COMPETACT 15 MG 850 MG

Israel - English - Ministry of Health

Buy It Now

Active ingredient:
METFORMIN HYDROCHLORIDE; PIOGLITAZONE AS HYDROCHLORIDE
Available from:
ABIC MARKETING LTD, ISRAEL
ATC code:
A10BA02
Pharmaceutical form:
FILM COATED TABLETS
Composition:
METFORMIN HYDROCHLORIDE 850 MG; PIOGLITAZONE AS HYDROCHLORIDE 15 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
TAKEDA PHARMA A/S, DENMARK
Therapeutic group:
METFORMIN
Therapeutic area:
METFORMIN
Therapeutic indications:
Competact is indicated as second line treatment of type 2 diabetes mellitus adult patients,particularly overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose of oral metformin alone.After initiation of therapy with pioglitazone, patients should be reviewed after 3 to 6 months to assess adequacy of response to treatment (e.g. reduction in HbA1c). In patients who fail to show an adequate response, pioglitazone should be discontinued. In light of potential risks with prolonged therapy, prescribers should confirm at subsequent routine reviews that the benefit of pioglitazone is maintained.
Authorization number:
150 65 33826 00
Authorization date:
2018-07-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Hebrew

21-01-2020

يف لكاشم كيدل تناك اذإ وأ انسم تنك اذإ رثكأ ةبيرق نايحأ يف( ،لقلأا ىلع ،ةنسلا يف ةرم بيبطلا كنم بلطي فوس .داتعملاك نلامعت كاتيلك تناك اذإ ةفرعمل صحف ءارجإ )ىلكلا ىلعأ ةعرج تلوانت اذإ ىلإ هجوت ،ءاودلا نم ةيمك لفط وأ أطخلا قيرط نع رخآ صخش علتبا اذإ وأ أطخلا قيرط نع ةطرفم ةعرج تلوانت اذإ .كعم ءاودلا ةوبع ا

بحطصم ،ا

روف ىفشتسملل ةعباتلا ئراوطلا ةفرغ ىلإ وأ بيبطلا نأ نسحتس

ي .ركسلا لوانت للاخ نم هعفر كنكمي ،كلذ ثدح اذإ ،ميلسلا ىوتسملا نود كمد يف ركسلا ىوتسم ضفخني دق .ولحلا ةهكافلا ريصع وأ ،تيوكسبلا ،تايولحلا ،ركسلا صارقأ ضعب كعم ذخأت ضامحلل ضرعتلا رطخ" - 2 دنبلا رظنا( يكيتكلالا ضامحلاب باصت دق ،تكاتيپموك نم ةطرفم ةعرج تلوانت اذإ .)"يكيتكلالا ءاودلا لوانت تيسن اذإ لوانتو ،ةيسنملا ةعرجلا ىطخت ،ةعرج لوانت تيسن اذإ ،اذه مغر .بيبطلا ةيصوتل اعبت ايموي تكاتيپموك لوانت كيلع .اهت

وف يتلا ةعرجلا نع اضيوعت ةفعاضم ةعرج لوانت عنم

ي .داتعملاك ةيلاتلا ةعرجلا .بيبطلا ةيصوتل ا

قفو جلاعلا ىلع ةبظاوملا كيلع ءاودلا لامعتسا نع تفقوت اذإ .كمد يف ركسلا ىوتسم عفتري فوس ،تكاتيپموك لوانت نع تفقوت اذإ .يغبني امك لمعي يكل ايموي تكاتيپموك لوانت كيلع .جلاعلا اذه فاقيإ لبق كبيبط رشتسا .ءاود اهيف لوانتت ة

ّ

رم

ّ

لك يف ة

ّ

يئاودلا ةعرجلا نمو ءاودلا ة

ّ

وبع ىلع قصلملا نم ق

ّ

قحت !ملاظلا يف ةيودلأا لوانت عنم

ُ

ي

.اهيلإ ةجاحب تنك اذإ ةي

ّ

بطلا تارا

ّ

ظنلا عض .يلديصلا وأ بيبطلا ر

ِ

شتسا ،ءاودلا لامعتساب ق

ّ

لعتت ةيفاضإ ةلئسأ

َ

كيدل تناك اذإ

.4

ةيبناجلا ضارعلأا ضارعلأا ةمئاق ةءارق دنع عزفت لا .نيم

دختسملا ضعب ىدل ةيبناج ا

ضارعأ تكاتيپموك لامعتسا ب

بسي دق ،ةيودلأا عيمجك .اهنم

يأ نم يناعت لا دق .ة

يبناجلا

ىعديو ،ادج ريطخ هنكلو ،)لمعتسم 10,000 نيب نم 1 ىتح يف رثؤي( ادج ردان يبناج ضراع ىلإ تكاتيپموك يدؤي دق فقوتلا كيلع ،يبناجلا ضراعلا اذه رهظ اذإ .)"يكيتكلالا ضامحلا ثودح رطخ" - 2 دنبلا رظنا( يكيتكلالا ضامحلا .ةبوبيغلا ىلإ يدؤي دق يكيتكلالا ضامحلا نلأ ،لااح برقلأا ىفشتسملا وأ بيبطلا ىلإ ه

ّ

جوتلاو تكاتيپموك لوانت نع

.تكاتيپموك نوقلتي نيجلاعتم ىدل )لمعتسم 100 نيب نم 1 ىتح يف رثؤي( عئاش ريغ لكشب ةناثملا ناطرس رهظي دق نم يأ دوجوب كش كيدل ناك اذإ .ل

وبتلل ةيئاجف ةجاح وأ ل

وبتلا دنع ملأ ،لوبلا يف مد ىلع ضارعلأاو تاملاعلا لمتشت .نكمم تقو عرسأ يف بيبطلا رشتسا ،تاملاعلاو ضارعلأا هذه

نلوانتي يتاوللا ءاسنلا ىدل )نيلمعتسم 10 نيب نم 1 ىتح يف رثؤي( عئاش لكشب ماظعلا يف روسك نع غلابلإا مت تانايبلا ىلإ ادانتسا راشتنلاا ىوتسم مييقت نكمي لا( اضيأ تكاتيپموك نولوانتي نيذلا لاجرلا ىدل كلذكو ،تكاتيپموك .اروف بيبطلا رشتسا ،يبناجلا ضراعلا اذهل تضرعت اذإ .)ةرفوتملا

راشتنلاا ىوتسم مييقت نكمي لا( )ةيعقب ةمذو( نيعلا نم يفلخلا ءزجلا يف )لئاوس وأ( مروت ببسب ةيبابض ةيؤر نع غلابلإا مت ،كلذ ىلإ ةفاضلإاب .لااح بيبطلا رشتسا ،ىلولأا ةرملل ةيبناجلا ضارعلأا هذهل تضرعت اذإ .)ةرفوتملا تامولعملا ىلإ ادانتسا .اعيرس بيبطلا رشتسا ،ضارعلأا ىلع روهدت أرط اذإو ،ةيؤرلا يف ةيبابض نم يناعت تنك اذإ

)ةرفوتملا تامولعملا ىلإ ادانتسا راشتنلاا ىوتسم مييقت نكمي لا( ةفورعم ريغ ةريتوب ة

يجرأ لعف دودر نع غلابلإا مت ناسللا ،نيتفشلا ،هجولا مروتو ىرش نمضتي ،ريطخ يسسحت لعف در كيدل ناك اذإ .تكاتيپموك نولوانتي نيجلاعتم ىدل

.اروف بيبطلا ةراشتساو ءاودلا اذه لوانت نع فقوتلا كيلع ،علاتبلاا وأ سفنتلا يف ةبوعص ببسي نأ نكمي ،ةرجنحلا وأ :تكاتيپموك نولوانتي نيذلا نيجلاعتملا نم مسق ىدل ةيلاتلا ةيبناجلا ضارعلأا ترهظ :)نيلمعتسم 10 ىتح 1 نم رثكأ يف رثؤت( ادج ةعئاش ةيبناج ضارعأ

