagliptin hydrochloride equivalent to 5 mg of saxagliptin and dapagliflozin monopropanediol monohydrate equivalent to 10 mg of dapagliflozin.
• The other components are:
• tablet core: microcrystalline cellulose (E460i), sodium croscarmellose (E468) (see section 2 “Qtern contains sodium”), lactose (see section 2 “Qtern contains lactose”), magnesium stearate (E470b), colloidal anhydrous silica (E551).
• film coating: polyvinyl alcohol (E1203), macrogol (3350) (E1521), titanium dioxide (E171), talc (E553b), yellow iron oxide (E172), red iron oxide (E172).
• printing ink: shellac, indigo carmine aluminium lake (E132).

Description of the appearance of Qtern and pack contents
Qtern 5 mg/10 mg film-coated tablets are film-coated tablets ranging in colour from light brown to brown, biconvex, round, 0.8 cm in diameter, with “5/10” printed on one side and “1122” printed on the other side in blue ink.
Qtern 5 mg/10 mg tablets are available in aluminium blisters in packs of 14, 28, or 98 film-coated tablets in calendar blisters and 30 film-coated tablets in blisters.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
AstraZeneca AB
SE-151 85 Södertälje
Sweden

Manufacturer
AstraZeneca AB
Gärtunavägen
SE-152 57 Södertälje
Sweden

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation 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 4455000 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
AstraZeneca Farmacéutica Spain, S.A. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +34 91 301 91 00 Tel.: +48 22 245 73 00

France Portugal
AstraZeneca AstraZeneca Produtos Farmacêuticos, Lda.
Tél: +33 1 41 29 40 00 Tel: +351 21 434 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 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
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://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 evaluation by the Pharmacovigilance Risk Assessment Committee (PRAC) of the Periodic Safety Update Reports (PSURs) for saxagliptin/dapagliflozin, the PRAC's scientific conclusions are as follows:
Based on the available data on polycythaemia from the literature and spontaneous reports for dapagliflozin, and considering a plausible mechanism of action, the PRAC considers there is sufficient evidence to justify a causal relationship between the use of saxagliptin/dapagliflozin and an increase in haematocrit. The PRAC concluded that the product information for medicinal products containing saxagliptin/dapagliflozin should therefore be amended accordingly.
Having reviewed the PRAC's recommendation, the Committee for Human Medicinal Products (CHMP) agrees with the general conclusions and the rationale of the recommendation.

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