VALSARTAN/HYDROCHLOROTHIAZIDE PHARMA COMBIX 160 MG/12.5 MG FILM-COATED TABLETS

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

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

See also the information under the heading "Do not take Valsartan/Hydrochlorothiazide Pharma Combix". If any of these situations apply to you, consult your doctor.

Valsartan/Hydrochlorothiazide is not recommended for use in children and adolescents (under 18 years of age).

If you are pregnant, think you may be pregnant, or plan to become pregnant, inform your doctor. Valsartan/Hydrochlorothiazide should not be used at the start of pregnancy (first 3 months) and should not be administered after the third month of pregnancy, as it may cause serious harm to your baby; see section Pregnancy, breastfeeding, and fertility.

Using Valsartan/Hydrochlorothiazide with other medications

Inform your doctor or pharmacist if you are using, have recently used, or might need to use any other medication.

The effect of treatment with Valsartan/Hydrochlorothiazide may be altered if taken with certain medications. Your doctor may need to adjust your dose and/or take other precautions or, in some cases, stop treatment with one of the medications. This is especially applicable to the following medications:

• lithium, a medication used to treat certain psychiatric disorders
• medications that may affect or be affected by potassium levels, such as digoxin, a medication to control heart rhythm, and some antipsychotic medications.
• medications or substances that may increase potassium levels in the blood. These include potassium supplements or salt substitutes that contain potassium, potassium-sparing medications, and heparin.
• medications that may decrease potassium levels in the blood, such as diuretics (medications to increase urine production), corticosteroids, laxatives, carbenoxolone, amphotericin, or penicillin G.
• certain antibiotics (from the rifampicin group), a medication used to protect against organ rejection in a transplant (cyclosporine), or an antiretroviral medication used to treat HIV/AIDS (ritonavir). These medications may increase the effect of Valsartan/Hydrochlorothiazide.
• medications that may induce "torsades de pointes" (irregular heartbeats), such as anti-arrhythmics (medications used to treat heart problems) and some antipsychotics.
• medications that may reduce sodium levels in the blood, such as antidepressants, antipsychotics, antiepileptics.
• medications used to treat gout, such as allopurinol, probenecid, sulfinpyrazone.
• therapeutic vitamin D and calcium supplements.
• medications used to treat diabetes (insulin or oral antidiabetics like metformin).
• other medications used to lower blood pressure, including methyldopa, an ACE inhibitor, or aliskiren (see also the information under the headings "Do not take Valsartan/Hydrochlorothiazide Pharma Combix" and "Warnings and precautions").
• medications that increase blood pressure, such as noradrenaline or adrenaline.
• digoxin or other digitalis glycosides (medications used to treat heart problems).
• medications that may increase blood sugar levels, such as diazoxide or beta-blockers.
• cytotoxic medications (used to treat cancer), such as methotrexate or cyclophosphamide.
• medications used for pain, such as non-steroidal anti-inflammatory agents (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and acetylsalicylic acid in doses above 3 g.
• muscle relaxants, such as tubocurarine.
• anticholinergic medications (used to treat a wide range of disorders, such as gastrointestinal cramps, bladder spasms, asthma, motion sickness, muscle spasms, Parkinson's disease, and as an aid to anesthesia).
• amantadine (a medication used to treat Parkinson's disease and also to treat or prevent certain viral infections).
• cholestyramine and colestipol (medications primarily used to treat high lipid levels in the blood).
• cyclosporine, a medication used to prevent organ rejection in transplants.
• alcohol, sleep medications, and anesthetics (medications with sedative effects or used for pain, e.g., during surgery).
• iodinated contrast media (used in diagnostic imaging tests).

Taking Valsartan/Hydrochlorothiazide Pharma Combix with food, drinks, and alcohol

You can take Valsartan/Hydrochlorothiazide with or without food.

Avoid taking alcohol until you have consulted your doctor. Alcohol may further lower your blood pressure and/or increase the risk of dizziness and weakness.

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

• You must inform your doctor if you are pregnant, think you may be pregnant, or plan to become pregnant. Your doctor will usually advise you to stop taking Valsartan/Hydrochlorothiazide before becoming pregnant or as soon as you become pregnant and recommend taking another anti-hypertensive medication instead. Valsartan/Hydrochlorothiazide should not be used at the start of pregnancy and should not be administered after the third month of pregnancy, as it may cause serious harm to your baby.

