Qtrilmet - patient leaflet, side effects, dosage

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) responsible for batch release

AstraZeneca AB

Gärtunavägen

SE-151 85 Södertälje

Sweden

AstraZeneca GmbH

Tinsdaler Weg 183 22880 Wedel Germany

The printed package leaflet of the medicinal product must state the name and address o manufacturer responsible for the release of the concerned batch.

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AN

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF AUTHORISATION

Periodic safety update reports (PSURs)

The requirements for submission of PSURs for th references dates (EURD list) provided for under A subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

Risk management pl

P)

An updated RMP should be submitted:

• At the request of the European Medicines Agency;
• Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets metformin hydrochloride/sa­xagliptin/dapa­gliflozin

Modified-release tablets

14 modified-release tablets

28 modified-release tablets

56 modified-release tablets

60 modified-release tablets

196 modified-release tablets

• 5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.

Oral use __

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

PVC/PCTFE/alu blister:

Do not store above 30°C.

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB SE-151 85 Södertälje Sweden

• 12. MARKETING AUTHORISATION NUMBER(S)

PVC/PCTFE/alu blister:

EU/1/19/1401/001 14 modified-release tablets

EU/1/19/1401/002 28 modified-release tablets

EU/1/19/1401/003 56 modified-release tablets

EU/1/19/1401/004 60 modified-release tablets

EU/1/19/1401/­005 196 modifi­ed-release tablets

EU/1/19/1401/006 14 modified-release tablets (calendar blister

EU/1/19/1401/007 28 modified-release tablets (calendar blis

EU/1/19/1401/008 56 modified-release tablets (calendar blis

EU/1/19/1401/­009 196 modifi­ed-release tablets (calenda

PA/alu/PVC/alu blister:

EU/1/19/1401/010 14 modified-release table

EU/1/19/1401/011 28 modified-release tabl

EU/1/19/1401/012 56 modified-release ta

EU/1/19/1401/013 60 modified-relea

EU/1/19/1401/­014 196 modifi­ed-r

• 14. GENER AL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Qtrilmet 850 mg/2.5 mg/5 mg

• 17. UNIQUE IDENTIFIER - 2D BARCODE 2D barcode carrying the unique identifier included.

  18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

  
  

  PC

  SN

  NN

  
  
  
  

BLISTERS 1. NAME OF THE MEDICINAL PRODUCT

Qtrilmet 850 mg/2.5 mg/5 mg tablets metformin HCl/saxagliptin/da­pagliflozin

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON

1. NAME OF THE MEDICINAL PRODUCT

Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets metformin hydrochloride/sa­xagliptin/dapa­gliflozin

Modified-release tablets

14 modified-release tablets

28 modified-release tablets

56 modified-release tablets

60 modified-release tablets

196 modified-release tablets

• 5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.

Oral use __

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

• 7. OTHER SPECIAL WARNING(S), IF NECESSARY

• 8. EXPIRY DATE

EXP

• 9. SPECIAL STORAGE CONDITIONS

PVC/PCTFE/alu blister:

Do not store above 30°C.

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

AstraZeneca AB SE-151 85 Södertälje Sweden

• 12. MARKETING AUTHORISATION NUMBER(S)

PVC/PCTFE/alu blister:

EU/1/19/1401/015 14 modified-release tablets

EU/1/19/1401/016 28 modified-release tablets

EU/1/19/1401/017 56 modified-release tablets

EU/1/19/1401/018 60 modified-release tablets

EU/1/19/1401/­019 196 modifi­ed-release tablets

EU/1/19/1401/020 14 modified-release tablets (calendar blister

EU/1/19/1401/021 28 modified-release tablets (calendar blis

EU/1/19/1401/022 56 modified-release tablets (calendar blis

EU/1/19/1401/­023 196 modifi­ed-release tablets (calenda

PA/alu/PVC/alu blister:

EU/1/19/1401/024 14 modified-release table

EU/1/19/1401/025 28 modified-release tabl

EU/1/19/1401/026 56 modified-release ta

EU/1/19/1401/027 60 modified-relea

EU/1/19/1401/­028 196 modifi­ed-r

• 14. GENER AL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Qtrilmet 1,000 mg/2.5 mg/5 mg

• 17. UNIQUE IDENTIFIER - 2D BARCODE 2D barcode carrying the unique identifier included.

