ZESTORETIC 20 mg/12.5 mg TABLETS

Introduction

Leaflet: information for thepatient

Zestoretic 20 mg/12.5 mg tablets

lisinopril/hydrochlorothiazide

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed to you only, and you should not give it to others, even if they have the same symptoms, as it may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

Contents of the leaflet

1. What is Zestoretic and what is it used for.
2. What you need to know before taking Zestoretic.
3. How to take Zestoretic.
4. Possible side effects.
5. Storage of Zestoretic.

1. Package contents and additional information.

1. What is Zestoretic and what is it used for

Zestoretic contains two medicines, lisinopril and hydrochlorothiazide. Each of them lowers blood pressure through a different mechanism. Lisinopril belongs to a group of medicines called ACE inhibitors. Lisinopril works by dilating blood vessels, helping to reduce blood pressure and make it easier for the heart 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).

2. What you need to know before taking Zestoretic

Do not take Zestoretic

• If you are allergic to lisinopril, hydrochlorothiazide, or any of the other ingredients of this medicine (listed in section 6).
• If you have previously taken a medicine from the same group of medicines as lisinopril (ACE inhibitors) and have experienced an allergic reaction that caused itching, hives, sudden drop 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 medicine 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 hydrochlorothiazide type, which are similar to sulfonamides (a type of antibiotic) or to any other component of this medicine.
• If you are pregnant for more than 3 months. It is also best to avoid this medicine at the beginning of pregnancy - see the section on pregnancy.
• If you have kidney function impairment.
• If you have recently undergone a kidney transplant.
• If you have decreased urine production or inability to urinate (anuria).
• If you have liver function impairment.
• If you have diabetes or kidney failure and are being treated with a blood pressure medicine 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 medicine.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Zestoretic if:

• You have a narrowing (stenosis) of the aorta (one of the arteries in the heart) or of the mitral valve (one of the valves 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 (a problem with the heart pumping enough blood to the body) and normal or low blood pressure.
• You have kidney problems or are on dialysis.
• You have liver problems.
• You have diabetes and are being treated with oral antidiabetics or insulin.
• If you are taking any of the following medicines used to treat high blood pressure (hypertension):

• An angiotensin II receptor antagonist (ARA) (also known as "sartans" - e.g., valsartan, telmisartan, irbesartan), especially if you have diabetic kidney problems.
• Aliskiren

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

See also the information under the heading "Do not take Zestoretic".

• If you are taking any medicine that may increase the risk of angioedema, see "Taking Zestoretic with other medicines":
• • Racecadotril, a medicine used to treat diarrhea.
  • Medicines used to prevent organ rejection and cancer (e.g., temsirolimus, sirolimus, everolimus).
  • Vildagliptin, a medicine used to treat diabetes.

• You have gout.
• You have recently had diarrhea or vomiting.
• You are on a low-salt diet, taking potassium supplements, or using salt substitutes that contain potassium.
• You are being treated with diuretics (medicines used to increase urine production) that spare potassium or medicines that may increase potassium levels in the blood, such as heparin.
• You have high cholesterol levels and are receiving a treatment called "LDL apheresis".
• You are black, as this medicine may be less effective. You are also more likely to develop the side effect "angioedema" (a severe allergic reaction).
• You have a persistent dry cough.
• You have persistently low potassium levels in the blood.
• You have persistently high calcium levels in the blood.
• You are undergoing tests to detect thyroid or parathyroid disorders.
• You must inform your doctor if you think you are (or plan to become) pregnant. It is not recommended to use lisinopril/hydrochlorothiazide at the beginning of pregnancy, and it should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to the baby if used during this period (see the section on pregnancy).
• 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 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, they could be symptoms of fluid accumulation in the vascular layer of the eye (choroidal effusion) or an increase in eye pressure, and they can occur within a few hours to a week after taking Zestoretic. If left untreated, this can lead to permanent vision loss. If you have previously been allergic to penicillin or sulfonamide, you may be at higher risk of developing it.
• 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 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 medicine.

Stop taking Zestoretic and seek medical attention immediately if:

• 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 can cause difficulty swallowing.
• You experience intense itching of the skin (with hives).

Treatment of allergies such as insect bites

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

Surgery

If you are going to undergo surgery (including dental surgery), inform your doctor or dentist that you are taking this medicine. This is because you may experience low blood pressure (hypotension) if you are given certain local or general anesthetics while taking lisinopril/hydrochlorothiazide.

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

Taking Zestoretic with other medicines

Inform your doctor or pharmacist if you are using, have recently used, or may need to use any other medicine. This is because this medicine may affect the way some medicines work, and some medicines may have an effect on this medicine. Your doctor may need to adjust your dose and/or take other precautions.

