Label: Information for thePatient

Zestoretic 20 mg/12.5 mg Tablets

lisinopril/hydrochlorothiazide

Read this label carefully before starting to use this medication, as it contains important information for you.

• Keep this label as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others who may 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 label. See section 4.

6. Contents of the pack and additional information.

Zestoretic contains two medications, lisinopril and hydrochlorothiazide. Each one reduces blood pressure through a different mechanism. Lisinopril belongs to a group of medications called ACE inhibitors. Lisinopril acts by dilating blood vessels, helping to reduce blood pressure to facilitate the heart's ability to pump blood throughout the body. Hydrochlorothiazide is a diuretic that increases the amount of urine produced by the kidneys.

Lisinopril/hydrochlorothiazide is indicated for the treatment of high blood pressure (hypertension).

Do not take Zestoretic

• If you are allergic to lisinopril, hydrochlorothiazide, or any of the other components of this medication (listed in section6).
• If you have previously received a medication from the same group as lisinopril (ACE inhibitors) and have experienced an allergic reaction that caused itching, hives, sudden decrease in blood pressure, swelling of hands, feet, or ankles, face, lips, tongue, and/or throat with difficulty swallowing or breathing (angioedema).
• If you have taken or are currently taking sacubitril/valsartan, a medication used to treat a type of long-term (chronic) heart failure in adults, as the risk of angioedema (rapid swelling under the skin in an area such as the throat) is high.
• If a family member has had a severe allergic reaction (angioedema) to an ACE inhibitor or if you have had a severe allergic reaction (angioedema) for unknown reasons.
• If you have ever had an allergic reaction to diuretics of the type of hydrochlorothiazide, which are similar to sulfonamides (a type of antibiotic) or to any other compound of this medication.
• If you are more than 3 months pregnant. It is also best to avoid this medication at the beginning of pregnancy - see section on pregnancy.
• If you have kidney function impairment.
• If you have recently undergone a kidney transplant.
• If you have decreased urine output or inability to urinate (anuria).
• If you have liver function impairment.
• If you have diabetes or kidney insufficiency and are being treated with a medication to lower blood pressure that contains aliskiren.

Do not take lisinopril/hydrochlorothiazide if you are in any of the situations described above. If you are unsure, consult your doctor or pharmacist before taking this medication.

Warnings and precautions

Consult your doctor or pharmacist before starting to takeZestoreticif:

• You have a narrowing (stenosis) of the aorta (one of the arteries that are in the heart) or the mitral valve (one of the valves that are in the heart).
• You have a narrowing (stenosis) of the renal artery.
• You have an increase in the thickness of the heart muscle (known as hypertrophic cardiomyopathy).

• You have low blood pressure (you may notice it as dizziness, especially when standing up. In these cases, lying down may help).
• You have heart failure (heart problem to pump enough blood to the body) and normal or low blood pressure.
• You have kidney problems or if you are on dialysis.
• You have liver problems.
• You have diabetes and are being treated with oral antidiabetic medications or insulin.
• If you are taking any of the following medications used to treat high blood pressure (hypertension):

-Angiotensin II receptor antagonist (ARA) (also known as "sartanes" - for example, valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.

-Aliskiren

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

See also the information under the heading “Do not take Zestoretic”.

• If you are taking any medication that may increase the risk of angioedema, see “Taking Zestoretic with other medications”:
• • Racecadotrilo, a medication used to treat diarrhea.
  • Medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus).
  • Vildagliptina, a medication used to treat diabetes.

• You have gout.
• You have recently had diarrhea or vomiting.
• You are following a low-sodium diet, taking potassium supplements or salt substitutes containing potassium.
• You are being treated with potassium-sparing diuretics or medications that may increase potassium levels in the blood, such as heparin.
• You have high cholesterol levels and are receiving a treatment called "apheresis of LDL”.
• You are of black race, as this medication may be less effective. You are also more likely to develop the adverse effect “angioedema” (a severe allergic reaction).
• You have persistent dry cough that lasts for a long time.
• You have persistent low levels of potassium in the blood.
• You have persistent high levels of calcium in the blood.
• You are undergoing tests to detect thyroid or parathyroid gland abnormalities.
• You should inform your doctor if you think you are (or plan to be) pregnant. Lisinopril/hydrochlorothiazide is not recommended at the beginning of pregnancy, and it should not be taken if you are more than 3 months pregnant as it may cause serious harm to the baby if used in this stage (see section on pregnancy).
• If you have had skin cancer or if a skin lesion appears unexpectedly during treatment. The treatment with hydrochlorothiazide, 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 Zestoretic.
• If you experience a decrease in vision or eye pain, it may be a symptom of fluid accumulation in the vascular layer of the eye (choroidal effusion) or increased pressure in the eye, which can occur within a few hours to a week after taking Zestoretic. If not treated, this can cause permanent vision loss. If you have previously had an allergy to penicillin or sulfonamide, you may be at higher risk of developing it.
• If you have had respiratory or pulmonary 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 Zestoretic, seek medical attention immediately

If you are unsure whether you are in any of the situations described above, consult your doctor or pharmacist before taking this medication.

