ZANIPRESS 20 mg/10 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Zanipress 20 mg/10 mg film-coated tablets

enalapril maleate/lercanidipine hydrochloride

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Zanipress and what is it used for
2. What you need to know before you take Zanipress
3. How to take Zanipress
4. Possible side effects
5. Storage of Zanipress
6. Contents of the pack and other information

1. What is Zanipress and what is it used for

Zanipress is a fixed combination of an ACE inhibitor (enalapril) and a calcium channel blocker (lercanidipine), two medicines that reduce blood pressure.

Zanipress is used to treat high blood pressure (hypertension) in adult patients whose blood pressure is not adequately controlled by enalapril 20 mg alone. Zanipress should not be used for the initial treatment of hypertension.

2. What you need to know before you take Zanipress

Do not take Zanipress:

• If you are allergic to enalapril maleate or lercanidipine hydrochloride, or to any of the other ingredients of this medicine (listed in section 6).
• If you have ever had an allergic reaction to a type of medicine similar to those contained in Zanipress, i.e. medicines called ACE inhibitors or calcium channel blockers.
• If you have ever experienced swelling of the face, lips, mouth, tongue, or throat that has caused difficulty swallowing or breathing (angioedema) after taking a type of medicine called ACE inhibitors, or if the cause of the reaction is unknown or if it is a hereditary condition.
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, the risk of angioedema (rapid swelling of the throat) is increased.
• If you have diabetes or kidney problems and are receiving treatment with a blood pressure-lowering medicine that contains aliskiren.
• If you are pregnant for more than 3 months (it is also recommended to avoid the use of Zanipress at the start of pregnancy, see section pregnancy).
• If you suffer from certain heart conditions:
• obstruction of blood flow from the heart
• untreated heart failure
• unstable angina (chest pain that occurs at rest or worsens progressively)
• within the first month after having a heart attack.
• If you have severe liver problems.

• If you have severe kidney problems or are undergoing dialysis.
• If you are taking medicines that inhibit liver metabolism, such as:
• antifungals (such as ketoconazole or itraconazole).
• macrolide antibiotics (such as erythromycin, troleandomycin, or clarithromycin).
• antivirals (such as ritonavir).
• If you are taking another medicine called ciclosporin (used after a transplant to prevent organ rejection).
• With grapefruit or grapefruit juice.

Warnings and precautions

Consult your doctor or pharmacist before starting to take Zanipress:

• If you have low blood pressure (which can manifest as dizziness or fainting, especially when standing up).
• If you have been very ill (with excessive vomiting) or have had diarrhea recently.
• If you are on a low-salt diet.
• If you have a heart condition.
• If you have a disorder that affects the blood vessels in the brain.
• If you have kidney problems (including kidney transplant). This can lead to high levels of potassium in the blood, which can be serious. Your doctor may need to adjust your dose of enalapril or monitor your potassium levels.
• If you have liver problems.
• If you have blood problems, such as a low or absent white blood cell count (leukopenia, agranulocytosis), a low platelet count (thrombocytopenia), or a decrease in the number of red blood cells (anemia).
• If you have a vascular disease of the collagen (e.g., lupus erythematosus, rheumatoid arthritis, or scleroderma), are undergoing immunosuppressive therapy, or are taking allopurinol or procainamide or a combination of both medicines.
• If you are a black patient, you should be aware that these patients have a higher risk of experiencing allergic reactions with inflammation of the face, lips, tongue, or throat, accompanied by difficulty swallowing or breathing, when taking ACE inhibitors.
• If you are diabetic, you should monitor your blood sugar levels, especially during the first month of treatment. Your potassium levels may also be elevated.
• If you are taking potassium supplements, potassium-sparing diuretics, or salt substitutes that contain potassium.
• If you are over 70 years old.
• If you have intolerance to certain sugars (lactose)

If you are taking any of the following medicines, the risk of angioedema may be increased:

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ rejection after a transplant or to treat cancer (e.g., temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medicine used to treat diabetes.

If you are taking any of the following medicines used to treat high blood pressure:

• a blocker of the angiotensin II receptor (ARB) (also known as sartans, such as valsartan, telmisartan, or irbesartan), especially if you have kidney problems related to diabetes.
• aliskiren.

Your doctor may need to check your kidney function, blood pressure, and the amount of electrolytes (e.g., potassium) in your blood at regular intervals.

Also, see the information included under the heading "Do not take Zanipress".

If you are going to undergo surgery or certain treatments soon

If you are going to undergo any of the following procedures, inform your doctor that you are taking Zanipress:

• any surgical procedure or if you are going to be given an anesthetic (even at the dentist)
• a treatment to remove cholesterol from the blood known as "LDL apheresis"
• a desensitization treatment to reduce the effect of an allergy to bees or wasps.

