Coaprovel: detailed information

Patient Information Leaflet

CoAprovel 150 mg/12.5 mg tablets

irbesartan/hydrochlorothiazide
Please read 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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people. This medicine may be harmful to others, even if their symptoms are the same as yours.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What CoAprovel is and what it is used for
What you need to know before taking CoAprovel
How to take CoAprovel
Possible side effects
How to store CoAprovel
Contents of the pack and other information

1. What CoAprovel is and what it is used for

CoAprovel is a combination of two active substances: irbesartan and hydrochlorothiazide.
Irbesartan belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II is a substance produced in the body that binds to its receptors located on blood vessels, causing them to narrow. This leads to an increase in blood pressure. Irbesartan prevents angiotensin-II from binding to these receptors, resulting in relaxation of the blood vessels and a reduction in blood pressure.
Hydrochlorothiazide belongs to a group of medicines (so-called thiazide diuretics) that increase urine production, thereby lowering blood pressure.
The two active ingredients in CoAprovel work together to reduce blood pressure to a greater extent than either medicine given alone.
CoAprovel is used to treat high blood pressure when treatment with irbesartan or hydrochlorothiazide alone has not adequately controlled your blood pressure.

2. What you need to know before taking CoAprovel

Do not take CoAprovel

if you are allergic to irbesartan or to any of the other ingredients of this medicine (listed in section 6).
if you are allergic to hydrochlorothiazide or to any sulfonamide-derived medicines
if you are more than 3 months pregnant (it is better to avoid taking CoAprovel even in early pregnancy - see Pregnancy section)
if you have severe liver or kidney problems
if you have difficulty urinating
if your doctor finds you have persistently high calcium levels or low potassium levels in the blood
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren.

Warnings and precautions
Talk to your doctor before taking CoAprovel and if you are in any of the following conditions:

excessive vomiting or diarrhoea
if you have kidney disorders or have had a kidney transplant
if you have heart problems
if you have liver disorders
if you have diabetes
if you develop low blood sugar levels (symptoms may include sweating, weakness, hunger, dizziness, trembling, headache, flushing or paleness, numbness, rapid and pounding heartbeat), especially if you are being treated for diabetes
if you have systemic lupus erythematosus (also known as lupus or SLE)
if you have primary hyperaldosteronism (a condition involving excessive production of the hormone aldosterone, causing sodium retention and subsequently increased blood pressure)
if you are taking any of the following medicines used to treat high blood pressure:
- an "ACE inhibitor" (e.g., enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes
- aliskiren
if you have previously had skin cancer or are developing an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of non-melanoma skin cancer and lip cancer. Protect your skin from sun and UV exposure while taking CoAprovel.
if you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop severe shortness of breath or difficulty breathing after taking CoAprovel, contact a doctor immediately.

Your doctor may check your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals.
See also the section "Do not take CoAprovel".
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). CoAprovel is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn baby if taken during this period (see Pregnancy section).
Also, inform your doctor:

if you are on a low-salt diet
if you experience symptoms such as excessive thirst, dry mouth, general weakness, drowsiness, muscle pain or cramps, nausea, vomiting, or an excessively rapid heartbeat, which may indicate an excessive effect of hydrochlorothiazide (contained in CoAprovel)
if you have noticed an unusually fast increase in skin sensitivity to sunlight, with symptoms of sunburn (such as redness, itching, swelling, rash)
if you are scheduled for surgery or need to take anaesthetics
if you experience vision changes or eye pain in one or both eyes while taking CoAprovel. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased eye pressure (glaucoma), which may occur from a few hours to a week after taking CoAprovel. If left untreated, these may lead to permanent vision loss. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing this condition. You must stop taking CoAprovel and contact your doctor promptly.

Hydrochlorothiazide, contained in this medicine, may produce positive results in anti-doping tests.
Children and adolescents
CoAprovel must not be given to children and adolescents (under 18 years of age).
Other medicines and CoAprovel
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Diuretics such as hydrochlorothiazide contained in CoAprovel may interact with other medicines. Preparations containing lithium must not be taken together with CoAprovel unless under strict medical supervision.
Your doctor may consider it necessary to adjust the dose and/or take other precautions:
If you are taking an ACE inhibitor or aliskiren (see also sections "Do not take CoAprovel" and "Warnings and precautions").
You may need blood tests if you are taking:

potassium supplements
salt substitutes containing potassium
potassium-sparing agents or other diuretics
certain laxatives
medicines for the treatment of gout
vitamin D supplements
medicines to control heart rhythm
medicines for diabetes (oral antidiabetics such as repaglinide or insulin)
carbamazepine (a medicine used to treat epilepsy).

