Lercaprel

Package Leaflet: Information for the Patient

Lercaprel, 20 mg + 20 mg, Film-Coated Tablets

Enalapril Maleate + Lercanidipine Hydrochloride

Read the Package Leaflet Carefully Before Taking the Medication, as it Contains Important Information for the Patient.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medication has been prescribed for your specific condition. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Lercaprel and What is it 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 is Lercaprel and What is it Used For

Lercaprel is a combination medication containing two active substances that lower blood pressure: an angiotensin-converting enzyme (ACE) inhibitor, enalapril, and a calcium antagonist, lercanidipine. Lercaprel is used to treat high blood pressure (hypertension) in adult patients who are already taking enalapril and lercanidipine as separate medications.

2. Important Information Before Taking Lercaprel

When Not to Take Lercaprel:

• if you are allergic (hypersensitive) to enalapril maleate or lercanidipine hydrochloride, or any of the other ingredients of this medication (listed in section 6);
• if you have ever had an allergic reaction after taking medications similar to the substances contained in Lercaprel, i.e., after taking other ACE inhibitors or other calcium antagonists;
• if you have ever had swelling of the face, lips, tongue, or throat, causing difficulty in swallowing or breathing (angioedema), caused by ACE inhibitor treatment, or if such swelling has occurred for unknown reasons or is hereditary;
• if you are taking sacubitril/valsartan, a medication used to treat a certain type of long-term (chronic) heart failure in adults, as the risk of angioedema (sudden swelling of the skin and mucous membranes) may increase;
• if you have diabetes or kidney problems and are taking a blood pressure-lowering medication containing aliskiren;
• after the third month of pregnancy (you should also avoid taking Lercaprel during early pregnancy - see section "Pregnancy, Breast-feeding, and Fertility");
• if you have certain heart conditions:
• narrowing of the outflow of blood from the left ventricle, including narrowing of the aortic valve,
• untreated heart failure,
• unstable angina pectoris (chest pain at rest or progressively increasing),
• within one month after a heart attack (myocardial infarction);
• if you have severe liver function disorders;
• if you have severe kidney function disorders or are undergoing dialysis;
• if you are taking medications that inhibit the activity of liver enzymes, such as:
• antifungal medications (such as ketoconazole, itraconazole),
• macrolide antibiotics (such as erythromycin, troleandomycin),
• antiviral medications (such as ritonavir);
• if you are taking a medication called cyclosporine (used to prevent rejection of a transplanted organ);
• together with grapefruit or grapefruit juice.

Warnings and Precautions

Before starting to take Lercaprel, discuss it with your doctor or pharmacist. Inform your doctor or pharmacist:

• if you have low blood pressure (which may cause dizziness or fainting, especially when standing up);
• if you have severe vomiting or have recently had diarrhea;
• if you are on a low-salt diet;
• if you have heart problems;
• if you have problems with blood vessels in the brain;
• if you have kidney problems (including after a kidney transplant). This may lead to a significant increase in potassium levels in the blood. Your doctor may adjust the dose of enalapril or monitor potassium levels in the blood;
• if you have liver problems;
• if you have blood disorders, such as a decrease in the number of or lack of white blood cells (leukopenia, agranulocytosis), low platelet count (thrombocytopenia), or a decrease in the number of red blood cells (anemia);
• if you have collagenosis (e.g., lupus erythematosus, rheumatoid arthritis, or systemic sclerosis), are undergoing immunosuppressive treatment, or are taking medications containing allopurinol or procainamide, or any combination of these medications;
• black patients should be aware of the increased risk of allergic reactions with swelling of the face, lips, tongue, or throat, causing difficulty in swallowing or breathing when taking ACE inhibitors;
• if you have diabetes. You should monitor your blood glucose levels to detect a decrease in glucose levels, especially during the first month of treatment. Potassium levels in the blood may also be increased;
• if you are taking potassium supplements, potassium-sparing diuretics, or potassium-containing salt substitutes;
• if you are over 70 years old;
• if you have intolerance to some sugars (lactose).

If you are taking any of the following medications, the risk of angioedema may increase:

• racecadotril, a medication used to treat diarrhea;
• medications used to prevent rejection of a transplanted organ and to treat cancer (e.g., temsirolimus, sirolimus, everolimus);
• wildagliptin, a medication used to treat diabetes.

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

• angiotensin II receptor antagonist (AIIRA), also known as a sartan (e.g., valsartan, telmisartan, irbesartan), especially if you have kidney problems related to diabetes;
• aliskiren.

Your doctor may recommend regular monitoring of kidney function, blood pressure, and electrolyte levels (e.g., potassium) in the blood. See also section "When Not to Take Lercaprel". If you are scheduled for a medical procedure, if you are scheduled for any of the following procedures, inform your doctor about taking Lercaprel:

• surgical procedure or anesthesia administration (including at the dentist);
• treatment to remove cholesterol from the blood (LDL apheresis);
• desensitization treatment to reduce allergy to bee or wasp stings.

