ZANIPRESS 20 MG/20 MG FILM-COATED TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Zanipress 20mg/20mg film-coated tablets

enalapril maleate/lercanidipine hydrochloride

Contents of the pack and other information

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. Storing Zanipress.

1. Contents of the pack and further information.

1. What is Zanipress and what is it used for

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

Zanipress is used to treat high blood pressure (hypertension) in adult patients who are currently taking enalapril and lercanidipine in separate tablets.

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 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 had 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 being treated with medicines that contain aliskiren.
• If you are more than 3 months pregnant (it is also recommended to avoid the use of Zanipress at the start of pregnancy, see section Pregnancy).
• If you have certain heart problems:
• obstruction of blood flow from the heart
• untreated heart failure
• unstable angina (chest pain that occurs at rest or worsens progressively)
• during the first month after having a heart attack.
• If you have severe liver problems
• If you have severe kidney problems or are on 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 problem.
• 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 (leucopenia, 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 on 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. The level of potassium in the blood 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 an 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 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 kidney problems related to diabetes.
• Aliskiren.

Your doctor may need to 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 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 breast-feeding (see the section Pregnancy, breast-feeding, 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 Zanipress is taken 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 immunosuppressive medicine used to prevent organ rejection; heparin, an anticoagulant medicine 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 treating mental problems, called "antipsychotics"
• non-steroidal anti-inflammatory medicines, including COX-2 inhibitors (medicines that reduce inflammation and can be used to treat pain)
• certain medicines for pain or arthritis, including gold therapy
• certain medicines for cough and cold and weight loss medicines that contain a substance called "sympathomimetic agent"
• medicines for treating diabetes (including oral antidiabetic medicines and insulin)
• astemizole or terfenadine (medicines for allergies)
• amiodarone, quinidine, or sotalol (medicines for treating a fast heart rate)
• phenytoin, phenobarbital, or carbamazepine (medicines for epilepsy)
• rifampicin (a medicine for treating tuberculosis)
• digoxin (a medicine for treating heart problems)
• midazolam (a medicine to help you sleep)
• beta-blockers, e.g., metoprolol (medicines that treat high blood pressure, heart failure, and irregular heart rhythm)
• cimetidine (given at daily doses above 800 mg, a medicine for ulcers, indigestion, or heartburn)

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 antagonist (ARA) or aliskiren (see also the information 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-hypotensive effect (see "Do not take Zanipress").

Pregnancy, breast-feeding, and fertility

Pregnancy and fertility

You should inform your doctor if you think you are (or might be) pregnant. Zanipress is not recommended for use in women who can become pregnant or at the start of pregnancy, and it should not be taken if you are more than 3 months pregnant, as it may seriously harm the fetus if used after the third month of pregnancy.

Breast-feeding

Zanipress should not be taken during breast-feeding.

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 certain sugars, consult with them 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 administration instructions of this medicine given by your doctor. If you are unsure, consult your doctor or pharmacist again.

Adults: unless your doctor tells 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".

Patient with kidney problems/elderly: your doctor will decide the dose of the medicine you should take, depending on 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 Zanipress 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 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 forgot to take your tablet, do not take the missed dose.
• Take the next dose following the usual schedule.
• Do not take a double dose to make up for the missed 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 occurs, it will be useful 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 values, such as a decrease in platelet count, increased potassium concentration in the blood, 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), increased 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 frequent (may affect more than 1 in 10 people)

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

Frequent (may affect up to 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, increased creatinine levels in the blood (usually detected by a test), high potassium levels in the blood, diarrhea, abdominal pain, fatigue, rash, allergic reaction with inflammation of the face, lips, tongue, or throat with difficulty swallowing or breathing.

Uncommon (may affect up to 1 in 100 people)

Anemia (including aplastic and hemolytic anemia), sudden drop in blood pressure, confusion, nervousness, somnolence or insomnia, sensation of pins and needles in the skin or numbness, myocardial infarction (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 sugar or sodium levels in the blood, high urea levels in the blood (all measured by a blood test), reddening, rapid or irregular heartbeats (palpitations), vertigo (feeling of dizziness), ringing in the ears (tinnitus), impotence.

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

Changes in blood test values, 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), increased 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 peeling 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 inflammation, gum inflammation, tongue inflammation, lip inflammation, or throat inflammation.

Very rare (may affect up to 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 (may affect up to 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.

Patient with pre-existing angina pectoris 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 myocardial infarction 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, heartburn, discomfort, stomach pain, skin rash, itching, muscle pain, increased urination, weakness or fatigue.

Rare (may affect up to 1 in 1,000 people): somnolence, 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 of 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 Pharmacovigilance System for Human Use Medicines: 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 stated 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 medicines you no longer need at the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. 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 20 mg of lercanidipine hydrochloride (equivalent to 18.88 mg of lercanidipine).

The other ingredients are:

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

Film coating: hypromellose, titanium dioxide (E171), macrogol 6000, yellow iron oxide (E172), talc, and red iron oxide (E172).

Appearance of the product and package contents

Zanipress 20 mg/20 mg tablets are 12 mm, orange, circular, and biconvex.

Zanipress 20 mg/20 mg is available in packs of 7, 14, 28, 30, 35, 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)

Manufacturer:

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

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

Austria: Zanipril 20 mg/20 mg film-coated tablets

Belgium, Luxembourg: Zanicombo

Bulgaria: Lercapril

Cyprus: Zaneril

Germany, Denmark, Finland, Iceland, Malta, Norway, Portugal, Spain: Zanipress

France: Zanextra

Greece, Latvia, Poland: Lercaprel

Hungary: Coripren

Ireland, Estonia: Lercaril

Italy: Zanipril

Lithuania: Lercaprel 20 mg/20 mg film-coated tablets

Netherlands: Lertec

Romania: Lercaril 20 mg/20 mg film-coated tablets

Slovenia: Lercaprel 20 mg/20 mg film-coated tablets

Sweden: Zanitek

Date of last revision of this leaflet: 07/2021

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/