IRBESARTAN HYDROCHLOROTHIAZIDE ZENTIVA 300 mg/25 mg FILM-COATED TABLETS

2. What you need to know before you take Irbesartan Hydrochlorothiazide Zentiva

Do not take Irbesartan Hydrochlorothiazide Zentiva

• 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 medication
• if you are pregnant more than 3 months. (In any case, it is best to avoid taking this medicine during the start of your 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 elevated calcium or low potassium levels in your blood
• if you have diabetes or kidney failureand are being treated with a blood pressure-lowering medicine that contains aliskiren.

Warnings and precautions

Consult your doctor before starting to take Irbesartan Hydrochlorothiazide Zentiva 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, tremors, headache, flushing or pallor, numbness, rapid 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 aldosteronism(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 medications used to treat high blood pressure (hypertension):

• an angiotensin-converting enzyme inhibitor (ACE inhibitor) (e.g., enalapril, lisinopril, ramipril), particularly if you have diabetes-related kidney problems.
• aliskiren.

• if you have had skin cancer or if you develop an unexpected skin lesionduring treatment. Treatment with hydrochlorothiazide, especially 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 sun exposure and UV rays while taking Irbesartan Hydrochlorothiazide Zentiva.
• 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 severe difficulty breathing after taking Irbesartan Hydrochlorothiazide Zentiva, seek medical attention immediately.

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

See also the information under the heading “Do not take Irbesartan Hydrochlorothiazide Zentiva”.

If you are pregnant, think you may be pregnant, or are planning to become pregnant, inform your doctor. Irbesartan Hydrochlorothiazide Zentiva is not recommended during the first trimester of pregnancy and must not be used 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 Irbesartan Hydrochlorothiazide Zentiva)
• 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 given anesthetics.
• if you experience a decrease in vision or eye painin one or both eyes when taking Irbesartan Hydrochlorothiazide Zentiva, 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 weeks after taking Irbesartan Hydrochlorothiazide Zentiva. This can lead to permanent vision loss if not treated. If you have previously shown an allergy to penicillin or sulfonamide, you are at higher risk of developing this. You must stop treatment with Irbesartan Hydrochlorothiazide Zentiva and seek immediate medical attention.

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

Children and adolescents

Irbesartan Hydrochlorothiazide Zentiva should not be given to children and adolescents (under 18 years of age).

Using Irbesartan Hydrochlorothiazide Zentiva 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 in Irbesartan Hydrochlorothiazide Zentiva, may interact with other medicines. Do not take preparations containing lithium with Irbesartan Hydrochlorothiazide Zentiva 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 Irbesartan Hydrochlorothiazide Zentiva” and “Warnings and precautions”).

You may need to have blood tests if you are taking:

• potassium supplements
• potassium-containing salt substitutes
• potassium-sparing diuretics or other diuretics (pills 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 epilepsy)

It is also important to inform your doctor if you are taking other blood pressure-lowering medicines, steroids, cancer treatments, painkillers, arthritis medicines, or cholestyramine or colestipol resins to reduce blood cholesterol levels.

Taking Irbesartan Hydrochlorothiazide Zentiva with food, drinks, and alcohol

Irbesartan Hydrochlorothiazide Zentiva can be taken with or without food.

Due to the hydrochlorothiazide in Irbesartan Hydrochlorothiazide Zentiva, if you drink alcohol while being treated with this medicine, you may experience a greater feeling of dizziness when standing up, especially when getting up from a sitting 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 Irbesartan Hydrochlorothiazide Zentiva before you become pregnant or as soon as you find out you are pregnant and will recommend that you take a different blood pressure-lowering medicine instead. Irbesartan Hydrochlorothiazide Zentiva is not recommended during the first trimester of pregnancy and must not be used 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, as Irbesartan Hydrochlorothiazide Zentiva is not recommended for use during breastfeeding. Your doctor may decide to give you a treatment that is more suitable if you wish to breastfeed, especially for newborns or premature babies.

Driving and using machines

It is unlikely that Irbesartan Hydrochlorothiazide Zentiva will 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.