نطبلا يف ملأ

نايثغ

تاؤيقت

لاهسإ

ةيهشلا نادقف :)نيلمعتسم 10 نيب نم 1 ىتح يف رثؤت( ةعئاش ةيبناج ضارعأ

)ةمذو( يعضوم مروت

نزولا ةدايز

عادص

يسفنتلا زاهجلا يف ثولت

ةذاش ةيؤر

لصافملا يف ملأ

(Erectile dysfunction( باصتنلاا ىلع ةردقلا مدع

لوبلا يف مد

)مدلا رقف( مدلا دادعت ضافخنا

ساسحلإا نادقف

معطلا ةساح يف تابارطضا :)لمعتسم 100 نيب نم 1 ىتح يف رثؤت( ةعئاش تسيل ةيبناج ضارعأ

(Sinusitis( ةيفنلأا بويجلا باهتلا

تازاغ

)قرأ( مونلا يف تابوعص :)لمعتسم 10,000 نيب نم 1 ىتح يف رثؤت( ادج ةردان ةيبناج ضارعأ

مدلا يف

نيماتيف ىوتسم ضافخنا

دلجلا رارمحا

دلجلا يف ةكح

)ىرش( ةكحو زراب حفط :)ةرفوتملا تامولعملا ىلإ ادانتسا راشتنلاا ىوتسم مييقت نكمي لا( ةفورعم ريغ اهراشتنا ةريتو ةيبناج ضارعأ

(Hepatitis( دبكلا باهتلا

)دبكلا تاميزنإ تايوتسم يف تارييغت( دبكلا ءادأ يف تابارطضا ،ةرشنلا يف ر

َ

كذ

ُ

ي مل

ّ

يبناج ض

ِ

راع نم تيناع اذإ وأ ،ةيبناجلا ضارعلأا نم

ٌّ

يأ مقافت اذإ ،ةيبناجلا ضارعلأا دحأ رهظ اذإ .بيبطلا ةراشتسا كيلع ةيبناجلا ضارعلأا نع غلابلإا جلاعلا ببسب ةيبناجلا ضارعلأا نع غلابلإا" طبار ىلع طغضلا ربع ةيبناجلا ضارعلأاب ة

حصلا ةرازو غلابإ نكمي ةرامتسا ىلإ كهجوي يذلا ) www.health.gov.il ( ة

حصلا ةرازو عقومل ةيسيئرلا ةحفصلا يف دوجوملا ،"يئاودلا :طبارلا ىلإ لوخدلا ربع وأ ةيبناجلا ضارعلأا نع غلابلإل ةبسوحم

https://sideeffects.health.gov.il

.5

؟ءاودلا ن

ّ

زخ

ُ

ي فيك وأ/و دلاولأا ةيؤر لاجمو يديأ لوانتم نع ا

ديعب ،قلغم ناكم يف ،رخآ ءاود

لكو ،ءاودلا اذه ظفح بجي !م

مستلا ب

نجت .بيبطلا نم ةحيرص تاميلعت نود ؤيقتلا ببست لا .م

مستلا ب

نجتت اذكهو ،لافطلأا ىلإ بسن

ي ة

يحلاصلا ءاهتنا خيرات .ة

وبعلا ىلع رهاظلا )Exp. Date( ةيحلاصلا ءاهتنا خيرات دعب ءاودلا لامعتسا ع

نم

.رهشلا سفن نم ريخلأا مويلا نيزختلا طورش . 25°C نم لقأ ةرارح ةجردب ،

ّ

فاج ناكم يف نيزختلا بجي ةيودلأا نم صلختلا كيلع فيك يلديصلا لأسا .ةيلزنملا تايافنلا ةيواح يف وأ يحصلا فرصلا هايم يف ةيودلأا ءاقلإ عنم

.ةئيبلا ىلع ظافحلا ىلع لئاسولا هذه دعاست .ةلمعتسملا ريغ

.6

ةيفاضإ تامولعم :ىلع ا

ً

ضيأ ءاودلا يوتحي ،ةلا

ّ

عفلا داوملا ىلإ ةفاضإ

Microcrystalline cellulose, Povidone, Croscarmellose sodium, Magnesium stearat,

Hypromellose, Macrogol 8000, Talc, Titanium dioxide.

ةو

ّ

بعلا يوحت اذامو ،ءاودلا ودبي فيك هيبناج دحأ ىلع موتخم ،ميرك ىتح ضيبأ هنول ،ل

وطمو ،ب

َّ

دحم ،يلطم صرق وه مغلم 850 /مغلم

تكاتيپموك صرق . '4833M ' موتخمف رخلآا بناجلا يف امأ ،'15 / 850' ددعلا اصرق 196 ىلع يوتحت ةوبع وأ ،اصرق 180 و ، 112 ، 98 ، 90 ، 60 ، 56 ، 50 ، 30 ، 28 ، 14 ىلع ةوبعلا يوتحت

( اصرق 98 ىلع اهنم لك يوتحي ناتوبع( .تا

وبعلا ماجحأ عيمج قيوست

متي لا دق :هناونعو ليجستلا بحاص مسا )عڨيت ةعومجم نم( ايناتن ، 8077 ،.ب .ص ،.ض.م قيوستلل كيبأ :هناونعو جتن

ُ

ملا مسا

كرامند ،س/أ ،امراف اديكات ةرازو تاميلعت قفو اهثيدحت متو ،2013 يناثلا نيرشت يف ة

حصلا ةرازو لب

ق نم اهيلع قيدصتلاو ةرشنلا هذه صحف

مت .2019 رايأ يف ة

حصلا :ةحصلا ةرازو يف يمسرلا ةيودلأا لجس يف ءاودلا ليجست مقر

150.65.33826

.نيسنجلا لاكل

دعم ءاودلاف اذه عم .ر

كذملا ةغيصب

صنلا درو اهليهستو ةرشنلا هذه ةءارق طيسبتل

Patient leaflet in accordance with the Pharmacists’ Regulations

(Preparations) - 1986

This medicine is dispensed with a doctor’s prescription only

Competact 15 mg/850 mg

Film-coated tablets

Composition of active ingredients

Each tablet contains:

pioglitazone (as hydrochloride) 15 mg

metformin hydrochloride 850 mg

For information about inactive ingredients and allergens see section 2 under ‘Important

information about some of this medicine’s ingredients’ and section 6 ‘Additional

information’.

Read the entire leaflet carefully before you start using this medicine. This leaflet

contains concise information about this medicine. If you have any further questions,

consult your doctor or pharmacist.

This medicine has been prescribed to treat your illness. Do not pass it on to others. It

may harm them, even if it seems to you that their medical condition is similar to yours.

Use of this medicine in children and adolescents under 18 years is not

recommended.

1. What is this medicine intended for?

This medicine is intended for treating type 2 diabetes mellitus )non-insulin dependent(

in adults with blood sugar levels that cannot be controlled with metformin treatment

alone.

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. Your doctor will check whether Competact is working properly 3 to 6 months

after you start taking it.

Competact helps control the level of sugar in your blood by helping your body make

better use of the insulin it produces.

Therapeutic group:

Pioglitazone: thiazolidinedione-type medicine.

Metformin: a biguanide.

2. Before using this medicine

Do not use this medicine if:

You are sensitive (allergic) to the active ingredients (pioglitazone and metformin) or

to any of the other ingredients in this medicine (see section 6).

You have heart failure or have had heart failure in the past.

You recently had a heart attack, have severe circulatory problems including shock,

or breathing difficulties.

You have liver disease.

You drink alcohol excessively (either every day or only from time to time).

You have uncontrolled diabetes, with for example severe hyperglycemia (high

blood glucose), nausea, vomiting, diarrhea, rapid weight loss, lactic acidosis (see

the 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 sweet smell.

