Prospect: information for the patient
Karvezide 150mg/12,5mg coated tablets

Irbesartán/hidroclorotiazida

Read this prospect thoroughly before starting to take the medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed only to you and should not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor or pharmacist, even if they do not appear in this prospect. See section 4.

1.What Karvezide is and for what it is used

2.What you need to know before starting to take Karvezide

3.How to take Karvezide

4.Possible adverse effects

5.Storage of Karvezide

6.Contents of the package and additional information

Karvezide is a combination of two active principles, irbesartan and hydrochlorothiazide.

Irbesartan belongs to a group of medications known as angiotensin-II receptor antagonists.

Angiotensin-II is a substance produced in the body that binds to blood vessel receptors, causing them to contract. This results in an increase in blood pressure. Irbesartan prevents the binding of angiotensin-II to these receptors, relaxing blood vessels and reducing blood pressure.

Hydrochlorothiazide belongs to a group of medications (called thiazide diuretics) that increase the amount of urine eliminated, reducing blood pressure.

The two active principles of Karvezide act together to achieve a decrease in blood pressure greater than that obtained with each one separately.

Karvezide is used to treat high blood pressure, when treatment with only irbesartan or only hydrochlorothiazide does not provide adequate control of your blood pressure.

Do not take Karvezide

• if you areallergicto irbesartan, or to any of the other ingredients of this medicine (listed in section 6)
• if you areallergicto hydrochlorothiazide or any other sulfonamide-derived medicine
• if you aremore than 3 months pregnant.(In any case, it is better to avoid taking this medicine also at the beginning of your pregnancy – see section “Pregnancy”)
• if you havesevere liver or kidney problems
• if you havedifficulty urinating
• if your doctor detects that you havepersistently elevated calcium levels or low potassium levels in your blood
• if you havediabetes or kidney insufficiencyandare being treated witha blood pressure-lowering medicine that contains aliskiren.

Warnings and precautions

Consult your doctor before starting to takeKarvezide andin any of the following cases:

• if you haveexcessive vomiting or diarrhea
• if you havekidney problemsor have had akidney transplant
• if you haveheart problems
• if you haveliver problems
• if you have diabetes
• if you experiencelow blood sugar levels(symptoms may include sweating, weakness, hunger, dizziness, tremors, headache, flushing, pallor, numbness, rapid and strong heartbeats), especially if you are being treated for diabetes
• if you havelupus erythematosus(also known as lupus or SLE)
• if you haveprimary aldosteronism(a condition related to the excessive production of the hormone aldosterone, which causes sodium retention and, in turn, an increase in blood pressure)
• if you are taking any of the following blood pressure-lowering medicines:

- 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 hadskin cancer or if you develop an unexpected skin lesionduring treatment. The 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 the sun and UV rays while taking Karvezide.
• if you have had respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you experience severe shortness of breath or difficulty breathing after taking Karvezide, seek medical attention immediately.

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

Consult your doctor if you experience abdominal pain, nausea, vomiting, or diarrhea after takingKarvezide. Your doctor will decide whether to continue treatment. Do not stop taking Karvezide in monotherapy.

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

If you are pregnant, if you suspect you may beor if you plan to become pregnant, you mustinform your doctor. It is not recommended to use Karvezideat the beginning of pregnancy (first 3 months), and in any case, it should not be administered from 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 following alow-sodium diet
• if you experience any of the following symptoms:thirst, dry mouth, generalized weakness, drowsiness, muscle pain or cramps, nausea, vomiting, orrapid heartbeats, as they may indicate excessive hydrochlorothiazide effect (contained in Karvezide)
• if you experience an increase insensitivity to the sunwith symptoms of sunburn (such as redness, itching, swelling, blisters) that occur more quickly than usual
• ifyou are to undergo surgery(surgical intervention) orif you are to receive anesthetics.
• if you experience vision loss or eye pain while taking Karvezide. These may be symptoms of fluid accumulation in the eye's vascular layer (choroidal effusion) or increased eye pressure (glaucoma) and may occur within a few hours to a week after taking Karvezide. This may lead to permanent vision loss if not treated. If you have previously had an allergy to penicillin or sulfonamide, you may be at higher risk of developing it. You must interrupt treatment with Karvezide and seek medical attention immediately.

The hydrochlorothiazide contained in this medicine may cause positive results in doping control.

Children and adolescents

Karvezide should not be administered to children and adolescents (under 18 years old).

Use of Karvezide with other medicines

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medicine.

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

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

if you are taking an ACE inhibitor or aliskiren (see also the information under the headings “Do not take Karvezide” and “Warnings and precautions”).

You may need to have blood tests if you take:

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

You should also inform your doctor if you are taking other blood pressure-lowering medicines, steroids, cancer medicines, painkillers, arthritis medicines, or cholestyramine or colestipol resins to reduce cholesterol in the blood.

Taking Karvezide with food, drinks, and alcohol

Karvezide can be taken with or without food.

Due to the hydrochlorothiazide contained in Karvezide, if you drink alcohol while taking this medicine, you may experience a greater sense of dizziness when standing up, especially when getting up from a seated position.

Pregnancy, breastfeeding, and fertility

Pregnancy

You must inform your doctor if you are pregnant, if you suspect you may beor if you plan to become pregnant. Your doctor will usually advise you to stop taking Karvezide before becoming pregnant or as soon as you become pregnant and recommend taking another antihypertensive medicine instead. It is not recommended to use Karvezide at the beginning of pregnancy and in any case, it should not be administered from the third month of pregnancy, as it may cause serious harm to your baby when administered from that point onwards.

Breastfeeding

Inform your doctor if you plan to start or are breastfeeding, as it is not recommended to administer Karvezide to women during this period. Your doctor may decide to administer a more suitable treatment if you want to breastfeed, especially to newborns or premature babies.

