VALSARTAN/HYDROCHLOROTHIAZIDE PHARMA COMBIX 160 mg/25 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the Patient

Valsartan/HydrochlorothiazidePharmaCombix160 mg/25 mg film-coated tablets EFG

Read the entire package leaflet carefully before you start taking this medicine, as it contains important information for you.

• Keep this package leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this package leaflet. See section 4.

Contents of the package leaflet

1. What Valsartan/Hydrochlorothiazide Pharma Combix is and what it is used for.
2. What you need to know before taking Valsartan/Hydrochlorothiazide Pharma Combix.
3. How to take Valsartan/Hydrochlorothiazide Pharma Combix.
4. Possible side effects.
5. Storage of Valsartan/Hydrochlorothiazide Pharma Combix.
6. Package contents and further information.

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

Valsartan/Hydrochlorothiazide Pharma Combix film-coated tablets contain two active substances called valsartan and hydrochlorothiazide. These components help control high blood pressure (hypertension).

• Valsartanbelongs to a class of medicines known as "angiotensin II receptor antagonists" that help control high blood pressure. Angiotensin II is a substance in the body that causes blood vessels to narrow, leading to an increase in blood pressure. Valsartan works by blocking the effect of angiotensin II. As a result, blood vessels relax and blood pressure decreases.
• Hydrochlorothiazidebelongs to a class of medicines known as thiazide diuretics. Hydrochlorothiazide increases urine production, which also decreases blood pressure.

Valsartan/Hydrochlorothiazide is used to treat high blood pressure that is not adequately controlled with the use of a single component.

Hypertension increases the workload of the heart and arteries. If left untreated, it can damage blood vessels in the brain, heart, and kidneys, and can lead to a stroke, heart failure, or kidney failure. High blood pressure increases the risk of heart attacks. Lowering blood pressure to normal levels reduces the risk of developing these disorders.

2. What you need to know before taking Valsartan/Hydrochlorothiazide Pharma Combix

Do not take Valsartan/Hydrochlorothiazide Pharma Combix

• if you are allergic to valsartan, hydrochlorothiazide, sulfonamide derivatives (chemically related to hydrochlorothiazide), or any of the other ingredients of this medicine (listed in section 6).
• if you are more than 3 months pregnant (in any case, it is recommended to avoid taking this medicine also at the beginning of your pregnancy – see section Pregnancy, breastfeeding, and fertility).
• if you have severe liver disease, destruction of the small bile ducts in the liver (biliary cirrhosis) leading to a buildup of bile in the liver (cholestasis).
• if you have severe kidney disease.
• if you are unable to produce urine (anuria).
• if you are undergoing dialysis.
• if you have low potassium or sodium levels in your blood, or if your blood calcium levels are higher than normal despite treatment.
• if you have gout.
• if you have diabetes or kidney failure and are being treated with a blood pressure-lowering medicine that contains aliskiren.

If any of these situations apply to you, do not take this medicine and consult your doctor.

Warnings and precautions

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

• if you are using potassium-sparing medicines, potassium supplements, salt substitutes that contain potassium, or other medicines that increase the amount of potassium in your blood, such as heparin. Your doctor may consider it necessary to regularly check your potassium levels.
• if you have low potassium levels in your blood.
• if you experience severe diarrhea or vomiting.
• if you are taking high doses of a diuretic.
• if you have severe heart disease.
• if you have heart failure or have had a heart attack. Follow your doctor's instructions carefully when starting treatment. Your doctor may also monitor your kidney function.
• if you have narrowing of the kidney artery.
• if you have recently had a kidney transplant.
• if you have hyperaldosteronism, a disease in which the adrenal glands produce too much aldosterone hormone. In this case, Valsartan/Hydrochlorothiazide is not recommended.
• if you have kidney or liver disease.
• if you have experienced swelling of the tongue and face caused by an allergic reaction called angioedema when taking other medicines (including ACE inhibitors), inform your doctor. If you have these symptoms when taking Valsartan/Hydrochlorothiazide, stop treatment with Valsartan/Hydrochlorothiazide immediately and never take it again. See also section 4 "Possible side effects".
• if you have fever, rash, and joint pain, which can be signs of systemic lupus erythematosus (a known autoimmune disease).
• if you have diabetes, gout, high cholesterol or triglyceride levels in your blood.
• if you have previously had an allergic reaction with the use of another medicine in this class to lower blood pressure (angiotensin II receptor antagonists), or if you suffer from any type of allergy or asthma.
• if you experience vision loss 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 time frame of several hours to a week after taking Valsartan/Hydrochlorothiazide. If left untreated, this can lead to permanent vision loss. You may be at higher risk of developing it if you have previously had an allergy to penicillin or sulfonamides.
• may cause increased sensitivity of the skin to the sun.
• 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), particularly 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 Valsartan/Hydrochlorothiazide Pharma 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 shortness of breath or severe difficulty breathing after taking Valsartan/Hydrochlorothiazide, see your doctor immediately.

