Lercaprel

Package leaflet: Information for the patient

Lercaprel, 20 mg + 20 mg, film-coated tablets
Enalapril maleate + Lercanidipine hydrochloride
Please read the entire leaflet carefully before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not give it to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

1. What Lercaprel is and what it is used for
2. Important information before taking Lercaprel
3. How to take Lercaprel
4. Possible side effects
5. How to store Lercaprel
6. Contents of the pack and other information

1. What Lercaprel is and what it is used for

Lercaprel is a combination medicine containing two active substances that lower blood pressure – an angiotensin-converting enzyme (ACE) inhibitor, enalapril, and a calcium antagonist, lercanidipine.
Lercaprel is used for the treatment of high blood pressure (hypertension) in adult patients who are already taking enalapril and lercanidipine as separate medicines.

2. Important information before taking Lercaprel

When not to take Lercaprel:

• if the patient is allergic (hypersensitive) to enalapril maleate or lerkanidipine hydrochloride, or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has ever had an allergic reaction after taking medicines similar to the substances contained in Lercaprel, i.e. after taking other ACE inhibitors or other calcium antagonists;
• if the patient has ever experienced swelling of the face, lips, mouth, tongue or throat causing difficulty in swallowing or breathing (angioedema), caused by treatment with an ACE inhibitor, or if such swelling occurred for unknown reasons, or is hereditary;
• if the patient has taken or is currently taking sacubitril with valsartan, a medicine used to treat certain types of chronic heart failure in adults, because the risk of angioedema (sudden subcutaneous swelling, e.g. in the throat) increases;
• if the patient has diabetes or kidney function disorders and is taking a blood pressure-lowering medicine containing aliskiren;
• after the 3rd month of pregnancy (Lercaprel should also be avoided during early pregnancy – see section "Pregnancy, breastfeeding and fertility");
• if the patient has certain heart diseases:
  • obstruction of blood outflow from the left ventricle of the heart, including aortic valve stenosis,
  • untreated heart failure,
  • unstable angina (chest pain at rest or progressively worsening),
  • within one month after myocardial infarction (heart attack);
• if the patient has severe liver function impairment;
• if the patient has severe kidney function impairment or is undergoing dialysis;
• if the patient is taking medicines that inhibit liver enzyme activity, such as:
  • antifungal medicines (e.g. ketoconazole, itraconazole),
  • macrolide antibiotics (e.g. erythromycin, troleandomycin),
  • antiviral medicines (e.g. ritonavir);
• if the patient is simultaneously taking cyclosporine (used to prevent organ transplant rejection);
• together with grapefruit or grapefruit juice.

Warnings and precautions
Before starting Lercaprel, discuss this with your doctor or pharmacist.
Inform your doctor or pharmacist:

• if the patient has low blood pressure (which may manifest as fainting or dizziness, especially when standing up);
• if the patient has severe vomiting or has recently had diarrhoea;
• if the patient is on a low-salt diet;
• if the patient has heart disorders;
• if the patient has disorders of blood vessels in the brain;
• if the patient has kidney function disorders (including after kidney transplantation). This may lead to a serious increase in serum potassium levels. The doctor may adjust the enalapril dose or monitor serum potassium levels;
• if the patient has liver function disorders;
• if the patient has blood disorders, such as reduced number or absence of white blood cells (leukopenia, agranulocytosis); low platelet count (thrombocytopenia), or reduced number of red blood cells (anaemia);
• if the patient has collagenosis (e.g. systemic lupus erythematosus, rheumatoid arthritis or systemic sclerosis), is undergoing immunosuppressive treatment, takes medicines containing allopurinol or procainamide, or any combination of these medicines;
• patients of Black race should be aware of an increased risk of allergic reactions with swelling of the face, lips, tongue or throat causing difficulty in swallowing or breathing while taking ACE inhibitors;
• if the patient has diabetes. Blood glucose levels should be monitored to detect hypoglycaemia, especially during the first month of treatment. Blood potassium levels may also be elevated;
• if the patient is taking potassium supplements, potassium-sparing diuretics or salt substitutes containing potassium;
• if the patient is over 70 years of age;
• if the patient has intolerance to certain sugars (lactose).

If the patient is taking any of the following medicines, the risk of angioedema
may increase:

• racecadotril, a medicine used to treat diarrhoea;
• medicines used to prevent organ transplant rejection and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus);
• vildagliptin, a medicine used to treat diabetes.

If the patient is taking any of the following medicines used to treat high
blood pressure:

• an angiotensin II receptor antagonist (AIIRA), also called a sartan – for example, valsartan, telmisartan, irbesartan), especially if the patient has kidney function disorders related to diabetes;
• aliskiren.