Inform your doctor about pregnancy, suspected pregnancy, or planning to become pregnant, as well as about breast-feeding (see section "Pregnancy, Breast-feeding, and Fertility").

Children and Adolescents

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

Lercaprel with Other Medications

Lercaprel should not be taken with certain medications. Inform your doctor or pharmacist about all medications you are currently taking or have recently taken, as well as any medications you plan to take, including those available without a prescription. If Lercaprel is taken with other medications, the effect of Lercaprel or the other medication may change, and certain side effects may occur more frequently. In particular, inform your doctor about taking any of the following medications:

• other blood pressure-lowering medications;
• potassium supplements (including salt substitutes), potassium-sparing diuretics, and other medications that increase potassium levels in the blood (e.g., trimethoprim and co-trimoxazole, used to treat bacterial infections; cyclosporine, an immunosuppressive medication used to prevent rejection of a transplanted organ, and heparin, a medication used to thin the blood to prevent clots). See section "When Not to Take Lercaprel";
• lithium (used to treat a certain type of depression);
• medications used to treat depression, known as tricyclic antidepressants;
• medications used to treat mental disorders, known as antipsychotics;
• non-steroidal anti-inflammatory medications (NSAIDs), including cyclooxygenase-2 (COX-2) inhibitors (medications that reduce inflammation and relieve pain);
• certain pain medications or medications used to treat arthritis, including gold salts;
• certain medications used to treat coughs and colds, as well as medications used to lose weight, containing sympathomimetics;
• antidiabetic medications (including oral antidiabetic medications and insulin);
• astemizole and terfenadine (antihistamines);
• amiodarone, quinidine, or sotalol (medications used to treat rapid heart rhythm);
• phenytoin, phenobarbital, and carbamazepine (antiepileptic medications);
• rifampicin (a medication used to treat tuberculosis);
• digoxin (a medication used to treat heart problems);
• midazolam (a medication used to treat sleep disorders);
• beta-blockers, e.g., metoprolol (medications used to treat high blood pressure, heart failure, and heart rhythm disorders);
• cimetidine (in a daily dose greater than 800 mg, a medication used to treat stomach ulcers and heartburn).

Do not take Lercaprel if you have taken or are currently taking sacubitril/valsartan, a medication used to treat a certain type of long-term (chronic) heart failure in adults, as the risk of angioedema (sudden swelling of the skin and mucous membranes) may increase. If you have taken or have recently taken any of the following medications, the risk of angioedema may increase:

• racecadotril, a medication used to treat diarrhea;
• medications used to prevent rejection of a transplanted organ and to treat cancer (e.g., temsirolimus, sirolimus, everolimus);
• wildagliptin, a medication used to treat diabetes.

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

• if you are 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 concentration of the medication in the blood.
• Alcohol may enhance the effect of Lercaprel. You should not drink alcohol during treatment with Lercaprel.
• Lercaprel should not be taken with grapefruit or grapefruit juice, as they may enhance the effect of the medication (see section "When Not to Take Lercaprel").

Pregnancy, Breast-feeding, and Fertility

Pregnancy and Fertility: If you are pregnant, think you may be pregnant, or are planning to have a baby, consult your doctor before taking this medication. Lercaprel is not recommended for patients planning to become pregnant, during early pregnancy, and should not be taken after the third month of pregnancy, as it may seriously harm the baby. Breast-feeding: You should not take Lercaprel while breast-feeding.

Driving and Using Machines

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

Lercaprel Contains Lactose and Sodium

If you have been told that you have an intolerance to some sugars, you should consult your doctor before taking this medication. This medication contains less than 1 mmol (23 mg) of sodium per tablet, which means it is essentially "sodium-free".

3. How to Take Lercaprel

This medication should always be taken exactly as directed by your doctor. If you are unsure, consult your doctor or pharmacist. Adults:If your doctor has not prescribed otherwise, the usual dose is one tablet once daily, taken at the same time every day. The tablet should be taken in the morning, at least 15 minutes before breakfast. The tablets should be swallowed whole with water. See section "Lercaprel with Food, Drink, and Alcohol". Patients with Kidney Problems or Elderly Patients:Your doctor will determine the appropriate dose of Lercaprel based on your kidney function.

Taking a Higher Dose of Lercaprel than Prescribed

Do not exceed the recommended dose. If you have taken more than the prescribed dose, contact your doctor or go to the emergency department of the nearest hospital immediately. Bring the package leaflet and any remaining tablets with you. Taking a higher dose than prescribed may cause excessive lowering of blood pressure and irregular or rapid heart rhythm.

Missing a Dose of Lercaprel

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

Stopping Treatment with Lercaprel

• Do not stop taking this medication unless your doctor tells you to.
• If you have any further questions about the use of this medication, ask your doctor or pharmacist.

4. Possible Side Effects

Like all medications, Lercaprel can cause side effects, although not everybody gets them. The following side effects may occur during treatment with Lercaprel:

Some Side Effects can be Serious.

Seek Immediate Medical Attention if you Experience any of the Following Side Effects:

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

After starting to take Lercaprel, you may experience fainting, dizziness, or blurred vision. This is due to a sudden drop in blood pressure. If you experience these symptoms, lie down until they pass. If you are unsure, consult your doctor.

