Eplerenonum + Furosemidum Lek-am

Package Leaflet: Information for the Patient

Eplerenonum + Furosemidum LEK-AM, 25 mg + 40 mg, Tablets

Eplerenonum + Furosemidum LEK-AM, 50 mg + 40 mg, Tablets

Eplerenonum + Furosemidum

Read the package leaflet carefully before taking the medicine, as it contains important information for the patient.

• Keep this package 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 symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor or pharmacist. See section 4.

Table of Contents of the Package Leaflet

• 1. What is Eplerenonum + Furosemidum LEK-AM and what is it used for
• 2. Important information before taking Eplerenonum + Furosemidum LEK-AM
• 3. How to take Eplerenonum + Furosemidum LEK-AM
• 4. Possible side effects
• 5. How to store Eplerenonum + Furosemidum LEK-AM
• 6. Contents of the pack and other information

1. What is Eplerenonum + Furosemidum LEK-AM and what is it used for

Eplerenonum + Furosemidum LEK-AM contains two active substances: eplerenone and furosemide.

• Eplerenone belongs to a group of medicines called selective aldosterone antagonists. These medicines block the action of aldosterone, a substance produced by the body that controls blood pressure and heart function. Increased levels of aldosterone can cause changes in the body that lead to heart failure.
• Furosemide belongs to a group of medicines called diuretics, which increase the amount of urine excreted by the kidneys, helping to remove excess fluid from the body. Diuretics are also known as water pills.

Eplerenonum + Furosemidum LEK-AM is used as replacement therapy in adult patients who are already taking furosemide and eplerenone in doses as in the combination product Eplerenonum + Furosemidum LEK-AM, to reduce the risk of mortality and morbidity due to cardiovascular events in patients with stable heart failure with left ventricular dysfunction, left ventricular ejection fraction ≤ 40% and clinical symptoms of heart failure (edema) after a recent myocardial infarction.

2. Important information before taking Eplerenonum + Furosemidum LEK-AM

When not to take Eplerenonum + Furosemidum LEK-AM:

• if you are allergic to eplerenone, furosemide or any of the other ingredients of this medicine (listed in section 6),
• if you are allergic to amiloride, sulfonamides or sulfonamide derivatives, such as sulfadiazine or cotrimoxazole,
• if you have high levels of potassium in the blood (hyperkalemia),
• if you have severe kidney disease,
• if you have severe liver disease,
• if you are taking potassium-sparing diuretics (medicines that help remove excess fluid from the body),
• if you are taking antifungal medicines (ketoconazole or itraconazole),
• if you are taking anti-HIV medicines (nelfinavir or ritonavir),
• if you are taking antibiotics (clarithromycin or telithromycin),
• if you are taking nefazodone, used to treat depression,
• if you are taking medicines used to treat certain heart conditions or high blood pressure (so-called ACE inhibitors in combination with angiotensin II receptor antagonists (AIIRA)),
• if you have reduced intravascular volume or are dehydrated (with or without low blood pressure),
• if you are unable to urinate,
• if you have kidney failure - in some types of kidney failure, this medicine can still be taken, but the doctor will decide,
• if you have severe liver disease with brain disorders (hepatic encephalopathy),
• if you have pre-coma and coma conditions associated with liver cirrhosis,
• if you have electrolyte deficiencies (e.g. low potassium or sodium levels in the blood, as shown by blood tests),
• if you have a condition called Addison's disease, which can cause fatigue and weakness,
• if you are taking other medicines that change potassium levels in the blood (see "Eplerenonum + Furosemidum LEK-AM and other medicines"),
• digitalis poisoning,
• porphyria,
• if you are breastfeeding (see "Pregnancy, breastfeeding and fertility").

Warnings and precautions

Before taking Eplerenonum + Furosemidum LEK-AM, discuss with your doctor, pharmacist or nurse:

• if you have kidney or liver disease (see also "When not to take Eplerenonum + Furosemidum LEK-AM"),
• if you are taking lithium salts (usually used to treat manic-depressive disorders, also known as bipolar disorders),
• if you are taking tacrolimus or cyclosporin (used to treat skin diseases, such as psoriasis or eczema, and to prevent rejection of a transplanted organ),
• if you are 65 years of age or older,
• if you have difficulty urinating,
• if you have diabetes (high blood sugar levels),
• if you are pregnant,
• if you have gout, liver or kidney disorders,
• if you have low blood pressure, it is necessary to regularly check electrolyte levels and adjust the dose accordingly, and also, if you experience dizziness when standing up,
• if you have low protein levels in the blood (hypoproteinemia),
• if you are taking risperidone,
• if you have prostate disorders,
• if you feel dizzy or are dehydrated - such symptoms may occur if you have lost a lot of fluid due to vomiting, diarrhea or frequent urination, and also if you have difficulty drinking or eating,
• if you will be taking NSAIDs at the same time,
• if you will have a glucose tolerance test,
• if you are taking other diuretics,
• if you have systemic lupus erythematosus (an autoimmune disease that attacks the skin, bones, joints and internal organs),
• if you are elderly, taking other medicines that can cause low blood pressure or have other conditions that can cause low blood pressure.

