Zanipress 20 mg/20 mg film-coated tablets

Patient Information Leaflet

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Zanipress 20mg/20mg film-coated tablets

enalapril maleate/lercanidipine hydrochloride

Package leaflet:

1. What Zanipress is and what it is used for

2. What you need to know before taking Zanipress

3. How to take Zanipress

4. Possible side effects

5. How to store Zanipress

6. Contents of the pack and other information

1. What Zanipress is and what it is used for

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

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

2. What you need to know before taking 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 similar type of medicine to those contained in Zanipress, that is, medicines known as ACE inhibitors or calcium channel blockers.
• If you have ever experienced swelling of the face, lips, mouth, tongue, or throat causing difficulty in swallowing or breathing (angioedema) after taking a medicine known as an ACE inhibitor, or if the cause of such a reaction was unknown, or if it was a hereditary condition.
• If you have taken or are currently taking sacubitril/valsartan, a medicine used to treat chronic heart failure in adults, as this increases the risk of developing angioedema (rapid swelling of the throat).
• If you have diabetes or kidney failure and are being treated with medicines containing aliskiren.
• If you are more than 3 months pregnant (use of Zanipress is also not recommended at the beginning of pregnancy; see section Pregnancy).
• If you have certain heart conditions:
  • obstruction of blood outflow from the heart
  • untreated heart failure
  • unstable angina (chest discomfort occurring at rest or progressively worsening)
  • during the first month after a myocardial infarction.
• If you have severe liver problems.
• If you have severe kidney problems or are undergoing dialysis.
• If you are taking drugs that inhibit liver metabolism, such as:
  • antifungals (e.g., ketoconazole or itraconazole).
  • macrolide antibiotics (e.g., erythromycin, troleandomycin, or clarithromycin).
  • antivirals (e.g., ritonavir).
• If you are taking another medicine called cyclosporine (used after transplantation to prevent organ rejection).
• Together with grapefruit or grapefruit juice.

Warnings and precautions

Talk to your doctor or pharmacist before taking Zanipress:

• If you have low blood pressure (which may cause dizziness or fainting, especially when standing up).
• If you have been severely ill (with excessive vomiting) or have recently had diarrhea.
• If you are on a salt-restricted diet.
• If you have a heart condition.
• If you have a disorder affecting the blood vessels in the brain.
• If you have kidney problems (including kidney transplant). This may lead to high levels of potassium in the blood, which can be serious. Your doctor may need to adjust your enalapril dose or monitor your potassium levels.
• If you have liver problems.
• If you have blood disorders, such as low or absent white blood cells (leucopenia, agranulocytosis), low platelet count (thrombocytopenia), or reduced number of red blood cells (anemia).
• If you have a collagen vascular disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, or scleroderma), are undergoing immunosuppressive therapy, or are taking allopurinol or procainamide, or a combination of both.
• If you are of Black race, you should be aware that such patients have a higher risk of allergic reactions with swelling 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 glucose levels, especially during the first month of treatment, as they may become low. Blood potassium levels may also increase.
• If you are taking potassium supplements, potassium-sparing agents, or salt substitutes containing potassium.
• If you are over 70 years of age.
• If you have intolerance to certain sugars (lactose).

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

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ rejection after transplantation 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-II) (also known as “sartans,” e.g., valsartan, telmisartan, irbesartan), particularly if you have kidney problems related to diabetes.
• Aliskiren.

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

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

If you are about to undergo surgery or certain treatments

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

• Any surgical procedure or if you are to receive an anesthetic (even at the dentist’s office).
• A treatment to remove cholesterol from your blood known as “LDL apheresis.”
• A desensitization treatment to reduce the effect of an allergy to bees or wasps.

You must inform your doctor if you think you are (or could be) pregnant or if you are breastfeeding (see section Pregnancy, breastfeeding, and fertility).

Children and adolescents

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

Other medicines and Zanipress

Zanipress must not be taken with certain medicines.

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including over-the-counter medicines. This is because when Zanipress is taken with other medicines, the effect of Zanipress or of the other medicines may be altered, or certain adverse effects may occur more frequently.