You have or have had in the past bladder cancer.

You have blood in your urine that your doctor has not checked yet.

You have severely reduced kidney function.

You have a severe inflammation or are dehydrated.

You are going to have a certain type of X-ray with an injectable dye: Talk to your

doctor because you must stop taking Competact for a certain period of time before

and after the examination.

You are breastfeeding.

Special warnings about using this medicine

Talk to your doctor or pharmacist before taking Competact (see also 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 together with insulin, developed 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 localized swelling (edema).

If you have fluid retention or have heart failure problems, particularly 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 certain type of eye disease that is typical for diabetics called macular

edema (swelling of the back of the eye). Consult 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 Competact. 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 Competact you will

have a blood test to check your liver function. This blood test should be repeated at

intervals. Inform your doctor as soon as possible if you develop symptoms suggesting

a problem with your liver (like unexplained nausea, 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 (anemia).

Risk of lactic acidosis

Competact 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 the following conditions: 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 and severe heart disease).

If any of these conditions apply to you, talk to your doctor for further instructions.

Stop taking Competact for a short time if you have a condition that may be

associated with dehydration (significant loss of body fluids) such as severe vomiting,

diarrhea, fever, exposure to heat or if you drink less fluid than normal. Talk to your

doctor for further instructions.

Stop taking Competact and contact a doctor or the nearest hospital immediately

if you experience some of the symptoms of lactic acidosis, because this condition

may lead to coma. Symptoms of lactic acidosis include:

- vomiting

- stomach ache

- 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 Competact, 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 are about to have major surgery, you must stop taking Competact during and

for some time after surgery. Your doctor will decide when you must stop and when to

restart your treatment with Competact.

Hypoglycemia

If you take Competact with other medicines for diabetes, it is more likely that your blood

sugar could fall below the normal level (hypoglycemia). If you experience symptoms of

hypoglycemia such as weakness, dizziness, increased sweating, fast heartbeat, 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 recognize this condition. It is recommended that you carry some sugar

lumps, sweets, biscuits or sweet fruit juice.

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.

Use in children and adolescents

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

Other medicines and Competact

If you need to have an injection of a contrast dye that contains iodine into your

bloodstream, for example in the context of an X-ray or scan, you must stop taking

Competact before or at the time of the injection. Your doctor will decide when you must

stop and when to restart your treatment with Competact.

If you are taking or have recently taken other medicines, including nonprescription

medications and dietary supplements, tell your doctor or pharmacist. You may

need more frequent blood glucose and kidney function tests, or your doctor may need

to adjust the dose of Competact.

It is especially important to tell your doctor if you are taking any of the following

medicines:

gemfibrozil (used to lower cholesterol)

rifampicin (used to treat tuberculosis and other infections)

cimetidine (used to reduce stomach acid)

glucocorticoids (used to treat inflammation)

beta-2-agonists )used to treat asthma(

medicines which increase urine production (diuretics)

medicines used to treat pain and inflammation )nonsteroidal anti-inflammatory drugs

[NSAIDs] and COX-2-inhibitors, such as ibuprofen and celecoxib(

certain medicines for the treatment of high blood pressure )angiotensin-converting

enzyme (ACE) inhibitors and angiotensin II receptor antagonists)

Using this medicine and food

Swallow the tablets with a glass of water. You may take your tablets with or just after a

meal to reduce the chance of an upset stomach.

Using this medicine and alcohol consumption

Avoid excessive alcohol intake while taking Competact since this may increase the

risk of lactic acidosis (see section 2 under ‘Risk of lactic acidosis’).

Pregnancy and breastfeeding

- You must tell your doctor if you are pregnant, think you may be pregnant or are

planning to have a baby. Competact is not recommended in pregnancy. If you wish

to become pregnant, your doctor will advise you to discontinue this medicine.

- Do not use Competact if you are breastfeeding or are planning to breastfeed (see

section 2 under ‘Do not use this medicine if:’).

Driving and using machines

This medicine will not affect your ability to drive or use machines, but take care if you

experience abnormal vision.

Important information about some of this medicine’s ingredients

This medicine contains less than 23 mg of sodium per tablet so it is considered

sodium-free.

. How to use this medicine?

Always use this medicine according to your doctor’s instructions.

Check with your doctor or pharmacist if you are not sure about your dose or about how

to take this medicine.

Dosage:

Only your doctor will determine your dose and how you should take this medicine.

The recommended dosage is usually:

one Competact tablet twice a day. If necessary, your doctor may decide to give you

a different dose.

If you have reduced kidney function, your doctor may prescribe a lower dose, which

you may need to take as separate tablets of pioglitazone and metformin.

Do not exceed the recommended dose.

Swallow the tablets with a glass of water. You may take your tablets with or just after a

meal to reduce the chance of an upset stomach.

Do not crush, split, or chew the tablets.

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

are taking Competact.

Tests and follow-up

Your weight must 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

Competact. 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 have taken a higher dose

If you have taken an overdose, or if another person or a child has accidentally

swallowed some medicine, immediately see a doctor or go to a hospital emergency

room and bring the medicine package with you.

Your blood sugar level 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 sweet

fruit juice.

If you have taken an overdose of Competact, you may experience lactic acidosis (see

section 2 under ‘Risk of lactic acidosis’).

If you forget to take this medicine

Take Competact every day as prescribed by your doctor. However, if you miss a dose,

skip the missed dose and take your next dose as usual. Do not take a double dose to

make up for a missed dose.

Adhere to the treatment as recommended by your doctor.

If you stop taking this medicine

Competact should be used every day to work properly. If you stop taking Competact,

your blood sugar level may go up. Consult your doctor before stopping this treatment.

Do not take medicines in the dark! Check the label and dose every time you take

medicine. Wear glasses if you need them.

If you have any further questions about using this medicine, consult your doctor

or pharmacist.

4. Side effects

Like with all medicines, using Competact may cause side effects in some users. Do

not be alarmed by this list of side effects; you may not experience any of them.

Competact may cause a very rare (affects up to 1 in 10,000 users), but very serious

side effect called lactic acidosis (see section 2 under ‘Risk of lactic acidosis’). If this

happens you must stop taking Competact and contact a doctor or the nearest

hospital immediately, because lactic acidosis may lead to coma.

Bladder cancer may occur uncommonly (affects up to 1 in 100 users) in patients

taking Competact. 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.

Broken bones have been reported commonly (affect up to 1 in 10 users) in women

taking Competact and have also been reported in men (frequency cannot be

estimated from the available data) taking Competact. 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 edema)

has been reported (frequency cannot be estimated from available data). If you

experience these symptoms for the first time, talk to your doctor as soon as possible.

Also, if you already have blurred vision and the symptoms get worse, talk to your

doctor as soon as possible.

Allergic reactions have been reported with unknown frequency (frequency cannot be

estimated from available data) in patients taking Competact. 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

Competact:

Very common side effects (may affect more than 1 in 10 users):

- stomach ache

- nausea

- vomiting

- diarrhea

- loss of appetite

Common side effects (may affect up to 1 in 10 users):

- localized swelling (edema)

- weight gain

- headache

- respiratory infection

- abnormal vision

- joint pain

- impotence

- blood in urine

- reduction in blood count (anemia)

- numbness

- taste disturbance

Uncommon side effects (may affect up to 1 in 100 users):

- inflammation of the sinuses (sinusitis)

- gas

- difficulty sleeping (insomnia)

Very rare side effects (may affect up to 1 in 10,000 users):

- reduced blood level of vitamin B

in the blood

- redness of the skin

- itchy skin

- raised and itchy rash (hives)

Side effects of unknown frequency (frequency cannot be estimated from the

available data):

- inflammation of the liver (hepatitis)

- impaired liver function (changes in levels of liver enzymes)

If you experience any side effect, if any side effect gets worse, or if you

experience a side effect not mentioned in this leaflet, consult your doctor.

