IRBESARTAN/HYDROCHLOROTHIAZIDE COMBIX 300 mg/12.5 mg FILM-COATED TABLETS

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

Do not take Irbesartan/Hydrochlorothiazide Combix

• if you are allergicto the active substances or any of the other ingredients of this medicine (listed in section 6)
• if you are pregnant more than 3 months. (In any case, it is better to avoid taking this medicine also at 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 high levels of calcium or low levels of potassium in your blood
• if you have diabetes or kidney failureand are being treated with a blood pressure-lowering medicine that contains aliskiren.

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

Warnings and precautions

Consult your doctor or pharmacist before starting to take Irbesartan/Hydrochlorothiazide Combix.

Tell your doctorin 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 have systemic lupus erythematosus(also known as lupus or SLE)
• if you have primary aldosteronism(a condition related to high production of the hormone aldosterone, leading to sodium retention and, in turn, high blood pressure)
• if you are taking any of the following medicines used to treat high blood pressure (hypertension):

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

• if you have had skin cancer or if you develop an unexpected skin lesion during 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 Combix.
• if you experience a decrease in vision or eye pain, these could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, and can occur within a few hours to a week after taking Irbesartan/Hydrochlorothiazide Combix.
• 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 severe shortness of breath or difficulty breathing after taking Irbesartan/Hydrochlorothiazide Combix, 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 Combix”.

If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor. The use of Irbesartan/Hydrochlorothiazide Combix is not recommended at the start of pregnancy (first 3 months), and in no case should it be administered from the third month of pregnancy onwards, 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, generalized weakness, feeling sleepy, muscle cramps or spasms, nausea, vomiting, or rapid heartbeat, as these may indicate an excessive effect of hydrochlorothiazide (contained in Irbesartan/Hydrochlorothiazide Combix)
• if you experience an increased sensitivity of your skin to the sunwith symptoms of sunburn (such as redness, itching, swelling, blisters) that occur more quickly than usual
• if you are going to have surgery(surgical intervention) or if you are going to be given anesthetics.

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

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

Using Irbesartan/Hydrochlorothiazide Combix with other medicines

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

Diuretics, such as hydrochlorothiazide contained in Irbesartan/Hydrochlorothiazide Combix, may have an effect on other medicines. You should not take preparations containing lithium with Irbesartan/Hydrochlorothiazide Combix without your doctor's supervision.

Your doctor may need to change 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 Combix” and “Warnings and precautions”).

You may need to have blood tests if you take:

• potassium supplements
• salt substitutes that contain potassium
• potassium-sparing medicines 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 or insulins)
• carbamazepine (a medicine for the treatment of epilepsy)

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

Using Irbesartan/Hydrochlorothiazide Combix with food and drinks

Irbesartan/Hydrochlorothiazide Combix can be taken with or without food.

Due to the hydrochlorothiazide contained in Irbesartan/Hydrochlorothiazide Combix, if you drink alcohol while being treated with this medicine, you may have a greater feeling of dizziness when standing up, especially when getting up from a sitting position.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will normally advise you to stop taking Irbesartan/Hydrochlorothiazide Combix before you become pregnant or as soon as you know you are pregnant and will recommend that you take another blood pressure-lowering medicine instead. The use of Irbesartan/Hydrochlorothiazide Combix is not recommended at the start of pregnancy and should not be taken from the third month of pregnancy onwards, as it may cause serious harm to your baby.

Breastfeeding

Tell your doctor if you are about to start or are already breastfeeding, as Irbesartan/Hydrochlorothiazide Combix is not recommended for use during this period. Your doctor may decide to give you a treatment that is more suitable if you want to breastfeed, especially for newborns or premature babies.

Driving and using machines

No studies have been performed on the ability to drive and use machines. It is unlikely that Irbesartan/Hydrochlorothiazide Combix 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 Combix contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Irbesartan/Hydrochlorothiazide Combix

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

Dose

The normal dose of Irbesartan/Hydrochlorothiazide Combix is one or two tablets a day. In general, your doctor will prescribe Irbesartan/Hydrochlorothiazide Combix when previous treatments you received did not sufficiently reduce your blood pressure. Your doctor will indicate how to switch from previous treatments to Irbesartan/Hydrochlorothiazide Combix.

Method of administration

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

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

If you take more Irbesartan/Hydrochlorothiazide Combix than you should

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

Children should not take Irbesartan/Hydrochlorothiazide Combix

Irbesartan/Hydrochlorothiazide 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 Irbesartan/Hydrochlorothiazide Combix

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 side effects

Like all medicines, Irbesartan/Hydrochlorothiazide Combix can cause side effects, although not everybody gets them.

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

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

Side effects reported in clinical studies for patients treated with irbesartan/hydrochlorothiazide were:

Common side effects(affect 1 to 10 in every 100 patients):

• 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 side effects bother you, talk to your doctor

Uncommon side effects(affect 1 to 10 in every 1,000 patients):

• diarrhea
• low blood pressure
• fainting
• rapid heartbeat
• flushing
• fluid retention (edema)
• sexual dysfunction (sexual function disorders)
• 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 (signs include severe difficulty breathing, fever, weakness, and confusion).

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

Side effects reported since the marketing of irbesartan/hydrochlorothiazide

Since the marketing of irbesartan/hydrochlorothiazide, 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, 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. Cases of jaundice (yellowing of the skin and/or whites of the eyes) have also been observed.

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, chest pain and a decrease 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 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 abdominal 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 (cells essential for blood clotting), decreased red blood cell count (anemia) characterized by fatigue, headaches, shortness of breath 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; inflammation of blood vessels; 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 a change in body position; 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]; 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.

Frequency not known

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

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 through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Irbesartan/Hydrochlorothiazide Combix

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

Do not use this medicine 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 via wastewater or household waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE Point. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Irbesartan/Hydrochlorothiazide Combix

• The active ingredients are irbesartan and hydrochlorothiazide. Each film-coated tablet of Irbesartan/Hydrochlorothiazide 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 corn starch, yellow iron oxide (E172), red iron oxide (E172), calcium stearate, and Opadry 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 Package Contents

Film-coated tablets, pink, biconvex, capsule-shaped, with the mark "ZF7" on one side and smooth on the other.

PVC/PVDC/Aluminum blisters.

Irbesartan/Hydrochlorothiazide Combix is also available in packages of 28 tablets of 150 mg of irbesartan and 12.5 mg of hydrochlorothiazide.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Combix Laboratories, S.L.U.

C/ Badajoz, 2. Building 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

25, Parc d'activités des Peupliers, Bâtiment L

92000 Nanterre

France

or

Centre Spécialités Pharmaceutiques

ZAC des Suzots

35 rue de la Chapelle

63450 Saint Amant Tallende

France

Date of the Last Revision of this ProspectusFebruary 2025

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/