You should inform your doctor if you think you are (or might become) pregnant or if you are breastfeeding (see the section Pregnancy, breastfeeding, and fertility).

Children and adolescents

The safety and efficacy of Zanipress in children under 18 years have not been established.

Other medicines and Zanipress

Zanipress should not be taken with certain medicines.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription. This is because when you take Zanipress with other medicines, the effect of Zanipress or the other medicines may be altered, or certain side effects may occur more frequently.

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

• other medicines that lower blood pressure
• potassium supplements (including salt substitutes in the diet), potassium-sparing diuretics, and other medicines that may increase potassium levels in the blood (e.g., trimethoprim and sulfamethoxazole for bacterial infections; ciclosporin, an immunosuppressant used to prevent organ rejection; heparin, an anticoagulant used to prevent blood clots). See section "Do not take Zanipress"
• lithium (a medicine used to treat a certain type of depression)
• medicines for depression called "tricyclic antidepressants"
• medicines for the treatment of mental problems, called "antipsychotics"
• non-steroidal anti-inflammatory drugs, including COX-2 inhibitors (medicines that reduce inflammation and can be used to relieve pain)
• certain medicines for pain or arthritis, including gold therapy
• certain medicines for the treatment of cough and cold and weight-reducing medicines that contain a substance called "sympathomimetic agent"
• medicines for the treatment of diabetes (including oral antidiabetic medicines and insulin),
• astemizole or terfenadine (medicines for allergies)

• amiodarone, quinidine, or sotalol (medicines for the treatment of a fast heart rate)
• phenytoin, phenobarbital, or carbamazepine (medicines for epilepsy)
• rifampicin (a medicine for the treatment of tuberculosis)
• digoxin (a medicine for the treatment of heart problems)
• midazolam (a medicine to help you sleep)
• beta-blockers, e.g., metoprolol (medicines that treat high blood pressure, heart failure, and abnormal heart rhythm)
• cimetidine (administered at daily doses above 800 mg, a medicine for ulcers, indigestion, or acidity)

Do not take Zanipress if you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as the risk of angioedema (rapid swelling of the throat) is increased.

If you are taking any of the following medicines, the risk of angioedema may be increased:

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ rejection after a transplant or to treat cancer (e.g., temsirolimus, sirolimus, everolimus).
• Vildagliptin, a medicine used to treat diabetes.

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

• If you are taking an angiotensin II receptor blocker (ARB) or aliskiren (see also the information included under the headings "Do not take Zanipress" and "Warnings and precautions").

Taking Zanipress with food, drinks, and alcohol

• Zanipress should be taken at least 15 minutes before meals.
• A fatty meal significantly increases the levels of the medicine in the blood.
• Alcohol may increase the effect of Zanipress. During treatment with Zanipress, you should not consume alcohol.
• Zanipress should not be taken with grapefruit or grapefruit juice, as it may increase its anti-hypertensive effect (see "Do not take Zanipress").

Pregnancy, breastfeeding, and fertility

Pregnancy and fertility

You should inform your doctor if you think you are (or might be) pregnant. Your doctor will normally advise you to stop taking Zanipress before you become pregnant or as soon as you know you are pregnant and will recommend that you take another medicine instead of Zanipress. The use of Zanipress is not recommended in women who can become pregnant or at the start of pregnancy, and it should not be taken if you are pregnant for more than 3 months, as it may seriously harm the fetus if used after the third month of pregnancy.

Breastfeeding

Zanipress should not be taken during breastfeeding.

Driving and using machines

If you experience dizziness, weakness, or drowsiness with this medicine, you should not drive or operate machinery.

Zanipress contains lactose and sodium

If your doctor has told you that you have an intolerance to some sugars, contact your doctor before taking this medicine.

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; this is essentially "sodium-free".

3. How to take Zanipress

Follow exactly the instructions of administration of this medicine given to you by your doctor. If you are not sure, consult your doctor or pharmacist again.

Adults:unless your doctor has told you otherwise, the recommended dose is one tablet once a day, at the same time each day. The tablet should be taken preferably in the morning, at least 15 minutes before breakfast. The tablets should be swallowed whole with water. See "Taking Zanipress with food, drinks, and alcohol".

Patients with kidney problems/elderly:your doctor will decide the dose of medicine that you should take, taking into account how well your kidneys are working.

If you take more Zanipress than you should

Do not exceed the prescribed dose. If you have taken more than you should or in case of overdose, consult your doctor or pharmacist immediately, or call the Toxicology Information Service, telephone (91) 562 04 20, or go to the hospital immediately. Take the package and the leaflet of the medicine with you to the healthcare professional. A dose higher than the correct one may cause a significant drop in blood pressure and your heart may beat irregularly or faster.

