RANEXA 500 mg PROLONGED-RELEASE TABLETS

2. What you need to know before you take RANEXA

Do not take Ranexa

• If you are allergic to ranolazine or any of the other ingredients of this medicine listed in section 6 of this leaflet.
• If you have severe kidney problems.
• If you have moderate or severe liver problems.
• If you are taking certain medicines for bacterial infections (clarithromycin, telithromycin), fungal infections (itraconazole, ketoconazole, voriconazole, posaconazole), HIV infection (protease inhibitors), depression (nefazodone) or heart rhythm disorders (e.g. quinidine, dofetilide or sotalol).

Warnings and precautions

Consult your doctor before taking Ranexa:

• If you have mild or moderate kidney problems.
• If you have mild liver problems.
• If you have ever had an electrocardiogram (ECG) abnormality
• If you are an elderly person.
• If you are a person of low weight (60 kg or less).

• If you have heart failure.

If you are in any of these situations, your doctor may decide to give you a lower dose of the medicine or take other precautions.

Using Ranexa with other medicines

Do not use any of the following medicines if you are taking Ranexa:

• Certain medicines for the treatment of bacterial infections (clarithromycin, telithromycin), fungal infections (itraconazole, ketoconazole, voriconazole, posaconazole), HIV infection (protease inhibitors), depression (nefazodone) or heart rhythm disorders (e.g. quinidine, dofetilide or sotalol).

Tell your doctor or pharmacist before taking Ranexa if you are using:

• Certain medicines for treating bacterial infections (erythromycin) or fungal infections (fluconazole), a medicine used to prevent organ rejection after a transplant (cyclosporin), or if you are taking heart tablets such as diltiazem or verapamil. These medicines may cause a greater number of side effects, such as dizziness, nausea or vomiting, which are possible side effects of treatment with Ranexa (see section 4). If you are taking these medicines, your doctor may decide to give you a lower dose of Ranexa.
• Medicines for the treatment of epilepsy or other neurological disorders (e.g. phenytoin, carbamazepine or phenobarbital); if you are taking rifampicin to treat an infection (e.g. tuberculosis); or if you are taking a herbal medicine called St. John's Wort, you should inform your doctor because these medicines may make Ranexa less effective.
• Heart medicines that contain digoxin or metoprolol, as your doctor may decide to change the dose while you are taking Ranexa.
• Certain medicines for treating allergies (e.g. terfenadine, astemizole, mizolastine), heart rhythm disorders (e.g. disopyramide, procainamide) and medicines for treating depression (e.g. imipramine, doxepin, amitriptyline), as these medicines may alter your electrocardiogram (ECG).
• Certain medicines for treating depression (bupropion), psychosis, HIV infection (efavirenz) or cancer (cyclophosphamide).
• Certain medicines for treating high cholesterol levels in the blood (e.g. simvastatin, lovastatin, atorvastatin). These medicines may cause muscle pain and damage. Your doctor may decide to change the dose of this medicine while you are taking Ranexa.
• Certain medicines used to prevent organ rejection after a transplant (e.g. tacrolimus, cyclosporin, sirolimus, everolimus), so your doctor may decide to change the dose of this medicine while you are taking Ranexa.

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

Using Ranexa with food and drinks

Ranexa can be taken with or without food. While you are being treated with Ranexa, you should not drink grapefruit juice.

Pregnancy

Do not take Ranexa if you are pregnant unless your doctor has told you that you can.

Breast-feeding

Do not take Ranexa if you are breast-feeding. Consult your doctor if you are breast-feeding.

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

Driving and using machines

No studies on the effects of Ranexa on the ability to drive and use machines have been performed. Ask your doctor if you can drive or use machines.

Ranexa may cause side effects such as dizziness (frequent), blurred vision (uncommon), confusion (uncommon), hallucinations (uncommon), double vision (uncommon), coordination problems (rare), which may affect your ability to drive or use machines. If you notice any of these symptoms, do not drive or use machines until they have passed.

Ranexa 750 mg prolonged-release tablets contain the azoic colorant E102 (tartrazine). This colorant may cause allergic reactions.

