Zestoretic 20 mg/12.5 mg tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Zestoretic 20 mg/12.5 mg tablets

lisinopril/hydrochlorothiazide

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

• Keep this leaflet as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Zestoretic is and what it is used for.

2. What you need to know before taking Zestoretic.

3. How to take Zestoretic.

4. Possible adverse effects.

5. How to store Zestoretic.

6. Contents of the container and other information.

1. What Zestoretic is and what it is used for

Zestoretic contains two medicines, lisinopril and hydrochlorothiazide. Each of these lowers blood pressure through a different mechanism. Lisinopril belongs to a group of medicines known as ACE inhibitors. Lisinopril works by dilating blood vessels, helping to reduce blood pressure and making it easier for the heart to pump blood around the body. Hydrochlorothiazide is a diuretic that increases the amount of urine produced by your 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 class of drugs as lisinopril (ACE inhibitors) and experienced an allergic reaction causing 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 areas such as the throat) is high.
• If any member of your family has had a severe allergic reaction (angioedema) to an ACE inhibitor, or if you have had a severe allergic reaction (angioedema) of unknown cause.
• If you have ever had an allergic-type reaction to diuretics of the hydrochlorothiazide type, which are drugs similar to sulfonamides (a type of antibiotic), or to any other component of this medicine.
• If you are more than 3 months pregnant. It is also advisable to avoid this medicine in early pregnancy – see pregnancy section.
• If you have impaired kidney function.
• If you have recently undergone a kidney transplant.
• If you have reduced urine output or inability to urinate (anuria).
• If you have impaired liver function.
• If you have diabetes or renal impairment and are being treated with a blood pressure-lowering medicine containing 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 taking Zestoretic if:

• You have narrowing (stenosis) of the aorta (one of the arteries in the heart) or of the mitral valve (one of the heart valves).

• You have narrowing (stenosis) of the renal artery.

• You have thickening of the heart muscle (known as hypertrophic cardiomyopathy).

• You have low blood pressure (you may feel dizzy, especially when standing up. In such cases, lying down may help).

• You have heart failure (a condition where the heart cannot pump 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 antidiabetic medicines or insulin.

• 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), particularly if you have kidney problems related to diabetes.

• 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 rejection of transplanted organs and for 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 potassium-containing salt substitutes.

• You are being treated with potassium-sparing diuretics or medicines that may increase blood potassium levels, such as heparin.

• You have high cholesterol and are receiving a treatment called "LDL apheresis".

• You are of Black race, as this medicine may be less effective. You are also more likely to develop the adverse effect “angioedema” (a severe allergic reaction).

• You have a persistent dry cough.

• You have persistently low blood potassium levels.

• You have persistently high blood calcium levels.

• 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. Use of lisinopril/hydrochlorothiazide is not recommended in early pregnancy, and it must not be taken if you are more than 3 months pregnant, as it may cause severe harm to the baby if used during this stage (see pregnancy section).

• If you have had skin cancer or 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 and lip cancer (non-melanoma skin cancer). Protect your skin from exposure to sunlight and UV rays while taking Zestoretic.

• 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 eye pressure, which may occur within hours to a week after taking Zestoretic. If untreated, this may lead to permanent vision loss. If you previously had an allergy to penicillin or sulfonamide, you may be at higher risk.

• If you have had respiratory or lung problems (such as inflammation or fluid in the lungs) after taking hydrochlorothiazide in the past. If you develop severe shortness of breath or difficulty breathing after taking Zestoretic, seek medical help immediately.

If you are unsure whether any of the above situations apply to you, consult your doctor or pharmacist before taking this medicine.

Stop taking Zestoretic and seek immediate medical help 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 may cause difficulty swallowing.
• You develop intense itching of the skin (with hives).

Treatment of allergies such as insect stings

Inform your doctor if you are receiving or are about to receive treatment to reduce the effect of an allergy to insect stings (desensitization treatment). Taking lisinopril/hydrochlorothiazide during such treatment may cause you to have a severe allergic reaction.

Surgery

If you are undergoing 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 certain local or general anesthetics are administered while you are taking lisinopril/hydrochlorothiazide.

Take special care with the initial dose of this medicine, as it may cause a more pronounced drop in blood pressure than normally seen with continued treatment. This effect may manifest as dizziness or vertigo; in such cases, lying down may help. However, if you are concerned, consult your doctor.

