COAPROVEL 300 mg/25 mg FILM-COATED TABLETS

2. What you need to know before you take CoAprovel

Do not take CoAprovel

• if you are allergicto irbesartan or any of the other ingredients of this medicine (listed in section 6)
• if you are allergicto hydrochlorothiazide or any other sulfonamide-derived medicines
• if you are more than 3 months pregnant. (In any case, it is recommended to avoid taking this medicine during the first trimester of pregnancy – see section “Pregnancy”)
• if you have severe liver or kidney problems
• if you have difficulty urinating
• if your doctor detects that you have persistently high calcium or low potassium levels in your blood
• if you have diabetes or kidney impairmentand are being treated with a blood pressure-lowering medicine containing aliskiren.

Warnings and precautions

Consult your doctor before starting to take CoAprovel and in any of the following cases:

• if you have excessive vomiting or diarrhea
• if you have kidney problemsor have had a kidney transplant
• if you have heart problems
• if you have liver problems
• if you have diabetes
• if you experience low blood sugar levels(symptoms may include sweating, weakness, hunger, dizziness, trembling, headache, flushing, or paleness), 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 related to excessive production of the hormone aldosterone, leading to sodium retention and increased blood pressure)
• if you are taking any of the following medicines used to treat high blood pressure:

• an angiotensin-converting enzyme inhibitor (ACE inhibitor) (e.g., enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes.
• aliskiren.
• if you have had skin cancer or if you develop an unexpected skin lesionduring treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of certain types of skin cancer and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking CoAprovel.
• if you have had respiratory or lung problems(such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience shortness of breath or difficulty breathing after taking CoAprovel, seek medical attention immediately.

Your doctor may monitor your kidney function, blood pressure, and blood electrolyte levels (e.g., potassium) at regular intervals.

Consult your doctor if you experience abdominal pain, nausea, vomiting, or diarrhea after taking CoAprovel. Your doctor will decide whether to continue treatment. Do not stop taking CoAprovel on your own.

See also the information under the heading “Do not take CoAprovel”.

If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor. CoAprovel is not recommended during the first trimester of pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to your baby (see section “Pregnancy”).

You must also inform your doctor:

• if you are on a low-salt diet
• if you experience any of the following signs: feeling thirsty, dry mouth, weakness, feeling sleepy, muscle cramps, nausea, vomiting, or rapid heartbeat, as these may indicate an excessive effect of hydrochlorothiazide (contained in CoAprovel)
• if you experience an increased sensitivity of your skin to the sunwith symptoms of sunburn (such as redness, itching, swelling, blisters) that occurs more quickly than usual
• if you are going to have surgery(surgical procedure) or if you are going to be administeredanesthetics.
• if you experience decreased vision or eye painwhen 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 can occur within hours to a week after taking CoAprovel. This can lead to permanent vision loss if not treated. If you have previously been allergic to penicillin or sulfonamide, you may be at higher risk of developing this. You must discontinue treatment with CoAprovel and seek immediate medical attention.

Hydrochlorothiazide contained in this medicine may cause positive results in doping tests.

Children and adolescents

CoAprovel must not be given to children and adolescents (under 18 years of age).

Using CoAprovel with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Diuretics, such as hydrochlorothiazide contained in CoAprovel, may affect other medicines. Do not take preparations containing lithium with CoAprovel without your doctor's supervision.

Your doctor may need to adjust your dose and/or take other precautions:

If you are taking an angiotensin-converting enzyme inhibitor (ACE inhibitor) or aliskiren (see also the information under the headings “Do not take CoAprovel” and “Warnings and precautions”).

You may need to have blood tests if you take:

• potassium supplements
• potassium-containing salt substitutes
• potassium-sparing diuretics or other diuretics (tablets that increase urine production)
• certain laxatives
• medicines used to treat gout
• vitamin D supplements
• medicines to control heart rhythm
• medicines for diabetes (oral agents such as repaglinide or insulins)
• carbamazepine (a medicine for treating epilepsy)

It is also important to inform your doctor if you are taking other medicines to lower your blood pressure, steroids, medicines to treat cancer, painkillers, medicines for arthritis, or cholestyramine or colestipol resins to lower cholesterol in the blood.

Taking CoAprovel with food, drinks, and alcohol

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 experience increased dizziness when standing up, especially when getting up from a sitting or lying position.

Pregnancy, breastfeeding, and fertility

Pregnancy

Inform your doctor if you are pregnant, think you may be pregnant, or are planning to become pregnant. Your doctor will normally advise you to stop taking CoAprovel before you become pregnant or as soon as you know you are pregnant and will recommend that you take another medicine to lower your blood pressure instead. CoAprovel is not recommended during the first trimester of pregnancy and must not be taken after the third month of pregnancy, as it may cause serious harm to your baby.

Breastfeeding

Inform your doctor if you are about to start or are breastfeeding. CoAprovel is not recommended for women who are breastfeeding, and your doctor may decide to give you a different treatment that is more suitable, especially if you are breastfeeding a newborn or premature baby.

Driving and using machines

CoAprovel is unlikely to affect your ability to drive or use machines. However, during treatment for high blood pressure, dizziness or fatigue may occasionally occur. If you experience these symptoms, talk to your doctor before driving or using machines.

CoAprovel contains lactose. If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

CoAprovel contains sodium. This medicine contains less than 1 mmol of sodium (23 mg) per tablet, which is essentially “sodium-free”.

3. How to take CoAprovel

Take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.