It is also important to inform your doctor if you are taking other medicines to lower blood pressure, steroids, cancer treatments, painkillers, medicines for arthritis, or cholestyramine and colestipol to lower blood cholesterol levels.
CoAprovel with food and drink
CoAprovel can be taken with or without food.
Due to the hydrochlorothiazide contained in CoAprovel, if you drink alcohol while being treated with this medicine, you may feel more dizzy when standing up, especially when changing from a sitting to an upright position.
Pregnancy, breast-feeding and fertility
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking CoAprovel before becoming pregnant or as soon as you know you are pregnant, and will recommend another medicine instead of CoAprovel. CoAprovel is not recommended during early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn baby if taken after the third month of pregnancy.
Breast-feeding
Inform your doctor if you are breast-feeding or planning to breast-feed. CoAprovel is not recommended for women who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if the baby is a newborn or was born prematurely.
Driving and using machines
It is unlikely that CoAprovel will affect your ability to drive or operate machinery.
However, dizziness or fatigue may occasionally occur during treatment for high blood pressure. If this happens to you, talk to your doctor before driving or using machinery.
CoAprovel contains lactose. If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.
CoAprovel contains sodium. This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially 'sodium-free'.

3. How to take CoAprovel

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Dosage
The recommended dose of CoAprovel is one or two tablets daily. CoAprovel will be prescribed by your doctor if your previous treatment has not sufficiently lowered your blood pressure. Your doctor will advise you on how to switch from your previous treatment to CoAprovel.
Method of administration
CoAprovel is for oral use. Swallow the tablets with a sufficient amount of liquid (for example, a glass of water). You may take CoAprovel with or without food. Try to take the medicine at the same time every day. It is important to continue treatment unless otherwise instructed by your doctor.
Maximum blood pressure-lowering effect is achieved within 6-8 weeks after starting treatment.
If you take more CoAprovel than you should
If you accidentally take too many tablets, contact your doctor immediately.
Children must not take CoAprovel
CoAprovel must not be given to children under 18 years of age. If a child swallows any tablets, contact your doctor immediately.
If you forget to take CoAprovel
If you forget to take a dose, simply take the next dose as scheduled. Do not take a double dose to make up for the missed dose.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Some of these effects may be serious and may require medical attention.
Rare cases of skin allergic reactions (rash, urticaria) as well as localized swelling of the face, lips and/or tongue have been reported in patients treated with irbesartan. If you experience any of these symptoms or have difficulty breathing, stop taking CoAprovel and contact your doctor immediately.

The frequency of the side effects listed below is defined using the following convention:
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people

The side effects reported in clinical studies in patients treated with CoAprovel were:

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

nausea/vomiting
urinary disorders
fatigue
dizziness (also when moving from a sitting or lying position to standing)
blood tests may show increased levels of an enzyme that measures muscle and heart function (creatine kinase) or increased levels of substances that measure kidney function (azotemia, creatinine). Inform your doctor if any of these side effects cause you problems.

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

diarrhoea
hypotension
weakness
rapid heartbeat
hot flushes
swelling
sexual dysfunction (problems with sexual activity)
blood tests may show decreased levels of potassium and sodium in the blood. Inform your doctor if any of these side effects cause you problems.

Side effects reported after the marketing of CoAprovel
Since the launch of CoAprovel, some side effects have been reported. The side effects with unknown frequency include headache, tinnitus, cough, taste disturbances, indigestion, joint and muscle pain, liver function abnormalities and renal dysfunction, elevated blood potassium levels, and allergic reactions (rash, urticaria, localized swelling of the face, lips, mouth, tongue or throat). Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported.
As with any combination of two active substances, side effects associated with each component cannot be excluded.

Side effects associated with irbesartan alone
In addition to the side effects listed above, chest pain, severe allergic reactions (anaphylactic shock), reduced number of red blood cells (anaemia - symptoms may include fatigue, headache, shortness of breath during physical activity, dizziness and pale appearance), and reduced platelet count (blood cells essential for blood clotting) have also been reported.