Taking Zestoretic with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might need to use any other medicines. This is because this medicine may affect how some medicines work, and some medicines may affect 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 taking any of the following medicines:

• Medicines that decrease blood potassium levels, such as amphotericin (for treatment of fungal infections), carbenoxolone (for treatment of esophageal disease or oral ulcers), corticosteroids (e.g., prednisone), pituitary hormone (ACTH), or certain laxatives, other diuretics (medicines used to increase urine output, including potassium-sparing ones), and salicylic acid derivatives.
• Potassium supplements (including potassium-containing salt substitutes), potassium-sparing diuretics, and other medicines that may increase blood potassium levels (e.g., trimethoprim and cotrimoxazole for bacterial infections; cyclosporine, an immunosuppressant used to prevent organ transplant rejection; and heparin, a medicine used to thin blood and prevent clots).
• Medicines that may cause arrhythmias.
• Medicines for depression and mental disorders, including lithium.
• Anesthetic medicines, barbiturates, or alcohol, which may worsen the drop in blood pressure (you may feel dizzy, especially when standing up).
• Non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid, ibuprofen, and indomethacin, used to treat pain and arthritis.
• Injectable medicines for rheumatoid arthritis containing gold salts (e.g., sodium aurothiomalate).
• Medicines to control heart rhythm (antiarrhythmics) such as digoxin and beta-blockers (sotalol).
• Other medicines for treating high blood pressure (antihypertensives), including angiotensin II receptor antagonists (ARA) or aliskiren (see “Do not take Zestoretic”).
• Nitrate-containing medicines (for heart problems).
• Medicines for treating 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 increase blood potassium levels, such as heparin (to prevent blood clotting).
• Calcium or vitamin D supplements.
• Cholesterol-lowering medicines such as colestipol or cholestyramine or lovastatin.
• Muscle relaxants such as tubocurarine.
• Trimethoprim (an antibiotic).
• Allopurinol (for gout).
• Cyclosporine (a medicine to prevent organ transplant rejection and other immune system disorders).
• Medicines for treating cancer, such as cyclophosphamide or methotrexate.

If you are taking any of the following medicines, your risk of developing 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), usually administered in hospital.
• Medicines used to prevent rejection of organ transplants and for 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

Inform your doctor if you think you are (or plan to become) pregnant. Your doctor will usually advise you to stop taking lisinopril/hydrochlorothiazide before becoming pregnant or as soon as you know you are pregnant, and will recommend an alternative medicine. Lisinopril/hydrochlorothiazide is not recommended in early pregnancy and must not be taken if you are more than 3 months pregnant, as it may cause severe harm to the baby if used after the third month of pregnancy.

Lisinopril/hydrochlorothiazide should normally be replaced with an appropriate antihypertensive treatment before pregnancy begins. The medicine should not be used during the second and third trimesters of pregnancy.

Your doctor will usually advise you to stop taking lisinopril/hydrochlorothiazide as soon as you know you are pregnant.

If you become pregnant while taking this medicine, inform and consult your doctor immediately.

Breastfeeding

Inform your doctor if you are breastfeeding or plan to breastfeed. Hydrochlorothiazide (one of the components of the medicine) is excreted in small amounts in breast milk and at high doses may inhibit milk production. Use of this medicine is not recommended in breastfeeding mothers, and your doctor may choose an alternative treatment if you wish to breastfeed, especially if your baby is a newborn or was premature.

Driving and using machines

• It is unlikely that Zestoretic will 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 alcohol is consumed. 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 these activities.

Important information about some of the components of Zestoretic

May cause a mild laxative effect because it contains mannitol.

Use in athletes:

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

3. How to use Zestoretic

Follow exactly the instructions for using this medicine as given 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 each 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.
• If you think that the effect of this medicine is too strong or too weak, consult your doctor or pharmacist.

Taking the first dose

• Take special care when taking the first dose of this medicine or when your dose is increased. It may cause a greater drop in blood pressure than subsequent doses.
• This effect may make you feel dizzy or lightheaded. If this occurs, 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 daily.

Use in children and adolescents:

The use of lisinopril/hydrochlorothiazide is not recommended in children and adolescents, as 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, contact the Toxicology Information Service. Telephone: 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 forgotten doses.
• Do not stop treatment before your doctor tells you to.

If you have any further 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 everyone experiences them.

If you experience any of the following reactions, stop taking Zestoretic and contact your doctor immediately.

• Severe allergic reactions (uncommon, may affect up to 1 in 100 people). Signs may include sudden onset of:

• Swelling of the face, lips, tongue, or throat. This may make swallowing difficult.

