Patient Information Leaflet
Karvezide 300mg/12,5mg Film-Coated Tablets

Irbesartán/hidroclorotiazida

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as 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 pass it on to others even if they have similar symptoms, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1.What Karvezide is and what it is used for

2.What you need to know before you start taking Karvezide

3.How to take Karvezide

4.Possible side effects

5.Storage of Karvezide

6.Contents of the pack 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 components of this medication (listed in section 6)
• if you areallergicto hydrochlorothiazide or any other medication derived from sulfonamides
• if you aremore than 3 months pregnant.(In any case, it is better to avoid taking this medication 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 medication to lower blood pressure 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 havediabetes
• if you experiencelow blood sugar levels(symptoms may include sweating, weakness, hunger, dizziness, tremors, headache, flushing, or paleness, numbness, rapid and strong heartbeats), especially if you are being treated for diabetes
• if you havelupus erythematosus(also known as lupus or LES)
• 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 medications used to treat high blood pressure (hypertension):

- an angiotensin-converting enzyme inhibitor (ACEI) (for example 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 its 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 renal function, blood pressure, and electrolyte levels (such as potassium) at regular intervals.

Consult your doctor if you experience abdominal pain, nausea, vomiting, or diarrhea after taking Karvezide. 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 be pregnantor 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 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 following alow-sodium diet
• if you experience any of the following symptoms:thirst, dry mouth, generalized weakness, feeling of drowsiness, muscle pain or cramps, nausea, vomiting, orrapid heartbeats, as they may indicate an excessive effect of hydrochlorothiazide (contained in Karvezide)
• if you experience an increase insensitivity to the sunwith symptoms of sunburn (such as redness, itching, swelling, or blisters) that occur more quickly than usual
• ifyou are to undergo surgery(surgical intervention) orif you are to receive anesthetics.
• if you experience a decrease in vision or eye pain while taking Karvezide. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or an increase in 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 a higher risk of developing it. You must interrupt treatment with Karvezide and seek medical attention immediately.

The hydrochlorothiazide contained in this medication 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 medications

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

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

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

if you are taking an ACEI 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
• sodium-free salt substitutes that contain potassium
• potassium-sparing diuretics (tablets that increase urine production)
• some laxatives
• medications used to treat gout
• vitamin D supplements
• medications used to control heart rhythm
• diabetes medications (oral agents such as repaglinide or insulin)
• carbamazepine (a medication used to treat epilepsy)

You should also inform your doctor if you are taking other medications to lower your blood pressure, steroids, cancer medications, analgesics, medications for arthritis, 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 medication, you may experience a greater sensation 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 be pregnantor 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 medication instead. It is not recommended to use Karvezide at the beginning of pregnancy and in any case, it should not be administered after 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 for newborns or premature babies.

Driving and operating machines

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

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 medication.

Karvezide contains sodium. This medication 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 tabletper day. In general, your doctor will prescribe Karvezide when previous treatments you received have not sufficiently reduced 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-lowering 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 forgot 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 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 above 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 (blood urea nitrogen, creatinine).

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

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

• Diarrhea
• Low blood pressure
• Fainting
• Tachycardia
• Redness
• 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, ringing in the ears, 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, swelling of the face, lips, mouth, tongue, or throat.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 excluded.

Side effects associated only with irbesartan

In addition to the side effects described above, chest pain, severe allergic reactions (anaphylactic shock), decreased red blood cell count (anemia - symptoms may include fatigue, headaches, difficulty breathing during exercise, dizziness, and paleness), and decreased platelet count (a blood cell essential for blood clotting) 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; decreased platelet count (blood cells essential for blood clotting), decreased red blood cell count (anemia) characterized by fatigue, headaches, shortness of breath during exercise, dizziness, and paleness; kidney disease; pulmonary alterations 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 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 ispossibleside effects that do not appear in this prospectus.You can also report them directly throughthenational notification system included in theAppendix V. By reporting side effects, you can contributeto providing more information about 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 packaging and blister after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature 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 containers 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 300 mg/12.5 mg film-coated tablet contains 300 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 300 mg/12.5 mg film-coated tablets are orange in color, biconvex, oval in shape, with a trochead heart on one face and the number 2876 engraved on the other.

Karvezide 300 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 unit dose blister packs of 56 x 1 film-coated tablet for hospital supply.

Only some pack sizes may be marketed.

Marketing Authorization 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 authorization 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.