• Inform your doctor if you are about to start or are breastfeeding, as Valsartan/Hydrochlorothiazide is not recommended for women during this period. Your doctor may decide to administer a treatment that is more suitable if you want to breastfeed, especially newborns or premature babies.

Driving and using machines

Before driving a vehicle, using tools, or operating machinery, or engaging in other activities that require concentration, make sure you know how Valsartan/Hydrochlorothiazide affects you. Like many other medications used to treat high blood pressure, Valsartan/Hydrochlorothiazide may, in rare cases, cause dizziness and affect your ability to concentrate.

Use in athletes

This medication contains hydrochlorothiazide, which may produce a positive result in doping tests.

3. How to take Valsartan/Hydrochlorothiazide Pharma Combix

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

People with high blood pressure often do not notice any signs of the disease; many feel normal. This makes it very important to attend your doctor's appointments, even if you feel well.

Your doctor will indicate exactly how many Valsartan/Hydrochlorothiazide tablets you should take. Depending on how you respond to treatment, your doctor may suggest increasing or decreasing the dose.

• The usual dose of Valsartan/Hydrochlorothiazide is one tablet per day.
• Do not change the dose or stop treatment without consulting your doctor.
• This medication should be taken at the same time every day, usually in the morning.
• You can take Valsartan/Hydrochlorothiazide with or without food.
• Swallow the tablet with a glass of water.

If you take more Valsartan/Hydrochlorothiazide Pharma Combix than you should

If you notice severe dizziness and/or fainting, lie down and contact your doctor immediately.

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

If you forget to take Valsartan/Hydrochlorothiazide Pharma Combix

If you forget to take a dose, take it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose.

Do not take a double dose to make up for missed doses.

If you stop taking Valsartan/Hydrochlorothiazide Pharma Combix

If you stop your treatment with Valsartan/Hydrochlorothiazide, your high blood pressure may worsen. Do not stop taking the medication unless your doctor tells you to.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

These adverse effects may occur with certain frequencies, which are defined below:

• very frequent: may affect more than 1 in 10 patients
• frequent: may affect up to 1 in 10 patients
• infrequent: may affect up to 1 in 100 patients
• rare: may affect up to 1 in 1,000 patients
• very rare: may affect up to 1 in 10,000 patients
• frequency not known: the frequency cannot be estimated from the available data

Some adverse effects can be serious and require immediate medical attention:

You should visit your doctor immediately if you notice symptoms of angioedema, such as:

• swelling in the face, tongue, or pharynx
• difficulty swallowing
• hives and difficulty breathing.

If you experience any of these symptoms, stop taking Valsartan/Hydrochlorothiazide and contact your doctor immediately (see also section 2 "Warnings and Precautions").

Other adverse effects include:

Infrequent

• cough
• low blood pressure
• dizziness
• dehydration (with symptoms of thirst, dry mouth and tongue, reduced urination frequency, dark urine, dry skin)
• muscle pain
• fatigue
• tingling or numbness
• blurred vision
• noises (e.g. ringing or buzzing) in the ears

Very rare

• dizziness
• diarrhea
• joint pain

Frequency not known

• difficulty breathing
• severe decrease in diuresis
• low sodium levels in the blood (which, in severe cases, can cause fatigue, confusion, muscle fasciculation and/or convulsions)
• low potassium levels in the blood (sometimes with muscle weakness, muscle spasms, abnormal heart rhythm)
• low white blood cell count (with symptoms such as fever, skin infections, sore throat or mouth ulcers due to infections, weakness)
• increased bilirubin levels in the blood (which, in severe cases, can cause the skin and eyes to turn yellow)
• increased urea and creatinine levels in the blood (which may indicate abnormal kidney function)
• increased uric acid levels in the blood (which, in severe cases, can trigger a gout attack)
• syncope (fainting)

The following adverse effects have been observed with medicines that contain valsartan or hydrochlorothiazide separately:

Valsartan

Infrequent

• feeling of rotation
• abdominal pain

Very rare

• Intestinal angioedema: swelling in the intestine with symptoms such as abdominal pain, nausea, vomiting, and diarrhea