In particular, inform your doctor or pharmacist if you are using any of the following medicines:

• Medicines that may decrease potassium levels in the blood, such as amphotericin (for the treatment of fungal infections), carbenoxolone (for the treatment of esophageal disease or oral ulcers), corticosteroids (e.g., prednisone), pituitary hormone (ACTH), or certain laxatives, other diuretics (including potassium-sparing diuretics), and salicylate derivatives.
• Potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ rejection; and heparin, a medicine used to thin the blood to prevent clots).
• Medicines that may cause arrhythmias.
• Medicines for depression and mental disorders, including lithium.
• Anesthetic medicines, barbiturates, or alcohol, which may enhance the decrease in blood pressure (you may notice it as dizziness, especially when standing up).
• Non-steroidal anti-inflammatory medicines (NSAIDs), including acetylsalicylic acid, ibuprofen, and indomethacin, for the treatment of pain and arthritis.
• Injectable medicines for rheumatoid arthritis that contain gold salts (e.g., sodium aurothiomalate).
• Medicines to control heart rhythm (antiarrhythmic agents) such as digoxin and beta-blockers (sotalol).
• Other medicines for the treatment of high blood pressure (antihypertensives) including angiotensin II receptor antagonists (ARAs) or aliskiren (see "Do not take Zestoretic").
• Nitrate-derived medicines (for heart problems).
• Medicines for the treatment of diabetes (such as insulin and oral antidiabetics like sulfonylureas). The dose of your antidiabetic medicine may need to be adjusted while taking thiazide diuretics.
• Medicines that may increase potassium levels in the blood, such as heparin (to prevent blood clot formation).
• Calcium or vitamin D supplements.
• Medicines to lower cholesterol, such as colestipol or cholestyramine or lovastatin.
• Muscle relaxants like tubocurarine.
• Trimethoprim (an antibiotic).
• Allopurinol (for gout).
• Cyclosporine (a medicine to prevent organ rejection and other immune system diseases).
• Medicines for the treatment of cancer, such as cyclophosphamide or methotrexate.

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

• Medicines to dissolve blood clots (tissue plasminogen activator) that are usually administered in the hospital.
• Medicines used to prevent organ rejection and cancer (e.g., temsirolimus, sirolimus, everolimus).
• Racecadotril, a medicine used to treat diarrhea.
• Vildagliptin, a medicine used to treat diabetes.

Pregnancy, breastfeeding, and fertility

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

Pregnancy

You must inform your doctor if you think you are (or plan to become) pregnant. Normally, your doctor will advise you to stop taking lisinopril/hydrochlorothiazide before becoming pregnant or as soon as you know you are pregnant and recommend that you take another medicine instead of this one. Lisinopril/hydrochlorothiazide is not recommended at the beginning of pregnancy, and it should not be taken if you are pregnant for more than 3 months, as it may cause serious harm to the baby if used during this period.

Normally, lisinopril/hydrochlorothiazide should be replaced with a suitable antihypertensive treatment before starting pregnancy. The medicine should not be used during the 2nd and 3rd trimesters of pregnancy.

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

If you become pregnant during treatment with this medicine, inform and consult 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 medicine) is excreted in small amounts in breast milk and, at high doses, may inhibit milk production. It is not recommended to use this medicine in breastfeeding mothers, and your doctor may choose another treatment for you if you wish to start breastfeeding, especially if your baby is newborn or premature.

Driving and using machines

• Zestoretic is unlikely to affect your ability to drive or use machines. However, like other medicines used to treat high blood pressure, Zestoretic may cause dizziness or drowsiness in some people, especially at the start of treatment, when changing doses, or if you consume alcohol. If you experience dizziness or drowsiness, consult your doctor before performing these activities.
• You should wait to see how the medicine affects you before attempting to perform these activities.

Important information about some of the ingredients of Zestoretic

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

Athletes:

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

3. How to use Zestoretic

Follow the administration instructions of this medicine indicated by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Taking the medicine

• 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 medicine before or after meals.
• Do not stop taking your tablets if you feel well, unless your doctor tells you to do so.
• If you think the effect of this medicine is too strong or too weak, consult your doctor or pharmacist.

Taking the first dose

• Be careful when taking the first dose of this medicine or if your dose is increased. It may cause a more pronounced decrease in blood pressure than what is normally achieved with continued treatment.
• This effect may make you feel dizzy or lightheaded. If this happens, lying down may help. If you are concerned, consult your doctor as soon as possible.

Adults

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

Use in children and adolescents:

The use of lisinopril/hydrochlorothiazide is not recommended 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 Toxicology Information Service. Phone 91 562 04 20.

If you forget to take Zestoretic

• 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 missed doses.
• Do not stop treatment before your doctor tells you to do so.

If you have any other questions about the use of this product, 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.

If you experience any of the following reactions, stop takingZestoretic and consult your doctor immediately.

• Severe allergic reactions (rare, may affect up to 1 in 100 people). The signs may include the sudden appearance of:

• Swelling of the face, lips, tongue, or throat. This can make swallowing difficult.
• Severe or sudden swelling of the hands, feet, or ankles.
• Breathing difficulties.
• 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).
• An infection with symptoms such as fever and severe deterioration of your general condition, or fever with symptoms of local infection such as throat/pharynx/mouth irritation or urinary disorders (very rare, may affect up to 1 in 10,000 people).
• Acute pain with redness in the eye, as if left untreated, it could lead to permanent vision loss.