If you forget to take Zanipress

• If you forget to take your tablet, do not take the forgotten dose.
• Take the next dose following the usual schedule.
• Do not take a double dose to make up for the forgotten doses.

If you stop taking Zanipress

• Do not stop taking your medicine unless your doctor tells you to.
• If you have any further questions on the use of this medicine, 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. This medicine may cause the following adverse effects:

Some adverse effects can be serious.

Tell your doctor immediately if you notice any of the following adverse effects:

An allergic reaction accompanied by swelling of the face, lips, tongue, or throat that can cause difficulty breathing or swallowing;

When you start taking Zanipress, you may feel weakness or dizziness, or notice that your vision becomes blurred; this is caused by a sudden drop in blood pressure, and if it happens, it will be helpful to lie down. If you are concerned, consult your doctor.

Adverse Effects Observed with Zanipress

Frequent (may affect up to 1 in 10 people)

Cough, feeling of dizziness, headache.

Uncommon (may affect up to 1 in 100 people)

Changes in blood test results, such as a decrease in platelet count, increase in blood potassium levels, nervousness (anxiety), feeling of dizziness when standing up, vertigo, rapid heartbeat, rapid or irregular heartbeat (palpitations), sudden reddening of the face, neck, or upper chest (erythema), low blood pressure, abdominal pain, constipation, feeling sick (nausea), increase in liver enzyme levels, skin reddening, joint pain, increased urination frequency, feeling of weakness, fatigue, feeling of heat, ankle swelling.

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

Anemia, allergic reactions, ringing in the ears (tinnitus), fainting, dry throat, sore throat, indigestion, salty taste in the mouth, diarrhea, dry mouth, gum inflammation, allergic reaction with swelling of the face, lips, tongue, or throat that causes difficulty swallowing or breathing, skin rash, hives, nocturia, production of large amounts of urine, impotence.

Additional Adverse Effects Observed with Enalapril or Lercanidipine Alone

Enalapril

Very common (affects more than 1 in 10 people)

Blurred vision, feeling of dizziness, weakness or discomfort, and cough.

Frequent (affects less than 1 in 10 people)

Depression, headache, fainting (syncope), chest pain, dizziness due to low blood pressure, changes in heart rate, rapid heartbeats, angina, shortness of breath, alterations in taste, increase in blood creatinine levels (usually detected by a test), high blood potassium levels, diarrhea, abdominal pain, fatigue, rash, allergic reaction with inflammation of the face, lips, tongue, or throat with difficulty swallowing or breathing.

Uncommon (affects less than 1 in 100 people)

Anemia (including aplastic anemia and hemolytic anemia), sudden drop in blood pressure, confusion, nervousness, drowsiness or insomnia, feeling of pins and needles in the skin or numbness, heart attack (possibly caused by very low blood pressure in certain high-risk patients, including those with coronary or cerebral blood supply problems), stroke (possibly due to very low blood pressure in high-risk patients), runny nose, sore throat and hoarseness, asthma associated with chest tightness, slowing of food movement through the intestine (ileus), pancreatitis, feeling sick (vomiting), indigestion, constipation, stomach irritation (gastric irritation), dry mouth, ulcer, anorexia, itching or hives, hair loss, kidney function alteration, kidney failure, increased sweating, high protein levels in the urine (measured by a test), muscle cramps, feeling of general discomfort, high temperature (fever), low blood sugar or sodium levels, high blood urea levels (all measured by a blood test), reddening, rapid or irregular heartbeats (palpitations), vertigo (feeling of dizziness), ringing in the ears (tinnitus), impotence.

Rare (affects less than 1 in 1,000 people)

Changes in blood test results, such as a decrease in white blood cell count, bone marrow depression, autoimmune diseases, strange dreams or sleep disorders, Raynaud's phenomenon (in which the hands and feet can become intensely cold and turn white due to low blood flow), nasal inflammation, pneumonia, liver problems, such as decreased liver function, liver inflammation, jaundice (yellowing of the skin or eyes), increase in liver enzyme or bilirubin levels (measured by a blood test), erythema multiforme (red spots of different shapes that appear on the skin), Stevens-Johnson syndrome, and toxic epidermal necrolysis (a severe skin condition in which the skin turns red and forms scales, blisters, or open sores), exfoliative dermatitis/erythroderma (severe skin rash with scaling or shedding of the skin), pemphigus (small blisters filled with fluid on the skin), decreased urine production, gynecomastia (breast enlargement in men), inflamed glands in the neck, armpits, or groin, fluid accumulation or other substances in the lungs (as seen on X-rays), cheek, gum, tongue, lip, or throat inflammation.