  18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

  
  

  PC

  SN

  NN

  
  
  
  

BLISTERS 1. NAME OF THE MEDICINAL PRODUCT

Qtrilmet 1,000 mg/2.5 mg/5 mg tablets metformin HCl/saxagliptin/da­pagliflozin

Package leaflet: Information for the patient

Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets

Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets metformin hydrochloride/sa­xagliptin/dapa­gliflozin

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 further questions, ask your doctor, pharmacist or nurse.

This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What Qtrilmet is and what it is used for

What you need to know before you take Qtrilmet

How to take Qtrilmet

Possible side effects

How to store Qtrilmet

Contents of the pack and other information

What Qtrilmet is and what it is used for

Qtrilmet contains the active substances metformin, saxagliptin, and dapagliflozin. Each belongs to a group of medicines called “oral anti-diabetics”. This medicine is taken by mouth to treat diabetes and each of the active substances works in a

This medicine is for a type of diabete led “type 2 diabetes”. If you have type 2 diabetes, your pancreas does not make enough insul your body is not able to use the insulin it produces properly.

This leads to a high level of sugar (gle) in your blood. The three medicines in Qtrilmet lower the amount of sugar in the blood by causing it to be taken up into cells or passed out of the body in the urine.

Qtrilmet is only given tots aged 18 years and older. Itis used if other oral diabetes medicines, along with diet and exercise, cannot control your diabetes well enough. It is taken on its own, or it can be combined with a different type of diabetes medicine called a sulphonylurea.

hat you need to know before you take Qtrilmet

Do not take Qtrilmet:

• – if you are allergic to metformin, saxagliptin, dapagliflozin, or any of the other ingredients of this

medicine (listed in section 6);

if you have had a serious allergic reaction to some other medicines used to control your blood sugar, namely:

o ‘gliptins’ (or DPP-4 inhibitors) – like alogliptin, linagliptin and sitagliptin or,

o ‘gliflozins’ (or SGLT2 inhibitors) – like canagliflozin and empagliflozin;

if you have uncontrolled diabetes, with:

o severe hyperglycaemia (very high blood glucose),

o nausea, vomiting, diarrhoea, rapid weight loss,

o lactic acidosis (see “Risk of lactic acidosis” below),

o ketoacidosis, where substances called ‘ketone bodies’ build up in the blood and which can

lead to a diabetic pre-coma. Symptoms include stomach pain, fast and deep breathing, sleepiness, or your breath developing an unusual fruity smell;

• – if you have ever had a diabetic coma;

• – if you have severely reduced kidney function;

• – if you have a severe infection;

• – if you have lost a lot of water from your body (dehydration) – due to long-lasting or severe

diarrhoea, or if you have vomited several times in a row (see “Warnings and precautions” below);

• – if you have recently had a heart attack or if you have heart failure or serious problems with your

blood circulation or difficulties in breathing;

• – if you have problems with your liver;

• – if you drink large amounts of alcohol, either every day or only from time to time (please see

section “Qtrilmet with alcohol”).

Do not take Qtrilmet if any of the above apply to you. If you are not sure, talk to your doctor, pharmacist or nurse before taking Qtrilmet.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Qtrilmet, and during treatment:

• – if you experience vomiting, stomach ache (abdominal pain), muscle cramps, a general feeling of

not being well with severe tiredness, difficulty breathing, reduced body temperature or slow heartbeat. These may be symptoms ofa very rare, but very serious side effect called lactic acidosis which can occur with Qtrilmet, particularly if your kidneys are not working properly. The risk of lactic acidosis is also increased with uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake, dehydration (see further information below), liver problems, and medical conditions in which a part of the body has a reduced supply of oxygen (such as acute severe heart disease). Stop taking Qtrilmet and contact a doctor or go to the nearest hospital immediately if you experience symptoms of lactic acidosis , as this condition is a medical emergency that may lead to coma;

