Nonpres Duo

Leaflet accompanying the packaging: patient information

Nonpres Duo, 25 mg + 40 mg, tablets

Nonpres Duo, 50 mg + 40 mg, tablets

Eplerenone + Furosemide

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet

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

1. What is Nonpres Duo and what is it used for

Nonpres Duo 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.

Nonpres Duo is used as replacement therapy in adult patients who are already taking furosemide and eplerenone in doses as in the combination product Nonpres Duo, 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 Nonpres Duo

When not to take Nonpres Duo:

• if the patient is allergic to eplerenone, furosemide or any of the other ingredients of this medicine (listed in section 6),

or

• if the patient is allergic to amiloride, sulfonamides or sulfonamide derivatives, such as sulfadiazine or cotrimoxazole,
• if the patient has high levels of potassium in the blood (hyperkalemia),
• if the patient has severe kidney disease,
• if the patient has severe liver disease,
• if the patient is taking potassium-sparing diuretics (diuretics that help the body retain potassium),
• if the patient is taking antifungal medicines (ketoconazole or itraconazole),
• if the patient is taking anti-HIV medicines (nelfinavir or ritonavir),
• if the patient is taking antibiotics used to treat bacterial infections (clarithromycin or telithromycin),
• if the patient is taking nefazodone, used to treat depression,
• if the patient is 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 the patient has reduced intravascular volume or is dehydrated (with or without low blood pressure),
• if the patient has anuria ( inability to urinate),
• if the patient has kidney failure - in some types of kidney failure, this medicine can still be taken, but the doctor will decide,
• if the patient has severe liver disease with brain disorders (hepatic encephalopathy),
• if the patient has pre-coma or coma associated with liver cirrhosis,
• if the patient has electrolyte disturbances (e.g. low potassium or sodium levels in the blood, as shown by blood tests),
• if the patient has a disease called Addison's disease, which can cause fatigue and weakness,
• if the patient is taking other medicines that change potassium levels in the blood (see "Nonpres Duo and other medicines"),
• digitalis toxicity,
• porphyria,
• if the patient is breastfeeding (see "Pregnancy, breastfeeding and fertility").

Warnings and precautions

Before starting treatment with Nonpres Duo, the patient should discuss it with their doctor, pharmacist or nurse:

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

In case of doubt whether any of the above conditions apply to the patient, before taking Nonpres Duo, the patient should consult a doctor or pharmacist.

Children and adolescents

The safety and efficacy of eplerenone in children and adolescents have not been established, therefore Nonpres Duo should not be used in this patient group.

Nonpres Duo and other medicines

The patient should tell their doctor or pharmacist about all medicines they are taking, have recently taken or might take.

Nonpres Duo may affect the action of the following medicines, and these medicines may affect the action of Nonpres Duo:

• 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 Nonpres Duo, thereby prolonging its effect on the body.
• Potassium-sparing diuretics (diuretics that help the body retain potassium) 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, 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 certain prostate disorders) - may cause low blood pressure and dizziness when changing body position to standing.
• 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 in cases of increased muscle tension) - these medicines may cause low blood pressure and dizziness when changing body position to standing.
• Corticosteroids, such as hydrocortisone or prednisone (used to treat inflammatory conditions and certain skin diseases) and tetracosactide (mainly used to diagnose and treat adrenal cortex disorders) - may weaken the blood pressure-lowering effect of Nonpres Duo.
• Digoxin (used to treat heart conditions) - concomitant use with Nonpres Duo may increase digoxin levels in the blood. The 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 disrupt the effect of Nonpres Duo 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 Nonpres Duo, 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 Nonpres Duo, thereby weakening its effect.
• Medicines such as losartan, candesartan, irbesartan (so-called angiotensin II receptor antagonists). The doctor may change the dose or recommend stopping them.
• Medicines used to treat high blood pressure or heart conditions. The 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, it is necessary to ensure that the doctor or nurse knows that the patient is taking furosemide.

• Antidiabetic medicines - their effect may be weakened when taking furosemide.
• Theophylline - used in cases of wheezing or difficulty breathing.
• Phenytoin - used to treat epilepsy - may weaken the effect of furosemide.
• Medicines used to treat mental disorders called psychoses, such as risperidone, amisulpride, sertindole, pimozyde and chlorpromazine. It is recommended to avoid taking pimozide with 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 intestinal 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, in case of prolonged administration.
• 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, in case of high doses.
• 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 in injections before X-ray examinations (contrast agents used in radiology).
• Laxatives (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 in case of low potassium levels in the blood.
• Medicines used to treat Parkinson's disease, such as levodopa.
• Other diuretics (water pills), such as bendroflumethiazide. The 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.

Nonpres Duo with food and drink

Nonpres Duo is best taken on an empty stomach, with a large amount of liquid.

During treatment with Nonpres Duo, the patient should avoid consuming alcohol, as it may lower blood pressure.

Pregnancy and breastfeeding

If the patient is pregnant or breastfeeding, thinks she may be pregnant or plans to have a baby, she should consult a doctor or pharmacist before taking this medicine.

The effect of Nonpres Duo 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, breastfeeding should be avoided while taking this medicine.

The patient should consult a doctor whether to stop breastfeeding or stop taking the medicine.

Driving and using machines

After taking Nonpres Duo, the patient may experience weakness, dizziness and blurred vision. In this case, the patient should not drive vehicles or operate machines.

Nonpres Duo contains lactose monohydrate and sodium

Nonpres Duo contains lactose monohydrate (a type of sugar). If the patient has been diagnosed with intolerance to some sugars, they should consult a doctor before taking the medicine.