Stop taking Zestoretic and seek medical attention immediatelyif:

• You have difficulty breathing with or without swelling of the face, lips, tongue, and/or throat.
• You have swelling of the face, lips, tongue, and/or throat, which may cause difficulty swallowing.
• You experience intense itching on the skin (with hives).

Treatment of allergies such as insect bites

Inform your doctor if you are receiving or will be receiving a treatment to reduce the effect of an allergy to an insect bite (allergy desensitization). If you take lisinopril/hydrochlorothiazide while receiving this treatment, it may cause a severe allergic reaction.

Surgery

Inform your doctor or dentist that you are takingthis medicationbefore undergoing any surgical procedure (including dental surgery). This is because you may experience low blood pressure (hypotension) if you are given certain local or general anesthetics while taking lisinopril/hydrochlorothiazide.

Be especially careful with the initial dose ofthis medication, as it may cause a more pronounced decrease in blood pressure than what is normally achieved with continued treatment.This effect may be noticeable as dizziness or vertigo, in which case lying down may help.However, if you are concerned, consult your doctor.

Taking Zestoretic with other medications

Inform your doctor or pharmacist if you areusing, haveusedrecently or may need to use anyother medication. This is becausethis medicationmay affect how some medications work and some medications may have an effect onthis medication. Your doctor may need to adjust your dose and/or take other precautions.

Especially, inform your doctor or pharmacist if you are using any of the following medications:

• Medications that cause a decrease in potassium levels in the blood, such as anfotericina (for fungal infections), carbenoxolona (for esophageal disease or oral ulcers), corticosteroids (e.g., prednisona), pituitary hormone (ACTH) or some laxatives,otherdiuréticos(medications used to increase urine output, including potassium-sparing diuretics) and salicylate derivatives.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medications that may increase potassium levels in the blood (e.g., trimetoprima and cotrimoxazol for bacterial infections: ciclosporina, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medication used to prevent blood clotting).
• Medications that cause arrhythmias.
• Medications for depression and mental disorders, including lithium.
• Anesthetics, barbiturates, or alcohol that may exacerbate low blood pressure (you may notice it as dizziness, especially when standing up).
• Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, and indomethacin, for pain and arthritis treatment.
• Injectable medications for rheumatoid arthritis that contain gold salts (e.g., aurotiomalato de sodio).
• Medications to control heart rate (antiarrhythmic agents) such as digoxina and beta-blockers (sotalol).
• Other medications for high blood pressure treatment (anithipertensivos) including angiotensin II receptor antagonists (ARA) or aliskiren (see “Do not take Zestoretic”).
• Nitrate-derived medications (for heart problems).
• Medications for diabetes treatment (such as insulin and oral antidiabetic medications like sulfonylureas). You may need to adjust your antidiabetic medication dose while taking diuretic thiazides.
• Medications that cause an increase in potassium levels in the blood, such as heparin (to prevent blood clotting).
• Calcium or vitamin D supplements.
• Medications to lower cholesterol, such as colestipol or colestiramina or lovastatina.
• Muscle relaxants such as tubocurarina.
• Trimetoprim (an antibiotic).
• Alopurinol (for gout).
• Ciclosporina (medication to prevent organ transplant rejection and other immune system disorders).
• Medications for cancer treatment, such as ciclofosfamida or metotrexato.

If you are taking any of the following medications, the risk of developing angioedema may increase (the signs of angioedema include swelling of the face, lips, tongue, and/or throat with difficulty swallowing or breathing):

• Medications to dissolve blood clots (tissue plasminogen activator) that are usually administered in the hospital.
• Medications used to prevent organ transplant rejection and for cancer (e.g., temsirolimus, sirolimus, everolimus).
• Racecadotrilo, a medication used to treat diarrhea.
• Vildagliptina, a medication used to treat diabetes.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

You should inform your doctor if you think you are (or plan to be) pregnant. Your doctor will usually advise you to stop taking lisinopril/hydrochlorothiazidebefore becoming pregnant or as soon as you find out you are pregnant and recommend that you take another medication instead ofthis medication. Lisinopril/hydrochlorothiazide is not recommended at the beginning of pregnancy, and it should not be taken if you are more than 3 months pregnant as it may cause serious harm to the baby if used after the third month of pregnancy.

Usually, lisinopril/hydrochlorothiazide should be replaced with an appropriate antihypertensive treatment before starting pregnancy. The medication should not be used during the 2nd and 3rd trimesters of pregnancy.