Driving and operating machinery

It is unlikely that Karvezide will affect your ability to drive vehicles or operate machinery. However, during hypertension treatment, you may occasionally experience dizziness or fatigue. If you experience these symptoms, consult your doctor before driving or operating machinery.

Karvezide contains lactose. If your doctor has told you that you have an intolerance to certain sugars (e.g. lactose), consult with them before taking this medicine.

Karvezide contains sodium. This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

Dose

The recommended dose of Karvezide isone or two tabletsper day. In general, your doctor will prescribe Karvezide when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will instruct you on how to switch from previous treatments to Karvezide.

Administration Form

Karvezide is administered byoral route.Tablets should be swallowed with a sufficient amount of liquid (e.g. a glass of water). You can take Karvezide with or without food. Try to take your daily dose at the same time each day. It is essential that you continue taking Karvezide until your doctor advises you otherwise.

The maximum blood pressure-reducing effect should be achieved within 6-8weeks after starting treatment.

If you take more Karvezide than you should

If you accidentally take too many tablets, contact your doctor immediately.

Children should not take Karvezide

Karvezide should not be given to children under 18years of age. If a child swallows some tablets, contact your doctor immediately.

If you forget to take Karvezide

If you accidentally forget to take a dose, simply take your regular dose when it is due next. Do not take a double dose to compensate for the missed doses.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, Karvezide can cause side effects, although not everyone will experience them.

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

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

The frequency of the side effects listed below is defined using the following convention:

Frequent: may affect up to 1 in 10 people

Rare: may affect up to 1 in 100 people

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

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

• Nausea/vomiting
• Urinary abnormalities
• Fatigue
• Dizziness (including dizziness that occurs 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 nitrogen in the blood, creatinine).

If any of these side effects cause you problems, consult your doctor

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

• Dyspepsia
• Low blood pressure
• Fainting
• Tachycardia
• Flushing
• Swelling due to fluid retention (edema)
• Sexual dysfunction (alterations in sexual function)
• Blood tests may show low levels of sodium and potassium in your blood.

If any of these side effects cause you problems, consult your doctor

Side effects since the marketing of Karvezide

Since the marketing ofKarvezide, some side effects have been reported. The side effectsobserved with unknown frequencyare: headache, tinnitus, cough, alteration of taste, indigestion, joint and muscle pain, liver function alterations and kidney insufficiency, elevated levels of potassium in your blood, and allergic reactions such as skin rash, urticaria, facial swelling, lip, mouth, tongue, or throat swelling.Also, cases of jaundice (yellowing of the skin and/or white of the eyes) have been observed.

As with all combinations of two active principles, the side effects associated with each component cannot be ruled out.

Side effects associated only with irbesartan

In addition to the side effects described above, angina pectoris, severe allergic reactions (anaphylactic shock), anemia (the symptoms may include fatigue, headaches, difficulty breathing when exercising, dizziness, and paleness), and low blood sugar levels have been observed.

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

Side effects associated with hydrochlorothiazide in monotherapy

Loss of appetite; stomach irritation; stomach cramps; constipation; jaundice (yellowing of the skin and/or white of the eyes); pancreatitis characterized by severe upper abdominal pain, often with nausea and vomiting; sleep disturbances; depression; blurred vision; lack of white blood cells, which may lead to frequent infections, fever; low platelet count (blood cells essential for blood clotting), low red blood cell count (anemia) characterized by fatigue, headaches, shortness of breath when exercising, dizziness, and paleness; kidney disease; pulmonary disorders including pneumonia or fluid accumulation in the lungs; increased skin sensitivity to the sun; inflammation of blood vessels; a skin disease characterized by peeling of the skin all over the body; cutaneous lupus erythematosus, identified by a rash that may appear on the face, neck, and scalp; allergic reactions; muscle weakness and spasms; alteration of heart rhythm; reduction of blood pressure after a change in body position; swelling of salivary glands; high blood sugar levels; sugar in the urine; increases in some types of blood fats; high levels of uric acid in the blood, which may cause gout.

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

Frequency «unknown»(Cannot be estimated from available data): Skin and lip cancer (non-melanoma skin cancer), decreased vision or eye pain due to high pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma).

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

Reporting of side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly throughthenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the carton and blister after CAD. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Store in the original packaging to protect it from moisture.

Medicines should not be disposed of through drains or trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Karvezide

• The active ingredients are irbesartan and hydrochlorothiazide. Each Karvezide 150 mg/12.5 mg film-coated tablet contains 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
• The other components are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, colloidal silicon dioxide, magnesium stearate, titanium dioxide, macrogol 3000, iron oxide red and yellow, carnauba wax. See section 2 "Karvezide contains lactose".

Appearance of the product and contents of the pack

Karvezide 150 mg/12.5 mg film-coated tablets are orange, biconvex, oval-shaped, with a trochead heart on one face and the number 2875 engraved on the other.

Karvezide 150 mg/12.5 mg film-coated tablets are available in blister packs containing 14, 28, 30, 56, 84, 90 or 98 film-coated tablets. They are also available in a blister pack of 56 x 1 film-coated tablet for hospital supply.

Only some pack sizes may be marketed.

Marketing authorisation holder

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Responsible person

SANOFI WINTHROP INDUSTRIE
1, rue de la Vierge
Ambarès & Lagrave
F-33565Carbon Blanc Cedex - France

SANOFI WINTHROP INDUSTRIE
30-36Avenue Gustave Eiffel
37100Tours - France

SANOFI-AVENTIS, S.A.

Ctra.C-35 (La Batlloria-Hostalric), km. 63.09

17404 Riells i Viabrea (Girona)

Spain

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Last update of the summary of product characteristics:

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