Nonpres Duo contains less than 1 mmol (23 mg) of sodium per tablet, which means that the medicine is considered "sodium-free".

3. How to take Nonpres Duo

This medicine should always be taken exactly as prescribed by the doctor or pharmacist.

In case of doubts, the patient should consult a doctor or pharmacist.

Nonpres Duo tablets are best taken on an empty stomach, with a large amount of liquid.

Nonpres Duo is a combination product that can only be used in patients who have been established on a stable dose of the individual components (furosemide and eplerenone) and do not require dose adjustments. If the combination product causes side effects indicating the need for dose adjustment, the product should be discontinued and the doctor should determine the appropriate dose for the patient 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 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, the doctor may recommend checking potassium levels in the blood, and if necessary, adjust the dose based on potassium levels in the blood, using furosemide and eplerenone in separate products.

If the patient has mild or moderate kidney disease, the doctor may recommend adjusting the dose, taking into account potassium levels in the blood, using furosemide and eplerenone in separate products. In patients with severe kidney disease, the use of Nonpres Duo is contraindicated.

In case of liver or kidney disease, it may be necessary to check potassium levels in the blood more frequently (see also "When not to take Nonpres Duo").

Use in children and adolescents:

Nonpres Duo is not recommended for use in children and adolescents.

Use in the elderly:

The doctor may recommend periodic checking of potassium levels in the blood, and if necessary, adjust the dose based on potassium levels in the blood, using furosemide and eplerenone in separate products.

Use in patients with renal impairment

In patients with mild or moderate renal impairment, the doctor may recommend periodic checking of potassium levels in the blood, and if necessary, adjust the dose based on potassium levels in the blood, using furosemide and eplerenone in separate products.

Use in patients taking other medicinal products

In 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 Nonpres Duo

In case of overdose of Nonpres Duo or ingestion of any dose by a child, the patient should immediately consult a doctor or go to the emergency department of the nearest hospital, even if no symptoms are present. The patient should bring the packaging of the medicine with them, so that the doctor knows what medicine was 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, and discoloration), disorientation, lack of concentration, lack of emotions or interest in anything. There may also be kidney or blood disorders.

Missed dose of Nonpres Duo

If it is almost time for the next dose, the patient should skip the missed dose and take the next dose at the usual time.

In other cases, the patient should take the dose as soon as they remember, provided that there are more than 12 hours until the next dose. Then the patient should return to their usual dosing schedule.

The patient should not take a double dose to make up for the missed dose.

Stopping treatment with Nonpres Duo

It is important to take Nonpres Duo as prescribed, unless the doctor recommends stopping treatment.

In case of further doubts about the use of this medicine, the patient should consult a doctor or pharmacist.

4. Possible side effects

Like all medicines, Nonpres Duo can cause side effects, although not everybody gets them.

If any of the following symptoms occur, the patient should stop taking the medicine and consult a 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 accompanying fever and blisters on the skin/exfoliation of the skin and petechiae.
• acute pancreatitis, which is accompanied by severe abdominal pain radiating to the back.

Other possible side effects:

The patient should inform their 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,
• central dizziness,
• 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 number of a type of white blood cell),
• thrombocytopenia,
• hypothyroidism,
• low sodium levels in the blood,
• dehydration, dryness of the mucous membranes, 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 to standing,
• bloating,
• angioedema (symptoms 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 feeling of being unwell,
• high blood sugar levels,
• changes in some blood test results (e.g. transient increases in creatinine and urea),
• abnormal platelet count, 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 (reduced number of white blood cells), which may be accompanied by increased susceptibility to infections,
• increased number of certain white blood cells (eosinophils) in the blood,
• bone marrow suppression
• feeling of crawling on the skin, itching or tingling without cause,
• life-threatening loss of consciousness,
• hearing disorders and ringing in the ears, which are usually transient,
• blood vessel inflammation,
• acute kidney failure,
• kidney inflammation with blood in the urine, fever and pain in the flank area - in case of urinary tract obstruction, urine retention may occur,
• if the patient has a bladder disorder, prostate enlargement or urethral stricture, sudden urinary retention may occur,
• shock (significant drop in blood pressure, extreme pallor, anxiety, weak and rapid pulse, moist skin, disorders of consciousness) due to a 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 (reduced number of white blood cells) with accompanying high fever, severe throat pain and ulcers in the mouth,
• 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 (frequency cannot be estimated from the available data)

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

Reporting of side effects

If side effects occur, including any side effects not listed in this leaflet, the patient should tell their 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

Jerozolimskie Avenue 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, more information can be collected on the safety of the medicine.

5. How to store Nonpres Duo

The medicine should be stored out of 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 stated on the carton and blister after EXP:.

The expiry date refers to the last day of the month stated.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Nonpres Duo contains

The active substances of Nonpres Duo are:

• Nonpres Duo, 25 mg + 40 mg, tablets: each tablet contains 25 mg eplerenone and 40 mg furosemide
• Nonpres Duo, 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 Nonpres Duo looks like and contents of the pack

Nonpres Duo, 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 imprint "25/40" on one side. The tablet surface may have dark spots.

Nonpres Duo, 50 mg + 40 mg, tablets: white or almost white, biconvex, oval tablets, 19 mm x 9.6 mm in size, with the imprint "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 packaging contains 30 tablets.

Marketing authorization holder

Adamed Pharma S.A.

Pieńków, ul. M. Adamkiewicza 6A

05-152 Czosnów

Tel: +48 22 732 77 00

Manufacturer

Przedsiębiorstwo Farmaceutyczne LEK-AM Sp. z o.o.

ul. Ostrzykowizna 14A

05-170 Zakroczym

Date of last revision of the leaflet