Reporting side effects

You can report side effects to the Ministry of Health by following the link ‘Reporting

Side Effects of Drug Treatment’ on the Ministry of Health home page (www.health.gov.il)

which links to an online form for reporting side effects. You can also use this link:

https://sideeffects.health.gov.il

5. How to store the medicine?

Prevent poisoning! To prevent poisoning, keep this, and all other medicines, in a

closed place, out of the reach and sight of children and/or infants. Do not induce

vomiting unless explicitly instructed to do so by a doctor.

Do not use the medicine after the expiry date (exp. date) which is stated on the

package. The expiry date refers to the last day of that month.

Storage conditions

Store in a dry place, below 25°C.

Do not throw away any medicines via wastewater or household waste. Ask the

pharmacist how to throw away medicines you no longer use. These measures will

help protect the environment.

6. Additional information

In addition to the active ingredients, this medicine also contains:

microcrystalline cellulose, povidone, croscarmellose sodium, magnesium stearate,

hypromellose, macrogol 8000, talc, titanium dioxide.

What the medicine looks like and contents of the pack

A Competact 15 mg/850 mg film-coated tablet is white to off white, oblong, convex,

embossed ‘15 / 850’ on one side and ‘4833M’ on the other.

Packs contain 14, 28, 30, 50, 56, 60, 90, 98, 112, 180 tablets or multipack of 196

tablets (2 packs of 98).

Not all pack sizes may be marketed.

Registration holder’s name and address:

Abic Marketing Ltd., POB 8077, Netanya (Teva Group)

Manufacturer’s name and address:

Takeda Pharma A/S, Denmark

This leaflet was reviewed and approved by the Ministry of Health in November 2013

and revised in May 2019 in accordance with Ministry of Health guidelines.

Registration number of the medicine in the Ministry of Health’s National Drug

Registry:

150.65.33826

DOR-Com-PIL-1119-04

DOR-Com-PIL-1119-04

Competact 15mg/850mg MF 05/2019 Certification

Competact 15 mg/850 mg

Film-coated tablets

SUMMARY OF PRODUCT CHARACTERISTICS

1.

NAME OF THE MEDICINAL PRODUCT

Competact 15 mg/850 mg film-coated tablets

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 15 mg of pioglitazone (as hydrochloride) and 850 mg of metformin

hydrochloride.

Excipient with known effect:

Each tablet contains

3.3-5

mg of sodium.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablet (tablet).

The tablets are white to off-white, oblong, convex, film-coated, embossed ‘15 / 850’ on one face

and ‘4833M’ on the other.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Competact is indicated as second line treatment of type 2 diabetes mellitus adult patients,

particularly overweight patients, who are unable to achieve sufficient glycaemic control at their

maximally tolerated dose of oral metformin alone.

After initiation of therapy with pioglitazone, patients should be reviewed after 3 to 6 months to

assess adequacy of response to treatment (e.g. reduction in HbA

). In patients who fail to show

an adequate response, pioglitazone should be discontinued. In light of potential risks with

prolonged therapy, prescribers should confirm at subsequent routine reviews that the benefit of

pioglitazone is maintained (see section 4.4).

4.2

Posology and method of administration

Posology

Adults with normal renal function (GFR ≥ 90 mL/min)

recommended

dose

Competact

30 mg/day

pioglitazone

plus

1,700 mg/day

metformin hydrochloride (this dose is achievable with one tablet of Competact 15 mg/850 mg,

taken twice a day).

Competact 15mg/850mg MF 05/2019 Notification

Dose titration with pioglitazone (added to the optimal dose of metformin) should be considered

before the patient is switched to Competact.

When clinically appropriate, direct change from metformin monotherapy to Competact may be

considered.

Special populations

Elderly

As metformin is excreted via the kidney, and elderly patients have a tendency to decreased renal

function, elderly patients taking Competact should have their renal function monitored regularly

(see sections 4.3 and 4.4).

Physicians should start treatment with the lowest available dose and increase the dose gradually,

particularly

when

pioglitazone

used

combination

with

insulin

(see

section 4.4 Fluid

retention and cardiac failure).

Renal impairment

A GFR should be assessed before initiation of treatment with metformin containing products

and at least annually thereafter. In patients at increased risk of further progression of renal

impairment and in the elderly, renal function should be assessed more frequently, e.g. every

3-6 months.

The maximum daily dose of metformin should preferably be divided into 2-3 daily doses.

Factors that may increase the risk of lactic acidosis (see section 4.4) should be reviewed before

considering initiation of metformin in patients with GFR < 60 mL/min.

If no adequate strength of Competact is available, individual monocomponents should be used

instead of the fixed dose combination.

GFR mL/min

Metformin

Pioglitazone

60-89

Maximum daily dose is 3,000 mg.

Dose reduction may be considered

in

relation

to

declining

renal

function.

No dose adjustment.

Maximum daily dose is 45 mg

45-59

Maximum daily dose is 2,000 mg.

The starting dose is at most half of

the maximum dose.

30-44

Maximum daily dose is 1,000 mg.

The starting dose is at most half of

the maximum dose.

< 30

Metformin is contra-indicated

Hepatic impairment

Competact should not be used in patients with hepatic impairment (see sections 4.3 and 4.4).

Paediatric population

The safety and efficacy of Competact in children and adolescents under 18 years of age have not

been established. No data are available.

Method of administration

Competact 15mg/850mg MF 05/2019 Notification

Tablets should be swallowed with a glass of water. Taking Competact with, or just after food,

may reduce gastrointestinal symptoms associated with metformin.

4.3

Contraindications

Competact is contraindicated in patients with:

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1

Cardiac failure or history of cardiac failure (NYHA stages I to IV)

Current bladder cancer or a history of bladder cancer

Uninvestigated macroscopic haematuria

Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory

failure, recent myocardial infarction, shock

Hepatic impairment

Acute alcohol intoxication, alcoholism

Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)

Diabetic pre-coma

Severe renal failure (GFR < 30 mL/min)

Acute conditions with the potential to alter renal function such as:

- Dehydration

- Severe infection

- Shock

Intravascular administration of iodinated contrast agents (see section 4.4)

Breast-feeding (see section 4.6)

4.4

Special warnings and precautions for use

There is no clinical experience of pioglitazone in triple combination with other oral antidiabetic

medicinal products.

Lactic acidosis

Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute

worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation

occurs at acute worsening of renal function and increases the risk of lactic acidosis.

In case of dehydration (severe diarrhoea or vomiting, fever, heat, reduced fluid intake),

Competact should be temporarily discontinued and contact with a health care professional is

recommended.

Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics

nonsteroidal

anti-inflammatory

drugs

(NSAIDs))

should

initiated

with

caution

metformin treated patients. Other risk factors for lactic acidosis are excessive alcohol intake,

hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any

conditions associated with hypoxia, as well as concomitant use of medicinal products that may

cause lactic acidosis (see sections 4.3 and 4.5).

Patients and/or care-givers should be informed on the risk of lactic acidosis. Lactic acidosis is

characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia

followed by coma. In case of suspected symptoms, the patient should stop taking Competact

and seek immediate medical attention. Diagnostic laboratory findings are decreased blood pH

(< 7.35),

increased

plasma

lactate

levels

(> 5 mmol/L)

increased

anion

lactate/pyruvate ratio.

Competact 15mg/850mg MF 05/2019 Notification

Renal function

GFR should be assessed before treatment initiation and regularly thereafter, see section 4.2.

Metformin is contraindicated in patients with GFR <30 mL/min and should be temporarily

discontinued in the presence of conditions that alter renal function, see section 4.3.

