Glubrava - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Glubrava 15 mg/850 mg film-coated tablets pioglitazone/met­formin hydrochloride

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 or pharmacist.

• – 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 is in this leaflet:

• 1. What Glubrava is and what it is used for

• 2. What you need to know before you take Glubrava

• 3. How to take Glubrava

• 4. Possible side effects

• 5 How to store Glubrava

• 6. Contents of the pack and other information

1. What Glubrava is and what it is used for

Glubrava contains pioglitazone and metformin which are anti-diabetic medicines, used to control blood sugar level.

It is used in adults to treat type 2 (non-insulin dependent) diabetes mellitus when treatment with metformin alone is not sufficient. This type 2 diabetes usually develops in adulthood particularly as a result of the person being overweight and where the body either does not produce enough insulin (a hormone that controls blood sugar levels), or cannot effectively use the insulin it produces.

Glubrava helps control the level of sugar in your blood when you have type 2 diabetes by helping your body make better use of the insulin it produces. If 3 to 6 months after starting Glubrava your sugar control is not improved, the medicine should be discontinued.

2. What you need to know before you take Glubrava

Do not take Glubrava

• – if you are allergic to pioglitazone, metformin or any of the other ingredients of this medicine (listed in section 6).

• – if you have heart failure or have had heart failure in the past.

• – if you recently had a heart attack, have severe circulatory problems including shock, or breathing difficulties.

• – if you have liver disease.

• – if you drink alcohol excessively (either every day or only from time to time).

• – if you have uncontrolled diabetes with, for example, severe hyperglycaemia (high blood

glucose), nausea, vomiting, diarrhoea, rapid weight loss, lactic acidosis (see section “Risk of lactic acidosis”) or ketoacidosis. Ketoacidosis is a condition in which substances called ‚ketone bodies‘ accumulate in the blood and which can lead to diabetic pre-coma. Symptoms include stomach pain, fast and deep breathing, sleepiness or your breath developing an unusual fruity smell.

• – if you have or have ever had bladder cancer.

• – if you have blood in your urine that your doctor has not checked.

• – if you have severely reduced kidney function.

• – if you have a severe infection or are dehydrated.

• – if you are going to have a certain type of X-ray with an injectable dye, talk to your doctor as you must stop taking Glubrava for a certain period of time before and after the examination.

• – if you are breast-feeding.

Warnings and precautions

Talk to your doctor or pharmacist before taking Glubrava (also see section 4)

• – if you have a problem with your heart. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin together experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

• – if you retain water (fluid retention) or have heart failure problems in particular if you are over 75 years old. If you take anti-inflammatory medicines which can also cause fluid retention and swelling, you must also tell your doctor.

• – if you have a special type of diabetic eye disease called macular oedema (swelling of the back of the eye), talk to your doctor if you notice any change to your vision.

• – if you have cysts on your ovaries (polycystic ovary syndrome). There may be an increased possibility of becoming pregnant because you may ovulate again when you take Glubrava. If this applies to you, use appropriate contraception to avoid the possibility of an unplanned pregnancy.

• – if you have a problem with your liver. Before you start taking Glubrava you will have a blood sample taken to check your liver function. This check should be repeated at intervals. Inform your doctor as soon as possible if you develop symptoms suggesting a problem with your liver (like feeling sick without explanations, vomiting, stomach ache, tiredness, loss of appetite and/or dark urine) as your liver function should be checked.

You may also experience a reduction in blood count (anaemia).

Your doctor may take blood tests to monitor your blood cell levels and liver function.

Risk of lactic acidosis

Glubrava may cause a very rare, but very serious side effect called lactic acidosis, particularly if your kidneys are not working properly. The risk of developing lactic acidosis is also increased with uncontrolled diabetes, serious infections, prolonged fasting or alcohol intake, dehydration (see further information below), liver problems and any medical conditions in which a part of the body has a reduced supply of oxygen (such as acute severe heart disease).