If you are unsure whether any of the above conditions apply to you, consult your doctor or pharmacist before taking Eplerenonum + Furosemidum LEK-AM.

Children and adolescents

The safety and efficacy of eplerenone in children and adolescents have not been established, therefore Eplerenonum + Furosemidum LEK-AM should not be used in this patient group.

Eplerenonum + Furosemidum LEK-AM and other medicines

Tell your doctor or pharmacist about all medicines you are taking now or have taken recently, and about any medicines you plan to take.

• Itraconazole or ketoconazole (used to treat fungal infections), ritonavir, nelfinavir (anti-HIV medicines), clarithromycin, telithromycin (used to treat bacterial infections) or nefazodone (used to treat depression) - these medicines slow down the metabolism of Eplerenonum + Furosemidum LEK-AM, thereby prolonging its effect on the body.
• Potassium-sparing diuretics (medicines that help remove excess fluid from the body) and potassium supplements - these medicines increase the risk of high potassium levels in the blood.
• ACE inhibitors (such as ramipril, enalapril, perindopril) in combination with angiotensin II receptor antagonists (AIIRA) used to treat high blood pressure, heart disease and some kidney diseases - these medicines may increase the risk of high potassium levels in the blood.
• Lithium (usually used to treat manic-depressive disorders, also known as bipolar disorders) - concomitant use of lithium with diuretics and ACE inhibitors has increased lithium levels in the blood, which can cause side effects such as loss of appetite, vision disturbances, fatigue, muscle weakness, and tremors.

Cyclosporin or tacrolimus (used to treat skin diseases, such as psoriasis or eczema, and to prevent rejection of a transplanted organ) - these medicines may cause kidney dysfunction and thereby increase the risk of high potassium levels in the blood.

• Non-steroidal anti-inflammatory drugs (NSAIDs - some painkillers, such as aspirin, ibuprofen, ketoprofen or indomethacin, used to relieve pain, stiffness and inflammation) - these medicines may cause kidney dysfunction and thereby increase the risk of high potassium levels in the blood.
• Trimethoprim (used to treat bacterial infections) - may increase the risk of high potassium levels in the blood.
• Alpha-1 adrenergic blockers, such as prazosin or alfuzosin (used to treat high blood pressure and some prostate disorders) - may cause low blood pressure and dizziness when changing body position.
• Tricyclic antidepressants, such as amitriptyline or amoxapine (used to treat depression), antipsychotic medicines, also known as neuroleptics, such as chlorpromazine or haloperidol (used to treat mental disorders), amifostine (used in cancer chemotherapy) and baclofen (used to treat increased muscle tone) - these medicines may cause low blood pressure and dizziness when changing body position.
• Corticosteroids, such as hydrocortisone or prednisone (used to treat inflammatory conditions and some skin diseases) and tetracosactide (mainly used to diagnose and treat adrenal cortex disorders) - may weaken the blood pressure-lowering effect of Eplerenonum + Furosemidum LEK-AM.
• Digoxin (used to treat heart conditions) - concomitant use with Eplerenonum + Furosemidum LEK-AM may increase digoxin levels in the blood. Your doctor may change the dose of the medicine.
• Warfarin (an anticoagulant) - caution should be exercised when using warfarin, as increased warfarin levels in the blood may interfere with the effect of Eplerenonum + Furosemidum LEK-AM on the body.
• Erythromycin (used to treat bacterial infections), saquinavir (an anti-HIV medicine), fluconazole (used to treat fungal infections), amiodarone, diltiazem and verapamil (used to treat heart conditions and high blood pressure) - slow down the metabolism of Eplerenonum + Furosemidum LEK-AM, thereby prolonging its effect on the body.
• St. John's Wort (a herbal medicine), rifampicin (used to treat bacterial infections), carbamazepine, phenytoin and phenobarbital (used, among other things, to treat epilepsy) - may accelerate the metabolism of Eplerenonum + Furosemidum LEK-AM, thereby weakening its effect.
• Medicines such as losartan, candesartan, irbesartan (so-called angiotensin II receptor antagonists). Your doctor may change the dose or discontinue them.
• Medicines used to treat high blood pressure or heart conditions. Your doctor may change the dose of the medicine.
• Other diuretics (water pills), such as amiloride, spironolactone, acetazolamide and metolazone.
• Medicines that affect potassium levels in the blood. These include potassium supplements, such as potassium chloride or certain diuretics.
• Medicines used to treat heart rhythm disorders, such as amiodarone, disopyramide, flecainide,

lidocaine, sotalol and mexiletine.