Irbesartan Hydrochlorothiazide Zentiva contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

Irbesartan Hydrochlorothiazide Zentiva contains sodium. This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Irbesartan Hydrochlorothiazide Zentiva

Follow exactly the instructions of your doctor for taking this medicine. If you are not sure, ask your doctor or pharmacist.

Dose

The recommended dose of Irbesartan Hydrochlorothiazide Zentiva is one tablet per day. In general, your doctor will prescribe Irbesartan Hydrochlorothiazide Zentiva when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will tell you how to switch from previous treatments to Irbesartan Hydrochlorothiazide Zentiva.

Method of administration

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

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

Children must not take Irbesartan Hydrochlorothiazide Zentiva

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

If you take more Irbesartan Hydrochlorothiazide Zentiva than you should

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

If you forget to take Irbesartan Hydrochlorothiazide Zentiva

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

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

4. Possible Adverse Effects

Like all medicines, Irbesartan Hydrochlorothiazide Zentiva can cause adverse effects, although not all people suffer from them.

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

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

The frequency of the adverse 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

Rare: may affect up to 1 in 1,000 people

Very rare: may affect up to 1 in 10,000 people

The adverse effects reported in clinical studies for patients treated with Irbesartan Hydrochlorothiazide Zentiva were:

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

• Nausea/vomiting
• Urination anomalies
• 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 nitrogen in blood, creatinine).

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

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

• Diarrhea
• Low blood pressure
• Fainting
• Tachycardia
• Flushing
• Fluid retention (edema)
• Sexual dysfunction (sexual function disorders)
• Blood tests may show low levels of sodium and potassium in your blood.

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

Adverse effects reported since the marketing of Irbesartan Hydrochlorothiazide Zentiva

Since the marketing of Irbesartan Hydrochlorothiazide Zentiva, some adverse effects have been reported. The adverse effects with unknown frequency are: headache, ringing in the ears, cough, taste alteration, indigestion, joint and muscle pain, liver function disorders, and kidney failure, high levels of potassium in the blood, and allergic reactions such as skin rash, hives, 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 observed.

As with all combinations of two active ingredients, the adverse effects associated with each component cannot be excluded.

Adverse effects associated only with irbesartan

In addition to the adverse effects described above, chest pain, severe allergic reactions (anaphylactic shock), decreased red blood cell count (anemia - symptoms may include fatigue, headaches, difficulty breathing when exercising, dizziness, and paleness), and decreased platelet count (a blood cell essential for blood clotting) and low blood sugar levels have also been observed.

Adverse effects associated with hydrochlorothiazide in monotherapy

Loss of appetite; stomach irritation; 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 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; 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; heart rhythm disorders; decreased 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 levels of uric acid in the blood, which can cause gout.

Very rare adverse effects(may affect up to 1 in 10,000 people):

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

Frequency "not known"(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 effusion) or acute angle-closure glaucoma].

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

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Irbesartan Hydrochlorothiazide Zentiva

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

Do not use this medicine after the expiration date stated on the carton and blister after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Store in the original packaging 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 protect the environment.

6. Package Contents and Additional Information

Composition of Irbesartan Hydrochlorothiazide Zentiva

• The active ingredients are irbesartan and hydrochlorothiazide. Each film-coated tablet of Irbesartan Hydrochlorothiazide Zentiva 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, iron oxide red, yellow, and black, pregelatinized starch, carnauba wax. See section 2 "Irbesartan Hydrochlorothiazide Zentiva contains lactose".

Appearance and Package Contents

The film-coated tablets of Irbesartan Hydrochlorothiazide Zentiva 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.

Irbesartan Hydrochlorothiazide Zentiva 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 Authorization Holder

Zentiva k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

Manufacturer

Sanofi Winthrop Industrie

1 Rue de la vierge

Ambarès et Lagrave

33 565 Carbon Blanc Cedex

France

Sanofi Winthrop Industrie

30-36 Avenue Gustave Eiffel

37 100 Tours

France

Zentiva k.s.

U Kabelovny 130

102 37 Prague 10

Czech Republic

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

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