If any of the above apply to you, talk to your doctor for further instructions.

Stop taking Glubrava for a short time if you have a condition that may be associated with dehydration (significant loss of body fluids) such as severe vomiting, diarrhoea, fever, exposure to heat or if you drink less fluid than normal. Talk to your doctor for further instructions.

Stop taking Glubrava and contact a doctor or the nearest hospital immediately if you experience some of the symptoms of lactic acidosis , as this condition may lead to coma.

Symptoms of lactic acidosis include:

• – vomiting

• – stomach ache (abdominal pain)

• – muscle cramps

• – a general feeling of not being well with severe tiredness

• – difficulty in breathing

• – reduced body temperature and heartbeat

Lactic acidosis is a medical emergency and must be treated in a hospital.

During treatment with Glubrava, your doctor will check your kidney function at least once a year or more frequently if you are elderly and/or if you have worsening kidney function.

If you need to have major surgery you must stop taking Glubrava during and for some time after the procedure. Your doctor will decide when you must stop and when to restart your treatment with Glubrava.

Hypoglycaemia

If you take Glubrava with other medicines for diabetes, it is more likely that your blood sugar could fall below the normal level (hypoglycaemia). If you experience symptoms of hypoglycaemia such as weakness, dizziness, increased sweating, fast heart-beating, vision disorders or difficulty in concentration, you should take some sugar to increase your blood sugar level again. Ask your doctor or pharmacist for more information if you are not sure how to recognise this. It is recommended that you carry some sugar lumps, sweets, biscuits or sugary fruit juice.

The level of sugar in your blood or urine should be checked regularly.

Broken bones

A higher number of bone fractures was seen in patients, particularly women taking pioglitazone. Your doctor will take this into account when treating your diabetes.

Children and adolescents

Use in children and adolescents under 18 years is not recommended.

Other medicines and Glubrava

If you need to have an injection of a contrast medium that contains iodine into your bloodstream, for example in the context of an X-ray or scan, you must stop taking Glubrava before or at the time of the injection. Your doctor will decide when you must stop and when to restart your treatment with Glubrava.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. You may need more frequent blood glucose and kidney function tests, or your doctor may need to adjust the dose of Glubrava. This is because some medicines can weaken or strenghten the effect of Glubrava on the level of sugar in your blood.

The following medicines can increase the blood sugar lowering effect of Glubrava. This can lead to a risk of hypoglycaemia (low blood sugar):

• – gemfibrozil (to lower high cholesterol level)

• – angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (to

treat high blood pressure)

• – cimetidine (to reduce stomach acid)

The following medicines may decrease the blood sugar lowering effect of Glubrava. This can lead to a risk of hyperglycaemia (high blood sugar level):

• – rifampicin (to treat tuberculosis and other infections)

• – glucocorticoids (to treat allergies and inflammation)

• – beta-2-agonists (to treat asthma)

• – medicines which increase urine production (diuretics, to treat high blood pressure)

Other:

Medicines used to treat pain and inflammation (NSAID and COX-2-inhibitors, such as ibuprofen and celecoxib).

Glubrava with alcohol

Avoid excessive alcohol intake while taking Glubrava since this may increase the risk of lactic acidosis (see section “Risk of lactic acidosis”).

Pregnancy and breast-feeding

• – you must tell your doctor if you are pregnant, think you may be pregnant or are planning to have a baby. You should not use this medicine if you are pregnant. If you wish to become pregnant, your doctor will advise you to discontinue this medicine.

• – do not use this medicine if you are breastfeeding or are planning to breast-feed (see section “Do not take Glubrava”).

Driving and using machines

This medicine will not affect your ability to drive or use machines but take care if you experience abnormal vision.

Glubrava contains sodium

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

3. How to take Glubrava

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

The recommended dose is one tablet taken twice daily. If necessary your doctor may tell you to take a different dose. If you have reduced kidney function, your doctor may prescribe a lower dose, which may need to be given as separate tablets of pioglitazone and metformin.