Side effects associated with hydrochlorothiazide alone
Loss of appetite; stomach irritation; stomach cramps; constipation; jaundice (yellowing of the skin and/or whites of the eyes); inflammation of the pancreas characterized by severe pain in the upper stomach, often with nausea and vomiting; sleep disorders; depression; blurred vision; lack of white blood cells, which may lead to frequent infections and fever; reduced platelet count (a component essential for blood clotting), reduced red blood cell count (anaemia) characterized by fatigue, headache, shortness of breath during exercise, dizziness and pale appearance; kidney problems; lung problems including pneumonia or fluid accumulation in the lungs; increased sensitivity of the skin to sunlight; inflammation of blood vessels; a skin disorder characterized by peeling of the skin over the entire body; lupus erythematosus, identified by a rash that may appear on the face, neck and scalp; allergic reactions; muscle weakness and spasms; altered heartbeat; drop in blood pressure upon changing body position; swelling of the salivary glands; elevated blood sugar levels; sugar in the urine; increases in certain types of fat in the blood; elevated levels of uric acid in the blood which may cause gout.

Very rare (may affect up to 1 in 10,000 people): acute respiratory distress (symptoms include severe shortness of breath, fever, weakness and confusion).

Not known (frequency cannot be estimated from the available data): skin and lip cancer (non-melanoma skin cancer), decreased vision or eye pain due to increased pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma).

It is known that side effects associated with hydrochlorothiazide may increase with higher doses of hydrochlorothiazide.

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

5. How to store CoAprovel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
Do not store above 30°C.
Store in the original packaging to protect from moisture.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What CoAprovel contains

The active substances are irbesartan and hydrochlorothiazide. Each CoAprovel 150 mg/12.5 mg tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
The other components are: microcrystalline cellulose, cross-linked sodium carmellose, monohydrate lactose, magnesium stearate, hydrated colloidal silica, pregelatinized corn starch, red and yellow iron oxides (E172). See Section 2 “CoAprovel contains lactose”.

Description of the appearance of CoAprovel and package contents
CoAprovel 150 mg/12.5 mg tablets are peach-coloured, biconvex, oval, with a heart imprint on one side and the number 2775 on the other side.
CoAprovel 150 mg/12.5 mg tablets are supplied in packs containing blisters of 14, 28, 56, or 98 tablets. Packs containing unit-dose divisible blisters of 56 x 1 tablet for hospital use are also available.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Sanofi Winthrop Industrie
82 avenue Raspail
94250 Gentilly
France

Manufacturer
SANOFI WINTHROP INDUSTRIE
1, rue de la Vierge
Ambarès & Lagrave
F-33565 Carbon Blanc Cedex - France
SANOFI WINTHROP INDUSTRIE
30-36 Avenue Gustave Eiffel
37100 Tours - France

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Sanofi Belgium Swixx Biopharma UAB
Tél/Tel: +32 (0)2 710 54 00 Tel: +370 5 236 91 40

България Luxembourg/Luxemburg
Swixx Biopharma EOOD Sanofi Belgium
Тел.: +359 (0)2 4942 480 Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika Magyarország
sanofi-aventis, s.r.o. sanofi-aventis zrt., Magyarország
Tel: +420 233 086 111 Tel.: +36 1 505 0050

Danmark Malta
Sanofi A/S Sanofi S.r.l.
Tlf: +45 45 16 70 00 Tel: +39 02 39394275

Deutschland Nederland
Sanofi-Aventis Deutschland GmbH Sanofi B.V.
Tel: 0800 52 52 010 Tel: +31 20 245 4000
Tel. aus dem Ausland: +49 69 305 21 131

Eesti Norge
Swixx Biopharma OÜ sanofi-aventis Norge AS
Tel: +372 640 10 30 Tlf: +47 67 10 71 00

Ελλάδα Österreich
Sanofi-Aventis Μονοπρόσωπη AEBE sanofi-aventis GmbH
Τηλ: +30 210 900 16 00 Tel: +43 1 80 185 – 0

España Polska
sanofi-aventis, S.A. sanofi-aventis Sp. z o.o.
Tel: +34 93 485 94 00 Tel.: +48 22 280 00 00

France Portugal
Sanofi Winthrop Industrie Sanofi - Produtos Farmacêuticos, Lda
Tél: 0 800 222 555 Tel: +351 21 35 89 400
Appel depuis l’étranger: +33 1 57 63 23 23