Dose

The recommended dose of CoAprovel is one tablet per day. In general, your doctor will prescribe CoAprovel when previous treatments you have taken have not adequately controlled your blood pressure. Your doctor will tell you how to switch from your previous treatments to CoAprovel.

Method of administration

CoAprovel is taken by mouth. The tablets should be swallowed with a sufficient amount of liquid (e.g., a glass of water). You can take CoAprovel with or without food. Try to take your daily dose at the same time each day. It is important to continue taking CoAprovel until your doctor tells you to stop.

The maximum blood pressure-lowering effect should be achieved after 6-8 weeks of 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 some tablets, contact your doctor immediately.

If you forget to take CoAprovel

If you accidentally miss a dose, simply take your normal dose when it is due. Do not take a double dose to make up for a forgotten dose.

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

4. Possible side effects

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

Some of these side effects can be serious and may require medical attention.

Rarely, cases of allergic skin reactions (rash, urticaria) have been reported in patients treated with irbesartan, as well as localized swelling in the face, lips, and/or tongue. If you have any of these symptoms or experience difficulty breathing, stop taking CoAprovel and contact your doctor immediately.

The frequency of side effects 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 for patients treated with CoAprovel were:

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

• nausea/vomiting
• urination abnormalities
• fatigue
• dizziness (including dizziness when standing up from a lying or sitting position)
• blood tests may show elevated levels of an enzyme that measures muscle and heart function (creatine kinase) or elevated levels of substances that measure kidney function (urea, creatinine).

If any of these side effects bother you, talk to your doctor

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

• diarrhea
• low blood pressure
• fainting
• rapid heartbeat
• flushing
• swelling due to fluid retention (edema)
• sexual dysfunction (sexual function disorders)
• blood tests may show low sodium and potassium levels in your blood.

If any of these side effects bother you, talk to your doctor

Side effects reported since CoAprovel has been on the market

Since CoAprovel has been on the market, some side effects have been reported. The frequency of these side effects is not known: headache, ringing in the ears, cough, altered taste, indigestion, muscle and joint pain, liver function disorders, kidney failure, high potassium levels in the blood, and allergic reactions such as rash, urticaria, swelling of the face, lips, mouth, tongue, or throat. Rare cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been reported.

As with all combinations of two active substances, it cannot be excluded that side effects associated with each of the components may occur.

Side effects associated only with irbesartan

In addition to the side effects described above, the following have also been reported: chest pain, severe allergic reactions (anaphylactic shock), decreased red blood cell count (anemia - symptoms may include tiredness, headaches, difficulty breathing when exercising, dizziness, and paleness), and decreased platelet count, as well as low blood sugar levels.

Rare (may affect up to 1 in 1,000 people): intestinal angioedema: swelling in the intestine that presents with symptoms such as abdominal pain, nausea, vomiting, and diarrhea.

Side effects associated with hydrochlorothiazide in monotherapy

Lack of appetite; stomach upset; stomach cramps; constipation; jaundice (yellowing of the skin and/or whites of the eyes); pancreatitis characterized by severe upper stomach pain, often with nausea and vomiting; sleep disorders; depression; blurred vision; low white blood cell count, which can lead to frequent infections, fever; decreased platelet count (a blood cell essential for blood clotting), decreased red blood cell count (anemia) characterized by tiredness, headaches, difficulty breathing when exercising, dizziness, and paleness; kidney disease; lung disorders including pneumonia or fluid accumulation in the lungs; increased sensitivity of the skin to the sun; blood vessel inflammation; a skin disease characterized by peeling of the skin all over the body; cutaneous lupus erythematosus, which is identified by a rash that can appear on the face, neck, and scalp; allergic reactions; weakness and muscle spasms; irregular heartbeat; low blood pressure after changing body position; swelling of the salivary glands; high blood sugar levels; sugar in the urine; increased levels of certain blood fats; high uric acid levels in the blood, which can cause gout.

Very rare:Acute respiratory distress (signs include severe difficulty breathing, fever, weakness, and confusion).

Frequency “not known”(cannot be estimated from available data): skin cancer 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 glaucoma).

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

Reporting of side effects

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

5. Storage of CoAprovel

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

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

Do not store above 30 °C.

Store in the original package to protect from moisture.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help to protect the environment.

6. Package contents and further information

Composition of CoAprovel

• The active substances are irbesartan and hydrochlorothiazide. Each film-coated tablet of CoAprovel 300 mg/25 mg contains 300 mg of irbesartan and 25 mg of hydrochlorothiazide.
• The other ingredients are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, colloidal silicon dioxide, magnesium stearate, titanium dioxide, macrogol 3350, red, yellow, and black iron oxides, pregelatinized starch, carnauba wax. See section 2 "CoAprovel contains lactose".

Appearance and package contents of the product

The film-coated tablets of CoAprovel 300 mg/25 mg are pink, biconvex, oval-shaped, with a heart-shaped indentation on one side and the number 2788 engraved on the other.

CoAprovel 300 mg/25 mg film-coated tablets are available in blister packs of 14, 28, 30, 56, 84, 90, or 98 film-coated tablets. They are also available in unit dose blister packs of 56 x 1 film-coated tablet for hospital use.

Not all pack sizes may be marketed.

Marketing authorisation holder

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Manufacturer

SANOFI WINTHROP INDUSTRIE1, rue de la ViergeAmbarès & LagraveF‑33565 Carbon Blanc Cedex - France

SANOFI WINTHROP INDUSTRIE30-36 Avenue Gustave Eiffel37100 Tours - France

For further information about this medicine, please contact the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:

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