• – if you experience rapid weight loss, feeling sick or being sick, stomach pain, excessive thirst,

fast and deep breathing, confusion, unusual sleepiness or tiredness, a sweet smell to your breath, a sweet or metallic taste in your mouth, or a different odour to your urine or sweat. These may be symptoms of another rare, but very serious, sometimes life-threatening condition called diabetic ketoacidosis. With this condition, the levels of substances called “ketone bodies” increase in your urine or blood and this can be picked up in tests. The risk of developing diabetic ketoacidosis may be increased with prolonged fasting, excessive alcohol consumption, dehydration, sudden reductions in insulin dose, or major surgery or serious illness (which increase the body’s needs for insulin). Stop taking Qtrilmet and contact a doctor or go to the nearest hospital immediately if you experience some of the symptoms of diabetic ketoacidosis, as this condition is a medical emergency;

if you lose a lot of body fluids, such as with severe vomiting, diarrhoea, fever, nausea (feeling sick), increased sweating in heat, or if you are not able to eat or drink. Stop taking Qtrilmet for a short time if you have a condition that leads to dehydration and talk to your doctor about what to do and when to start taking Qtrilmet again;

if you have “type 1 diabetes”. Qtrilmet should not be used to treat this condition;

if you have or have had a disease of the pancreas;

if you have reduced kidney function or liver problems;

if your body’s ability to fight infections (immunity) is reduced, such as with a disease like AIDS or from medicines that you take after an organ transplant;

if you have ever had a serious hypersensitivity (allergic) reaction or your doctors have told you that you may have had one;

if you have or have had serious heart disease;

if you have risk factors for developing heart failure, such as problems with your kidneys. Your doctor will advise you of the signs and symptoms of heart failure. Symptoms can include shortness of breath, rapid increase in weight, and swelling of the ankles or feet (pedal oedema). Watch out for these symptoms and call your doctor, pharmacist, or nurse immediately if you get any of them;

if you have or have had low blood pressure (hypotension);

if you have very high levels of sugar in your blood which may make you dehydrated (lose too much body fluid). Possible signs of dehydration are listed in section 4. Tell your doctor before you start taking Qtrilmet if you have any of these signs;

if you often get infections of the urinary tract or have a serious infection of the urinary tract, including urosepsis or pyelonephritis, which can cause fever, chills, burning sensation when passing water (urinating), blood in urine, and pain in your back or side. You should call your doctor, pharmacist, or nurse immediately if you experience any of these symptoms;

if you have severe joint pain;

if you take pioglitazone to lower your blood sugar, Qtrilmet may not be recomm if you take any of the following medicines: glucocorticoids, beta-2 agonists, diur carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampici the effect of Qtrilmet (see “Other medicines and Qtrilmet”);

if you are 75 years old or older;

if blood tests show that the amount of red blood cells in your blood is too high.

If any of the above apply to you (or you are not sure), talk to yo taking Qtrilmet.

Surgery and operations

If you need major surgery, you must stop taking Qtrilmet during and for some time after the operation.

Your doctor will decide when to stop and when to

ommon complication of diabetes. Rash can occur with both ). Follow the recommendations for skin care from your

encounter blistering of the skin, as it may be a sign for a. Your doctor may ask you to stop Qtrilmet.

It is important to check your feet regularly – and follow the advice on foot care from your health care professional.

tely if you develop a combination of symptoms of pain, tenderness, enitals or the area between the genitals and the anus with fever or feeling ese symptoms could be a sign of a rare but serious or even life-threatening lled necrotising fasciitis of the perineum or Fournier’s gangrene which destroys the tissue in. Fournier’s gangrene has to be treated immediately.

Kidney function

You should have a blood test to check how well your kidneys are working before you start taking and while you are on this medicine. Your kidney function will be checked at least once every year or more frequently if you are elderly or if you have worsening kidney function.

Urine test

Because of how Qtrilmet works, your urine will test positive for sugar while you are on this medicine.

Children and adolescents

Qtrilmet is not recommended for children and adolescents under 18 years of age because it has not been studied in these patients.