Side Effects Observed 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 decreased platelet count
• increased potassium levels in the blood
• irritability (nervousness)
• dizziness when standing up, feeling of spinning (vertigo)
• rapid or irregular heart rhythm (palpitations)
• sudden flushing of the face, neck, or upper chest (hot flashes), low blood pressure
• abdominal pain, constipation, nausea
• increased liver enzyme activity
• skin rash
• joint pain
• increased urination frequency
• feeling of weakness, fatigue, hot flashes, swelling of the ankles

Rare (may affect up to 1 in 1000 people):

• anemia
• allergic reactions
• ringing in the ears (tinnitus)
• fainting
• dryness of the throat, sore throat
• indigestion, unpleasant taste, diarrhea, dry mouth, swelling of the gums
• allergic reactions with swelling of the face, lips, tongue, or throat, which may cause difficulty in swallowing or breathing, skin rash, hives
• nocturia, increased urine volume
• impotence

Additional Side Effects Related to the Individual Components of Lercaprel (Enalapril or Lercanidipine)

Enalapril

Very common (may affect more than 1 in 10 people):
blurred vision, dizziness, 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, irregular heart rhythm, rapid heart rhythm, angina pectoris, shortness of breath, taste disturbances, increased creatinine levels in the blood (usually detected in laboratory tests), high potassium levels in the blood, diarrhea, abdominal pain, fatigue, skin 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):
changes in blood parameters, such as decreased white blood cell count, bone marrow suppression, autoimmune diseases, strange dreams or sleep disturbances, Raynaud's phenomenon (feeling of coldness and paleness of the fingers and toes due to reduced blood flow), nasal congestion, pneumonia, liver function disorders, including liver failure, hepatitis, jaundice (yellowing of the skin or eyes), high liver enzyme or bilirubin levels in the blood (detected in laboratory tests), erythema multiforme (red patches of various shapes on the skin), Stevens-Johnson syndrome, and toxic epidermal necrolysis (severe skin reaction with redness and shedding of the skin, blistering, or separation of the upper layer of the skin from the lower layers)
Rare (may affect up to 1 in 1000 people):
gastrointestinal angioedema (angioedema of the gastrointestinal tract)
Unknown frequency (cannot be estimated from the available data):
excessive production of antidiuretic hormone, leading to water retention, resulting in weakness, fatigue, or confusion.
A syndrome has been reported that may include some or all of the following symptoms:
fever, vasculitis (inflammation of the blood vessels), muscle pain (myalgia/myositis), joint pain (arthralgia/arthritis).
Skin rash, increased sensitivity to light, or other skin symptoms may occur.

Lercanidipine

Some Side Effects can be Serious.

Seek Immediate Medical Attention if you Experience any of the Following Side Effects:

Rare (may affect up to 1 in 1000 people):
angina pectoris (chest pain due to insufficient blood supply to the heart), allergic reactions (symptoms include itching, rash, hives), fainting
In patients with angina pectoris, the use of medications from the same class as lercanidipine may cause an increase in the frequency, duration, or severity of angina attacks. Isolated cases of myocardial infarction have been observed.
Other Possible Side Effects:

Common (may affect up to 1 in 10 people): headache, rapid heart rhythm, rapid or irregular heart rhythm (palpitations), sudden flushing of the face, neck, or upper chest (hot flashes), swelling of the ankles
Uncommon (may affect up to 1 in 100 people): dizziness, sudden drop in blood pressure, heartburn, nausea, abdominal pain, skin rash, itching, muscle pain, increased urination frequency, feeling of weakness or fatigue
Rare (may affect up to 1 in 1000 people): drowsiness, vomiting, diarrhea, hives, increased urination frequency, chest pain
Unknown frequency (cannot be estimated from the available data): gum swelling, liver function disorders (detected in laboratory tests), cloudy dialysate (during dialysis through a tube in the abdomen), swelling of the face, lips, tongue, or throat, which may cause difficulty in swallowing or breathing
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. Your doctor or pharmacist can provide more information about side effects. They have a more detailed list of side effects.

Reporting Side Effects

If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Drug Safety Monitoring of the 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. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medication.

5. How to Store Lercaprel

Keep this medication out of the sight and reach of children. Do not use this medication after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of the month stated. 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 package to protect from light and moisture. Do not store above 25°C. Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Contents of the Pack and Other Information

What Lercaprel Contains

• The active substances of Lercaprel 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: Tablet core: lactose monohydrate, microcrystalline cellulose, sodium carboxymethylcellulose (type A), povidone (K 30), sodium hydrogen carbonate, 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 of 14, 28, or 56 film-coated tablets. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization 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 Medication is Authorized 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 film-coated tablets
Netherlands
Lertec
Romania
Lercaril 20mg/20mg film-coated tablets
Slovenia
Lercaprel 20 mg/20 mg film-coated tablets
Sweden
Zanitek

Date of Last Revision of the Package Leaflet: 07/2021