Nonpres duo

Package leaflet: Information for the patient

Nonpres Duo, 25 mg + 40 mg, tablets
Nonpres Duo, 50 mg + 40 mg, tablets
Eplerenonum + Furosemidum

Read the entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this 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 a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

1. What Nonpres Duo is and what it is 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 pack and other information

1. What Nonpres Duo is and what it is 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 regulates blood pressure and heart function. Increased levels of aldosterone may cause changes in the body leading to heart failure.
• Furosemide belongs to a group of medicines called diuretics, which increase the amount of urine produced by the kidneys, helping to remove excess fluid from the body. Diuretics are also known as water tablets.

Nonpres Duo is used as replacement therapy in adult patients who are already taking furosemide and eplerenone at the same doses as contained in the fixed-dose combination product Nonpres Duo, to reduce the risk of cardiovascular mortality and morbidity in patients with stable left ventricular systolic dysfunction, left ventricular ejection fraction ≤ 40%, and clinical signs of heart failure (e.g. oedema) following a recent acute myocardial infarction.

2. Important information before using Nonpres Duo

When not to use Nonpres Duo:

• if the patient is allergic to eplerenone, furosemide, or any of the other components of this medicine (listed in section 6),
• if the patient is allergic to amiloride, sulfonamides, or sulfonamide derivatives such as sulfadiazine or cotrimoxazole,
• if the patient has high potassium levels in the blood (hyperkalemia),
• if the patient has severe kidney disease,
• if the patient has severe liver disease,
• if the patient is taking medications that remove excess fluid from the body (potassium-sparing diuretics),
• if the patient is taking antifungal medicines (ketoconazole or itraconazole),
• if the patient is taking antiviral medicines for HIV (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 angiotensin-converting enzyme inhibitors (ACE inhibitors) in combination with angiotensin II receptor antagonists (AIIRAs)),
• if the patient has reduced intravascular volume or is dehydrated (with or without low blood pressure),
• if the patient is not passing urine,
• if the patient has kidney failure – in some types of kidney failure this medicine may still be taken – a doctor will decide,
• if the patient has severe liver disease with brain dysfunction (hepatic encephalopathy),
• if the patient has pre-comatose or comatose states related to liver cirrhosis,
• if the patient has electrolyte deficiency (e.g. low potassium or sodium levels in the blood, detected in blood tests),
• if the patient has Addison's disease, which may cause fatigue and weakness,
• if the patient is taking other medicines that affect potassium levels in the blood (see "Nonpres Duo and other medicines"),
• glycoside intoxication (e.g. digoxin toxicity),
• porphyria,
• if the patient is breastfeeding (see "Pregnancy, breastfeeding and fertility").

Warnings and precautions
Before starting treatment with Nonpres Duo, discuss this with your doctor, pharmacist, or nurse:

• if the patient has kidney or liver disease (see also section "When not to use 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 cyclosporine (used to treat skin conditions such as psoriasis or eczema, and to prevent rejection of transplanted organs),
• if the patient is 65 years of age or older,
• if the patient has difficulty passing urine,
• if the patient has diabetes (high blood sugar levels),
• if the patient is pregnant,
• if the patient has gout, or impaired liver or kidney function,
• if the patient has low blood pressure, regular monitoring of electrolyte levels is necessary, with appropriate dose adjustments, and especially if the patient experiences dizziness upon standing,
• if the patient has low blood protein levels (hypoproteinemia),
• if the patient is taking risperidone,
• if the patient has prostate gland disorders,
• if the patient experiences dizziness or dehydration – these symptoms may occur if the patient has lost significant fluids due to vomiting, diarrhea, or excessive urination, or if the patient has difficulty drinking or eating,
• if the patient will be using non-steroidal anti-inflammatory drugs (NSAIDs) concomitantly,
• if the patient will undergo glucose tolerance testing,
• if the patient is taking other diuretic medicines,
• if the patient has systemic lupus erythematosus (an autoimmune disease affecting the skin, bones, joints, and internal organs),
• if the patient is elderly, taking other medicines that may lower blood pressure, or has other conditions that may increase the risk of low blood pressure.

