Enplerasa

Patient Information Leaflet

Enplerasa, 25 mg, film-coated tablets
Enplerasa, 50 mg, film-coated tablets
Eplerenone
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please 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 as yours.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet Contents:

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

1. What Enplerasa is and what it is used for

Enplerasa belongs to a group of medicines called selective aldosterone antagonists. These medicines inhibit the action of aldosterone, a substance produced by the body that regulates blood pressure and heart function. High levels of aldosterone may cause changes in the body that lead to heart failure.

Enplerasa is used in the treatment of heart failure to prevent disease progression and reduce the number of hospitalizations in patients who:

1. Have recently had a heart attack – in combination with other medicines used to treat heart failure, or
2. Have persistent, mild symptoms despite ongoing treatment.

2. Important information before using Enplerasa

When not to use Enplerasa

• if the patient is allergic to eplerenone or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has high blood potassium levels (hyperkalaemia);
• if the patient is taking medicines that remove excess fluid from the body (potassium-sparing diuretics);
• if the patient has severe kidney disease;
• if the patient has severe liver disease;
• if the patient is taking antifungal medicines (ketoconazole or itraconazole);
• if the patient is taking antiviral medicines used to treat HIV infection (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 simultaneously medicines used to treat certain heart conditions or high blood pressure (so-called angiotensin-converting enzyme inhibitors - ACE inhibitors and angiotensin receptor blockers (ARBs)).

Warnings and precautions
Before taking Enplerasa, discuss this with your doctor or pharmacist:

• if the patient has kidney or liver disease (see also "When not to use Enplerasa");
• if the patient is taking lithium (usually used in the treatment of bipolar affective disorder);
• if the patient is taking tacrolimus or cyclosporine (medicines used to treat skin conditions such as psoriasis or eczema, and to prevent rejection of transplanted organs).

Children and adolescents
The safety and efficacy of eplerenone in children and adolescents have not been established.

Enplerasa and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.

• Itraconazole or ketoconazole (medicines used to treat fungal infections), ritonavir, nelfinavir (antiviral medicines used to treat HIV infection), clarithromycin, telithromycin (medicines used to treat bacterial infections), or nefazodone (a medicine used to treat depression) may reduce the breakdown of Enplerasa, thereby prolonging its effect in the body;

• Potassium-sparing diuretics (medicines that help remove excess fluid from the body) and potassium supplements (salt substitutes), as these may increase the risk of high blood potassium levels;

• Concomitant use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) (used to treat high blood pressure, heart conditions, or certain kidney diseases), as these may increase blood potassium levels;

• Lithium (usually used in the treatment of bipolar affective disorder). It has been shown that taking lithium together with diuretics and ACE inhibitors (used to treat high blood pressure and heart conditions) increases blood lithium levels, which may cause adverse effects such as loss of appetite, vision disturbances, feeling of fatigue, muscle weakness, and muscle tremors;

• Cyclosporine or tacrolimus (medicines used to treat skin conditions such as psoriasis or eczema and to prevent rejection of transplanted organs). These medicines may cause kidney function disorders and thereby increase the risk of high blood potassium levels;

• Non-steroidal anti-inflammatory drugs (NSAIDs, certain painkillers such as ibuprofen, used to relieve pain, stiffness, and inflammation). These medicines may cause kidney function disorders and thereby increase the risk of high blood potassium levels;

• Trimethoprim (a medicine used to treat bacterial infections) may increase the risk of high blood potassium levels;

• Alpha-1-adrenergic blockers, such as prazosin or alfuzosin (used to treat high blood pressure and certain prostate gland conditions), may cause low blood pressure and dizziness upon standing;

• Tricyclic antidepressants, such as amitriptyline or amoxapine (used to treat depression), antipsychotics (also known as neuroleptics), such as chlorpromazine or haloperidol (medicines used to treat mental disorders),
  amifostine (a medicine used in cancer chemotherapy), and baclofen (a medicine used
  to treat increased muscle tension). These medicines may cause low blood pressure and dizziness upon standing;

• Glucocorticoids, such as hydrocortisone or prednisone (used to treat inflammatory conditions and certain skin diseases) and tetracosactide (a medicine mainly used in the diagnosis and treatment of adrenal cortex disorders), may reduce blood pressure and thereby weaken the effect of Enplerasa;

• Digoxin (a medicine used to treat heart conditions). Concomitant use with Enplerasa may increase digoxin blood levels;

• Warfarin (an anticoagulant medicine): caution is advised when using warfarin, as high blood levels may alter the effect of Enplerasa on the body;

• Erythromycin (a medicine used to treat bacterial infections), saquinavir (an antiviral medicine used to treat HIV infections), fluconazole (a medicine used to treat fungal infections), amiodarone, diltiazem, and verapamil (medicines used to treat heart conditions and high blood pressure) may reduce the breakdown of Enplerasa, thereby prolonging its effect in the body;

• St. John's wort (a herbal remedy), rifampicin (a medicine used to treat bacterial infections), carbamazepine, phenytoin, and phenobarbital (medicines used, among others, in the treatment of epilepsy) may increase the breakdown of Enplerasa, thereby weakening its effect.

Enplerasa with food and drink
Enplerasa can be taken independently of meals.

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
The effect of Enplerasa in pregnant women has not been evaluated.
It is not known whether eplerenone passes into human milk. Consult your doctor whether to discontinue breastfeeding or discontinue the use of the medicine.

Driving and operating machinery
Dizziness may occur while taking Enplerasa. Do not drive or operate machinery if this occurs.