Decreased renal function in elderly patients is frequent and asymptomatic. Special caution

should be exercised in situations where renal function may become impaired, for example when

initiating antihypertensive therapy or diuretic therapy and when starting treatment with a

NSAID.

Fluid retention and cardiac failure

Pioglitazone can cause fluid retention, which may exacerbate or precipitate heart failure. When

treating patients who have at least one risk factor for development of congestive heart failure

(e.g. prior

myocardial

infarction

symptomatic

coronary

artery

disease

elderly),

physicians should start with the lowest available dose and increase the dose gradually. Patients

should be observed for signs and symptoms of heart failure, weight gain or oedema; particularly

those with reduced cardiac reserve. There have been post-marketing cases of cardiac failure

reported when pioglitazone was used in combination with insulin or in patients with a history of

cardiac

failure.

Since

insulin

pioglitazone

both

associated

with

fluid

retention,

concomitant administration of insulin and Competact may increase the risk of oedema. Post-

marketing cases of peripheral oedema and cardiac failure have also been reported in patients

with concomitant use of pioglitazone and nonsteroidal anti-inflammatory drugs, including

selective COX-2 inhibitors. Competact should be discontinued if any deterioration in cardiac

status occurs.

A cardiovascular outcome study of pioglitazone has been performed in patients under 75 years

with type 2 diabetes mellitus and pre-existing major macrovascular disease. Pioglitazone or

placebo was added to existing antidiabetic and cardiovascular therapy for up to 3.5 years. This

study showed an increase in reports of heart failure; however this did not lead to an increase in

mortality in this study.

Elderly

Combination use with insulin should be considered with caution in the elderly because of

increased risk of serious heart failure.

In light of age- related risks (especially bladder cancer, fractures and heart failure), the balance

of benefits and risks should be considered carefully both before and during treatment in the

elderly.

Bladder Cancer

Cases of bladder cancer were reported more frequently in a meta-analysis of controlled clinical

trials with pioglitazone (19 cases from 12,506 patients, 0.15%) than in control groups (7 cases

from 10,212 patients, 0.07%) HR=2.64 (95% CI 1.11-6.31, P=0.029). After excluding patients

in whom exposure to study drug was less than one year at the time of diagnosis of bladder

cancer, there were 7 cases (0.06%) on pioglitazone and 2 cases (0.02%) in control groups.

Epidemiological studies have also suggested a small increased risk of bladder cancer in diabetic

patients treated with pioglitazone, although not all studies identified a statistically significant

increased risk.

Risk factors for bladder cancer should be assessed before initiating pioglitazone treatment (risks

include

age,

smoking

history,

exposure

some

occupational

chemotherapy

agents

Competact 15mg/850mg MF 05/2019 Notification

e.g. cyclophosphamide or prior radiation treatment in the pelvic region). Any macroscopic

haematuria should be investigated before starting pioglitazone therapy.

Patients should be advised to promptly seek the attention of their physician if macroscopic

haematuria or other symptoms such as dysuria or urinary urgency develop during treatment.

Monitoring of liver function

There have been rare reports of elevated liver enzymes and hepatocellular dysfunction during

post-marketing experience with pioglitazone (see section 4.8). Although in very rare cases fatal

outcome has been reported, causal relationship has not been established.

It is recommended, therefore, that patients treated with Competact undergo periodic monitoring

of liver enzymes. Liver enzymes should be checked prior to the initiation of therapy with

Competact in all patients. Therapy with Competact should not be initiated in patients with

increased baseline liver enzyme levels (ALT > 2.5 X upper limit of normal) or with any other

evidence of liver disease.

Following initiation of therapy with Competact, it is recommended that liver enzymes be

monitored periodically according to clinical judgement. If ALT levels are increased to 3 x upper

limit of normal during Competact therapy, liver enzyme levels should be reassessed as soon as

possible. If ALT levels remain > 3 x the upper limit of normal, therapy should be discontinued.

patient

develops

symptoms

suggesting

hepatic

dysfunction,

which

include

unexplained

nausea,

vomiting, abdominal pain, fatigue,

anorexia

and/or dark

urine,

liver

enzymes should be checked. The decision whether to continue the patient on therapy with

Competact should be guided by clinical judgement pending laboratory evaluations. If jaundice

is observed, the medicinal product should be discontinued.

Weight gain

In clinical trials with pioglitazone there was evidence of dose related weight gain, which may be

due to fat accumulation and in some cases associated with fluid retention. In some cases weight

increase may be a symptom of cardiac failure; therefore weight should be closely monitored.

Haematology

There was a small reduction in mean haemoglobin (4% relative reduction) and haematocrit

(4.1% relative reduction) during therapy with pioglitazone, consistent with haemodilution.

Similar changes were seen in metformin (haemoglobin 3-4% and haematocrit 3.6-4.1% relative

reductions) treated patients in comparative controlled trials with pioglitazone.

Hypoglycaemia

Patients receiving pioglitazone in dual oral therapy with a sulphonylurea may be at risk for

dose-related hypoglycaemia, and a reduction in the dose of the sulphonylurea may be necessary.

Eye disorders

Post-marketing reports of new-onset or worsening diabetic macular oedema with decreased

visual acuity have been reported with thiazolidinediones, including pioglitazone. Many of these

patients reported concurrent peripheral oedema. It is unclear whether or not there is a direct

association between pioglitazone and macular oedema but prescribers should be alert to the

possibility of macular oedema if patients report disturbances in visual acuity; an appropriate

ophthalmological referral should be considered.

Competact 15mg/850mg MF 05/2019 Notification

Surgery

As Competact contains metformin hydrochloride, it must be discontinued at the time of surgery

under general, spinal or epidural anesthesia. Therapy may be restarted no earlier than 48 hours

following surgery or resumption of oral nutrition and provided that renal function has been

re-evaluated and found to be stable.

Administration of iodinated contrast agent

Intravascular

administration

iodinated

contrast

agents

lead

contrast

induced

nephropathy, resulting in metformin accumulation and an increased risk of lactic acidosis.

Competact should be discontinued prior to or at the time of the imaging procedure and not

restarted until at least 48 hours after, provided that renal function has been re-evaluated and

found to be stable, see sections 4.2 and 4.5.

Polycystic ovarian syndrome

As a consequence of enhancing insulin action, pioglitazone treatment in patients with polycystic

ovarian syndrome may result in resumption of ovulation. These patients may be at risk of

pregnancy. Patients should be aware of the risk of pregnancy and if a patient wishes to become

pregnant or if pregnancy occurs, the treatment should be discontinued (see section 4.6).

Others

An increased incidence in bone fractures in women was seen in a pooled analysis of adverse

reactions

bone

fracture

from

randomised,

controlled,

double

blind

clinical

trials

(see

section 4.8).

The fracture incidence calculated was 1.9 fractures per 100 patient years in women treated with

pioglitazone and 1.1 fractures per 100 patient years in women treated with a comparator. The

observed excess risk of fractures for women in this dataset on pioglitazone is therefore 0.8

fractures per 100 patient years of use.

Some epidemiological studies have suggested a similarly increased risk of fracture in both men

and women. The risk of fractures should be considered in the long term care of patients treated

with pioglitazone (see section 4.8).

Pioglitazone should be used with caution during concomitant administration of cytochrome

P450 2C8 inhibitors (e.g. gemfibrozil) or inducers (e.g. rifampicin). Glycaemic control should

be monitored closely. Pioglitazone dose adjustment within the recommended posology or

changes in diabetic treatment should be considered (see section 4.5).

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

‘sodium-free’.

4.5

Interaction with other medicinal products and other forms of interaction

There have been no formal interaction studies for Competact. The following statements reflect

the information available on the individual active substances (pioglitazone and metformin).

Metformin

Concomitant use not recommended

Alcohol

Competact 15mg/850mg MF 05/2019 Notification

Alcohol intoxication is associated with an increased risk of lactic acidosis, particularly in case

of fasting, malnutrition or hepatic impairment.