• Sedatives and tranquilizers, such as chloral hydrate.
• Medicines used for general anesthesia to relax muscles during surgery. In case of anesthesia, make sure the doctor or nurse knows that you are taking furosemide.
• Antidiabetic medicines - when taking furosemide, their effect may be weakened.
• Theophylline - used to treat wheezing or difficulty breathing.
• Phenytoin - used to treat epilepsy - may weaken the effect of furosemide.
• Medicines used to treat mental disorders, such as risperidone, amisulpride, sertindole, pimozyd and chlorpromazine. Pimozyd should be avoided when taking furosemide.
• Platinum compounds.
• Cisplatin - used to treat certain cancers.
• Carbamazepine - used to treat epilepsy.
• Aminoglutethimide - used to treat breast cancer.
• Aldesleukin - used to prevent rejection of a transplanted organ.
• Moxisylyte - used to treat Raynaud's syndrome.
• Medicines used to treat angina pectoris in the form of inhalers or tablets that dissolve under the tongue, such as glyceryl trinitrate or isosorbide dinitrate.
• Methotrexate - used to treat skin, joint or bowel diseases.
• Carbenoxolone and sucralfate - used to treat esophageal and stomach ulcers.
• Reboxetine, amitriptyline and phenelzine - used to treat depression.
• Amphotericin - used to treat fungal infections, especially when given for a long time.
• Corticosteroids - used to treat inflammatory conditions, such as prednisolone.
• Atomoxetine - used to treat attention deficit hyperactivity disorder (ADHD).
• Muscle relaxants, such as tizanidine.
• Antihistamines, used to treat allergies, such as cetirizine.
• Alprostadil, used to treat impotence in men.
• Estrogens and drospirenone, used as contraceptives or in hormone replacement therapy (HRT).
• Liquorice, often found in cough medicines, when taken in large amounts.
• Probenecid (used with other medicines for HIV infection).
• Medicines used to treat infections, such as gentamicin, amikacin, neomycin, netilmicin, tobramycin, vancomycin or cephalosporins in high doses.
• Substances used for injection before X-ray examinations (contrast agents used in radiology).
• Laxatives (used to treat constipation), used for a long time, such as bisacodyl or senna.
• Asthma medicines, used in high doses, such as salbutamol, terbutaline sulfate, salmeterol, formoterol or bambuterol.
• Medicines used to treat nasal congestion, such as ephedrine and xylometazoline.
• Potassium salts, used to treat low potassium levels in the blood.
• Medicines used to treat Parkinson's disease, such as levodopa.
• Other diuretics (water pills), such as bendroflumethiazide. Your doctor may change the dose of the medicine.
• High doses of furosemide given with levothyroxine may initially cause a transient increase in free thyroid hormones, followed by a general decrease in total thyroid hormone levels.

Eplerenonum + Furosemidum LEK-AM with food and drink

Eplerenonum + Furosemidum LEK-AM should be taken on an empty stomach, with a large amount of fluid. When taking Eplerenonum + Furosemidum LEK-AM, you should avoid consuming alcohol, as it may lower blood pressure.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. The effect of Eplerenonum + Furosemidum LEK-AM during pregnancy has not been evaluated in humans. One of the active substances of this medicine, furosemide, may pass into breast milk in small amounts. Therefore, you should not breastfeed while taking this medicine. Ask your doctor whether to stop breastfeeding or stop taking the medicine.

Driving and using machines

After taking Eplerenonum + Furosemidum LEK-AM, you may experience weakness, dizziness and blurred vision. In this case, do not drive or operate machinery.

Eplerenonum + Furosemidum LEK-AM contains lactose monohydrate and sodium

Eplerenonum + Furosemidum LEK-AM contains lactose monohydrate (a type of sugar). If you have been diagnosed with intolerance to some sugars, you should consult your doctor before taking the medicine. Eplerenonum + Furosemidum LEK-AM contains less than 1 mmol (23 mg) of sodium per tablet, which means that the medicine is considered "sodium-free".

