EPLERENONE COMBIX 50 mg FILM-COATED TABLETS

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

Eplerenone Combix 50 mg film-coated tablets EFG

Read all of this leaflet carefully before you start 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, 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 signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

Contents of the pack

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

1. What Eplerenone Combix is and what it is used for

Eplerenone Combix belongs to a group of medicines known as selective aldosterone blockers. These blockers inhibit the action of aldosterone, a substance produced by the body that controls blood pressure and cardiac function. High levels of aldosterone can cause changes in your body that lead to heart failure.

Eplerenone Combix is used to treat heart failure to prevent worsening and reduce hospitalization if you have

1. A recent myocardial infarction, in combination with other medicines used to treat your heart failure or
2. Mild persistent symptoms, despite the treatment you have been receiving so far.

2. What you need to know before you take Eplerenone Combix

Do not take Eplerenone Combix

• If you are hypersensitive (allergic) to eplerenone or any of the other ingredients of Eplerenone Combix
• If you have high levels of potassium in your blood (hyperkalemia).
• If you are taking medicines that help eliminate excess fluid in the body (potassium-sparing diuretics) or "salt tablets" (potassium supplements).
• If you have severe kidney problems.
• If you have severe liver problems.
• If you are taking medicines used to treat fungal infections (ketoconazole or itraconazole).
• If you are taking antiviral medicines for the treatment of HIV (ritonavir or nelfinavir).
• If you are taking antibiotics used to treat bacterial infections (clarithromycin or telithromycin).
• If you are taking nefazodone for the treatment of depression.
• If you are taking medicines used to treat certain heart diseases or high blood pressure (such as ACE inhibitors and angiotensin receptor antagonists) at the same time.

Warnings and precautions

Consult your doctor or pharmacist before starting to take eplerenone:

• If you have kidney or liver disease (see "Do not take Eplerenone Combix")
• If you are taking lithium (used to treat manic-depressive disorders, also called bipolar disorder)
• If you are taking tacrolimus or cyclosporine (used to treat skin diseases such as psoriasis or eczema and to prevent organ transplant rejection)

Using Eplerenone Combix with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Eplerenone may affect other medicines. These, in turn, may affect the proper functioning of eplerenone.

Do not take Eplerenone Combix with the following medicines (see section "Do not use Eplerenone Combix"):

• Itraconazole or ketoconazole (used to treat fungal infections), ritonavir, nelfinavir (antiviral medicines for the treatment of AIDS), clarithromycin, telithromycin (used to treat bacterial infections) or nefazodone (used to treat depression), as these medicines reduce the metabolism of Eplerenone Combix, and thus prolong its effect in the body.

• Potassium-sparing diuretics (medicines that help eliminate excess fluid in the body) or potassium supplements (salt tablets), as these medicines increase the risk of high levels of potassium in the blood.

• ACE inhibitors and angiotensin receptor antagonists (used to treat high blood pressure, heart disease, or certain kidney diseases) at the same time, as these medicines may increase the risk of high levels of potassium in the blood.

Tell your doctor if you are taking any of the following medicines:

• Lithium (used to treat manic-depressive disorders, also called bipolar disorder). The use of lithium with diuretics and ACE inhibitors has been shown to cause high levels of lithium in the blood, which can cause the following adverse reactions: loss of appetite, vision changes, fatigue, muscle weakness, and muscle cramps.
• Cyclosporine or tacrolimus (used to treat skin diseases such as psoriasis or eczema and to prevent organ transplant rejection). These medicines can cause kidney problems and thus increase the risk of high levels of potassium in the blood.
• Non-steroidal anti-inflammatory medicines (NSAIDs - certain pain relievers such as ibuprofen, used to relieve pain, stiffness, and inflammation). These medicines can cause kidney problems and thus increase the risk of high levels of potassium in the blood.
• Trimethoprim (used to treat bacterial infections) may increase the risk of high levels of potassium in the blood.
• Alpha-1 blockers, such as prazosin or alfuzosin (used to treat high blood pressure and certain prostate diseases), may lead to a decrease in blood pressure and dizziness when standing up.
• Tricyclic antidepressants such as amitriptyline or amoxapine (for the treatment of depression), antipsychotics (also known as neuroleptics) such as chlorpromazine or haloperidol (for the treatment of psychiatric disorders), amifostine (used during cancer chemotherapy), and baclofen (used to treat muscle spasms). These medicines may lead to a decrease in blood pressure and dizziness when standing up.
• Corticosteroids, such as hydrocortisone or prednisone (used to treat inflammation and certain skin diseases), and tetracosactide (mainly used to diagnose and treat adrenal cortex diseases), may reduce the blood pressure-lowering effect of Eplerenone Combix.
• Digoxin (used to treat heart diseases). Blood levels of digoxin may increase when taken with Eplerenone Combix.
• Warfarin (an anticoagulant medicine): Caution is required when taking warfarin because high levels of warfarin in the blood may cause changes in the effect of Eplerenone Combix in the body.
• Erythromycin (used to treat bacterial infections), saquinavir (an antiviral medicine for the treatment of HIV infections), fluconazole (used to treat fungal infections), amiodarone, diltiazem, and verapamil (for the treatment of heart problems and high blood pressure) reduce the metabolism of Eplerenone Combix, thus prolonging its effect in the body.
• Hypericum perforatum or St. John's Wort (a medicinal plant), rifampicin (used to treat bacterial infections), carbamazepine, phenytoin, and phenobarbital (used, among others, to treat epilepsy) may increase the metabolism of Eplerenone Combix and thus reduce its effect.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Taking Eplerenone Combix with food and drinks

Eplerenone Combix can be taken with or without food.