The doctor may recommend regular monitoring of kidney function, blood pressure, and blood
electrolyte levels (e.g. potassium).
See also the section "When not to take Lercaprel".
If the patient is scheduled for a medical procedure
If the patient is scheduled for any of the following procedures, inform the doctor about
taking Lercaprel:

• surgical procedure or administration of anaesthesia (including at the dentist);
• treatment aimed at removing cholesterol from the blood (LDL apheresis);
• desensitisation treatment to reduce allergy to bee or wasp venom.

Inform your doctor if you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding
(See section "Pregnancy, breastfeeding and fertility").
Children and adolescents
The safety and efficacy of Lercaprel in children under 18 years of age have not been established.
Lercaprel and other medicines
Lercaprel must not be taken with certain medicines.
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take, including those available without a prescription. If Lercaprel is taken together with other medicines, the effect of Lercaprel or the other medicine may change, and certain adverse effects may occur more frequently.
In particular, inform your doctor if the patient is taking any of the following
medicines:

• other medicines that lower blood pressure;
• potassium supplements (including salt substitutes), potassium-sparing diuretics and other medicines that increase blood potassium levels (e.g. trimethoprim and co-trimoxazole, used in bacterial infections; cyclosporine, an immunosuppressive medicine used to prevent organ transplant rejection, and heparin, a medicine used to thin the blood to prevent clots). See section "When not to take Lercaprel";
• lithium (used to treat a certain type of depression);
• medicines used to treat depression, called tricyclic antidepressants;
• medicines used to treat mental disorders, called antipsychotics;
• non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors (medicines that reduce inflammation and relieve pain);
• certain painkillers or medicines used to treat joint inflammation, including gold salts;
• certain medicines used for cough and colds and for weight reduction, containing so-called sympathomimetics;
• antidiabetic medicines (including oral antidiabetic medicines and insulin);
• astemizole and terfenadine (antihistamine medicines);
• amiodarone, quinidine or sotalol (medicines used to treat rapid heart rate);
• phenytoin, phenobarbital and carbamazepine (antiepileptic medicines);
• rifampicin (a medicine used to treat tuberculosis);
• digoxin (a medicine used to treat heart disorders);
• midazolam (a medicine used in sleep disorders);
• beta-blockers, e.g. metoprolol (medicines used to treat high blood pressure, heart failure and heart rhythm disorders);
• cimetidine (at a daily dose exceeding 800 mg, a medicine used to treat peptic ulcer disease and heartburn).

Do not take Lercaprel if the patient has taken or is currently taking sacubitril with
valsartan, a medicine used to treat certain types of chronic (long-term) heart failure in adults, because the risk of angioedema (sudden subcutaneous swelling, e.g. in the throat) increases.
If the patient is taking or has recently taken any of the following medicines, the risk of
angioedema may increase:

• racecadotril, a medicine used to treat diarrhoea;
• medicines used to prevent organ transplant rejection and in cancer treatment (e.g. temsirolimus, sirolimus, everolimus);
• vildagliptin, a medicine used to treat diabetes.

The doctor may recommend changing the dose and/or taking other precautions:

• if the patient is taking an angiotensin II receptor antagonist (AIIRA) or aliskiren (see also sections "When not to take Lercaprel" and "Warnings and precautions").

Lercaprel with food, drink and alcohol

• Lercaprel should be taken at least 15 minutes before a meal.
• A high-fat meal significantly increases the blood concentration of the medicine.
• Alcohol may enhance the effect of Lercaprel. Alcohol should not be consumed during treatment with Lercaprel.
• Lercaprel must not be taken together with grapefruit or grapefruit juice, as they may enhance the effect of the medicine (see section "When not to take Lercaprel").

Pregnancy, breastfeeding and fertility
Pregnancy and effect on fertility
If the patient is pregnant, suspects she may be pregnant, or is planning to become pregnant, she should
consult her doctor before using this medicine. Lercaprel is not recommended for patients planning pregnancy, during early pregnancy, and must not be taken during later pregnancy (from the 3rd month), as it may seriously harm the unborn child when administered after the third month of pregnancy.
Breastfeeding
Lercaprel should not be used during breastfeeding.
Driving and operating machinery
If dizziness, weakness or drowsiness occur, the patient must not drive or
operate machinery.
Lercaprel contains lactose and sodium
If the patient has been previously diagnosed with intolerance to certain sugars, the patient should
consult a doctor before taking the medicine.
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. the medicine is considered "sodium-free".

