Package Insert: Information for the Patient

Valsartan/HydrochlorothiazidePharmaCombix160 mg/25 mg Film-Coated Tablets

Read this package insert carefully before taking this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed for you, and you should not give it to others who have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Valsartán/Hidroclorotiazida Pharma Combix co m p rimidos recubiertos con pelí c ula contiene dos princ i pios activos conocidos co m o valsartán e hidroclorotiazida. Estos co m ponentes a y udan a controlar la presión arterial alta (hipertensión).

• Valsartán pertenece a una clase de medicamentos conocidos como “antagonistas de los receptores de la angiotensina II” que ayudan a controlar la presión arterial alta. La angiotensina II es una sustancia del cuerpo que hace que los vasos sanguíneos se estrechen, causando un aumento de la presión arterial. Valsartán actúa bloqueando el efecto de la angiotensina II. Como consecuencia, los vasos sanguíneos se relajan y la presión arterial disminuye.
• Hidroclorotiazida pertenece a una clase de medicamentos conocidos como diuréticos tiazídicos. Hidroclorotiazida aumenta la diuresis, lo que también disminuye la presión arterial.

Valsartán/Hidroclorotiazida se usa para tratar la presión arterial alta que no se controla adecuadamente con el uso de un único componente.

La hipertensión aumenta la carga del corazón y de las arterias. Si no se trata, puede dañar los vasos sanguíneos del cerebro, corazón y riñones y puede provocar un infarto cerebral, insuficiencia cardiaca o insuficiencia renal. La presión arterial alta aumenta el riesgo de ataques cardíacos. La disminución de la presión arterial a valores normales reduce el riesgo de desarrollar estos trastornos.

Do not take Valsartán/HidroclorotiazidaPharmaCombix

· if you are allergic to valsartan, hidroclorotiazida, sulfonamide derivatives (chemical substances related to hidroclorotiazida) or to any of the other components of this medication (listed in section 6).

· if you are more than 3 months pregnant (in any case, it is better to avoid taking this medication also at the beginning of your pregnancy – see Pregnancy, breastfeeding and fertility section).

· if you have severe liver disease, small bile duct destruction in the liver (biliary cirrhosis) that leads to bile accumulation in the liver (cholestasis).

· if you have severe kidney disease.

· if you cannot produce urine (anuria).

· if you are undergoing dialysis.

· if you have lower than normal levels of potassium or sodium 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 insufficiency and are being treated with a medication to reduce blood pressure that contains aliskirén.

If any of these situations affect you, do not take this medication and consult your doctor.

Warnings and precautions

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

· if you are using potassium-sparing medications, potassium supplements, salt substitutes containing potassium or other medications that increase the amount of potassium in the blood, such as heparin. Your doctor may consider it necessary to control your potassium levels regularly.

· if you have low levels of potassium 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 to start treatment. Your doctor may also monitor your renal function.

· if you have a narrowing of the renal artery.

· if you have recently undergone a kidney transplant.

· if you have hyperaldosteronism, a disease in which the adrenal glands produce too much aldosterone hormone. In this case, Valsartán/Hidroclorotiazida 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 medications (including ACE inhibitors), inform your doctor. If you have these symptoms when taking Valsartán/Hidroclorotiazida, stop taking it immediately and never take it again. See also section 4 “Possible side effects”.

· if you have fever, skin rash and joint pain, which may be signs of systemic lupus erythematosus (a known autoimmune disease).

· if you have diabetes, gout, high levels of cholesterol or triglycerides in your blood.

· if you have previously experienced an allergic reaction with the use of another medication of this class to reduce blood pressure (angiotensin II receptor antagonists), or if you have any type of allergy or asthma.

· if you experience vision loss or eye pain. These may be symptoms of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or increased eye pressure and may occur during a period of time ranging from several hours to a week after taking Valsartán/Hidroclorotiazida. If not treated, this can lead to permanent vision loss. You may have a higher risk of developing it if you have previously been allergic to penicillin or sulfonamides.

· it may cause increased sensitivity to the sun.

· if you are taking any of the following medications used to treat high blood pressure:

-a converting enzyme inhibitor (ACE inhibitor) (for example 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 hidroclorotiazida, 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 sun exposure and UV rays while taking Valsartán/Hidroclorotiazida Pharma Combix.

· if you have respiratory or pulmonary problems (such as inflammation or fluid in the lungs) after taking hidroclorotiazida in the past. If you experience severe shortness of breath or difficulty breathing after taking Valsartán/Hidroclorotiazida, see your doctor immediately.

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

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

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

Ifany of these situations affect you, consult your doctor.

It is not recommended to use Valsartán/Hidroclorotiazida in children and adolescents (under 18 years old).