Pregnancy and breast-feeding

The effect of Eplerenone Combix during pregnancy in humans has not been evaluated.

It is not known whether eplerenone is excreted in breast milk. Your doctor will decide with you whether to interrupt breast-feeding or to suspend treatment.

If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

After taking Eplerenone Combix, you may feel dizzy. If this happens, do not drive or use machines.

Eplerenone Combix contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Eplerenone Combix

Follow exactly the administration instructions of Eplerenone Combix indicated by your doctor. Consult your doctor or pharmacist again if you have any doubts.

The tablets of Eplerenone Combix can be taken with or without food. Swallow the tablets whole with plenty of water.

Eplerenone Combix is usually administered together with other medicines for heart failure, such as beta-blockers. The usual initial dose is one 25 mg tablet once a day, increasing later after about 4 weeks to 50 mg daily (one 50 mg tablet or two 25 mg tablets). The maximum dose regimen is 50 mg per day.

Potassium levels in the blood should be measured before starting treatment with Eplerenone Combix, during the first week, and after one month of starting treatment or after a change in dose.

Your doctor may adjust the dose based on your potassium levels in the blood.

If you have mild kidney problems, you should start treatment with one 25 mg tablet per day, and if you have moderate kidney problems, you should start treatment with one 25 mg tablet every other day. These doses may be adjusted, if your doctor indicates, and according to your blood potassium levels.

Eplerenone Combix is not recommended in patients with severe kidney disease.

No initial dose adjustment is necessary in patients with mild to moderate liver problems. If you have liver or kidney problems, it may be necessary to perform potassium blood tests more frequently (see also "Do not take Eplerenone Combix").

In elderly patients: no initial dose adjustment is required.

In children and adolescents: Eplerenone Combix is not recommended.

If you take more Eplerenone Combix than you should

If you take more Eplerenone Combix than you should, inform your doctor or pharmacist immediately. If you have taken too much medicine, the most likely symptoms will be low blood pressure (manifested as dizziness, blurred vision, weakness, sudden loss of consciousness) or hyperkalemia, high levels of potassium in the blood (manifested by muscle cramps, diarrhea, nausea, dizziness, or headache).

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, telephone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to take Eplerenone Combix

If it is almost time to take the next tablet, skip the missed dose and take the next tablet at the corresponding time.

Otherwise, take the tablet as soon as you remember, provided that there are more than 12 hours left until the time of taking the next tablet. Then, take your medicine as usual. Do not take a double dose to make up for forgotten doses.

If you stop taking Eplerenone Combix

It is important to keep taking Eplerenone Combixas your doctor indicated, unless your doctor tells you to stop treatment. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, Eplerenone Combix can cause side effects, although not everybody gets them.

If any of the following happen:

Seek medical attention immediately

• Swelling of the face, tongue, or throat
• Difficulty swallowing
• Blisters and difficulty breathing

These are symptoms of angioedema.

Other side effects reported include:

Common side effects(occur in 1 to 10 of every 100 patients):

• Myocardial infarction
• High levels of potassium in the blood (these symptoms include muscle cramps, diarrhea, nausea, dizziness, or headache)
• Dizziness
• Fainting
• Infection
• Cough
• Constipation
• Low blood pressure
• Diarrhea
• Nausea
• Abnormal kidney function
• Rash
• Itching
• Muscle spasms and pain
• Increased levels of urea in the blood

Uncommon side effects(occur in 1 to 10 of every 1,000 patients):

• Eosinophilia (increase in certain white blood cells)
• Dehydration
• High levels of cholesterol or triglycerides (fats) in the blood
• Low levels of sodium in the blood
• Insomnia (difficulty sleeping)
• Headache
• Heart problems such as irregular heartbeats, rapid heartbeats, and heart failure
• Inflammation of the gallbladder
• Low blood pressure that can cause dizziness when standing up
• Blood clots in the legs
• Sore throat
• Flatulence
• Vomiting
• Underactive thyroid
• Increased blood sugar levels
• Decreased sense of touch
• Increased sweating
• Back pain
• Weakness and general malaise
• Increased levels of creatinine in the blood, which may indicate kidney problems
• Kidney inflammation
• Enlargement of the breasts in men
• Changes in certain blood tests.

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet.

5. Storing Eplerenone Combix

Keep this medicine out of the sight and reach of children.

Do not use Eplerenone Combix after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

No special storage conditions are required.

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

Composition of Eplerenone Combix

• The active substance is eplerenone. Each tablet contains 50 mg of eplerenone.
• The other ingredients are lactose monohydrate, microcrystalline cellulose (type 101), sodium croscarmellose, hypromellose (type 2910), microcrystalline cellulose (type 102), sodium lauryl sulfate, talc, magnesium stearate (core of the tablet);

Opadry II. white OY-L-28900: lactose monohydrate, hypromellose (Type 2910), titanium dioxide (E171), macrogol 4000 (tablet coating).

Appearance of the product and contents of the pack

50 mg tablet: white or almost white, round, biconvex, film-coated tablets, marked "CG4" on one face of the tablet and smooth (unmarked) on the other face.

Eplerenone Combix 50 mg film-coated tablets EFG are available in blister packs of 30 and 50 tablets.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Laboratorios Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcon (Madrid)

Manufacturer:

Laboratorios LICONSA S.A.

Avenida Miralcampo 7, Polígono Industrial Miralcampo

19200 Azuqueca de Henares, Guadalajara

Spain

Date of last revision of this leaflet: August 2012

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS)http://www.aemps.gob.es/