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 are planning to become pregnant, inform your doctor. Valsartan/Hydrochlorothiazide is not recommended during the first trimester of pregnancy (first 3 months) and should not be taken 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 medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

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

• lithium, a medicine used to treat certain psychiatric disorders.
• medicines that may affect or be affected by potassium levels, such as digoxin, a medicine to control heart rhythm, and some antipsychotic medicines.
• medicines or substances that may increase potassium levels in the blood. These include potassium supplements or salt substitutes that contain potassium, potassium-sparing medicines, and heparin.
• medicines that may decrease potassium levels in the blood, such as diuretics (medicines to urinate), corticosteroids, laxatives, carbenoxolone, amphotericin, or penicillin G.
• certain antibiotics (of the rifampicin group), a medicine used to protect against transplant rejection (cyclosporine), or an antiretroviral medicine used to treat HIV/AIDS (ritonavir). These medicines may increase the effect of Valsartan/Hydrochlorothiazide.
• medicines that may induce "torsades de pointes" (irregular heartbeats), such as antiarrhythmics (medicines used to treat heart problems) and some antipsychotics.
• medicines that may reduce sodium levels in the blood, such as antidepressants, antipsychotics, antiepileptics.
• medicines to treat gout, such as allopurinol, probenecid, sulfinpyrazone.
• therapeutic vitamin D and calcium supplements.
• medicines to treat diabetes (insulin or oral antidiabetics like metformin).
• other medicines to lower blood pressure, including methyldopa, an angiotensin-converting enzyme inhibitor (ACE inhibitor), or aliskiren (see also the information under the headings "Do not take Valsartan/Hydrochlorothiazide Pharma Combix" and "Warnings and precautions").
• medicines that increase blood pressure, such as noradrenaline or adrenaline.
• digoxin or other digitalis glycosides (medicines used to treat heart problems).
• medicines that may increase blood sugar levels, such as diazoxide or beta-blockers.
• cytotoxic medicines (used to treat cancer), such as methotrexate or cyclophosphamide.
• pain relievers, such as non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and acetylsalicylic acid in doses above 3 g.
• muscle relaxants, such as tubocurarine.
• anticholinergic medicines (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 medicine used to treat Parkinson's disease and also to treat or prevent certain viral diseases).
• cholestyramine and colestipol (medicines primarily used to treat high lipid levels in the blood).
• cyclosporine, a medicine used to prevent organ rejection after transplantation.
• alcohol, sleeping pills, and anesthetics (medicines with a sedative effect or for pain used, for example, in surgery).
• iodinated contrast media (used for 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 or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

• You must 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 Valsartan/Hydrochlorothiazide before you become pregnant or as soon as you find out you are pregnant, and will recommend that you take another blood pressure-lowering medicine instead. Valsartan/Hydrochlorothiazide is not recommended during the first trimester of pregnancy and should not be taken 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 mothers who are breastfeeding. Your doctor may decide to prescribe a treatment that is more suitable if you want to breastfeed, especially for 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 medicines used to treat high blood pressure, Valsartan/Hydrochlorothiazide can, in rare cases, cause dizziness and affect your ability to concentrate.

Use in athletes

This medicine 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 medicine exactly as indicated by your doctor or pharmacist. If you are unsure, 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 tell you exactly how many Valsartan/Hydrochlorothiazide tablets to 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 medicine 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 a strong 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 medicine and the amount taken.

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 your next dose, skip the missed dose.

Do not take a double dose to make up for forgotten 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 medicine unless your doctor tells you to.

If you have any further questions on the use of this medicine, 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 sensitivity to the sun)
• 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 disorder or kidney failure)
• 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)
• 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 leaflet. 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 via wastewater or household waste. Deposit the packaging and medicines you no longer need at the SIGRE collection point in your pharmacy. If in 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 25 mg of hydrochlorothiazide.
• The other ingredients are: crospovidone, microcrystalline cellulose (E460i), colloidal anhydrous silica (E551), hypromellose (E464), anhydrous calcium hydrogen phosphate (E341i), and magnesium stearate (E470b)
• The tablet coating contains: hypromellose (E464), titanium dioxide (E171), polyethylene glycol 4000 (E1521), yellow iron oxide (E172), talc (E553b), red iron oxide (E172), and black iron oxide (E172).

Appearance of the Product and Package Contents

Film-coated tablets of brown color, oval, biconvex, with beveled edges, with the mark "25" on one face and smooth on the other.

Aluminum-Aluminum blisters.

Valsartan/Hydrochlorothiazide Pharma Combix 160 mg/25 mg is available in packs 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 Leaflet: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/.