If you are pregnant, if you suspect you may be pregnant or if you plan to become pregnant, inform your doctor. It is generally recommended that you stop taking Valsartán/Hidroclorotiazida before becoming pregnant or as soon as you become pregnant, and your doctor will recommend taking another antihypertensive medication instead. Valsartán/Hidroclorotiazida is not recommended for use at the beginning of pregnancy and should not be administered after the third month of pregnancy as it may cause serious harm to your baby when administered from that point on.

Use of Valsartán/Hidroclorotiazida with other medications

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

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

· lithium, a medication used to treat certain types of psychiatric disorders

· medications that may affect or be affected by potassium levels, such as digoxin, a medication to control heart rhythm, some antipsychotics.

· medications or substances that may increase the amount of potassium in the blood. These include potassium supplements or salt substitutes containing potassium, potassium-sparing medications and heparin

· medications that may decrease the amount of potassium in the blood, such as diuretics (medications to urinate), corticosteroids, laxatives, carbenoxolona, amfotericina or penicillin G.

· some antibiotics (of the rifampicin group), a medication used to protect against rejection in a transplant (ciclosporina) or an antiretroviral medication used to treat HIV/AIDS (ritonavir). These medications may increase the effect of Valsartán/Hidroclorotiazida

· medications that may induce “torsades de pointes” (irregular heartbeats), such as antiarrhythmics (medications used to treat heart problems) and some antipsychotics

· medications that may reduce the amount of sodium in the blood, such as antidepressants, antipsychotics, antiepileptics

· medications to treat gout, such as alopurinol, probenecid, sulfinpirazona

· vitamin D therapy and calcium supplements

· medications to treat diabetes (insulin or oral antidiabetic medications such as metformin)

· other medications to reduce blood pressure including metildopa, a converting enzyme inhibitor (ACE inhibitor) or aliskirén (see also the information under the headings “Do not take Valsartán/Hidroclorotiazida 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 diazoxida or beta-blockers

· cytotoxic medications (used to treat cancer), such as methotrexate or cyclophosphamide

· pain medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors and aspirin in doses above 3 g

· muscle relaxants, such as tubocurarina

· anticholinergic medications (medications used to treat a wide variety of disorders such as gastrointestinal cramps, urinary tract spasms, asthma, motion sickness, muscle spasms, Parkinson's disease and as an aid to anesthesia)

· amantadina (a medication used to treat Parkinson's disease and also to treat or prevent certain diseases caused by viruses)

· cholestyramine and colestipol (medications used mainly to treat high levels of lipids in the blood)

· ciclosporina, a medication used to prevent organ rejection after transplant

· alcohol, sleep medications and anesthetics (medications with sedative or pain-relieving effects used, for example, in surgery)

· iodinated contrast media (used for diagnostic imaging tests)

Taking Valsartán/Hidroclorotiazida with food, drinks, and alcohol

You can take Valsartán/Hidroclorotiazida 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, if you suspect you may be pregnant or if you plan to become pregnant, consult your doctor or pharmacist before using this medication.

·You must inform your doctor if you are pregnant, if you suspect you may be pregnant or if you plan to become pregnant.Generally, your doctor will advise you to stop taking Valsartán/Hidroclorotiazida before becoming pregnant or as soon as you become pregnant, and will recommend taking another antihypertensive medication instead. Valsartán/Hidroclorotiazida is not recommended for use at the beginning of pregnancy and should not be administered after the third month of pregnancy as it may cause serious harm to your baby when administered from that point on.

·Inform your doctor if you are planning to start or are breastfeeding, as it is not recommended to administer Valsartán/Hidroclorotiazida to women during this period. Your doctor may decide to administer a treatment that is more suitable if you want to breastfeed, especially to newborns or premature babies.

Driving and operating machines

Before driving a vehicle, using tools or operating machines, or carrying out other activities that require concentration, make sure you know your reactions to the effects of Valsartán/Hidroclorotiazida. Like many other medications used to treat high blood pressure, Valsartán/Hidroclorotiazida may cause, in rare cases, dizziness and affect concentration.

Use in athletes

Thismedicationcontainshidroclorotiazidawhichmayproduceapositiveresultindrugtests.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of 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 appointments with your doctor, even if you feel well.

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

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

If you take more Valsartán/Hidroclorotiazida Pharma Combix than you should

If you experience 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 Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Valsartán/Hidroclorotiazida 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, omit the missed dose.

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

If you interrupt the treatment with Valsartán/Hidroclorotiazida Pharma Combix

If you stop taking Valsartán/Hidroclorotiazida, your high blood pressure may worsen. Do not stop taking the medication unless your doctor tells you to.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

• Very common:mayaffect more than 1 in 10 patients
• Common:mayaffect up to 1 in 10 patients
• Uncommon:mayaffect up to 1 in 100 patients
• Rare:mayaffect up to 1 in 1,000 patients
• Very rare:mayaffect up to 1 in 10,000 patients
• Frequency not known: the frequency cannot be estimated from the available data

Some side effects may be severe 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
• Urticaria and difficulty breathing.