Iodinated contrast agents

Competact must be discontinued prior to or at the time of the imaging procedure and not

restarted until at least 48 hours after, provided that renal function has been re-evaluated and

found to be stable, see sections 4.2 and 4.4.

Combinations requiring precautions for use

Some medicinal products that can adversely affect renal function which may increase the risk of

lactic

acidosis,

e.g.

NSAIDS,

including

selective

cyclo-oxygenase

(COX)

inhibitors,

angiotensin-converting

enzyme

(ACE)

inhibitors,

angiotensin

receptor

antagonists

diuretics, especially loop diuretics. When starting or using such products in combination with

Competact, close monitoring of renal function is necessary.

Cationic medicinal products that are eliminated by renal tubular secretion (e.g. cimetidine) may

interact with metformin by competing for common renal tubular transport systems. A study

conducted in seven normal healthy volunteers showed that cimetidine, administered as 400 mg

twice

daily,

increased

metformin

systemic

exposure

(AUC)

81%.

Therefore, close monitoring of glycaemic control, dose adjustment within the recommended

posology and changes in diabetic treatment should be considered when cationic medicinal

products that are eliminated by renal tubular secretion are co-administered.

Pioglitazone

Co-administration of pioglitazone with gemfibrozil (an inhibitor of cytochrome P450 2C8) is

reported to result in a 3-fold increase in AUC of pioglitazone. Since there is a potential for an

increase in dose-related adverse events, a decrease in the dose of pioglitazone may be needed

when gemfibrozil is concomitantly administered. Close monitoring of glycaemic control should

be considered (see section 4.4). Co-administration of pioglitazone with rifampicin (an inducer

of cytochrome P450 2C8) is reported to result in a 54% decrease in AUC of pioglitazone. The

pioglitazone dose may need to be increased when rifampicin is concomitantly administered.

Close monitoring of glycaemic control should be considered (see section 4.4).

Glucocorticoids (given by systemic and local

routes), beta-2-agonists, and diuretics have

intrinsic hyperglycaemic activity. The patient should be informed and more frequent blood

glucose monitoring performed, especially at the beginning of treatment. If necessary, the dose of

the antihyperglycaemic medicinal product should be adjusted during therapy with the other

medicinal product and on its discontinuation.

ACE-inhibitors

decrease

blood

glucose

levels.

necessary,

dose

antihyperglycaemic

medicinal

product

should

adjusted

during

therapy

with

other

medicinal product and on its discontinuation.

Interaction

studies

have

shown

that

pioglitazone

relevant

effect

either

pharmacokinetics or pharmacodynamics of digoxin, warfarin, phenprocoumon and metformin.

Studies in man suggest no induction of the main inducible cytochrome P450, 1A, 2C8/9 and

3A4. In vitro studies have shown no inhibition of any subtype of cytochrome P450. Interactions

with substances metabolised by these enzymes, e.g. oral contraceptives, cyclosporin, calcium

channel blockers, and HMGCoA reductase inhibitors are not to be expected.

4.6

Fertility, pregnancy and lactation

For Competact no preclinical or clinical data on exposed pregnancies or lactation are available.

Competact 15mg/850mg MF 05/2019 Notification

Women of childbearing potential / Contraception in males and females

Competact is not recommended in women of childbearing potential not using contraception. If a

patient wishes to become pregnant, treatment with Competact should be discontinued.

Pregnancy

Risk related to pioglitazone

There are no adequate human data from the use of pioglitazone in pregnant women. Animal

studies

have

shown

teratogenic

effects

have

shown

foetotoxicity

related

pharmacologic action (see section 5.3).

Risk related to metformin

Animal studies have not revealed teratogenic effects. Small clinical trials have not revealed

metformin to have malformative effects.

Competact should not be used

during pregnancy.

If a

pregnancy

occurs,

treatment

with

Competact should be discontinued.

Breast-feeding

Both pioglitazone and metformin have been shown to be present in the milk of lactating rats. It

is not known whether breast-feeding will lead to exposure of the infant to the medicinal product.

Competact must therefore not be used in women who are breast-feeding (see section 4.3).

Fertility

In animal fertility studies with pioglitazone, there was no effect on copulation, impregnation or

fertility index.

Fertility of male or female rats was unaffected by metformin when administered at doses as high

as 600 mg/kg/day, which is approximately three times the maximum recommended human daily

dose based on body surface area comparisons.

4.7

Effects on ability to drive and use machines

Competact has no or negligible influence on the ability to drive and use machines. However

patients who experience visual disturbance should be cautious when driving or using machines.

4.8

Undesirable effects

Summary of the safety profile

Clinical trials have been conducted with Competact tablets and co-administered pioglitazone

and metformin (see section 5.1). At the initiation of the treatment abdominal pain, diarrhoea,

loss of appetite, nausea and vomiting may occur, these reactions are very common but usually

disappear spontaneously in most cases. Lactic acidosis is a serious reaction which may occur

very rarely (< 1/10,000) (see section 4.4) and other reactions such as bone fracture, weight

increase and oedema may occur commonly (≥ 1/100 to < 1/10) (see section 4.4).

Tabulated list of adverse reactions

Adverse reactions reported in double-blind studies and post-marketing experience are listed

below as MedDRA preferred term by system organ class and absolute frequency. Frequencies

are defined as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to

< 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated

from the available data). Within each system organ class, adverse reactions are presented in

order of decreasing incidence followed by decreasing seriousness.

Competact 15mg/850mg MF 05/2019 Notification

Adverse reaction

Frequency of adverse reactions

Pioglitazone

Metformin

Competact

Infections and infestations

upper respiratory tract infection

common

common

sinusitis

uncommon

uncommon

Neoplasms benign, malignant and unspecified

(including cysts and polyps)

bladder cancer

uncommon

uncommon

Blood and lymphatic system disorders

anaemia

common

Immune System Disorders

hypersensitivity and allergic reactions

not known

not known

Metabolism and nutrition disorders

Vitamin B12 absorption decreased

very rare

very rare

lactic acidosis

very rare

very rare

Nervous system disorders

hypo-aesthesia

common

common

insomnia

uncommon

uncommon

headache

common

taste disturbance

common

common

Eye disorders

visual disturbance

common

common

macular oedema

not known

not known

Gastrointestinal disorders

abdominal pain

very common

very common

diarrhoea

very common

very common

flatulence

uncommon

loss of appetite

very common

very common

nausea

very common

very common

vomiting

very common

very common

Hepatobiliary disorders

hepatitis

not known

not known

Skin and subcutaneous tissue disorders

erythema

very rare

very rare

pruritis

very rare

very rare

urticaria

very rare

very rare

Musculoskeletal and connective tissue disorders

Competact 15mg/850mg MF 05/2019 Notification

Adverse reaction

Frequency of adverse reactions

Pioglitazone

Metformin

Competact

bone fracture

common

common

arthralgia

common

Renal and urinary disorders

haematuria

common

Reproductive system and breast disorders

erectile dysfunction

common

General disorders and administration site

conditions

oedema

common

Investigations

weight increased

common

common

alanine aminotransferase increased

not known

not known

liver function tests abnormal

not known

not known

Description of selected adverse reactions

Post-marketing reports of hypersensitivity reactions in patients treated with pioglitazone have

been reported. These reactions include anaphylaxis, angioedema, and urticaria.

Long term treatment of metformin has been associated with a decrease of vitamin B12

absorption with decrease of serum levels. Consideration of such aetiology is recommended if a

patient presents with megaloplastic anaemia.

Visual disturbance has been reported mainly early in treatment and is related to changes in

blood glucose due to temporary alteration in the turgidity and refractive index of the lens.

Gastrointestinal disorders occur most frequently during initiation of therapy and resolve

spontaneously in most cases.

Isolated reports: liver function tests abnormalities or hepatitis resolving upon metformin

discontinuation.