Frequency not known

• skin rash with or without itching along with some of the following signs or symptoms: fever, joint pain, muscle pain, lymph node inflammation and/or flu-like symptoms
• skin rash, red-purple spots, fever, itching (symptoms of blood vessel inflammation)
• low platelet count (sometimes with bleeding or bruising more frequently than usual)
• high potassium levels in the blood (sometimes with muscle spasms, abnormal heart rhythm)
• allergic reactions (with symptoms such as skin rash, itching, hives, difficulty breathing or swallowing, dizziness)
• swelling mainly of the face and throat; skin rash; itching
• elevated liver function values
• decrease in hemoglobin and red blood cell percentage in the blood (which, in severe cases, can cause anemia)
• renal failure
• low sodium levels in the blood (which, in severe cases, can cause fatigue, confusion, muscle fasciculation and/or convulsions)

Hydrochlorothiazide

Very frequent

• low potassium levels in the blood
• increased lipids in the blood

Frequent

• low sodium levels in the blood
• low magnesium levels in the blood
• high uric acid levels in the blood
• skin rash with itching and other types of rash
• decreased appetite
• mild vomiting and nausea
• dizziness, dizziness when standing up
• inability to achieve or maintain an erection

Rare

• swelling and blisters on the skin (due to increased sun sensitivity)
• high calcium levels in the blood
• high sugar levels in the blood
• sugar in the urine
• worsening of diabetic metabolic state
• constipation, diarrhea, stomach or intestinal discomfort, liver changes that may appear along with yellowing of the skin and eyes
• irregular heartbeat
• headache
• sleep disturbances
• sadness (depression)
• low platelet count (sometimes with bleeding or bruising under the skin)
• dizziness
• tingling or numbness
• vision changes

Very rare

• inflammation of the blood vessels with symptoms such as skin rash, red-purple spots, fever (vasculitis)
• rash, itching, hives, difficulty breathing or swallowing, dizziness (hypersensitivity reactions)
• severe skin disease that causes skin rash, skin redness, blisters on the lips, eyes or mouth, skin peeling, fever (toxic epidermal necrolysis)
• rash on the face, joint pain, muscle disorders, fever (lupus erythematosus)
• severe pain in the upper abdomen (pancreatitis)
• difficulty breathing with fever, cough, wheezing, shortness of breath (breathing difficulties that include pneumonitis and pulmonary edema)
• fever, sore throat, increased frequency of infections (agranulocytosis)
• pale skin, fatigue, shortness of breath, dark urine (hemolytic anemia)
• fever, sore throat or mouth ulcers due to infections (leukopenia)
• confusion, fatigue, muscle twitches and spasms, rapid breathing (hypochloremic alkalosis)
• acute breathing difficulties (signs include severe breathing difficulties, fever, weakness, and confusion)

Frequency not known

• weakness, bruising, and frequent infections (aplastic anemia)
• significant decrease in urine production (possible signs of kidney damage or kidney failure)
• decreased vision or eye pain due to high blood pressure (possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma)
• skin rash, skin redness, blisters on the lips, eyes or mouth, skin peeling, fever (possible signs of erythema multiforme)
• muscle spasms
• fever (pyrexia)
• weakness (asthenia)
• skin and lip cancer (non-melanoma skin cancer)

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Valsartan/Hydrochlorothiazide Pharma 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 through wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE point in the pharmacy. 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 Valsartan/Hydrochlorothiazide Pharma Combix

• The active ingredients are valsartan and hydrochlorothiazide. Each tablet contains 160 mg of valsartan and 12.5 mg of hydrochlorothiazide.
• The other components are: crospovidone, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), hypromellose (E464), anhydrous calcium hydrogen phosphate (E341i), and magnesium stearate (E470b)
• The tablet coating contains: hypromellose (E464), titanium dioxide (E171), red iron oxide (E172), macrogol 4000 (E1521), yellow iron oxide (E172), talc (E553b), and black iron oxide (E172).

Appearance of the Product and Package Contents

Film-coated tablets of brown-red color, oval, biconvex, with beveled edges, smooth on both sides.

Aluminum-Aluminum blisters.

Valsartan/Hydrochlorothiazide Pharma Combix 160 mg/12.5 mg is available in packages of 28 tablets.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Laboratorios Combix, S.L.U.

C/ Badajoz, 2. Edificio 2

28223 Pozuelo de Alarcón (Madrid)

Spain

Manufacturer

Zydus France

Zac Les Hautes Pâturages

Parc d'Activités des Pleupliers

25 rue des Pleupliers

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 Prospectus:February 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/.