Enplerasa contains lactose and sodium
If the patient has previously been diagnosed with intolerance to certain sugars, consult a doctor before using this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".

3. How to use Enplerasa

This medicine should always be used as directed by a doctor or pharmacist. If in doubt,
consult a doctor or pharmacist.
Enplerasa may be taken with or without food. Tablets should be swallowed whole with a large amount of water.
Enplerasa is usually taken together with other medicines used to treat heart failure, such as beta-blockers. The usual starting dose is one 25 mg tablet once daily, increased after approximately 4 weeks to 50 mg once daily (as one 50 mg tablet or two 25 mg tablets). The maximum dose is 50 mg per day.
Your doctor will recommend checking blood potassium levels before starting Enplerasa, during the first week of treatment, and one month after starting treatment or after any dose adjustment.
Depending on blood potassium levels, your doctor may adjust the dose accordingly.
Patients with mild kidney disease should start treatment with one 25 mg tablet once daily.
If kidney disease is moderate, the initial dose is one 25 mg tablet every other day. Your doctor may adjust these doses depending on the patient's blood potassium levels.
Use of Enplerasa is not recommended in patients with severe kidney disease.
No initial dose adjustment is necessary in patients with mild or moderate liver disease. In patients with impaired liver or kidney function, more frequent monitoring of blood potassium levels may be required (see also “When not to use Enplerasa”).
Elderly patients: no initial dose adjustment is necessary.
Children and adolescents: use of Enplerasa is not recommended.
Taking more Enplerasa than recommended
If you take more Enplerasa than recommended, contact your doctor or pharmacist immediately. The most likely symptoms of overdose are low blood pressure (felt as dizziness, blurred vision, weakness, sudden loss of consciousness) or hyperkalaemia (high blood potassium levels), which may cause muscle cramps, diarrhoea, nausea, dizziness, or headache.
If you forget to take Enplerasa
If it is almost time for the next dose, skip the missed tablet and take the next dose at the usual time.
Otherwise, take the tablet as soon as remembered, provided that more than 12 hours remain before the next scheduled dose. Then return to the regular dosing schedule.
Do not take a double dose to make up for a missed dose.
Stopping Enplerasa
It is important to take Enplerasa exactly as prescribed, unless your doctor advises stopping treatment.
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
If the patient experiences any of the following symptoms, seek immediate medical help:

• swelling of the face, tongue or throat;
• difficulty swallowing;
• hives and breathing difficulties. These are symptoms of angioedema, an uncommon adverse reaction (occurring in no more than 1 in 100 people).

Other reported adverse reactions include:
Common adverse reactions (occur in no more than 1 in 10 patients):

• increased potassium levels in the blood (symptoms include muscle cramps, diarrhoea, nausea, dizziness or headache),
• fainting,
• dizziness,
• increased blood cholesterol levels,
• insomnia (difficulty falling asleep),
• headache,
• heart disorders, e.g. irregular heartbeat and heart failure,
• cough,
• constipation,
• low blood pressure,
• diarrhoea,
• nausea,
• vomiting,
• kidney dysfunction,
• rash,
• itching,
• back pain,
• feeling of weakness,
• muscle cramps,
• increased blood urea levels,
• increased blood creatinine levels, which may indicate kidney disease.

Uncommon adverse reactions (occur in no more than 1 in 100 patients):

• infection,
• eosinophilia (increased number of white blood cells),
• decreased sodium levels in the blood,
• dehydration,
• increased blood triglyceride (fat) levels,
• rapid heartbeat,
• gallbladder inflammation,
• decreased blood pressure which may cause dizziness when changing position to standing,
• deep vein thrombosis (blood clots in the lower limbs),
• sore throat,
• bloating,
• hypothyroidism,
• increased blood glucose levels,
• reduced sensitivity to touch,
• increased sweating,
• musculoskeletal pain,
• general malaise,
• kidney inflammation,
• enlargement of breast glands in men,
• changes in blood test results.

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

5. How to store Enplerasa

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton following EXP.
The expiry date refers to the last day of the stated month.
No special storage conditions apply for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Enplerasa contains

• The active substance is eplerenone. Each tablet contains 25 mg or 50 mg of eplerenone.
• The other ingredients are:
  Tablet core: lactose monohydrate, microcrystalline cellulose, sodium croscarmellose, hypromellose, magnesium stearate, sodium lauryl sulfate.
  Coating: hypromellose, titanium dioxide (E 171), macrogol 400, polysorbate 80, iron oxide yellow (E 172).
  See section 2 "Enplerasa contains lactose and sodium".

What Enplerasa looks like and contents of the pack
Enplerasa 25 mg: Yellow, round, biconvex film-coated tablets marked with "25" on one side.
Dimensions: 6 mm in diameter.
Enplerasa 50 mg: Yellow, round, biconvex film-coated tablets marked with "50" on one side.
Dimensions: 7.5 mm in diameter.
Enplerasa is available in cardboard boxes containing:

• 10, 20, 28, 30, 50, 90 and 100 film-coated tablets in blister packs.
• 10 x 1, 20 x 1, 28 x 1, 30 x 1, 50 x 1, 90 x 1 and 100 x 1 film-coated tablets in single-dose perforated blister packs.

Not all pack sizes may be marketed.

Marketing Authorisation Holder
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

For more detailed information about the medicinal product, please contact the local representative of the marketing authorisation holder:
KRKA-POLSKA Sp. z o.o.
Równoległa Street 5
02-235 Warsaw
Tel. 22 57 37 500