3. How to take Lercaprel

This medicine should always be taken as directed by your doctor. If in doubt, consult your doctor or pharmacist.
Use in adults: Unless otherwise prescribed by your doctor, the usual dose is one tablet once daily, taken at the same time every day. It is best to take the tablet in the morning, at least 15 minutes before breakfast. Swallow the tablet whole with water. See section "Lercaprel with food, drink and alcohol".
Use in patients with renal impairment/elderly patients: Your doctor will determine the appropriate dose depending on kidney function.
Taking more Lercaprel than prescribed
Do not exceed the recommended dose. If you take more than the prescribed amount, contact your doctor immediately or go to the nearest hospital emergency department. Take the medicine package with you. Taking more than the recommended dose may cause excessive lowering of blood pressure and irregular or rapid heartbeat.
If you miss a dose of Lercaprel

• If you miss a dose, skip the missed dose.
• Then take your next dose at the usual time.
• Do not take a double dose to make up for a missed dose.

Stopping Lercaprel

• Do not stop taking this medicine unless your doctor tells you to.
• If you have any further questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
The following adverse effects may occur during treatment with this medicine:
Some adverse effects may be serious.
Seek immediate medical attention or go to hospital if any of the following adverse effects occur:

• Allergic reaction with swelling of the face, lips, tongue or throat, which may cause difficulty in breathing or swallowing.

After starting treatment with Lercaprel, fainting, dizziness or blurred vision may occur. These symptoms are caused by a sudden drop in blood pressure. If such symptoms occur, lie down until they resolve. In case of any doubts, consult your doctor.
Adverse effects observed during treatment with Lercaprel
Common (may affect up to 1 in 10 people):

• Cough
• Dizziness, headache

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

• Changes in blood parameters such as reduced platelet count
• Increased blood potassium levels
• Nervousness (anxiety)
• Dizziness upon standing, sensation of spinning (vertigo)
• Increased heart rate, rapid or irregular heartbeat (palpitations)
• Sudden flushing of the face, neck or upper chest (hot flushes), low blood pressure
• Abdominal pain, constipation, nausea
• Increased liver enzyme activity
• Skin redness
• Joint pain
• Increased frequency of urination
• Feeling of weakness, fatigue, hot flushes, swelling around the ankles

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

• Anaemia
• Allergic reactions
• Ringing in the ears (tinnitus)
• Fainting
• Dryness of the throat mucosa, sore throat
• Indigestion, salty taste sensation, diarrhoea, dryness of the oral mucosa, gum swelling
• Allergic reactions with swelling of the face, lips, tongue or throat, which may cause difficulty in swallowing or breathing, skin rash, urticaria
• Nocturnal urination, increased urine volume
• Impotence