Specifically, inform your doctor or pharmacist if you are taking any of the following medicines:

• Other medicines that lower blood pressure.
• Potassium supplements (including dietary salt substitutes), potassium-sparing diuretics, and other medicines that may increase potassium levels in blood (e.g., trimethoprim and sulfamethoxazole for bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ rejection; heparin, a medicine used as an anticoagulant 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 mental disorders called "antipsychotics."
• Non-steroidal anti-inflammatory drugs, including COX-2 inhibitors (medicines that reduce inflammation and may be used to relieve pain).
• Certain medicines for pain or arthritis, including gold therapy.
• Certain medicines for cough and cold or weight-loss medicines containing a substance called a "sympathomimetic agent."
• Medicines for diabetes (including oral antidiabetic medicines and insulin).
• Astemizole or terfenadine (medicines for allergies).
• Amiodarone, quinidine, or sotalol (medicines for treating rapid heartbeat).
• 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 used to treat high blood pressure, heart failure, and abnormal heart rhythm).
• Cimetidine (when taken at daily doses exceeding 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 this increases the risk of angioedema (rapid swelling under the skin, such as in the throat).

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

• Racecadotril, a medicine used to treat diarrhea.
• Medicines used to prevent organ rejection after transplantation 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-II) or aliskiren (see also 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 high-fat meal significantly increases the levels of the medicine in the blood.
• Alcohol may enhance the effect of Zanipress. Alcohol must not be consumed during treatment with Zanipress.
• Zanipress must not be taken with grapefruit or grapefruit juice, as this may increase its antihypertensive effect (see “Do not take Zanipress”).

Pregnancy, breastfeeding, and fertility

Pregnancy and fertility

Inform your doctor if you think you are (or could be) pregnant. Use of Zanipress is not recommended in women who may become pregnant, nor at the beginning of pregnancy, and must 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.

Breastfeeding

Zanipress must not be taken during breastfeeding.

Driving and using machines

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

Zanipress contains lactose and sodium

If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

This medicine contains less than 23 mg of sodium (1 mmol) per tablet; hence, it is essentially “sodium-free.”

3. How to take Zanipress

Follow exactly the instructions given by your doctor for taking this medicine. If in doubt, consult your doctor or pharmacist again.

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

Patients with renal impairment/elderly patients: Your doctor will decide the dose of medicine you should take, based on how well your kidneys are functioning.

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, contact your doctor or pharmacist immediately, call the Toxicology Information Service at telephone (91) 562 04 20, or go to the hospital immediately. Take the medicine package and leaflet with you when seeing a healthcare professional. A dose higher than the correct one may cause excessive 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 missed dose.
• Take your next dose at the usual time according to your regular schedule.
• Do not take a double dose to make up for forgotten doses.

If you interrupt treatment with Zanipress

• Do not stop taking your medication unless your doctor tells you to.

If you have any further questions about 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 everybody gets them. This medicine may cause the following adverse effects:

Some adverse effects may 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 which may cause difficulty breathing or swallowing;

When you start taking Zanipress you may feel weak or dizzy, or notice that your vision becomes blurred; this is caused by a sudden drop in blood pressure, and if it occurs, lying down may be helpful. If you are concerned, consult your doctor.

Adverse effects observed with Zanipress

Frequent (may affect up to 1 in 10 people)

Cough, dizziness, headache.

Uncommon (may affect up to 1 in 100 people)

Changes in blood test parameters such as decreased platelet count, increased blood potassium concentration, nervousness (anxiety), dizziness upon standing, vertigo, fast heartbeat, fast or irregular heartbeat (palpitations), sudden redness of the face, neck or upper chest (erythema), low blood pressure, abdominal pain, constipation, feeling sick (nausea), increased levels of liver enzymes, skin redness, joint pain, increased frequency of urination, feeling of weakness, tiredness, sensation of warmth, swelling of the ankles.

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

Anaemia, allergic reactions, ringing in the ears (tinnitus), fainting, dry throat, sore throat, indigestion, salty taste sensation in the mouth, diarrhoea, dry mouth, gum swelling, allergic reaction with swelling of the face, lips, tongue or throat causing difficulty swallowing or breathing, skin rash, urticaria, 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, dizziness, weakness or malaise, 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 heartbeat, angina, dyspnoea, disturbances in taste, increased creatinine levels in blood (usually detected by a blood test), elevated blood potassium levels, diarrhoea, abdominal pain, fatigue, rash, allergic reaction with swelling of the face, lips, tongue or throat with difficulty swallowing or breathing.

