LOSARTAN/HYDROCHLOROTHIAZIDE COMBIX 50 mg/12.5 mg FILM-COATED TABLETS

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

Do not take Losartan/Hydrochlorothiazide Combix

• If you are allergic (hypersensitive) to losartan, hydrochlorothiazide, or any of the other ingredients of this medicine.
• If you are allergic (hypersensitive) to sulfonamide-derived substances (e.g., other thiazides, some antibacterials such as cotrimoxazole; ask your doctor if you are unsure).
• If you are more than 3 months pregnant (it is also recommended to avoid Losartan/Hydrochlorothiazide Combix during the first months of pregnancy - see section Pregnancy).
• If you have severe hepatic impairment.
• If you have severe renal impairment or your kidneys are not producing urine.
• If you have low levels of potassium or sodium, high levels of calcium that cannot be corrected by treatment.

• If you have gout.
• If you have diabetes or renal impairment and are being treated with a blood pressure medicine that contains aliskiren.

Warnings and precautions

Tell your doctor if you are pregnant (or think you might be). Losartan/Hydrochlorothiazide Combix is not recommended during the first trimester of pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby.

It is important that you tell your doctor before taking Losartan/Hydrochlorothiazide Combix:

• If you have previously experienced swelling of the face, lips, tongue, or throat.
• If you are taking diuretics (water tablets).
• If you are on a low-salt diet.
• If you have had excessive vomiting and/or diarrhea.
• If you have heart failure.
• If you have narrowings of the arteries that supply the kidneys (renal artery stenosis), if you only have one functioning kidney, or if you have recently had a kidney transplant.
• If you have narrowing of the arteries (atherosclerosis), angina (chest pain due to poor heart function).
• If you have narrowing of the heart valves (aortic or mitral stenosis) or hypertrophic cardiomyopathy (a disease that causes thickening of the heart valves).
• If you are diabetic.
• If you have had gout.
• If you have had an allergic disorder, asthma, or a condition that causes joint pain, skin rashes, and fever (systemic lupus erythematosus).
• If you have high levels of calcium or low levels of potassium, or if you are on a low-potassium diet.
• If you need to have anesthesia (even at the dentist) or before surgery, or if you are to have tests to determine your parathyroid function, you should inform your doctor or healthcare professional that you are taking losartan potassium and hydrochlorothiazide tablets.
• If you have primary hyperaldosteronism (a syndrome associated with high secretion of the hormone aldosterone by the adrenal gland due to an alteration of this gland).
• If you are taking any of the following medicines used to treat high blood pressure (hypertension):

• An angiotensin-converting enzyme inhibitor (ACEI) (e.g., enalapril, lisinopril, ramipril), particularly if you have diabetic-related kidney problems.

• Aliskiren. If you have had skin cancer or if you develop an unexpected skin lesion during treatment. Treatment with hydrochlorothiazide, particularly long-term use at high doses, may increase the risk of some types of skin and lip cancer (non-melanoma skin cancer). Protect your skin from sun exposure and UV rays while taking Losartan/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 hours to a week after taking Losartan/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 Losartan/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.

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

See also the information under the heading “Do not take Losartan/Hydrochlorothiazide Combix”.

Interaction of Losartan/Hydrochlorothiazide Combix with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including those obtained without a prescription.

Diuretics like hydrochlorothiazide contained in Losartan/Hydrochlorothiazide Combix may interact with other medicines. Preparations containing lithium should not be taken with Losartan/Hydrochlorothiazide Combix without your doctor's careful monitoring. Special precautions may be necessary (e.g., blood tests) if you take potassium supplements, salt substitutes that contain potassium, or potassium-sparing medicines, diuretics (water tablets), some laxatives, medicines for treating gout, medicines for controlling heart rhythm or diabetes (oral medicines or insulins). It is also important that your doctor knows if you are taking other medicines to lower your blood pressure, steroids, medicines to treat cancer, painkillers, medicines to treat fungal infections, or medicines for arthritis, cholesterol-lowering resins such as cholestyramine, muscle relaxants, sleeping tablets; opioid medicines like morphine, "pressor amines" like adrenaline or other medicines of the same group; (oral medicines for diabetes or insulins).

Your doctor may need to change your dose and/or take other precautions:

If you are taking an angiotensin-converting enzyme inhibitor (ACEI) or aliskiren (see also the information under the headings “Do not take Losartan/Hydrochlorothiazide Combix” and “Warnings and precautions”).