Additional adverse effects associated with the individual components of the medicine
(enalapril or lercanidipine)
Enalapril
Very common (may affect more than 1 in 10 people):
Blurred vision, dizziness, feeling of weakness, nausea, cough
Common (may affect up to 1 in 10 people):
Depression, headache, fainting, chest pain, feeling of emptiness in the head due to low blood pressure, heart rhythm disturbances, increased heart rate, palpitations, angina, shortness of breath, taste disturbances, increased blood creatinine levels (usually detected in laboratory tests), high blood potassium levels, diarrhoea, abdominal pain, fatigue, rash, allergic reactions with swelling of the face, lips, tongue or throat, which may cause difficulty in 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, insomnia or drowsiness, tingling or numbness sensations, heart attack (usually due to very low blood pressure in certain high-risk patients, including those with impaired blood flow to the heart and brain), stroke (usually due to very low blood pressure in high-risk patients), watery nasal discharge, sore throat and hoarseness, asthma with accompanying chest tightness, slowed intestinal peristalsis, pancreatitis, vomiting, indigestion, constipation, stomach irritation, dryness of the oral mucosa, peptic ulcer, loss of appetite, itching or hives, hair loss, kidney function disorders, kidney failure, excessive sweating, high protein levels in urine (detected in laboratory tests), muscle cramps, malaise, high temperature (fever), low blood sugar or sodium levels, high blood urea levels (detected in laboratory tests), hot flushes, rapid or irregular heartbeat (palpitations), vertigo (sensation of spinning), tinnitus, impotence
Rare (may affect up to 1 in 1,000 people):
Changes in blood parameters such as reduced white blood cell count, bone marrow suppression, autoimmune diseases, unusual dreams or sleep disturbances, Raynaud's phenomenon (feeling of coldness and paleness in fingers and toes due to reduced blood flow), nasal mucosa inflammation, pneumonia, liver function disorders including liver failure, hepatitis, jaundice (yellowing of the skin or eyes), high levels of liver enzymes or bilirubin in blood (detected in laboratory tests), erythema multiforme (red spots of various shapes appearing on the skin), Stevens-Johnson syndrome and toxic epidermal necrolysis (severe skin reaction with redness and peeling of the skin, formation of blisters or ulcers or separation of the upper skin layer from lower layers), exfoliative dermatitis/erythroderma (severe skin rash with peeling or shedding of the skin) or bullous eruption (formation of small fluid-filled blisters on the skin), reduced urine output, breast enlargement in men (gynaecomastia), enlarged lymph nodes in the neck, armpits and groin, accumulation of fluid or other substances in the lungs (detected on X-rays), inflammation of the mucosa of cheeks, gums, tongue, lips, throat
Very rare (may affect up to 1 in 10,000 people):
Intestinal angioedema (intestinal swelling)
Not known (frequency cannot be estimated from available data):
Excessive production of antidiuretic hormone, causing fluid retention, leading to weakness, fatigue or confusion.
A syndrome has been reported which may include some or all of the following symptoms: fever, vasculitis (serositis/vasculitis), muscle pain (myalgia/myositis), joint pain (arthralgia/arthritis). Skin rash, photosensitivity or other skin symptoms may also occur.
Lercanidipine
Some adverse effects may be serious.
Seek immediate medical attention if any of the following adverse effects occur:
Rare (may affect up to 1 in 1,000 people):
Angina (chest pain due to inadequate blood supply to the heart), allergic reactions (symptoms include itching, rash, urticaria), fainting
In patients with angina, treatment with medicines of the class to which lercanidipine belongs may increase the frequency, duration or severity of angina attacks. Isolated cases of myocardial infarction have been observed.
Other possible adverse effects:
Common (may affect up to 1 in 10 people): headache, increased heart rate, rapid or irregular heartbeat (palpitations), sudden flushing of the face, neck or upper chest (hot flushes), ankle swelling
Uncommon (may affect up to 1 in 100 people): dizziness, sudden drop in blood pressure, heartburn, nausea, abdominal pain, rash, itching, muscle pain, increased urine output, feeling of weakness or fatigue
Rare (may affect up to 1 in 1,000 people): drowsiness, vomiting, diarrhoea, urticaria, increased frequency of urination, chest pain
Not known (frequency cannot be estimated from available data): gum swelling, liver function disorders (detected in blood tests), cloudy fluid (during peritoneal dialysis via a catheter placed in the abdomen), swelling of the face, lips, tongue or throat, which may cause difficulty in swallowing or breathing

If adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor or pharmacist. Your doctor or pharmacist can provide further information about adverse effects and have access to a more detailed list.
Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can also be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl .
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Lercaprel

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard box after
"Expiry date (EXP)" and on the blister after: "EXP". The expiry date refers to the last day of the stated month.
The abbreviation "Lot" on the packaging and blister means "Batch number".
The abbreviation "EXP" on the packaging and blister means "Expiry date".
Store in the original packaging to protect from light and moisture.
Do not store above 25°C.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Lercaprel contains

• The active substances are enalapril maleate and levcarnidipine hydrochloride. Each film-coated tablet contains: 20 mg enalapril maleate (corresponding to 15.29 mg enalapril) and 20 mg levcarnidipine hydrochloride (corresponding to 18.88 mg levcarnidipine).
• Other ingredients:
  Core of the tablet: monohydrate lactose, microcrystalline cellulose, sodium carboxymethyl starch (type A), povidone (K 30), sodium bicarbonate, magnesium stearate.
  Tablet coating: hypromellose 5 cP, titanium dioxide (E 171), macrogol 6000, yellow iron oxide (E 172), talc, red iron oxide (E 172).

What Lercaprel looks like and contents of the pack
Orange, round, biconvex film-coated tablets, 12 mm in diameter.
Lercaprel is available in packs containing 14, 28, or 56 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Recordati Ireland Ltd.
Raheens East
Ringaskiddy, Co. Cork
Ireland

Manufacturer:
Recordati Industria Chimica e Farmaceutica S.p.A.
Via Matteo Civitali 1
20148 Milan
Italy

This medicinal product is authorised in the Member States of the European Economic Area under the following names:
Austria Zanipril 20 mg/20 mg Filmtabletten
Belgium, Luxembourg Zanicombo
Bulgaria Lercapril
Cyprus Zaneril
Denmark, Finland, Iceland, Malta,
Norway, Portugal, Spain, Germany Zanipress
France Zanextra
Greece, Latvia, Poland Lercaprel
Hungary Coripren
Ireland, Estonia Lercaril
Italy Zanipril
Lithuania Lercaprel 20 mg/20 mg plėvele dengtos tabletės
Netherlands Lertec
Romania Lercaril 20mg/20mg comprimate filmate
Slovenia Lercaprel 20 mg/20 mg filmsko obložene tablete
Sweden Zanitek