Uncommon (may affect up to 1 in 100 people)

Anaemia (including aplastic and haemolytic anaemia), sudden drop in blood pressure, confusion, nervousness, drowsiness or insomnia, skin tingling or numbness, myocardial infarction (possibly caused by very low blood pressure in certain high-risk patients, including those with impaired blood supply to the heart or brain), 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, irritated stomach (gastric irritation), dry mouth, ulcer, anorexia, itching or urticaria, hair loss, impaired kidney function, renal failure, increased sweating, high levels of protein in urine (measured by urine test), muscle cramps, general malaise, high temperature (fever), low blood sugar or sodium levels, high blood urea levels (all measured by blood test), flushing, rapid or irregular heartbeat (palpitations), vertigo (dizziness), ringing in the ears (tinnitus), impotence.

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

Changes in blood test parameters such as decreased white blood cell count, bone marrow depression, autoimmune disorders, unusual dreams or sleep disturbances, Raynaud's phenomenon (in which hands and feet may become intensely cold and turn white due to reduced blood flow), nasal inflammation, pneumonia, liver problems such as decreased liver function, liver inflammation, jaundice (yellowing of the skin or eyes), increased levels of liver enzymes or bilirubin (measured by blood test), erythema multiforme (red spots of various shapes appearing on the skin), Stevens-Johnson syndrome and toxic epidermal necrolysis (a serious skin condition involving redness, scaling or peeling of the skin, blistering or open sores), exfoliative dermatitis/erythroderma (severe skin rash with peeling or shedding of the skin), pemphigus (small fluid-filled blisters on the skin), decreased urine production, breast gland enlargement in men (gynaecomastia), swollen glands in the neck, armpits or groin, accumulation of fluid or other substances in the lungs (as seen on X-ray), swelling of cheeks, gums, tongue, lips and throat.

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

Intestinal inflammation (intestinal angioedema).

Frequency not known (cannot be estimated from available data)

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

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

Lercanidipine

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

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

Angina (chest pain due to insufficient blood supply to the heart), allergic reactions (with symptoms such as itching, rash, urticaria), fainting.

Patients with pre-existing angina may experience an increase in frequency, duration or severity of attacks associated with treatment with the class of medicines to which lercanidipine belongs. Isolated cases of myocardial infarction may occur.

Other possible adverse effects:

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

Uncommon (may affect up to 1 in 100 people): dizziness, drop in blood pressure, heartburn, malaise, stomach pain, skin rash, itching, muscle pain, increased amount of urine, weakness or tiredness.

Rare (may affect up to 1 in 1,000 people): drowsiness, vomiting, diarrhoea, urticaria, increased urinary frequency, chest pain.

Frequency not known (cannot be estimated from available data): gum swelling, changes in liver function (detected in blood tests), cloudy fluid (during haemodialysis through a tube inside the abdomen), swelling of the face, lips, tongue or throat which may cause difficulty breathing or swallowing.

If any of the adverse effects worsens, 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 both have access to a more complete list of adverse effects.

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide 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 expiry date which is stated on the blister and on the outer packaging following EXP. The expiry date refers to the last day of the month indicated.

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

Medicines must not be disposed of via wastewater or household waste. Dispose of unused medicines and their packaging at the SIGRE collection point at your pharmacy. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This way, you will help protect the environment.

6. Contents of the pack and other information

Composition of Zanipress

The active substances 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 components are:

Core: lactose monohydrate, microcrystalline cellulose, sodium starch glycolate from potato, 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).

Nature of the product and contents of the container

Zanipress 20 mg/20 mg tablets are 12 mm, orange-colored, round, biconvex film-coated tablets.

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

Only certain 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 medicinal product is authorized in the EEA Member States under the following brand names:

Austria: Zanipril 20 mg/20 mg Filmtabletten

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 plevele dengtos tabletes

Netherlands: Lertec

Romania: Lercaril 20 mg/20 mg comprimate filmate

Slovenia: Lercaprel 20 mg/20 mg filmsko obložene tablete

Sweden: Zanitek

Date of the most recent review of this summary: 07/2021

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/