If in doubt whether any of the above conditions apply to the patient, consult a doctor or pharmacist before using Nonpres Duo.
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
Inform your doctor or pharmacist about all medicines currently taken, recently taken, or planned for use.
Nonpres Duo may affect the action of the medicines listed below, and these medicines may also affect the action of Nonpres Duo:

• Itraconazole or ketoconazole (used to treat fungal infections), ritonavir, nelfinavir (antiviral medicines for HIV), 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 in the body.
• Potassium-sparing diuretics (medicines helping remove excess fluid from the body) and potassium supplements – these increase the risk of high potassium levels in the blood.
• Angiotensin-converting enzyme (ACE) inhibitors, such as ramipril, enalapril, perindopril, in combination with angiotensin II receptor antagonists (AIIRAs), used to treat high blood pressure, heart conditions, and certain 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 (used to treat high blood pressure and heart conditions) has increased lithium blood levels, potentially causing adverse effects such as loss of appetite, vision disturbances, fatigue, muscle weakness, and muscle tremors.
• Cyclosporine or tacrolimus (used to treat skin conditions such as psoriasis or eczema and to prevent rejection of transplanted organs) – these medicines may impair kidney function 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 may impair kidney function 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.
• Alpha1-adrenergic blockers such as prazosin or alfuzosin (used to treat high blood pressure and certain prostate conditions) – may cause a drop in blood pressure and dizziness upon standing.
• Tricyclic antidepressants such as amitriptyline or amoxapine (used to treat depression), antipsychotic medicines (also called neuroleptics) such as chlorpromazine or haloperidol (used to treat psychiatric disorders), amifostine (used in cancer chemotherapy), and baclofen (used for increased muscle tone) – these may cause a drop in blood pressure and dizziness upon standing.
• Glucocorticosteroids such as hydrocortisone or prednisone (used to treat inflammatory conditions and certain skin diseases) and tetracosactide (mainly used in diagnosing and treating 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 blood levels. The doctor may adjust the dose.
• Warfarin (an anticoagulant medicine) – caution is required when using warfarin, as increased warfarin blood levels may interfere with the effect of Nonpres Duo on the body.
• Erythromycin (used to treat bacterial infections), saquinavir (an antiviral medicine used to treat HIV infection), fluconazole (used to treat fungal infections), amiodarone, diltiazem, and verapamil (used to treat heart conditions and high blood pressure) – these slow down the metabolism of Nonpres Duo, thereby prolonging its effect.
• St. John's wort (herbal medicine), rifampicin (used to treat bacterial infections), carbamazepine, phenytoin, and phenobarbital (used, among others, 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 advise discontinuation.
• Medicines used for high blood pressure or heart disorders. The doctor may adjust the dose.
• Other medicines used to treat high blood pressure and other medicines used to remove excess water from the body, known as diuretics, 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.
• Sleeping and sedative medicines, e.g. chloral hydrate.
• Medicines used in general anesthesia to relax muscles during surgery.

If undergoing anesthesia, ensure that the doctor or nurse knows that the patient is taking furosemide.

• Antidiabetic medicines – their effect may be weakened during furosemide use.
• Theophylline – used for wheezing or breathing difficulties.
• Phenytoin – used to treat epilepsy – may weaken the effect of furosemide.
• Medicines used to treat psychiatric disorders called psychoses, such as risperidone, amisulpride, sertindole, pimozide, and chlorpromazine. Pimozide should not be used 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 transplanted organs.
• Moxisylyte – used to treat Raynaud's syndrome.
• Medicines used to treat angina pectoris in inhaled form or as sublingual tablets, such as glyceryl trinitrate or isosorbide dinitrate.
• Methotrexate – used for skin, joint, or intestinal diseases.
• Carbenoxolone and sucralfate – used to treat esophageal and gastric ulcers.
• Reboxetine, amitriptyline, and phenelzine – used for depression.
• Amphotericin – used for fungal infections, especially with long-term administration.
• Corticosteroids – used for 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 erectile dysfunction in men.
• Estrogens and drospirenone – used as contraceptives or in hormone replacement therapy (HRT).
• Liquorice – often found in cough medicines, especially when taken in large doses.
• Probenecid (used with other medicines in 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 constipation over a prolonged period, such as bisacodyl or senna.
• Anti-asthmatic medicines administered in high doses, such as salbutamol, terbutaline sulfate, salmeterol, formoterol, or bambuterol.
• Medicines used for nasal congestion, such as ephedrine and xylometazoline.
• Potassium salts used in cases of low potassium levels in the blood.
• Medicines used to treat Parkinson's disease, such as levodopa.
• Other diuretics (diuretics), such as bendroflumethiazide. The doctor may adjust the dose.
• High doses of furosemide administered with levothyroxine may initially lead to a transient increase in free thyroid hormones, followed by an overall decrease in total thyroid hormone levels.