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

comparator

controlled,

double

blind

clinical

trials

over

8,100

patients

pioglitazone-treated groups and 7,400 in the comparator-treated groups of up to 3.5 years

duration. A higher rate of fractures was observed in women taking pioglitazone (2.6%) versus

comparator (1.7%). No increase in fracture rates was observed in men treated with pioglitazone

(1.3%) versus comparator (1.5%).

3.5 year

PROactive

study,

44/870

(5.1%;

1.0 fractures

100 patient

years)

pioglitazone-treated

female

patients

experienced

fractures

compared

23/905

(2.5%;

0.5 fractures per 100 patient years) of female patients treated with comparator. The observed

excess risk of fractures for women on pioglitazone in this study is therefore 0.5 fractures per

100 patient years of use. No increase in fracture rates was observed in men treated with

pioglitazone

(1.7%)

versus

comparator

(2.1%).

Post-marketing,

bone

fractures

have

been

reported in both male and female patients (see section 4.4).

:ךיראת יאמ

2019

ה/דבכנ ת/חקור ,ה/אפור

העידומ עבט תרבח לע

ולעב םיאבה םינוכדעה

ן

ןכרצל

ו

ןולעב :רישכתה לש אפורל

Competact 15 mg/850 mg, Film-coated Tablets

טקטפמוק

15

/ג"מ

850

ג"מ

,

תופוצמ תוילבט

Contains: Metformin hydrochloride 850 mg

Pioglitazone (as hydrochloride) 15 mg

ןכרצל ןולעב םינוכדע

ו

אפורל ןולעב

------------------------------------------------------------------------------------------------------------

:םושירה תדועתב הרשואש יפכ היוותה

Competact is indicated as second line treatment of type 2 diabetes mellitus adult patients, particularly

overweight patients, who are unable to achieve sufficient glycaemic control at their maximally tolerated dose

of oral metformin alone.

After initiation of therapy with pioglitazone, patients should be reviewed after 3 to 6 months to assess

adequacy of response to treatment (e.g. reduction in HbA

). In patients who fail to show an adequate

response, pioglitazone should be discontinued. In light of potential risks with prolonged therapy, prescribers

should confirm at subsequent routine reviews that the benefit of pioglitazone is maintained.

ל ןולעהש עידוהל וננוצרב אפור

ןכרצל ןולעהו כדוע ונ תופסות( דבלב םיירקיעה םינוכדעה םילולכ ןלהלש טוריפב , תונמוסמ םודאב

:)קוחמ טסקטכ עדימ תורסהו

:אפורל ןולעב םינוכדע

4.2

Posology and method of administration

[...]

A GFR should be assessed before initiation of treatment with metformin containing products and at least

annually thereafter. In patients at increased risk of further progression of renal impairment and in the elderly,

renal function should be assessed more frequently, e.g. every 3-6 months.

The maximum daily dose of metformin should preferably be divided into 2-3 daily doses. Factors that may

increase the risk of lactic acidosis (see section 4.4) should be reviewed before considering initiation of

metformin in patients with GFR < 60 mL/min.

If no adequate strength of Competact is available, individual monocomponents should be used instead of the

fixed dose combination.

GFR mL/min

Metformin

Pioglitazone

60-89

Maximum daily dose is 3,000 mg.

Dose reduction may be considered in

relation to declining renal function.

No dose adjustment.

Maximum daily dose is 45 mg

45-59

Maximum daily dose is 2,000 mg.

The starting dose is at most half of the

maximum dose.

30-44

Maximum daily dose is 1,000 mg.

The starting dose is at most half of the

maximum dose.

< 30

Metformin is contra-indicated

[...]

4.3

Contraindications

[...]

Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)

Severe renal failure (GFR < 30 mL/min) Renal failure or renal dysfunction (creatinine clearance

<60 ml/min) (see section 4.4).

[...]

4.4

Special warnings and precautions for use

[...]

Lactic acidosis is a very rare, but serious, metabolic complication that can occur due to metformin

accumulation. Reported cases of lactic acidosis in patients on metformin have occurred primarily in diabetic

patients with significant renal failure. The incidence of lactic acidosis can and should be reduced by

assessing also other associated risk factors such as poorly controlled diabetes, ketosis, prolonged fasting,

excessive alcohol intake, hepatic insufficiency and any condition associated with hypoxia.

Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain and hypothermia followed by coma.

Diagnostic laboratory findings are decreased blood pH, plasma lactate levels above 5 mmol/l, and an

increased anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, treatment with the

medicinal product should be discontinued and the patient hospitalised immediately (see section 4.9).

Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal

function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal

function and increases the risk of lactic acidosis.

In case of dehydration (severe diarrhoea or vomiting, fever, heat, reduced fluid intake), Competact should be

temporarily discontinued and contact with a health care professional is recommended.

Medicinal

products

that

acutely

impair

renal

function

(such

antihypertensives,

diuretics

nonsteroidal anti-inflammatory drugs (NSAIDs)) should be initiated with caution in metformin treated

patients.

Other

risk

factors

lactic

acidosis

excessive

alcohol

intake,

hepatic

insufficiency,

inadequately controlled diabetes, ketosis, prolonged fasting and any conditions associated with hypoxia, as

well as concomitant use of medicinal products that may cause lactic acidosis (see sections 4.3 and 4.5).

Patients and/or care-givers should be informed on the risk of lactic acidosis. Lactic acidosis is characterised

by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case

of suspected symptoms, the patient should stop taking Competact and seek immediate medical attention.

Diagnostic

laboratory

findings

decreased

blood

(< 7.35),

increased

plasma

lactate

levels

(> 5 mmol/L) and an increased anion gap and lactate/pyruvate ratio.

Renal function

As metformin is excreted by the kidney, serum creatinine concentrations should be determined regularly:

at least once a year in patients with normal renal function

at least two to four times a year in patients with serum creatinine levels at the upper limits of normal

and in elderly subjects

GFR should be assessed before treatment initiation and regularly thereafter, see section 4.2. Metformin is

contraindicated in patients with GFR <30 mL/min and should be temporarily discontinued in the presence of

conditions that alter renal function, see section 4.3.

[...]

Surgery

As Competact contains metformin hydrochloride, it must be discontinued at the time of surgery under

general, spinal or epidural anesthesia. Therapy may be restarted no earlier than 48 hours following surgery or

resumption of oral nutrition and provided that renal function has been re-evaluated and found to be stable.

The treatment should be discontinued 48 hours before elective surgery with general anaesthesia and should

not be usually resumed earlier than 48 hours afterwards.

[...]

Others

The risk of fractures should be considered in the long term care of patients women treated with pioglitazone

(see section 4.8).

[...]

4.5

Interaction with other medicinal products and other forms of interaction

[...]

Combinations requiring precautions for use

Some medicinal products that can adversely affect renal function which may increase the risk of lactic

acidosis, e.g. NSAIDS, including selective cyclo-oxygenase (COX) II inhibitors, angiotensin-converting

enzyme (ACE) inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. When

starting or using such products in combination with Competact, close monitoring of renal function is

necessary.

[...]