Other possible adverse effects due to lisinopril:

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

• Dizziness, especially when standing up quickly
• Headache.
• Persistent dry cough.
• Fatigue.
• Diarrhea.
• Nausea.
• Kidney disorders (detected by blood tests).
• Fainting.

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

• Mood changes.
• Change in finger color (pale blue followed by redness) or numbness or tingling in the fingers.
• Dizziness.
• Drowsiness.
• Difficulty sleeping.
• Seeing and/or hearing hallucinations.
• Rhinitis.
• Nausea.
• Stomach pain or indigestion.
• Changes in blood tests to determine liver and kidney function.
• Skin rash or itching.
• Impotence.
• Feeling of fatigue or weakness.
• A significant decrease in blood pressure that can occur in people in the following situations: coronary artery disease, aortic stenosis (a heart artery), renal arteries, or heart valves; thickening of the heart muscle. If this happens to you, you may feel dizzy or lightheaded, especially when standing up quickly.
• Myocardial infarction.
• Stroke.
• Fast heartbeat.

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. The signs may include fatigue, pale skin, throat irritation, fever, joint and muscle pain, inflammation of the joints or glands, or sensitivity to sunlight.
• Confusion.
• Rash with hives.
• Dry mouth.
• Hair loss.
• Psoriasis (a skin problem).
• Development of breast tissue in men.
• Sudden kidney failure.
• Change in the smell of things
• Decrease in sodium levels in the blood (hyponatremia) (symptoms may be fatigue, headache, nausea, vomiting).

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

• Low blood sugar levels (hypoglycemia). The signs may include a feeling of hunger or weakness, sweating, and rapid heartbeat.
• Sinusitis (feeling of pain and pressure behind the cheeks and eyes).
• Shortness of breath.
• Lung inflammation. The signs include cough, shortness of breath, and high fever.
• Pancreatitis. This causes moderate to severe stomach pain.
• Intestinal inflammation.
• Yellowing of the skin or the whites of the eyes (jaundice).
• Liver inflammation. This can cause loss of appetite, yellowing of the skin and eyes, and dark urine.
• Liver failure.
• Sweating.
• Severe skin disorders. The symptoms include redness, blistering, and peeling.
• Hives.
• Decreased urine output or inability to urinate.

Frequency Not Known(cannot be estimated from the available data):

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

Other Adverse Effects Due to Hydrochlorothiazide

Very Rare

- Acute respiratory distress (the signs include severe breathing difficulties, fever, weakness, and confusion)

Frequencies Not Known

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

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

Blood and lymphatic system disorders

• Bone marrow depression.
• Decreased platelet count (thrombocytopenia).
• Decreased white blood cell count (leukopenia).
• Decreased granulocyte count (agranulocytosis).
• Anemia due to the destruction of red blood cells (hemolytic anemia).

Metabolic and nutritional disorders

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

Psychiatric disorders

• Restlessness.
• Depression.
• Sleep disturbances.

Nervous system disorders

• Lack of appetite.
• Numbness or tingling sensation in hands and feet.
• Dizziness.

Eye disorders

• Changes in vision that make you see objects yellowish.
• 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]. Patients who experience red eye with acute pain should seek immediate medical attention, as if left untreated, this can lead to permanent vision loss.

Ear disorders

• Dizziness.

Cardiac disorders

• Postural hypotension.

Vascular disorders

• Inflammation of blood vessels.

Respiratory disorders

• Shortness of breath.
• Lung inflammation.

Digestive disorders

• Stomach irritation.
• Diarrhea.
• Constipation.
• Pancreatitis.

Liver disorders

• Yellowing of the skin (jaundice).

Disorders of the skin and subcutaneous tissue

• Skin reaction caused by sensitivity to sunlight.
• Rash.
• Hives.
• Skin rash with hives.
• In some patients with lupus, it can reactivate or worsen symptoms.

Musculoskeletal disorders

• Muscle spasms.
• Muscle weakness.

Renal and urinary disorders

• Kidney function impairment.
• Kidney inflammation.

General disorders

• Fever.
• Weakness.

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 Zestoretic

• Keep this medicine out of the sight and reach of children.
• Do not store above 30°C. Store in the original packaging to protect it from light.
• Do not use this medicine after the expiration date shown on the packaging after CAD. The expiration date is the last day of the month indicated.

• 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 way, you will help protect the environment.

6. Package Contents and Additional Information

Zestoretic Composition

• The active ingredients 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 ingredients are: mannitol (E421), calcium hydrogen phosphate dihydrate, cornstarch, pregelatinized cornstarch, magnesium stearate (E470b).

Product Appearance and Package Contents

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

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Atnahs Pharma Netherlands B.V.,

Copenhagen Towers,

Ørestads Boulevard 108, 5.tv DK-2300,

København S, Denmark

Manufacturer:

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

Date of the Last Revision of this Leaflet: March 2022

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/