Nonpres Duo with food and drink
Nonpres Duo should preferably be taken on an empty stomach, with the tablet taken with a large amount of liquid. Alcohol should be avoided during treatment with Nonpres Duo, as it may lower blood pressure.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult a doctor or pharmacist before using this medicine. The effect of Nonpres Duo during pregnancy has not been evaluated in humans.
One of the active substances in this medicine, furosemide, may pass into breast milk in small amounts. Therefore, breastfeeding should not be continued during treatment with this medicine.
Consult a doctor whether to stop breastfeeding or discontinue the medicine.
Driving and operating machinery
After using Nonpres Duo, symptoms such as reduced attention, dizziness, and blurred vision may occur. In such cases, the patient should not drive or operate machinery.
Nonpres Duo contains lactose monohydrate and sodium
Nonpres Duo contains lactose monohydrate (a type of sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.
Nonpres Duo contains less than 1 mmol (23 mg) of sodium per tablet, meaning the medicine is considered "sodium-free".

3. How to use Nonpres Duo

This medicine should always be taken exactly as directed by your doctor or pharmacist. If in doubt,
you should consult your doctor or pharmacist.
Nonpres Duo tablets are best taken on an empty stomach, with a large amount of fluid.
Nonpres Duo is a fixed-combination product that should only be used in patients whose maintenance
doses have already been established with single-component medicines (furosemide and eplerenone used
as separate products), and who do not require dose adjustments. If the fixed-combination product causes
adverse effects indicating the need for dose re-adjustment, the product should be discontinued and the
doctor should determine an appropriate dose for the patient using furosemide and eplerenone as
separate products.
To allow individual dose adjustment, formulations containing 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, your doctor may recommend monitoring blood potassium levels, and if dose
adjustment becomes necessary depending on blood potassium levels, your doctor may adjust the dose
by using furosemide and eplerenone as separate products.
If the patient has mild or moderate kidney disease, the doctor may recommend dose adjustment based
on blood potassium levels, using furosemide and eplerenone as separate products.
Nonpres Duo must not be used in patients with severe kidney disease.
In case of liver or kidney disease, more frequent monitoring of blood potassium levels may be required
(see also "When not to use Nonpres Duo").

Use in children and adolescents:
Use of Nonpres Duo is not recommended.

Use in elderly patients:
The doctor may recommend periodic monitoring of blood potassium levels, and if dose adjustment becomes
necessary depending on blood potassium levels, the doctor may adjust the dose using furosemide and
eplerenone as separate products.

Use in patients with impaired kidney function
In patients with mild or moderate renal impairment, the doctor may recommend periodic monitoring of
blood potassium levels, and if dose adjustment becomes necessary depending on blood potassium levels,
the doctor may adjust the dose using furosemide and eplerenone as separate products.

Use in patients taking other medicinal products
When used concomitantly with weak or moderate CYP3A4 inhibitors, such as amiodarone, diltiazem, or
verapamil, the maintenance dose should not exceed 25 mg + 40 mg once daily.

Taking more Nonpres Duo than recommended
If you take more Nonpres Duo than recommended, or if a child takes any amount of this medicine, you
should contact your doctor or go immediately to the emergency department of the nearest hospital, even
if no symptoms are present. You should bring the medicine packaging with you so the doctor knows
which medicine has been taken. The most likely symptoms of overdose include: low blood pressure
(causing dizziness, blurred vision, weakness, sudden loss of consciousness), hyperkalaemia (high
potassium levels in the blood), causing muscle cramps, diarrhoea, nausea, dizziness or headache,
irregular heartbeat, blood clots (causing pain and swelling in the affected body part), disorientation,
inability to concentrate, lack of emotion or interest in anything. Kidney or blood disorders may also
occur.

If you miss a dose of Nonpres Duo
If it is almost time for your next dose, skip the missed dose and take the next tablet at the usual time.
Otherwise, take the tablet as soon as you remember, provided that more than 12 hours remain before
the next scheduled dose. Then return to your regular dosing schedule.
Do not take a double dose to make up for a missed dose.