You should swallow the tablets with a glass of water. You may take your tablets with or just after food to reduce the chance of an upset stomach.

If you are following a special diet for diabetes, you should continue with this while you are taking Glubrava.

Your weight should be checked at regular intervals; if your weight increases, inform your doctor.

Your doctor will ask you to have blood tests periodically during treatment with Glubrava. This is to check that your liver is working normally. At least once a year (more often if you are elderly or have kidney problems) your doctor will check that your kidneys are working normally.

If you take more Glubrava than you should

If you accidentally take too many tablets, or if someone else or a child takes your medicine, talk to a doctor or pharmacist immediately. Your blood sugar could fall below the normal level and can be increased by taking sugar. It is recommended that you carry some sugar lumps, sweets, biscuits or sugary fruit juice.

If you forget to take Glubrava

Take Glubrava daily as prescribed. However if you miss a dose, skip the missed dose and just carry on with the next dose as normal. Do not take a double dose to make up for a forgotten tablet.

If you stop taking Glubrava

Glubrava should be used every day to work properly. If you stop using Glubrava, your blood sugar may go up. Talk to your doctor before stopping this treatment.

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

4. Possible side effects

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

In particular, patients have experienced the following serious side effects:

Glubrava may cause a very rare (may affect up to 1 in 10,000), but very serious side effect called lactic acidosis (see section “Warnings and precautions”). If this happens you must stop taking Glubrava and contact a doctor or the nearest hospital immediately , as lactic acidosis may lead to coma.

Bladder cancer has been experienced uncommonly (may affect up to 1 in 100 people) in patients taking Glubrava. Signs and symptoms include blood in your urine, pain when urinating or a sudden need to urinate. If you experience any of these, talk to your doctor as soon as possible.

Localised swelling (oedema) has also been experienced commonly (may affect up to 1 in 10 people) in patients taking Glubrava in combination with insulin. If you experience this side effect, talk to your doctor as soon as possible.

Broken bones have been reported commonly (may affect up to 1 in 10 people) in female patients taking Glubrava and have also been reported in male patients (frequency cannot be estimated from the available data) taking Glubrava. If you experience this side effect, talk to your doctor as soon as possible.

Blurred vision due to swelling (or fluid) at the back of the eye (macular oedema) has also been reported in patients taking Glubrava (frequency cannot be estimated from the available data). If you experience this symptom for the first time, talk to your doctor as soon as possible. Also, if you already have blurred vision and the symptom gets worse, talk to your doctor as soon as possible.

Allergic reactions have been reported with frequency not known (cannot be estimated from the available data) in patients taking Glubrava. If you have a serious allergic reaction, including hives and swelling of the face, lips, tongue, or throat that may cause difficulty in breathing or swallowing stop taking this medicine and talk to your doctor immediately.

The following side effects have been experienced by some patients taking Glubrava

Very common (may affect more than 1 in 10 people)

• – stomach ache

• – feeling sick (nausea)

• – vomiting

• – diarrhoea

• – loss of appetite

Common

• – weight gain

• – headache

• – respiratory infection

• – abnormal vision

• – joint pain

• – impotence

• – blood in urine

• – reduction in blood count (anaemia)

• – numbness

• – taste disturbance

Uncommon

• – inflammation of the sinuses (sinusitis)

• – gas

• – difficulty sleeping (insomnia)

Very rare

• – decrease in amount of vitamin B12 in the blood

• – redness of the skin

• – itchy skin

• – raised and itchy rash (hives)

Not known

• – inflammation of the liver (hepatitis)

• – liver does not work as well as it should (changes in liver enzymes)

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. 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 reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Glubrava

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

Do not use this medicine after the expiry date which is stated on the carton and the blister after “EXP”. The expiry date refers to the last day of that month.

This medicine 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 protect the environment.