Usually, your doctor will advise you to stop taking lisinopril/hydrochlorothiazideas soon as you find out you are pregnant.

If you become pregnant while takingthis medication, inform and visit your doctor as soon as possible.

Breastfeeding

Inform your doctor if you are breastfeeding or plan to start breastfeeding. Hydrochlorothiazide (one of the components of the medication) is excreted in small amounts in breast milk, and at high doses, it may inhibit milk production. It is not recommended to usethis medicationin mothers during breastfeeding, and your doctor may choose another treatment for you if you want to start breastfeeding, especially if your baby is newborn or premature

Driving and operating machinery

• Zestoreticis unlikely to affect your ability to drive or operate machinery. However, like other medications used to treat high blood pressure,Zestoreticmay cause dizziness or drowsiness in some people, especially at the beginning of treatment, when changing doses, or if consuming alcohol. If you experience dizziness or drowsiness, consult your doctor before engaging in these activities.
• You should wait to see how the medication affects you before attempting these activities.

Important information about some of the components of Zestoretic

It may cause a mild laxative effect because it contains mannitol.

Use in athletes:

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

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.

Medication intake

• Swallow the tablet with water.
• Try to take your tablets at the same time every day, preferably in the morning. It does not matter whether you take this medicationbefore or after meals.
• Do not stop taking your tablets if you feel well, unless your doctor tells you to.
• If you estimate that the effect of this medicationis too strong or weak, consult your doctor or pharmacist.

First dose intake

• Be especially careful when taking the first dose of this medicationor if your doctor increases the dose. It may cause a further decrease in blood pressure than what will occur with subsequent doses.
• This effect may make you feel dizzy or experience vertigo. If this happens, lying down may help. If this concerns you, consult your doctor as soon as possible.

Adults

• The usual dose is one or two tablets once a day.

Use in children and adolescents:

This medication is not recommended for use in children and adolescents as the information on safety and efficacy in this age group is limited.

If you take more Zestoretic than you should

In case of overdose or accidental ingestion, consult the Toxicological Information Service. Phone 91 562 04 20.

If you forgot to take Zestoretic

• If you forgot 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 compensate for the missed doses.
• Do notsuspend treatment before your doctor tells you to.

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

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

If you experience any of the following reactions,stop takingZestoreticand seek medical attention immediately.

• Severe allergic reactions (rare, may affect up to 1 in 100 people). Symptoms may include:

• Swelling of the face, lips, tongue, or throat. This may make it difficult to swallow.
• Severe or sudden swelling of the hands, feet, or ankles.
• Difficulty breathing.
• Severe skin itching (with hives).

• Severe skin disorders, such as an unexpected and sudden rash, redness, or peeling of the skin (very rare, may affect up to 1 in 10,000 people).
• A severe infection with symptoms such as fever and a significant deterioration in your general condition, or fever with symptoms of local infection such as throat, pharynx, or mouth irritation, or urinary tract disorders (very rare, may affect up to 1 in 10,000 people).
• A sudden and severe eye pain with redness, as if not treated, it could lead to permanent vision loss.

Other possible side effects due to lisinopril:

Common(may affect up to 1 in 10 people):

• Dizziness, especially when standing up quickly
• Headache.
• Persistent dry cough.
• Fatigue.
• Diarhea.
• Nausea.
• Renal disorders (detected by blood tests).
• Loss of consciousness.

Rare(may affect up to 1 in 100 people):

• Mood changes.
• Changes in color of the fingers and toes (blue pale followed by redness) or numbness or tingling in the fingers or toes.
• Dizziness.
• Somnolence.
• Difficulty sleeping.
• Visual and/or auditory hallucinations.
• Rhinorrhea.
• Nausea.
• Abdominal pain or indigestion.
• Changes in blood tests to determine the proper functioning of your liver and kidneys.
• Skin rash or itching.
• Impotence.
• Sensation of fatigue or weakness (lack of strength).
• A significant decrease in blood pressure that may occur in people with the following conditions: coronary disease, aortic stenosis (a heart artery), renal artery stenosis, or heart valve disorders; a thickening of the heart muscle. If this happens, you may feel dizziness or dizziness, especially if you stand up quickly.
• Myocardial infarction.
• Cerebrovascular accident.
• Tachycardia.

Very rare(may affect up to 1 in 1,000 people):

• Changes in some blood cells or other components of your blood. Your doctor may take samples from time to time to check if lisinopril/hydrochlorothiazide is affecting your blood. Symptoms may include fatigue, pale skin, throat irritation, fever, joint and muscle pain, joint inflammation, or sensitivity to sunlight.
• Confusion.
• Hives.
• Dry mouth.
• Hair loss.
• Psoriasis (a skin disorder).
• Development of breasts in men.
• Acute renal failure.
• Change in the smell of things
• Decrease in sodium levels in the blood (hyponatremia) (symptoms may include fatigue, headache, nausea, vomiting).