Please, when taking Losartan/Hydrochlorothiazide Combix, inform your doctor when you are scheduled to have an iodine contrast medium.

Losartan/Hydrochlorothiazide Combix with food, drinks, and alcohol

It is recommended that you do not drink alcohol while taking these tablets: alcohol and Losartan/Hydrochlorothiazide Combix tablets may increase the effects of each other.

Excessive salt in the diet may counteract the effect of Losartan/Hydrochlorothiazide Combix tablets.

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

Pregnancy, breastfeeding, and fertility

Pregnancy:

You should inform your doctor if you are pregnant (or think you might be). Your doctor will normally advise you to stop taking Losartan/Hydrochlorothiazide Combix before you become pregnant or as soon as you know you are pregnant and will advise you to take another medicine instead of Losartan/Hydrochlorothiazide Combix. Losartan/Hydrochlorothiazide Combix is not recommended during the first trimester of pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause serious harm to your baby.

Breastfeeding:

Inform your doctor if you are breastfeeding or plan to breastfeed. Losartan/Hydrochlorothiazide Combix is not recommended during breastfeeding, and your doctor will choose another treatment for you if you want to breastfeed.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

When you start treatment with this medicine, you should not perform tasks that require special attention (e.g., driving a car or using hazardous machinery) until you know how your medicine affects you.

Important information about some of the ingredients of Losartan/Hydrochlorothiazide Combix

This medicine contains lactose. If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine.

Use in athletes

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

3. How to take Losartan/Hydrochlorothiazide Combix

Follow exactly the administration instructions of Losartan/Hydrochlorothiazide Combix given by your doctor. Your doctor will decide the appropriate dose of Losartan/Hydrochlorothiazide, depending on your condition and whether you are taking other medicines. It is important to continue taking Losartan/Hydrochlorothiazide Combix as long as your doctor prescribes it to maintain constant control of your blood pressure.

High blood pressure

For most patients with high blood pressure, the usual dose is 1 tablet of Losartan/Hydrochlorothiazide 50 mg/12.5 mg per day to control blood pressure for 24 hours. It can be increased to 2 tablets of losartan/hydrochlorothiazide 50 mg/12.5 mg per day or changed to 1 tablet of losartan/hydrochlorothiazide 100 mg/25 mg (a stronger dose) per day. The maximum daily dose is 2 tablets of 50 mg of losartan/12.5 mg of hydrochlorothiazide per day or 1 tablet of 100 mg of losartan/25 mg of hydrochlorothiazide per day.

Use in children and adolescents

There is no experience with the use of Losartan/Hydrochlorothiazide Combix in children. Therefore, Losartan/Hydrochlorothiazide Combix should not be given to children.

Use in elderly patients

Losartan/Hydrochlorothiazide Combix works as well and is as well tolerated by most elderly patients as by younger patients. Most elderly patients require the same dose as younger patients.

If you take more Losartan/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 taken.

Overdose may cause a drop in blood pressure, palpitations, slow pulse, changes in blood composition, and dehydration.

If you forget to take Losartan/Hydrochlorothiazide Combix

Try to take Losartan/Hydrochlorothiazide Combix as prescribed. However, if you miss a dose, do not take an extra dose. Simply return to your usual schedule.

4. Possible side effects

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

If you experience the following, stop taking Losartan/Hydrochlorothiazide Combix and inform your doctor immediately or go to the emergency department of your nearest hospital:

A severe allergic reaction (skin rash, itching, swelling of the face, lips, mouth, or throat that can cause difficulty swallowing or breathing).

This is a serious but rare side effect that affects more than 1 patient in 10,000 but less than 1 patient in 1,000. You may need urgent medical attention or hospitalization.

The following side effects have been reported:

Frequent (affecting less than 1 in 10 but more than 1 in 100):

• Cough, respiratory infection, nasal congestion, sinusitis, sinus disorder,
• Diarrhea, abdominal pain, nausea, indigestion,
• Muscle pain or cramps, leg pain, back pain,
• Insomnia, headache, dizziness,
• Weakness, fatigue, chest pain,
• High levels of potassium (which can cause an abnormal heart rhythm), decrease in hemoglobin levels.