If you experience any of these symptoms, stop taking Valsartán/Hidroclorotiazida and contact your doctor immediately (see also section 2 “Warnings and precautions”).

Other side effects include:

Uncommon

• Cough
• Low blood pressure
• Dizziness
• Dehydration (with symptoms of thirst, dry mouth and tongue, reduced urine output, dark-colored urine, dry skin)
• Muscle pain
• Fatigue
• Prickling 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 reduction in urine output
• Low sodium levels in the blood (which, in severe cases, may cause fatigue, confusion, muscle twitching, and/or convulsions)
• Low potassium levels in the blood (sometimes with muscle weakness, muscle spasms, abnormal heart rhythm)
• Low white blood cell count in the blood (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, may cause the skin and eyes to turn yellow)
• Increased levels of urea nitrogen and creatinine in the blood (which may indicate abnormal kidney function)
• Increased levels of uric acid in the blood (which, in severe cases, may trigger a gout attack)
• Syncope (fainting)

The following side effects have been observed with medications containing valsartan or hydrochlorothiazide separately:

Valsartan

Uncommon

• Sensation 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 one or more of the following signs or symptoms: fever, joint pain, muscle pain, lymph node inflammation, and/or symptoms similar to the flu
• Skin rash, red-purple spots, fever, itching (signs 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, urticaria, difficulty breathing or swallowing, dizziness)
• Swelling mainly of the face and throat; skin rash; itching
• Increased liver function values
• Decreased hemoglobin levels and reduced percentage of red blood cells in the blood (which, in severe cases, may cause anemia)
• Renal insufficiency
• Low sodium levels in the blood (which, in severe cases, may cause fatigue, confusion, muscle twitching, and/or convulsions)

Hydrochlorothiazide

Very common

• Low potassium levels in the blood
• Increased levels of lipids in the blood

Common

• 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
• Reduced appetite
• Mild vomiting and nausea
• Dizziness, dizziness when standing up
• Inability to achieve or maintain an erection

Rareas

• Swelling and blisters on the skin (due to increased sensitivity to the sun)
• High calcium levels in the blood
• High blood sugar levels
• Sugar in the urine
• Worsening of diabetic metabolic state
• Constipation, diarrhea, stomach or intestinal discomfort, liver changes that may appear with yellow skin and eyes
• Irregular heartbeat
• Headache
• Sleep disturbances
• Depression (sadness)
• Low platelet count (sometimes with bleeding or bruising under the skin)
• Dizziness
• Prickling or numbness
• Visual disturbances

Very rareas

• Inflammation of the blood vessels with symptoms such as skin rash, red-purple spots, fever (vasculitis)
• Skin rash, itching, urticaria, 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)
• Face rash, joint pain, muscle disorders, fever (lupus erythematosus)
• Severe stomach pain (pancreatitis)
• Difficulty breathing with fever, cough, wheezing, shortness of breath (difficulty breathing that includes pneumonitis and pulmonary edema)
• Fever, sore throat, increased frequency of infections (agranulocytosis)
• Pale skin, fatigue, shortness of breath, dark-colored urine (hemolytic anemia)
• Fever, sore throat, or mouth ulcers due to infections (leucopenia)
• Confusion, fatigue, muscle twitching, and spasms, rapid breathing (hypochloremic alkalosis)
• Acute respiratory distress (the signs include severe difficulty breathing, fever, weakness, and confusion)

Frequency not known

• Weakness, bruising, and frequent infections (aplastic anemia)
• Significant reduction in urine output (possible signs of renal impairment or renal failure)
• Visual disturbances or eye pain due to high blood pressure (possible signs of fluid accumulation in the eye's vascular layer (choroidal hemorrhage) 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 cancer and lip cancer (non-melanoma skin cancer)

Reporting of side effects

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

Keepthis medication out of 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.

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

Composition of Valsartán/HidroclorotiazidaPharmaCombix

• The active principles are valsartán and hidroclorotiazida. Each tablet contains 160 mg of valsartán and 25 mg of hidroclorotiazida.
• The other components are: crospovidona, microcrystalline cellulose (E460i), anhydrous colloidal silica (E551), hydroxypropylmethylcellulose (E464), anhydrous calcium hydrogen phosphate (E341i) and magnesium stearate (E470b)
• The tablet coating contains: hydroxypropylmethylcellulose (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 content of the packaging

Coated tablets with a brown film, oval, biconvex, with beveled edges, with the mark “25” on one face and smooth on the other.

Aluminum-Aluminum blisters.

Valsartán/HidroclorotiazidaPharma Combix160 mg/25 mg is available in packs of 28 tablets.

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

Zac Les Hautes Pâtures

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

Last review date of this leaflet:February 2025

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