Hrvatska România
Swixx Biopharma d.o.o. Sanofi Romania SRL
Tel: +385 1 2078 500 Tel: +40 (0) 21 317 31 36

Ireland Slovenija
sanofi-aventis Ireland Ltd. T/A SANOFI Swixx Biopharma d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 235 51 00

Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 208 33 600

Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: 800 536389 Puh/Tel: +358 (0) 201 200 300

Κύπρος Sverige
C.A. Papaellinas Ltd. Sanofi AB
Τηλ: +357 22 741741 Tel: +46 (0)8 634 50 00

Latvija United Kingdom (Northern Ireland)
Swixx Biopharma SIA sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6616 47 50 Tel: +44 (0) 800 035 2525

More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu.

Patient Information Leaflet

CoAprovel 300 mg/12.5 mg tablets

irbesartan/hydrochlorothiazide
Please read this leaflet carefully before you start taking this medicine, as it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people. This medicine may be harmful even if their symptoms are the same as yours.
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

What CoAprovel is and what it is used for
What you need to know before taking CoAprovel
How to take CoAprovel
Possible side effects
How to store CoAprovel
Contents of the pack and other information

1. What CoAprovel is and what it is used for

CoAprovel is a combination of two active substances: irbesartan and hydrochlorothiazide.
Irbesartan belongs to a group of medicines known as angiotensin-II receptor antagonists. Angiotensin-II is a substance produced in the body that binds to its receptors located on blood vessels, causing them to narrow. This leads to an increase in blood pressure. Irbesartan prevents angiotensin-II from binding to these receptors, resulting in relaxation of the blood vessels and a lowering of blood pressure.
Hydrochlorothiazide belongs to a group of medicines (so-called thiazide diuretics) that increase urine production, thereby lowering blood pressure.
The two active ingredients in CoAprovel work together to reduce blood pressure to a greater extent than either medicine alone.
CoAprovel is used to treat high blood pressure when treatment with either irbesartan or hydrochlorothiazide alone has not adequately controlled your blood pressure.

2. What you should know before taking CoAprovel

Do not take CoAprovel

if you are allergic to irbesartan or to any of the other ingredients of this medicine (listed in section 6).
if you are allergic to hydrochlorothiazide or to any sulfonamide-derived medicines
if you are more than 3 months pregnant (it is better to avoid taking CoAprovel even in early pregnancy – see section Pregnancy)
if you have severe liver or kidney problems
if you have difficulty urinating
if your doctor finds that you have persistently high calcium levels or low potassium levels in the blood
if you have diabetes or impaired kidney function and are being treated with a blood pressure-lowering medicine containing aliskiren

Warnings and precautions
Talk to your doctor before taking CoAprovel if you are in any of the following situations:

excessive vomiting or diarrhoea
if you have kidney problems or have had a kidney transplant
if you have heart problems
if you have liver problems
if you have diabetes
if you develop low blood sugar levels (symptoms may include sweating, weakness, hunger, dizziness, trembling, headache, flushing or paleness, numbness, rapid and pounding heartbeat), especially if you are being treated for diabetes
if you have systemic lupus erythematosus (also known as lupus or SLE)
if you have primary hyperaldosteronism (a condition involving excessive production of the hormone aldosterone, leading to sodium retention and subsequently increased blood pressure)
if you are taking any of the following medicines used to treat high blood pressure:
- an "ACE inhibitor" (e.g. enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes
- aliskiren
if you have previously had skin cancer or develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from exposure to sunlight and UV rays while taking CoAprovel.
if you have previously experienced breathing or lung problems (including inflammation or fluid in the lungs) after taking hydrochlorothiazide. If you develop shortness of breath or severe difficulty breathing after taking CoAprovel, contact a doctor immediately.