6. Contents of the pack and other information

What Glubrava contains

• – The active substances are pioglitazone and metformin hydrochloride. Each tablet contains 15 mg of pioglitazone (as hydrochloride) and 850 mg of metformin hydrochloride.

• – The other ingredients are microcrystalline cellulose, povidone (K30), croscarmellose sodium magnesium stearate, hypromellose, macrogol 8000, talc and titanium dioxide (E171).

What Glubrava looks like and contents of the pack

The film-coated tablets (tablets) are white to off white, oblong, convex, embossed ’15 / 850’ on one face and ‘4833M’ on the other. They are supplied in aluminium/aluminium blister in packs of 14, 28, 30, 50, 56, 60, 90, 98 or 180 tablets.

Not all pack sizes may be marketed.

Marketing authorisation holder:

Takeda Pharma A/S,

Delta Park 45

2665 Vallensbaek Strand

Denmark

Manufacturer:

Takeda Ireland Limited, Bray Business Park, Kilruddery, County Wicklow, Ireland

Delpharm Novara S.r.l., Via Crosa, 86, I-28065 Cerano (NO), Italy

Lilly S.A., Avda. de la Industria 30, 28108 Alcobendas, Madrid, Spain

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien Takeda Belgium Tél/Tel: +32 2 464 06 11	Lietuva Takeda UAB Tel: +370 521 09 070
Efcarapua Takega Etarapua Tea.: + 359 2 958 27 36; + 359 2 958 15 29	Luxembourg/Lu­xemburg Takeda Belgium Tél/Tel: +32 2 464 06 11
Česká republika Takeda Pharmaceuticals Czech Republic s.r.o. Tel: + 420 234722722	Magyarország Takeda Pharma Kft. Tel: +361 2707030
Danmark Takeda Pharma A/S Tlf: +45 46 77 11 11	Malta Takeda Italia S.p.A. Tel: +39 06 502601
Deutschland Takeda GmbH Tel: +49 (0) 800 825 3325	Nederland Takeda Nederland bv Tel: +31 20 203 5492
Eesti Takeda Pharma AS Tel: +372 6177 669	Norge Takeda AS Tlf: +47 6676 3030
EXXáSa TAKEDA EAAAZ A.E Tql: +30 210 6387800	Österreich Takeda Pharma Ges.m.b.H. Tel: +43(0)800 20 80 50
España Takeda Farmacéutica España S.A. Tel: +34 917 90 42 22	Polska Takeda Pharma sp. z o.o. Tel.: +48 22 608 13 00
France Takeda France SAS Tél: +33 1 40 67 33 00	Portugal Takeda – Farmacéuticos Portugal, Lda. Tel: + 351 21 120 1457

Hrvatska Takeda Pharmaceuticals Croatia d.o.o Tel: +385 1 377 88 96	Romania Takeda Pharmaceuticals SRL Tel: +40 21 335 03 91
Ireland Takeda Products Ireland Limited Tel: +353 (0) 1 6420021	Slovenija Takeda GmbH Podružnica Slovenija Tel:+ 386 (0) 59 082 480
island Vistor hf. Simi: +354 535 7000	Slovenská republika Takeda Pharmaceuticals Slovakia s.r.o. Tel: +421 (2) 20 602 600
Italia Takeda Italia S.p.A. Tel: +39 06 502601	Suomi/Finland Takeda Oy Puh/Tel: +358 20 746 5000
Kvnpog Takeda Pharma A/S Tql: +45 46 77 11 11	Sverige Takeda Pharma AB Tel: +46 8 731 28 00
Latvija Takeda Latvia SIA Tel: +371 67840082	United Kingdom Takeda UK Ltd Tel: +44 (0)1628 537 900

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: http : //www.ema.euro­pa.eu.

35

A pooled analysis was conducted of adverse event reports of bone fractures from randomised,

comparator controlled, double blind clinical trials in over 8,100 patients in the pioglitazone-treated

groups and 7,400 in the comparator-treated groups of up to 3.5 years duration. A higher rate of