Leaflet: information for the user

Irbesartan/HydrochlorothiazideCombix300 mg/12.5 mg film-coated tablets

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 give it to others, even if they have the same symptoms as you, as it may harm them.

-If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What is Irbesartan/Hydrochlorothiazide Combix and what it is used for

2. What you need to know before starting to take Irbesartan/Hydrochlorothiazide Combix

3. How to take Irbesartan/Hydrochlorothiazide Combix

4. Possible side effects

5. Storage of Irbesartan/Hydrochlorothiazide Combix

6. Contents of the pack and additional information

Irbesartán/Hidroclorotiazida Combix is an association of two active principles, irbesartan and hydrochlorothiazide. Irbesartan belongs to the group of medications known as angiotensin-II receptor antagonists

The angiotensin II is a substance produced in the body that binds to the 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 the blood vessels and reducing blood pressure.

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

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

Irbesartán/Hidroclorotiazida Combix 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 Irbesartán/Hidroclorotiazida Combix

• if you areallergicto the active ingredients or any of the other components of this medication (listed in section 6)
• 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 Pregnancy section)
• 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 insufficiencyand are being treated with a medication to lower blood pressure that contains aliskirén.

Irbesartán/Hidroclorotiazida Combix should not be administered to children and adolescents (under 18 years).

Warnings and precautions

Consult your doctor or pharmacist before starting to take Irbesartán/Hidroclorotiazida Combix.

Inform your doctorin 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 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):

• a converting enzyme inhibitor (ACEI) (e.g. enalapril, lisinopril, ramipril), particularly if you have kidney problems related to diabetes.
• aliskirén.

• if you have had skin cancer or if you develop an unexpected skin lesion during 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 Irbesartán/Hidroclorotiazida Combix.
• if you experience a decrease in vision or eye pain, which may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in eye pressure and may occur within a few hours to a week after taking Irbesartán/Hidroclorotiazida Combix.
• 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 shortness of breath or severe difficulty breathing after taking Irbesartán/Hidroclorotiazida, seek medical attention immediately.

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

See also the information under the heading “Do not take Irbesartán/Hidroclorotiazida Combix”.

If you are pregnant, if you suspect you may be pregnantor if you plan to become pregnant, inform your doctor. Irbesartán/Hidroclorotiazida Combix is not recommended for use at the beginning of pregnancy (first 3 months), and in no case should it be administered from the third month of pregnancy, as it may cause serious harm to your baby (see Pregnancy section).

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 heart rate, which may indicate excessive hydrochlorothiazide effect(contained in Irbesartán/Hidroclorotiazida Combix)
• 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.

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

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

Use of Irbesartán/Hidroclorotiazida with other medications

Inform your doctor or pharmacist that you are using or have recently used or may need to use any other medication.

Diuretics, such as the hydrochlorothiazide contained in Irbesartán/Hidroclorotiazida Combix, may affect other medications. Do not take with Irbesartán/Hidroclorotiazida Combix 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 aliskirén (see also the information under the headings “Do not take Irbesartán/Hidroclorotiazida Combix” and “Warnings and precautions”).

You may need to have blood tests if you take:

• potassium supplements
• sodium substitutes containing 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 or insulin)
• carbamazepine (a medication used to treat epilepsy)

It is also important to 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.

Use of Irbesartán/Hidroclorotiazida Combix with food and beverages

Irbesartán/Hidroclorotiazida Combix can be taken with or without food.

Due to the hydrochlorothiazide contained in Irbesartán/Hidroclorotiazida Combix, 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 and lactation

Pregnancy

If you are pregnant or breastfeeding, or if you suspect you may be pregnantor if you plan to become pregnant, consult your doctor or pharmacist before using this medication. Your doctor will usually advise you to stop taking Irbesartán/Hidroclorotiazida Combix before becoming pregnant or as soon as you become pregnant and recommend taking another antihypertensive medication instead. Irbesartán/Hidroclorotiazida Combix is not recommended for use at the beginning of pregnancy and should not be administered from the third month of pregnancy, as it may cause serious harm to your baby when administered from that point.