3. How to take Eplerenonum + Furosemidum LEK-AM

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist. Eplerenonum + Furosemidum LEK-AM tablets should be taken on an empty stomach, with a large amount of fluid. Eplerenonum + Furosemidum LEK-AM is a combination product that can only be used in patients who have been established on a stable dose based on individual components (furosemide and eplerenone used in separate products), and do not require dose adjustments. If the combination product causes side effects indicating the need to re-adjust the dose, the product should be discontinued and the doctor should determine the appropriate dose using furosemide and eplerenone in separate products. To allow for individual dose adjustment, 25 mg eplerenone and 40 mg furosemide and 50 mg eplerenone and 40 mg furosemide strengths are available. The maximum dose of eplerenone is 50 mg per day. The recommended maintenance dose is one tablet containing 50 mg eplerenone and 40 mg furosemide once daily. During treatment, your doctor may recommend that you have your potassium levels checked, and if necessary, adjust the dose based on potassium levels, using furosemide and eplerenone in separate products. If you have mild or moderate kidney disease, your doctor may recommend adjusting the dose, taking into account your potassium levels, using furosemide and eplerenone in separate products. In patients with severe kidney disease, the use of Eplerenonum + Furosemidum LEK-AM is contraindicated. In cases of liver or kidney disease, it may be necessary to check potassium levels in the blood more frequently (see also "When not to take Eplerenonum + Furosemidum LEK-AM").

Use in children and adolescents:

Eplerenonum + Furosemidum LEK-AM should not be used in children and adolescents.

Use in the elderly:

Your doctor may recommend periodic blood tests to check potassium levels, and if necessary, adjust the dose based on potassium levels, using furosemide and eplerenone in separate products.

Use in patients with kidney function disorders

In patients with mild or moderate kidney failure, your doctor may recommend periodic blood tests to check potassium levels, and if necessary, adjust the dose based on potassium levels, using furosemide and eplerenone in separate products.

Use in patients taking other medicines

In the case of concomitant use of weak or moderate CYP3A4 inhibitors, such as amiodarone, diltiazem and verapamil, the maintenance dose should not exceed 25 mg + 40 mg once daily.

Overdose of Eplerenonum + Furosemidum LEK-AM

In case of overdose of Eplerenonum + Furosemidum LEK-AM or ingestion of any dose by a child, immediately inform your doctor or go to the emergency department of the nearest hospital, even if no symptoms are present. Take the medicine package with you so that the doctor knows what medicine has been taken. The most likely symptoms of overdose are: low blood pressure (causing dizziness, dizziness, blurred vision, weakness, sudden loss of consciousness), hyperkalemia (high potassium levels in the blood), causing muscle cramps, diarrhea, nausea, dizziness or headache), irregular heartbeat, blood clots (causing pain and swelling of the affected limb, with or without low blood pressure), disorientation, lack of emotions or interest in anything. Kidney or blood disorders may also occur.

Missed dose of Eplerenonum + Furosemidum LEK-AM

If it is almost time for the next dose, skip the missed dose and take the next dose at the usual time. In other cases, take the dose as soon as you remember, provided that there are more than 12 hours until the next dose. Then return to the usual dosing schedule. Do not take a double dose to make up for the missed dose.

Stopping Eplerenonum + Furosemidum LEK-AM

It is important to take Eplerenonum + Furosemidum LEK-AM as directed, unless your doctor tells you to stop.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. If you experience any of the following symptoms, stop taking the medicine and contact your doctor immediately:

• swelling of the face, tongue or throat, difficulty swallowing, hives and difficulty breathing (these are symptoms of angioedema, a rare but serious side effect).
• allergic reactions, such as itching, skin rash with intense itching and hives, fever, sensitivity to light, severe allergic reaction with (high) fever, red spots on the skin, joint pain and (or) eye inflammation, severe, acute reaction (allergic) with fever and blisters on the skin/exfoliation and petechiae.
• acute pancreatitis, which is accompanied by severe abdominal pain radiating to the back.

Other possible side effects:

Tell your doctor if any of the following symptoms worsen or persist for more than a few days.

Common (may affect up to 1 in 10 people)

• high potassium levels in the blood (symptoms include muscle cramps, diarrhea, nausea, dizziness or headache),
• high cholesterol levels in the blood,
• insomnia (difficulty sleeping),
• fainting,
• dizziness of central origin,
• headache,
• heart disorders, such as arrhythmias and heart failure,
• low blood pressure,
• cough,
• diarrhea,
• nausea,
• constipation,
• vomiting,
• rash,
• itching,
• muscle cramps,
• back pain,
• kidney disorders,
• weakness,
• high urea levels in the blood,
• high creatinine levels in the blood, which may indicate kidney dysfunction.