Your doctor may check your kidney function, blood pressure, and levels of electrolytes
(e.g. potassium) in your blood at regular intervals.
See also the section "Do not take CoAprovel".
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming
pregnant). CoAprovel is not recommended in early pregnancy and must not be taken if you are more
than 3 months pregnant, as it may cause serious harm to the unborn baby if taken during this period (see section Pregnancy).
Also, inform your doctor:

if you are on a low-salt diet
if you experience symptoms such as excessive thirst, dry mouth, general weakness, drowsiness, muscle pain or cramps, nausea, vomiting, or an excessively rapid heartbeat, which may indicate an excessive effect of hydrochlorothiazide (contained in CoAprovel)
if you have noticed an unusually rapid increase in sensitivity of the skin to sunlight, with symptoms of sunburn (such as redness, itching, swelling, rash)
if you are due to undergo surgery or to receive anaesthetics
if you experience a decrease in vision or pain in one or both eyes while taking CoAprovel. These could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye (glaucoma), and may occur from a few hours to a week after taking CoAprovel. If untreated, they may lead to permanent loss of vision. If you previously had an allergy to penicillin or sulfonamides, you may be at higher risk of developing this condition. You must stop taking CoAprovel and consult your doctor promptly.

Hydrochlorothiazide, contained in this medicine, may produce positive results in anti-doping tests.
Children and adolescents
CoAprovel must not be given to children and adolescents (under 18 years of age).
Other medicines and CoAprovel
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Diuretics such as hydrochlorothiazide contained in CoAprovel may interact with other medicines. Medicines containing lithium must not be taken together with CoAprovel unless under strict medical supervision.
Your doctor may consider it necessary to adjust the dose and/or take additional precautions:
If you are taking an ACE inhibitor or aliskiren (see also sections: "Do not take CoAprovel" and "Warnings and precautions").
You may need blood tests if you are using:

potassium supplements
salt substitutes containing potassium
potassium-sparing agents or other diuretics
certain laxatives
medicines for the treatment of gout
vitamin D supplements
medicines to control heart rhythm
medicines for diabetes (oral antidiabetics such as repaglinide or insulin)
carbamazepine (a medicine used to treat epilepsy)

It is also important to inform your doctor if you are taking other medicines to lower blood pressure, steroids, cancer treatments, painkillers, arthritis medicines, or colestyramine and colestipol to lower cholesterol levels in the blood.
CoAprovel with food and drink
CoAprovel can be taken with or without food.
Due to the hydrochlorothiazide contained in CoAprovel, if you drink alcohol while being treated with this medicine, you may feel more dizzy when standing up, especially when moving from a sitting to a standing position.
Pregnancy, breast-feeding and fertility
Pregnancy
You must inform your doctor if you think you are pregnant (or if there is a possibility of becoming pregnant). Your doctor will usually advise you to stop taking CoAprovel before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine instead of CoAprovel. CoAprovel is not recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to the unborn baby if taken after the third month of pregnancy.
Breast-feeding
Inform your doctor if you are breast-feeding or planning to breast-feed. CoAprovel is not recommended for women who are breast-feeding, and your doctor may choose another treatment for you if you wish to breast-feed, especially if the baby is a newborn or was born prematurely.
Driving and using machines
It is unlikely that CoAprovel will affect your ability to drive or use machines.
However, dizziness or fatigue may occasionally occur during treatment for high blood pressure. If this happens to you, talk to your doctor before driving or using machines.
CoAprovel contains lactose. If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.
CoAprovel contains sodium. This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially 'sodium-free'.

3. How to take CoAprovel

Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.
Dosage
The recommended dose of CoAprovel is one tablet daily. CoAprovel will be prescribed by your doctor if your previous treatment has not sufficiently lowered your blood pressure. Your doctor will advise you on how to switch from your previous treatment to CoAprovel.
Method of administration
CoAprovel is for oral use. Swallow the tablets with a sufficient amount of liquid (for example, a glass of water). You may take CoAprovel with or without food. Try to take the medicine at the same time every day. It is important to continue treatment unless otherwise instructed by your doctor.
Maximum blood pressure lowering effect is achieved within 6–8 weeks after starting treatment.
If you take more CoAprovel than you should
If you accidentally take too many tablets, contact your doctor immediately.
Children must not take CoAprovel
CoAprovel must not be given to children under 18 years of age. If a child swallows any tablets, contact your doctor immediately.
If you forget to take CoAprovel
If you forget to take a dose, simply take your next dose at the usual time. Do not take a double dose to make up for the forgotten dose.
If you have any doubts about how to use 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.
Some of these side effects may be serious and may require medical attention.
Rare cases of skin allergic reactions (rash, urticaria) as well as localized swelling of the face, lips and/or tongue have been reported in patients treated with irbesartan. If you experience any of these symptoms or have difficulty breathing, stop taking CoAprovel and contact your doctor immediately.
The frequency of the side effects listed below is defined using the following convention:
Common: may affect up to 1 in 10 people
Uncommon: may affect up to 1 in 100 people

The side effects reported in clinical studies in patients treated with CoAprovel were:

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

nausea/vomiting
urinary disorders
fatigue
dizziness (also when moving from a sitting or lying position to standing)
blood tests may show increased levels of an enzyme that measures muscle and heart function (creatine kinase), or increased levels of substances that measure kidney function (azotemia, creatinine). Inform your doctor if any of these side effects cause you problems.