Other medicines and Qtrilmet

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. In particular, talk to your doctor before taking Qtrilmet if you are taking any of the following medicines:

medicines to lower blood pressure including ACE inhibitors (such as enalapril or ramipril),

angiotensin II receptor antagonists (such as losartan or candesartan);

insulin, sulphonylureas (such as glimepiride) or pioglitazone to lower your blood sugar; medicines that increase urine production and lower blood pressure (diuretics). Your doctor may ask you to stop taking Qtrilmet. Possible signs of losing too much fluid from your body are listed in section 4;

medicines that may change the amount of metformin in your blood, especially if you have reduced kidney function (such as verapamil, dolutegravir, ranolazine, trimethoprime, vandetanib, isavuconazole, crizotinib or olaparib);

if you are using medicines containing any of the following active substances:

beta-2 agonists – used to treat asthma, carbamazepine, phenobarbital or phenytoin – medicines for preven some types of long-term pain, cimetidine – used to treat stomach problems, corticosteroids such as dexamethasone – used to treat asthma and arthritis, diltiazem – used to treat angina (chest pain) and lower blood pressure, ketoconazole tablets – used to treat Cushing’s syndrome (when the body produces an excess of cortisol),

rifampicin – an antibiotic used to treat infections as tuberculosis,

non-steroidal anti-inflammatory drugs (NSAI uch as ibuprofen and celecoxib (a ‘COX-2-inhibitor’) – used to treat pain and mation.

Driving and using machines

Qtrilmet is not expected to affect you being able to drive a car or use any tools or machines. However, if you feel dizzy while taking Qtrilmet, do not drive or use tools or machines. Also, it may be dangerous to drive or use machines if your blood sugar levels fall too low (hypoglycaemia), which can cause shaking, sweating, fast heartbeat, change in vision, headache and confusion.

Qtrilmet contains lactose

Qtrilmet contains lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Sodium content

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

3. How to take Qtrilmet

Always take this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

How much to take

Your doctor will prescribe an appropriate dose of Qtrilmet depending on your blood sugar diabetes medicines you were taking before. The recommended dose is two tablets once a d

Your doctor may prescribe other medicines to lower the amount of sugar in your blood. Remember to take other medicines as your doctor has told you. This will help get the best results for your health.

Diet and exercise

To control your diabetes need to follow your doctor’s advice on diet and exercise, even when you

are taking this medicine. In particular, if you are following a diabetic weight control diet, continue to follow it while you are taking Qtrilmet.

trilmet than you should more Qtrilmet tablets than you should, talk to a doctor or go to a hospital straight away. edicine pack with you. High overdose may lead to lactic acidosis (see sections 2 and 4).

If you forget to take Qtrilmet

What to do if you forget to take Qtrilmet on time.

• – If it is less than 12 hours since you should have taken your daily dose, take a dose of Qtrilmet as

soon as you remember. Then take your next dose at the usual time.

• – If it is more than 12 hours since you should have taken your daily dose, skip the missed dose.

Then take your next dose at the usual time.

• – Do not take a double dose of Qtrilmet to make up for a forgotten dose.

If you stop taking Qtrilmet

Do not stop taking Qtrilmet without talking to your doctor first. Your blood sugar may rise without this medicine.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some symptoms need immediate medical attention:

Stop taking Qtrilmet and see a doctor straight away if you notice any of the following serious side effects:

Serious allergic (hypersensitivity) reaction, seen rarely (may affect up to 1 in 1,000 Symptoms of serious allergic reaction:

rash,

raised red patches on your skin (hives),

swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing.

Your doctor may prescribe a medicine to treat your diabetes medicine.

Lactic acidosis, seen very rarely (may affect up to 1 in 10,000

Qtrilmet may cause a very rare, but very serious side effect called lactic acidosis.

Symptoms of lactic acidosis include:

vomiting,

stomach ache (abdominal pain),

muscle cramps,

general feeling of not being well with severe tiredness, difficulty in breathing,

reduced body temperature and slower heartbeat.

If this happens you must stop taking Qtrilmet and contact a doctor or the nearest hospital immediately, as lactic acidosis may lead to coma.

o increased levels of “ketone bodies” seen in your urine or blood tests,

o rapid weight loss,

o feeling sick or being sick,

o stomach pain,

o excessive thirst,

o fast and deep breathing,

o confusion,

o unusual sleepiness or tiredness,

o a sweet smell to your breath, a sweet or metallic taste in your mouth, or a different odour

to your urine or sweat.