Uncommon (may affect up to 1 in 100 people)

• kidney inflammation,
• infection,
• throat inflammation,
• eosinophilia (increased levels of a type of white blood cell),
• thrombocytopenia,
• hypothyroidism,
• low sodium levels in the blood,
• dehydration, dry mouth, thirst
• high triglyceride levels in the blood,
• numbness,
• vision disturbances,
• rapid heartbeat,
• blood clots in the legs (causing pain and swelling of the affected limb),
• low blood pressure, which may cause dizziness when changing body position,
• bloating,
• angioedema (which may include swelling of the face, tongue or throat, difficulty swallowing, hives and difficulty breathing),
• increased sweating,
• musculoskeletal pain,
• gallbladder inflammation,
• breast enlargement in men,
• general malaise,
• high blood sugar levels,
• changes in some blood test results (e.g. transient increases in creatinine and urea),
• abnormal platelet count, which may be accompanied by bruising and a tendency to bleed,
• sensitivity to light,
• involuntary urination,
• in elderly patients - decreased intravascular volume, dehydration and hemoconcentration, which may cause blood clots,
• hearing loss (sometimes irreversible).

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

• abnormal blood count (low white blood cell count), which may be accompanied by increased susceptibility to infections,
• increased levels of certain white blood cells (eosinophils) in the blood,
• bone marrow suppression
• tingling sensation on the skin, itching or tingling without cause,
• life-threatening loss of consciousness,
• hearing disorders and tinnitus, which are usually transient,
• blood vessel inflammation,
• acute kidney failure,
• kidney inflammation with blood in the urine, fever and pain in the side of the back - in case of urinary tract obstruction, urine retention may occur,
• if you have a bladder disorder, prostate enlargement or urethral stricture, you may experience sudden urinary retention,
• shock (severe low blood pressure, extreme pallor, anxiety, weak and rapid pulse, moist skin, disorders of consciousness) due to severe allergic reaction to certain substances,
• fever.

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

• anemia (a condition characterized by a lack of red blood cells),
• severe blood disorders (low white blood cell count) with accompanying high fever, severe sore throat and mouth ulcers,
• certain liver function disorders,
• increased activity of certain liver enzymes. During treatment with furosemide, the levels of certain fats in the blood (cholesterol and triglycerides) may increase, but usually return to normal within 6 months.

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

• acute generalized exanthematous pustulosis (acute rash with fever),
• dizziness, fainting and loss of consciousness (caused by symptomatic hypotension).

Reporting of side effects

If you experience any side effects, including those not listed in this package leaflet, please inform your doctor, pharmacist or nurse. 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 medicine.

5. How to store Eplerenonum + Furosemidum LEK-AM

Keep this medicine out of the sight and reach of children. Store in a temperature below 30°C. Store the blister in the outer packaging to protect from light. Do not use this medicine after the expiry date which is stated on the carton and blister after EXP:. The expiry date refers to the last day of that month. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Eplerenonum + Furosemidum LEK-AM contains

The active substances of the medicine are:

• Eplerenonum + Furosemidum LEK-AM, 25 mg + 40 mg, tablets: each tablet contains 25 mg eplerenone and 40 mg furosemide
• Eplerenonum + Furosemidum LEK-AM, 50 mg + 40 mg, tablets: each tablet contains 50 mg eplerenone and 40 mg furosemide

The other ingredients are: lactose monohydrate, microcrystalline cellulose type 101, microcrystalline cellulose type 102, hydroxypropylcellulose 100 cPs, croscarmellose sodium, talc, magnesium stearate and sodium lauryl sulfate.

What Eplerenonum + Furosemidum LEK-AM looks like and contents of the pack

Eplerenonum + Furosemidum LEK-AM, 25 mg + 40 mg, tablets: white or almost white, biconvex tablets in the shape of a capsule, 20 mm x 8 mm in size, with the inscription "25/40" on one side. The tablet surface may have dark spots. Eplerenonum + Furosemidum LEK-AM, 50 mg + 40 mg, tablets: white or almost white, biconvex, oval tablets, 19 mm x 9.6 mm in size, with the inscription "50/40" on one side. The tablet surface may have dark spots. The tablets are packaged in PVC/PVDC/Aluminum blisters and placed in a cardboard box. The pack contains 30 tablets.

Marketing authorization holder and manufacturer

LEK-AM Pharmaceutical Company Ltd., ul. Ostrzykowizna 14A, 05-170 Zakroczym, Tel.: (22) 785 27 60

Date of last revision of the package leaflet