Very rare (affects less than 1 in 10,000 people)

Intestinal inflammation (intestinal angioedema).

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

Excessive production of antidiuretic hormone that causes fluid retention, leading to weakness, fatigue, or confusion.

A set of symptoms has been reported that may include one or more of the following: fever, blood vessel inflammation (serositis, vasculitis), muscle pain (myalgia, myositis), joint pain (arthralgia/arthritis). A rash, photosensitivity, or other skin manifestations may occur.

Lercanidipine

Some of these adverse effects can be serious. If you experience any of these adverse effects, consult your doctor.

Rare (affects less than 1 in 1,000 people)

Chest pain (pain in the chest caused by lack of blood supply to the heart), allergic reactions (with symptoms such as itching, rash, hives), fainting.

Patients with pre-existing chest pain may experience an increase in frequency, duration, or severity of attacks associated with treatment with the group of medicines to which lercanidipine belongs. Isolated cases of heart attack may be observed.

Other Possible Adverse Effects:

Frequent (may affect up to 1 in 10 people): headache, rapid or irregular heartbeats (palpitations), sudden reddening of the face, neck, or upper chest, ankle swelling.

Uncommon (may affect up to 1 in 100 people): dizziness, low blood pressure, stomach burning, discomfort, stomach pain, skin rash, itching, muscle pain, increased urination, weakness or fatigue.

Rare (may affect up to 1 in 1,000 people): drowsiness, vomiting, diarrhea, hives, increased urination frequency, chest pain.

Frequency not known (cannot be estimated from the available data): gum swelling, changes in liver function (detected by blood tests), cloudy fluid (when performing hemodialysis through a tube into the abdomen), swelling of the face, lips, tongue, or throat that can cause difficulty breathing or swallowing.

If any of the adverse effects worsen, or if you experience any adverse effect not listed in this leaflet, inform your doctor or pharmacist. You can consult your doctor or pharmacist for more information about adverse effects, as they have a more complete list of adverse effects.

Reporting Adverse Effects

If you experience any adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Medicines and Health Products Agency's website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Zanipress

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date shown on the blister pack and carton after EXP. The expiration date is the last day of the month indicated.

Store in the original packaging to protect from light and moisture. Do not store above 25°C.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the pharmacy's SIGRE collection point. Ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

Zanipress Composition

The active ingredients are enalapril maleate and lercanidipine hydrochloride.

Each film-coated tablet contains: 20 mg of enalapril maleate (equivalent to 15.29 mg of enalapril) and 10 mg of lercanidipine hydrochloride (equivalent to 9.44 mg of lercanidipine).

The other ingredients are:

Core: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate type A, povidone K30, sodium bicarbonate, and magnesium stearate.

Film coating: hypromellose 5 cP, titanium dioxide (E171), talc, macrogol 6000, yellow quinoline aluminum lake (E104), and yellow iron oxide (E172).

Product Appearance and Package Contents

Zanipress 20 mg/10 mg film-coated tablets are 8.5 mm, yellow, circular, and biconvex.

Zanipress 20 mg/10 mg is available in packs of 7, 14, 28, 30, 35, 42, 50, 56, 90, 98, and 100 tablets.

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Casen Recordati, S.L. Autovía de Logroño, km. 13,300. 50180 Utebo (Zaragoza), Spain.

Manufacturer

RECORDATI Industria Chimica e Farmaceutica S.p.A. – Via Matteo Civitali 1 – I-20148 Milan, Italy

Doppel Farmaceutici S.r.l., Via Volturno 48, Quinto de’Stampi, 20089 Rozzano (MI), Italy

This medicine is authorized in the Member States of the EEA under the following trade names:

Austria Zanipril 20 mg/10 mg film-coated tablets

Belgium Zanicombo

Bulgaria Lercapril

Cyprus Zaneril

Denmark Zanipress

Estonia Lercaril

Finland Zanipress

France Zanextra

Germany Zanipress

Greece Lercaprel

Hungary Coripren

Iceland Zanipress

Ireland Lercaril

Italy Zanipril

Latvia Lercaprel

Lithuania Lercaprel 20 mg/10 mg film-coated tablets

Luxembourg Zanicombo

Malta Zanipress

Netherlands Lertec

Norway Zanipress

Poland Lercaprel

Portugal Zanipress

Romania Lercaril 20 mg/10 mg

Slovenia Lercaprel 20 mg/10 mg

Spain Zanipress

Sweden Zanitek

United Kingdom (IN) Zaneril

Date of the last revision of this leaflet 07/2021

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