This may occur regardless of blood glucose level. Your doctor may decide to temporarily or

permanently stop your treatment with Qtrilmet.

Stop taking Qtrilmet and see a doctor straight away, if you notice any of the serious side above.

Contact a doctor or the nearest hospital straight away if you have any o effects:

Necrotising fasciitis of the perineum or Fournier’s gan­grene, a serious soft tissue infection of the genitals or the area between the genitals and the anus, seen very rarely (see section 2 “Diabetic skin and foot problems”).

Contact your doctor as soon as possible if you have any of th

Low blood sugar levels (hypoglycaemia) , seen very com may affect more than 1 in

10 people) if used with other diabetes medicines which cause hypoglycaemia.

Signs of low blood sugar:

shaking, sweating, feeling very anxious, fast heartbeat,

feeling hungry, headache, change in vision,

a change in your mood or feeling confused.

Your doctor will tell you how to treat low blood sugar levels and what to do if you get any of the signs above.

Other side effects when taking

Very common

• – nausea, vomiting

• – diarrhoea or stomach ache

loss of appetite

upper respiratory tract infection including: o infection of the upper chest or lungs,

o ction of the sinuses with a feeling of pain and fullness behind your cheeks and eyes

nose or throat (nasopharyngitis) (signs of this may include a cold or a sore throat).

genital infection (thrush) of your penis or vagina (signs may include irritation, itching, unusual discharge or odour)

back pain

passing more water (urine) than usual or needing to pass water more often

dizziness

tiredness

severe joint pain (arthralgia)

stomach ache and indigestion (dyspepsia)

vomiting, inflammation of the stomach (gastritis)

inflamed stomach or gut usually caused by an infection (gastroenteritis)

headache, muscle pain (myalgia)

changes in blood tests (changes in the amount of cholesterol or fats in your blood, increases in the amount of red blood cells in your blood or decreases in creatinine renal clearance)

rash

changes in taste

swelling of the hands, ankles or feet (peripheral oedema)

Uncommon

– thirst

constipation

awakening from sleep at night to pass urine

dry mouth

weight decrease

decrease in kidney function, increases in creatinine or urea (shown in blood tests)

skin rash that may include raised bumps, skin irritation, or itchiness

difficulties in getting or maintaining an erection (erectile dysfunction)

fungal infection

mild allergic (hypersensitivity) reaction (rash)

itching in the genital area (genital pruritus or vulvovaginal pruritus) or discomfort while urinating

Very rare

• – decreased vitamin B12 levels in the blood

• – abnormalities in liver function tests, inflammation of the liver (hepatitis)

• – redness of the skin (erythema), itching, or an itchy rash (hives)

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

• – blistering of the skin (bullous pemphigoid)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By repde effects, you can help provide more information on the safety of this medicine.

5. How to store

Keep this medicine out of the sight and reach of children.

Do not use this ine after the expiry date, which is stated on the blister and carton after ‘EXP’.

The expiry rs to the last day of that month.

alu blister: e above 30°C.

PA/alu/PVC/alu blister:

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6. Contents of the pack and other information

What Qtrilmet contains

• – The active substances are metformin, saxagliptin and dapagliflozin.

What Qtrilmet looks like and contents of the pack

Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets are beige with 3005 debossed on one side.

Qtrilmet 850 mg/2.5 mg/5 mg modified-release tablets and Qtrilmet 1,000 mg/2.5 mg/5 mg modified-release tablets are available in blister. The pack sizes are 14, 28, 56 and 196 modified-release

tablets in calendar blisters and 14, 28, 56, 6

Marketing Authorisation H

AstraZeneca AB SE-151 85 Södertälje Sweden

AstraZeneca GmbH Tinsdaler Weg 183 22880 Wedel Germany

Ísland

Vistor hf.

Sími: +354 535 7000

Slovenská republika AstraZeneca AB, o.z.

Tel: +421 2 5737 7777

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AstraZeneca Oy

Puh/Tel: +358 10 23 010

Latvija

SIA AstraZeneca Latvija

Tel: +371 67377100

United Kingdom

AstraZeneca UK Ltd

Tel: +44 1582 836 836

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