Uncommon (affecting less than 1 in 100 but more than 1 in 1,000):

• Anemia, red or brown spots on the skin, (sometimes especially on the feet, legs, arms, and buttocks, with joint pain, swelling of the hands and feet, and abdominal pain), bruising, reduction in white blood cells, blood clotting problems, and bruising,
• Loss of appetite, high levels of uric acid or gout, high blood sugar levels, abnormal blood electrolyte levels,
• Anxiety, nervousness, panic disorders (recurrent panic attacks), confusion, depression, abnormal dreams, sleep disorders, somnolence, memory impairment,
• Numbness or similar sensations, pain in the limbs, tremor, migraine, fainting,
• Blurred vision, eye irritation or itching, conjunctivitis, worsening of vision, seeing things in yellow,
• Decreased vision or eye pain due to high pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or glaucoma],
• Ringing, buzzing, noises, or clicking in the ears,
• Low blood pressure that may be associated with changes in posture (feeling dizzy or weak when standing up), angina (chest pain), abnormal heartbeats, stroke (transient stroke, "mini-stroke"), heart attack, palpitations,
• Inflammation of blood vessels that is often associated with a skin rash or bruising,
• Sore throat, shortness of breath, bronchitis, pneumonia, fluid in the lungs (which can cause difficulty breathing), nosebleeds, runny nose, congestion,
• Constipation, gas, stomach disorders, stomach spasms, vomiting, dry mouth, inflammation of a salivary gland, toothache,
• Jaundice (yellowing of the eyes and skin), pancreatitis,
• Hives, itching, skin inflammation, skin rash, redness of the skin, sensitivity to light, dry skin, flushing, sweating, hair loss,
• Pain in the arms, shoulders, hips, knees, or other joints, joint swelling, stiffness, muscle weakness,
• Frequent urination even at night, abnormal kidney function including kidney inflammation, urinary tract infection, sugar in the urine,
• Decreased sexual desire, impotence,
• Swelling of the face, fever.

Rare (affecting more than 1 in 10,000 but less than 1 in 1,000):

• Hepatitis (inflammation of the liver), abnormal liver function tests.
• Intestinal angioedema: swelling in the intestine that presents symptoms such as abdominal pain, nausea, vomiting, and diarrhea.

Very rare (affecting up to 1 in 10,000 patients):

• Acute respiratory distress (signs include severe shortness of breath, fever, weakness, and confusion).

Frequency not known

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

If you think any of the side effects you are experiencing are serious or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

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: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Losartan/Hydrochlorothiazide Combix

Keep out of the reach and sight of children.

Do not use Losartan/Hydrochlorothiazide Combix after the expiration date stated on the packaging after EXP. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Store Losartan/Hydrochlorothiazide Combix in its original packaging.

Keep the blister in the outer packaging. Do not open the blister until you are ready to take the tablet.

Medicines should not be disposed of via wastewater or household waste. Place the packaging and any unused medicine in the SIGRE collection point at your pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Packaging Content and Additional Information

Composition of Losartan/Hydrochlorothiazide Combix

The active ingredients are losartan potassium and hydrochlorothiazide.

Each Losartan/Hydrochlorothiazide Combix 50mg/12.5 mg film-coated tablet contains, as active ingredients, 50 mg of losartan (potassium) and 12.5 mg of hydrochlorothiazide.

Losartan/Hydrochlorothiazide Combix contains the following inactive ingredients: lactose monohydrate, corn starch, microcrystalline cellulose (E460i), low-substituted hydroxypropyl cellulose, anhydrous colloidal silica, sodium carboxymethyl starch (type A), magnesium stearate, hypromellose (E464), titanium dioxide (E171), macrogol, and talc (E553b).

Product Appearance and Packaging Content

Losartan/Hydrochlorothiazide Combix 50 mg/12.5 mg tablets are supplied as film-coated tablets, white or almost white in color, capsule-shaped, with the letters “ZD18” engraved on one side and smooth on the other.

Losartan/Hydrochlorothiazide Combix is supplied in the following package sizes:

Aluminum-Aluminum blisters, in packages of 28 tablets.

Marketing Authorization Holder

Combix Laboratories, S.L.U.

C/ Badajoz, 2. Building 2.

28223 Pozuelo de Alarcón (Madrid)

Spain

Phone: + 34 91 490 42 51

Fax: + 34 91 490 31 89

Manufacturer

Zydus France

ZAC Les Hautes Patures

Parc d’activités des Peupliers

25 Rue des Peupliers

92000 Nanterre

France

or

Centre Specialites Pharmaceutiques

ZAC du Suzot

35 rue de la Chapelle

63450 St Amant Tallende

France

The last revision of this prospectus was in February 2025

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