Lactation

Inform your doctor if you plan to start or are breastfeeding, as it is not recommended to administer Irbesartán/Hidroclorotiazida Combix 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 machinery

No studies have been conducted on the ability to drive and operate machinery. It is unlikely that Irbesartán/Hidroclorotiazida Combix will affect your ability to drive vehicles or operate machinery. However, during hypertension treatment, occasional dizziness or fatigue may occur. If you experience these symptoms, consult your doctor before driving or operating machinery.

Irbesartán/Hidroclorotiazida Combix contains lactose. If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

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

Dose

The usual dose of Irbesartán/Hidroclorotiazida Combix is one or two tablets per day. In general, your doctor will prescribe Irbesartán/Hidroclorotiazida Combix 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 Irbesartán/Hidroclorotiazida Combix.

Administration Form

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

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

If you take more Irbesartán/Hidroclorotiazida Combix than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone 91 562 04 20, indicating the medication and the amount ingested.

Children should not take Irbesartán/Hidroclorotiazida Combix

Irbesartán/Hidroclorotiazida Combix should 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 Irbesartán/Hidroclorotiazida Combix

If you accidentally forget to take a dose, simply take your regular dose when it is due. 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 medications, Irbesartán/Hidroclorotiazida Combix may cause side effects, although not everyone will experience them.

Some of these side effects may be severe 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 above symptoms or have difficulty breathing, stop taking Irbesartán/Hidroclorotiazida Combix and contact your doctor immediately.

The side effects reported in clinical studies for patients treated with irbesartan/hidroclorotiazide were:

Frequent side effects(affect between 1 and 10 of every 100 patients):

• 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(affect between 1 and 10 of every 1,000 patients):

• 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.

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

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

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

Side effects since the marketing of irbesartan/hidroclorotiazide

Since the marketing of irbesartan/hidroclorotiazide, some side effects have been reported. The side effects observed with unknown frequency are: headache, tinnitus, cough, alteration of taste, indigestion, joint and muscle pain, liver function alterations, and kidney insufficiency, elevated potassium levels 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, chest pain and a reduction in the number of platelets have also been observed.

Rare side effects (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 hidroclorotiazide 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; decrease in the number of platelets (essential blood cells for blood coagulation), decrease in the number of red blood cells (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 over the entire 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; decreased vision or eye pain due to increased pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma]; salivary gland swelling; 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.

Unknown frequency

• Skin and lip cancer (non-melanoma skin cancer)

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

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist. You can also report them directly through the Spanish System for the Pharmacovigilance of Medicines for Human Use:www.notificaram.es. 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 packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and medicines you no longer need at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. By doing so, you will help protect the environment.

Composition of Irbesartán /Hidroclorotiazida Combix

• The active principles are irbesartan and hydrochlorothiazide. Each film-coated tablet of Irbesartán/Hidroclorotiazida Combix 300 mg/12.5 mg contains 300 mg of irbesartan and 12.5 mg of hydrochlorothiazide.
• The other components are lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, pregelatinized cornstarch, yellow iron oxide (E172), red iron oxide (E172), calcium stearate andOpadry II Pink 30F84515, composed of: lactose monohydrate, hypromellose, macrogol, titanium dioxide (E171), red iron oxide (E172), yellow iron oxide (E172), and black iron oxide (E172).

Appearance of the product and content of the packaging

Film-coated tablets, pink in color, biconvex, capsule-shaped, with the mark “ZF7” on one face and smooth on the other.

PVC/PVDC/Aluminum blisters.

Irbesartán/Hidroclorotiazida Combix is also available in packaging of 28 tablets of 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization

Combix Laboratories, S.L.U.

C/ Badajoz, 2. Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Responsible for manufacturing

Zydus France

25, parc d’activités des Peupliers, Building L

92000 Nanterre

France

or

Centre Specialized Pharmaceuticals

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Last review date of this leafletFebruary 2025

The detailed and updated information of this medication is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/