• Severe or sudden swelling of the hands, feet, or ankles.

• Difficulty breathing.

• Severe skin itching (with hives).

• Serious skin disorders, such as an unexpected and sudden rash, redness, or skin peeling (very rare, may affect up to 1 in 10,000 people).

• An infection with symptoms such as fever and severe deterioration in your general condition, or fever with symptoms of localized infection such as sore throat/pharynx/mouth or urinary disorders (very rare, may affect up to 1 in 10,000 people).

• Sudden redness and pain in the eye, as untreated cases could lead to permanent vision loss.

Other possible adverse effects due to lisinopril:

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

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

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

• Mood changes
• Change in color of fingers and toes (pale blue followed by redness) or numbness or tingling in fingers or toes
• Dizziness
• Drowsiness
• Difficulty sleeping
• Visual and/or auditory hallucinations
• Rhinitis
• Nausea
• Stomach pain or indigestion
• Changes in blood tests used to monitor proper liver and kidney function
• Skin rash or itching
• Inability to achieve an erection (impotence)
• Feeling of tiredness or weakness (lack of strength)
• A significant drop in blood pressure that may occur in people with the following conditions: coronary artery disease, aortic stenosis (narrowing of a heart artery), renal arteries or heart valves; thickening of the heart muscle. If this occurs, you may feel dizzy or lightheaded, especially when standing up quickly.
• Myocardial infarction
• Stroke
• Rapid heartbeat

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

• Changes in certain blood cells or other blood components. Your doctor may take blood samples periodically to check whether lisinopril/hydrochlorothiazide is affecting your blood. Signs may include fatigue, pale skin, sore throat, fever, joint and muscle pain, joint or gland swelling, or sensitivity to sunlight.
• Confusion
• Hives rash
• Dry mouth
• Hair loss
• Psoriasis (a skin condition)
• Breast development in men
• Sudden kidney failure
• Change in the way things smell
• Decreased levels of sodium 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). Signs may include feeling hungry or weak, sweating, and rapid heartbeat.
• Sinusitis (feeling of pain and pressure behind the cheeks and eyes)
• Wheezing
• Lung inflammation. Signs include cough, shortness of breath, and high fever.
• Pancreatitis. This causes moderate to severe stomach pain.
• Intestinal inflammation
• Yellowing of the skin or whites of the eyes (jaundice)
• Liver inflammation. This may cause loss of appetite, yellowing of the skin and eyes, and dark urine.
• Liver failure
• 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
• Flushing (reddening)
• Severe allergic reaction

Other adverse effects due to hydrochlorothiazide

Very rare:

- Acute breathing difficulty (signs include severe shortness of breath, fever, weakness, and confusion)

Frequencies not known:

Neoplasms benign, malignant and unspecified (including cysts and polyps)

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

Blood and lymphatic system disorders

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

Metabolism and nutritional disorders

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

Psychiatric disorders

• Restlessness
• Depression
• Sleep disturbances

Nervous system disorders

• Loss of appetite
• Tingling sensation in hands and feet
• Dizziness

Eye disorders

• Visual disturbances causing objects to appear yellowish
• Decreased vision or eye pain due to elevated pressure [possible signs of fluid accumulation in the vascular layer of the eye (choroidal effusion) or acute angle-closure glaucoma]. Patients experiencing painful red eye should seek immediate medical attention, as untreated cases may lead to permanent vision loss.

Ear disorders

• Vertigo

Cardiac disorders

• Postural hypotension

Vascular disorders

• Inflammation of blood vessels

Respiratory system disorders

• Shortness of breath
• Pulmonary inflammation

Gastrointestinal disorders

• Stomach irritation
• Diarrhea
• Constipation
• Pancreatitis

Hepatic disorders

• Yellowing of the skin (jaundice)

Skin and subcutaneous tissue disorders

• Skin reaction caused by sensitivity to sunlight
• Rash
• Urticaria
• Skin rash with 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

• Impaired kidney function
• Kidney inflammation

General disorders

• Fever
• Weakness

Reporting of adverse effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: https://www.notificaram.es. By reporting adverse effects, you can help provide 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 from light.

• Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

• Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of containers and unused medicines. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of Zestoretic

• The active substances 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), anhydrous calcium hydrogen phosphate, maize starch, pregelatinized maize starch, magnesium stearate (E470b).

Nature and contents of the container

Zestoretic is presented as round, white, uncoated tablets, engraved with "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

Manufacturers:

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 most recent review of this leaflet: March 2022

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/