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

diarrhoea
hypotension
weakness
rapid heartbeat
hot flushes
swelling
sexual dysfunction (problems with sexual activity)
blood tests may show decreased levels of potassium and sodium in the blood. Inform your doctor if any of these side effects cause you problems.

Side effects reported after the marketing of CoAprovel
Since CoAprovel has been marketed, some side effects have been reported. The frequency of these side effects is not known: headache, tinnitus, cough, taste disturbances, indigestion, joint and muscle pain, liver function abnormalities and renal dysfunction, elevated potassium levels in the blood, and allergic reactions (rash, urticaria, localized swelling of the face, lips, mouth, tongue or throat). Uncommon cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported.
As with any combination of two active substances, side effects associated with each component cannot be excluded.

Side effects associated with irbesartan alone
In addition to the side effects listed above, chest pain, severe allergic reactions (anaphylactic shock), reduced number of red blood cells (anaemia – symptoms may include tiredness, headache, shortness of breath during physical activity, dizziness and pale appearance), and reduced number of platelets (blood cells essential for blood clotting) have been reported.

Side effects associated with hydrochlorothiazide alone
Loss of appetite; stomach irritation; stomach cramps; constipation; jaundice (yellowing of the skin and/or whites of the eyes); inflammation of the pancreas characterised by severe pain in the upper stomach, often with nausea and vomiting; sleep disorders; depression; blurred vision; lack of white blood cells, which may lead to frequent infections and fever; reduced number of platelets (an essential component for blood clotting), reduced number of red blood cells (anaemia) characterised by fatigue, headache, shortness of breath during exercise, dizziness and pale appearance; kidney problems; lung problems including pneumonia or fluid accumulation in the lungs; increased sensitivity of the skin to sunlight; inflammation of blood vessels; a skin disorder characterised by peeling of the skin over the entire body; lupus erythematosus, identified by a rash that may appear on the face, neck and scalp; allergic reactions; muscle weakness and spasms; irregular heartbeat; drop in blood pressure upon changing body position; swelling of the salivary glands; elevated blood sugar levels; sugar in the urine; increases in certain types of fat in the blood; elevated levels of uric acid in the blood which may cause gout.

Very rare (may affect up to 1 in 10,000 people): acute respiratory distress (symptoms include severe shortness of breath, fever, weakness and confusion).

It is known that side effects associated with hydrochlorothiazide may increase with higher doses of hydrochlorothiazide.

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

5. How to store CoAprovel

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after
Exp. The expiry date refers to the last day of that month.
Do not store above 30°C.
Keep in the original packaging to protect from moisture.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What CoAprovel contains

The active substances are irbesartan and hydrochlorothiazide. Each CoAprovel 300 mg/12.5 mg tablet contains 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
The other components are: microcrystalline cellulose, cross-linked carmellose sodium, monohydrate lactose, magnesium stearate, hydrated colloidal silica, pregelatinized maize starch, red and yellow iron oxides (E172). See section 2 "CoAprovel contains lactose".

Description of the appearance of CoAprovel and contents of the pack
CoAprovel 300 mg/12.5 mg tablets are peach-coloured, biconvex, oval tablets, with a heart imprint on one side and the number 2776 on the other side.
CoAprovel 300 mg/12.5 mg tablets are supplied in packs containing blisters of 14, 28, 56, or 98 tablets. Packs containing unit-dose divisible blisters of 56 x 1 tablet for hospital use are also available.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Sanofi Winthrop Industrie
82 avenue Raspail
94250 Gentilly
France

Manufacturer
SANOFI WINTHROP INDUSTRIE
1, rue de la Vierge
Ambarès & Lagrave
F-33565 Carbon Blanc Cedex - France
SANOFI WINTHROP INDUSTRIE
30-36 Avenue Gustave Eiffel
37100 Tours - France

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder: