PATIENT INFORMATION LEAFLET

Eplerenona Combix 50 mg Film-Coated Tablets

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet.

Eplerenona Combix belongs to a group of medications 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. Elevated levels of aldosterone can produce changes in the body that lead to heart failure.

Eplerenona 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 medications used to treat your heart failure or
2. Persistent mild symptoms, despite the treatment you have been receiving so far.

Do not take Eplerenona Combix

• If you are hypersensitive (allergic) to eplerenone or to any of the other components of Eplerenona Combix
• If you have high levels of potassium in your blood (hyperkalemia).
• If you are taking medications that help your body get rid of excess fluids (potassium-sparing diuretics) or "salt tablets" (potassium supplements).
• If you have severe kidney disease.
• If you have severe liver disease.
• If you are taking medications used to treat fungal infections (ketoconazole or itraconazole).
• If you are taking antiviral medications for HIV treatment (ritonavir or nelfinavir).
• If you are taking antibiotics used to treat bacterial infections (clarithromycin or telithromycin).
• If you are taking nefazodone to treat depression.
• If you are taking medications used to treat certain heart or high blood pressure conditions (such as ACE inhibitors and angiotensin receptor blockers) 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 Eplerenona Combix")
• If you are taking lithium (usually used to treat manic-depressive disorders, also known as bipolar disorder)
• If you are taking tacrolimus or cyclosporine (used to treat skin conditions such as psoriasis or eczema and to prevent organ transplant rejection)

Use of Eplerenona Combix with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

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

Do not take Eplerenona Combix with the following medications (see "Do not use Eplerenona Combix"):

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

• Potassium-sparing diuretics or potassium supplements (medications that help your body get rid of excess fluids), as these medications increase the risk of high potassium levels in the blood.

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

Inform your doctor if you are taking any of the following medications:

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

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.

Taking Eplerenona Combix with food and drinks

Eplerenona Combix can be taken with or without food.

Pregnancy and breastfeeding

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

It is unknown whether eplerenone is excreted in breast milk. Your doctor will decide with you whether to stop breastfeeding or suspend treatment.

If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

After taking Eplerenona Combix, you may feel dizzy. If this happens, do not drive or operate machinery.

Eplerenona Combix contains lactose

If your doctor has told you that you have a certain sugar intolerance, consult with them before taking this medication.

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

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

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

Blood potassium levels should be measured before starting treatment with Eplerenona Combix, during the first week, and one month after starting treatment or after a change in dosage.

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

If you have mild renal insufficiency, you should start treatment with one 25 mg tablet per day, and if you have moderate renal insufficiency, 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.

Eplerenona Combix is not recommended for patients with severe renal disease.

No initial dose adjustment is required for patients with mild to moderate liver insufficiency. If you have liver or kidney problems, you may need to have your blood potassium levels checked more frequently (see also “Do not take Eplerenona Combix”).

In the elderly: no initial dose adjustment is required.

In children and adolescents: Eplerenona Combix is not recommended.

If you take more Eplerenona Combix than you should

If you take more Eplerenona Combix than you should, inform your doctor or pharmacist immediately. If you have taken too much medication, the most likely symptoms will be low blood pressure (manifested as dizziness, blurred vision, weakness, acute 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, phone 91 562 04 20, indicating the medication and the amount ingested.

If you forget to take Eplerenona Combix

If it is almost time to take the next tablet, skip the dose you forgot and take the next tablet at the usual time.

Otherwise, take the tablet as soon as you remember, as long as more than 12 hours have passed since the usual time to take the next tablet. Then, resume your medication as usual. Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Eplerenona Combix

It is essential to continue taking Eplerenona Combix as instructed, unless your doctor tells you to stop treatment. If you have any other doubts about the use of this medication, ask your doctor or pharmacist.

Like all medications, Eplerenona Combix may have side effects, although not everyone will experience them.

If any of the following occur:

Seek immediate medical attention

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

These are symptoms of angioneurotic edema.

Other side effects reported include:

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

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

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

• Eosinophilia (increased levels of certain white blood cells)
• Dehydration
• Elevated levels of cholesterol or triglycerides (fats) in the blood
• Low sodium levels in the blood
• Insomnia (difficulty sleeping)
• Headache
• Cardiac discomfort such as irregular heartbeats, rapid heartbeats, or heart failure
• Inflammation of the gallbladder
• Low blood pressure that may cause dizziness when standing up
• Thrombosis (blood clot) in the legs
• Sore throat
• Flatulence
• Vomiting
• Underactive thyroid
• Increased blood glucose
• Decreased sense of touch
• Increased sweating
• Back pain
• Weakness and general discomfort
• Elevated levels of creatinine in the blood that may indicate kidney problems
• Renal inflammation
• Enlargement of the breasts in men
• Changesin certain blood tests.

If you experience side effects, consult your doctor or pharmacist, even if they are not listed in this prospectus.

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

Do not use Eplerenona Combix after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

No special storage conditions are required.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medications at the SIGRE collection point of the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and unused medications. By doing so, you will help protect the environment.

Composition of Eplerenona Combix

• The active ingredient is eplerenone. Each tablet contains 50 mg of eplerenone.
• The other components 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 packaging

50 mg tablet: white to off-white coated tablets, round, biconvex, marked “CG4” on one face of the tablet and smooth (unmarked) on the other face.

Eplerenona Combix 50 mg coated tablets are available in blister packs of 30 and 50 tablets.

Marketing authorization holder and responsible manufacturer

Marketing authorization holder:

Combix, S.L.U.

C/ Badajoz 2, Edificio 2

28223 Pozuelo de Alarcon (Madrid)

Responsible manufacturer:

Laboratorios LICONSA S.A.

Avenida Miralcampo 7, Polígono Industrial Miralcampo

19200 Azuqueca de Henares, Guadalajara

Spain

Last review date of this leaflet: August 2012

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