:ןכרצל ןולעב םינוכדע

2

ינפל . הפורתב שומישה

שמתשהל ןיא הפורתב

:םא

]...[

היה

ךל

הנורחאל

ףקתה

בל

שי

ךל

תויעב

תורומח

רוזחמב

םדה

ללוכ

םלה

קוש

וא

יישק

המישנ

ךל שי ,לושלש ,תואקה ,תוליחב ,)םדב ההובג זוקולג תמר( הרומח הימקילגרפיה אמגודל םע ,תנזואמ הנניאש תרכוס תיטקל תצמח ,ריהמ לקשמ דוביא תצמח .)סיזודיצאוטק( תיטוטק תצמח וא )"תיטקל תצמחל ןוכיס" ףיעס האר( רשאו םדב םירבטצמ "ןוטק יפוג" םיארקנה םירמוח ובש בצמ הניה תיטוטק ולע םורטל םורגל ל

.תיתרכוס תמדרת הריהמ המישנ ,ןטב באכ םיללוכ םינימסתה

.הפהמ גירח קתקתמ חיר וא תוינונשי ,הקומעו

.תוילכב היעבמ לבוס ךניהו הדימב הפורתב שמתשהל ןיא דורי יתיילכ דוקפת ךל שי רומח ןפואב

]...[

הפורתב שומישל תועגונה תודחוימ תורהזא

]...[

תצמחל ןוכיס תיטקל

דואמ הרידנ יאוול תעפותל םורגל הלולע טקטפמוק דואמ הרומח ךא ךלש תוילכה םא דחוימב ,תיטקל תצמח םשב .יוארכ תודקפתמ ןניא םימוהיז ,תנזואמ הנניאש תרכוס :םיאבה םיבצמב םג הלוע תיטקל תצמח תוחתפתהל ןוכיסה ךשוממ םוצ ,םירומח

,לוהוכלא תכירצ וא רחא יאופר בצמ לכו ,דבכב תויעב ,)ךשמהב ףסונ עדימ האר( תושבייתה .)הפירח הרומח בל תלחמ ומכ( ףוגהמ קלחל תתחפומ ןצמח תקפסא שי ובש

.תופסונ תויחנה תלבקל ךלש אפורל הנפ ,ךילע לח הלא םיבצממ דחא םא

רושק תויהל לולעה בצמ ךל שי םא רצק ןמז קרפל טקטפמוק לוטיל קיספהל שי תושבייתהל

לש יתועמשמ דוביא( אפורל הנפ .ליגרהמ םילזונ תוחפ התוש התא םא וא םוחל הפישח ,םוח ,לושלש ,תורומח תואקה ןוגכ )ףוגהמ םילזונ .תופסונ תויחנה תלבקל ךלש

אפורל דימ תונפלו טקטפמוק לוטיל קיספהל שי לש םינימסתהמ קלח הווח התא םא בורקה םילוחה תיבל וא תיטקל תצמח

,

תמדרתל םורגל לולע הז בצמו תויה :םיללוכ תיטקל תצמח לש םינימסת .

תואקה

ןטב באכ

םירירש תויוצווכתה

הרומח תופייע םע הבוט אל תיללכ השגרה

המישנב ישוק

קפודבו ףוגה םוחב הדירי

.םילוח תיבב תלפוטמ תויהל תבייח איהו יאופר םוריח בצמ הניה תיטקל תצמח

]...[

הימקילגופיה

ךלש םדב רכוסה תמרש רתוי ההובג תוריבס תמייק ,תרכוסל תורחא תופורת םע בולישב טקטפמוק לטונ התא םא .)הימקילגופיה( הניקתה המרל תחתמ דרת העזה ,תרוחרחס ,השלוח ןוגכ הימקילגופיה לש םינימסת הווח התא םא

ס טעמ לוטיל ךילע ,זוכירב ישוק וא הייארב תוערפה ,ריהמ קפוד ,תרבגומ רכוסה תמר תא בוש תולעהל תנמ לע רכו רפסמ ךתיא חקיתש ץלמומ .הז בצמ תוהזל דציכ חוטב ךניא םא ףסונ עדימל חקורב וא אפורב ץעוויה .ךלש םדב .קותמ תוריפ ץימ וא םיטיווקסיב ,הקיתמ ירבד ,רכוס תויבוק

]...[

ןיב תובוגת

-

תויתפורת

לש הקירז לבקל ךירצ התא םא ליכמה דוגינ רמוח דוי וא ןגטנר םוליצ לש רשקהב אמגודל ,םדה רוזחמ ךותל הקירס

לופיטל רוזחל ךילע יתמו קיספהל ךילע יתמ טילחי ךלש אפורה .הקרזהה תעב וא ינפל טקטפמוק לוטיל קיספהל ךילע .טקטפמוקב

רפס ,הנוזת יפסותו םשרמ אלל תופורת ללוכ תורחא תופורת ,הנורחאל תחקל םא וא ,חקול התא םא ךכ לע .חקורל וא אפורל

םדב זוקולג תוקידב עצבל ךרטצתש ןכתיי ךלש אפורהש וא רתוי ההובג תורידתב תוילכ ידוקפתו טקטפמוק לש ןונימה תא םיאתהל ךרטצי

:תואבה תופורתה תא לטונ התא םא אפורל חוודל שי דחוימב

]...[

אורטס םניאש תקלד ידגונ( תקלדבו באכב לופיטל תושמשמה תופורת ( םידי

NSAIDS

יבכעמו )

COX-2

ןוגכ , )ביסקוקלסו ןפורפוביא

ןיסנטויגנא ךפהמה םיזנאה יבכעמ( הובג םד ץחלב לופיטל תומיוסמ תופורת

(ACE)

םינטלוקה ימסוחו ןיסנטויגנאל

]...[

הקנהו ןויריה

תננכתמ תאש וא ןויריהב תויהל היושע תאש תבשוח ,ןויריהב תא םא אפורה תא עדייל ךילע

הניא טקטפמוק .ןויריה וז הפורת לוטיל קיספהל ךל ץעיי ךלש אפורה ,ןויריהל סנכיהל תננכתמ תא םא .ןויריהב תצלמומ

.ןוירה תננכתמ וא ןוירהב ךניה םא וז הפורתב שמתשהל ןיא

]...[

3

?הפורתב שמתשת דציכ .

]...[

תודרפנ תוילבטכ תחקל ךילע היהיו ןכתיי רשא ,רתוי ךומנ ןונימ םושרי אפורהש ןכתיי ,דורי יתיילכ דוקפת ךל שי םא ןימרופטמו ןוזאטילגויפ לש

]...[

רתוי הובג ןונימ תלטנ םא

]...[

תיטקל תצמח הווחתש ןכתיי ,טקטפמוק לש רתי ןונימ תלטנ םא

ףיעס האר(

.)"תיטקל תצמחל ןוכיס"

הפורתה תליטנ תא קיספמ התא םא

לע םוי לכב טקטפמוק לוטיל שי

.יוארכ לעפי אוהש תנמ ךלש םדב רכוסה תמר ,טקטפמוק לוטיל קיספמ התא םא .הלעת

.הז לופיט תקספה ינפל ךלש אפורב ץעוויה

]...[

4

יאוול תועפות .

]...[

טקטפמוק

הלולע

םורגל

תעפותל

יאוול

הרידנ

דואמ

העיפשמ

לע

דע

ךותמ

םישמתשמ

ךא

הרומח

דואמ

תארקנה

תצמח

תיטקל

האר

ףיעס

"

ןוכיס

תצמחל

תיטקל

.)"

םא

תעפות

יאוול

וז

העיפומ

ךילע

קיספהל

לוטיל

טקטפמוק

תונפלו

דימ

אפורל

וא

תיבל

םילוחה

בורקה

רתויב

תויה

תצמחו

תיטקל

הלולע

םורגל

תמדרתל

חיכש ןפואב וחווד תומצעב םירבש

דע לע עיפשמ

ךותמ

םישמתשמ

טקטפמוק תולטונה םישנב

םג וחוודו טקטפמוק םילטונה םירבגב

םימייקה םינותנהמ תוחיכשה תא ךירעהל ןתינ אל

וז יאוול תעפות הווח התא םא

ירשפאה םדקהב אפורב ץעוויה

]...[

ולעה אפורל םינ

ו

חלשנ ןכרצל

ו

תואירבה דרשמ לש טנרטניאה רתאבש תופורתה רגאמב םוסרפל

http://www.health.gov.il

לבקל ןתינו ,

ם

ספדומ םי

.עבט תרבחל הינפ י"ע

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