Stopping Nonpres Duo
It is important to take Nonpres Duo exactly as prescribed, unless your doctor advises you to stop
treatment.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will get them.
If any of the following symptoms occur, stop taking the medicine and consult a doctor immediately:

• swelling of the face, tongue or throat, difficulty swallowing, urticaria and breathing difficulties (these are symptoms of angioedema, an adverse effect that is not very common),
• allergic reactions such as itching, skin rash with intense itching and urticaria, fever, photosensitivity, severe allergic reaction with (high) fever, red skin spots, joint pain and (or) eye inflammation, severe acute allergic reaction accompanied by fever, skin blisters/skin peeling, and petechiae due to bleeding into the skin,
• acute pancreatitis, accompanied by severe upper abdominal pain radiating to the back.

Other possible adverse effects:
Inform your doctor if any of the following symptoms worsen or persist for longer than a few days.
Common (may occur in less than 1 in 10 people)

• increased potassium levels in the blood (symptoms include: muscle cramps, diarrhoea, nausea, dizziness or headache),
• increased cholesterol levels in the blood,
• insomnia (difficulty falling asleep),
• fainting,
• central dizziness,
• headache,
• heart disorders, e.g. heart rhythm disturbances and heart failure,
• low blood pressure,
• cough,
• diarrhoea,
• nausea,
• constipation,
• vomiting,
• rash,
• itching,
• muscle cramps,
• back pain,
• kidney function disorders,
• fatigue,
• increased blood urea levels,
• increased blood creatinine levels, which may indicate impaired kidney function.

Uncommon (may occur in less than 1 in 100 people)

• kidney inflammation,
• infection,
• sore throat,
• eosinophilia (increased number of one type of white blood cells),
• thrombocytopenia,
• hypothyroidism,
• low sodium levels in the blood,
• dehydration, dryness of the oral mucosa, thirst,
• increased levels of triglycerides (fats) in the blood,
• reduced sense of touch,
• visual disturbances,
• increased heart rate,
• deep vein thrombosis (blood clots in the lower limbs),
• reduced blood pressure, possibly causing dizziness upon changing to an upright position,
• bloating,
• angioedema (symptoms may include swelling of the face, tongue or throat, difficulty swallowing, urticaria and breathing difficulties),
• increased sweating,
• musculoskeletal pain,
• cholecystitis,
• gynaecomastia (breast enlargement in males),
• malaise,
• increased blood glucose levels,
• changes in certain blood test results (e.g. transient increase in creatinine and urea levels),
• abnormal platelet count associated with bruising and tendency to bleed,
• photosensitivity,
• involuntary leakage of urine,
• in elderly people – reduced intravascular volume, fluid deficiency and blood concentration, which may lead to thrombosis,
• deafness (sometimes irreversible).

Rare (may occur in less than 1 in 1000 people)

• abnormal blood cell count (leucopenia), associated with increased susceptibility to infections,
• increased number of certain white blood cells (eosinophils) in the blood,
• bone marrow suppression,
• sensation of skin crawling, itching or tingling without cause,
• life-threatening loss of consciousness,
• hearing disorders and tinnitus, usually transient,
• vasculitis,
• acute kidney failure,
• kidney inflammation with blood in urine, fever and back flank pain – in case of urinary tract obstruction, urine retention may occur,
• if the patient has bladder disorders, enlarged prostate or ureteral narrowing, acute urinary retention may occur,
• shock (severe drop in blood pressure, extreme pallor, restlessness, rapid weak pulse, cold clammy skin, altered consciousness) due to sudden, marked vasodilation caused by hypersensitivity to certain substances,
• fever.

Very rare (may occur in less than 1 in 10,000 people)

• anaemia (a condition characterized by deficiency of red blood cells),
• very severe blood disorders (leucopenia) with sudden high fever, severe sore throat and oral ulcers,
• some liver function disorders,
• increased activity of certain liver enzymes. During treatment with furosemide, levels of certain blood lipids (cholesterol and triglycerides) may increase, but usually return to normal within 6 months.

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

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

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions 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
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps provide more information on the safety of the medicine.

5. How to store Nonpres Duo

Keep the medicine out of the sight and reach of children.
Store below 30°C. Keep 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 stated month.
Medicines should 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 Nonpres Duo contains
The active substances in this medicine 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, sodium croscarmellose, 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, capsule-shaped tablets, 20 mm x 8 mm in size, with the imprint "25/40" on one side. Dark specks may be present on the tablet surface.

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. Dark specks may be present on the tablet surface.

The tablets are packed in PVC/PVDC/Aluminium blisters and placed in a cardboard box. The pack contains 30 tablets.

Marketing Authorisation 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