Very rare(may affect up to 1 in 10,000 people):

• Low blood glucose levels (hypoglycemia). Symptoms may include hunger or weakness, sweating, and rapid heartbeat.
• Sinusitis (sensation of pain and pressure behind the cheeks and eyes).
• Chills.
• Pulmonary inflammation. Symptoms include cough, shortness of breath, and high fever.
• Pancreatitis. This causes moderate to severe abdominal pain.
• Intestinal inflammation.
• Yellowing of the skin or white of the eyes (jaundice).
• Hepatitis. This may cause a loss of appetite, yellowing of the skin and eyes, and dark urine.
• Hepatic insufficiency.
• Sweating.
• Severe skin disorders. Symptoms include redness, blistering, and peeling.
• Hives.
• Decreased urine output or inability to urinate.

Frequency not known(cannot be estimated from available data):

• Depressive symptoms
• Flush (redness)
• Severe allergic reaction.

Other side effects due to hydrochlorothiazide

Very rare:

-Acute respiratory distress (symptoms include severe difficulty breathing, fever, weakness, and confusion)

Frequency not known:

Benign, malignant, and unspecified neoplasms (including cysts and polyps)

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

Blood and lymphatic system disorders

• Medullary bone depression.
• Reduction in platelet count (thrombocytopenia).
• Reduction in white blood cell count (leucopenia).
• Reduction in granulocyte count (agranulocytosis).
• Anemia due to the destruction of red blood cells (hemolytic anemia).

Metabolic and nutritional disorders

• Anorexia.
• High blood glucose levels (hyperglycemia).
• Presence of glucose in the urine.
• High levels of uric acid in the urine.
• Low levels of sodium, potassium, chloride, and magnesium in the blood.
• Increased levels of cholesterol and triglycerides in the blood.
• Gout.

Mental and behavioral disorders

• Anxiety.
• Depression.
• Sleep disturbances.

Nervous system disorders

• Loss of appetite.
• Sensation of tingling in the hands and feet.
• Sensation of dizziness.

Eye disorders

• Changes in vision that make objects appear yellow.
• Decreased vision or eye pain due to high pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal hemorrhage) or acute angle-closure glaucoma]. Patients who experience red eye with severe pain should seek immediate medical attention, as if not treated, this could lead to permanent vision loss.

Ear and labyrinth disorders

• Dizziness.

Cardiac disorders

• Postural hypotension.

Vascular disorders

• Phlebitis.

Respiratory, thoracic, and mediastinal disorders

• Sensation of shortness of breath.
• Pulmonary inflammation.

Gastrointestinal disorders

• Stomach irritation.
• Diarhea.
• Constipation.
• Pancreatitis.

Hepatic disorders

• Yellowing of the skin (jaundice).

Skin and subcutaneous tissue disorders

• Sunlight sensitivity reaction.
• Rash.
• Urticaria.
• Hives.
• In some patients with lupus, symptoms may be reactivated or worsened.

Musculoskeletal and connective tissue disorders

• Muscle spasms.
• Muscle weakness.

Renal and urinary disorders

• Renal function alteration.
• Renal inflammation.

General disorders and administration site conditions

• Fever.
• Weakness.

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.

• Keep this medication out of the sight and reach of children.
• Do not store at a temperature above 86°F (30°C). Store in the original packaging to protect it from light.
• 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.

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

Composition of Zestoretic

• The active principles are lisinopril and hydrochlorothiazide. Each tablet contains 21.8 mg of lisinopril dihydrate (equivalent to 20 mg of anhydrous lisinopril) and 12.5 mg of hydrochlorothiazide.
• The other components are: mannitol (E421), calcium hydrogen phosphate anhydrous, cornstarch, pregelatinized cornstarch, magnesium stearate (E470b).

Appearance of the product and contents of the packaging

Zestoretic is presented in the form of round, white, uncoated tablets, with the imprint 20 12.5 on one face and a bisecting line on the other.

Holder of the marketing authorization and responsible for manufacturing

Holder of the marketing authorization:

Atnahs Pharma Netherlands B.V.,

Copenhagen Towers,

Ørestads Boulevard 108, 5.tv DK-2300,

København S, Denmark

Responsible for manufacturing:

AstraZeneca AB

Gärtunavägen

SE-152 57 Södertälje

Sweden

AstraZeneca Reims Production

Parc Industriel Pompelle, Chemin de Vrilly, 51100

Reims, France

ROVI Pharma Industrial Services S.A.

Vía Complutense, 140

Alcalá de Henares, 28805 Madrid

Spain

Last review date of this leaflet: March 2022

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