Ranexa 750 mg prolonged-release tablets contain lactose monohydrate. If your doctor has told you that you have an intolerance to some sugars, consult with them before taking this medicine.

This medicine contains less than 1 mmol of sodium (23 mg) per prolonged-release tablet, which is essentially "sodium-free".

3. How to take RANEXA

Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.

Swallow the tablets whole with water. Do not chew, suck or crush the tablets or divide them in half, as this may affect the way the medicine is released in your body.

The initial dose for adults is one 375 mg tablet twice a day. After a period of time between 2 and 4 weeks, your doctor may increase the dose to achieve the desired effect. The maximum dose of Ranexa is 750 mg twice a day.

It is important that you inform your doctor if you experience side effects such as dizziness, nausea or vomiting. Your doctor may reduce the dose or, if that is not enough, tell you to stop taking Ranexa.

Use in children and adolescents

Children and adolescents under 18 years should not take Ranexa.

If you take more RANEXA than you should

If you accidentally take more Ranexa tablets than you should, or take tablets of a higher dose than recommended by your doctor, it is important that you inform your doctor immediately. If you cannot contact your doctor, go to the nearest emergency department. Take the remaining tablets, along with the blister pack (aluminum sheet that contains the tablets) and the packaging, so that hospital staff can easily see what you have taken.

If you forget to take RANEXA

If you forget to take a dose, take it as soon as you remember, unless it is almost time for your next dose (less than 6 hours). Do not take a double dose to make up for forgotten doses.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

You should stop taking Ranexa and consult your doctor immediately if you experience the following symptoms of angioedema, which is a rare but serious disorder:

• swelling of the face, tongue or throat
• difficulty swallowing
• hives or difficulty breathing

Tell your doctor if you experience frequent side effects such as dizziness, nausea or vomiting. Your doctor may reduce the dose or tell you to stop taking Ranexa.

The following are other side effects that you may experience:

Frequent side effects (occurring in between 1 and 10 of every 100 users):

Constipation

Dizziness

Headache

Nausea, vomiting

Weakness (asthenia)

Uncommon side effects (occurring in between 1 and 10 of every 1000 users):

Altered sensitivity

Anxiety, difficulty sleeping, confusion, hallucinations

Blurred vision, vision disorders

Sensory disturbances (touch or taste), tremors, fatigue or weakness, somnolence or lethargy, weakness or fainting, dizziness when standing up

Dark urine, blood in the urine, difficulty urinating

Dehydration

Breathing difficulties, cough, nosebleeds

Double vision

Excessive sweating, itching

Feeling of swelling or bloating

Hot flashes, low blood pressure

Increased levels of a substance called creatinine, urea in the blood, platelet or white blood cell counts, altered electrocardiogram (ECG)

Swollen joints, pain in the limbs

Lack of appetite and/or weight loss

Muscle cramps, muscle weakness

Ringing in the ears and/or feeling of spinning

Stomach pain or discomfort, indigestion, dry mouth, or gas

Rare side effects (occurring in between 1 and 10 of every 10,000 users):

Urination problems

Altered liver laboratory values

Acute kidney failure

Disturbances in the sense of smell, numbness of the mouth or lips, hearing loss

Cold sweat, rash

Coordination problems

Low blood pressure when standing up

Decreased level of consciousness or loss of consciousness

Disorientation

Feeling of cold in hands and feet

Hives, allergic skin reactions

Impotence

Inability to walk due to balance problems

Pancreatitis or intestinal inflammation

Memory loss

Throat tightness

Low sodium levels in the blood (hyponatremia) that can cause fatigue and confusion, muscle contractions, cramps, and coma.

Side effects with unknown frequency (cannot be estimated from the available data): Myoclonus

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of RANEXA

Keep out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on each blister strip of tablets and on the outer packaging and carton after EXP.

This medicine does not require any special storage conditions.

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 Ranexa

The active substance of Ranexa is ranolazine. Each tablet contains 375 mg, 500 mg or 750 mg of ranolazine.

The other ingredients are: hypromellose, magnesium stearate, methacrylic acid-ethyl acrylate copolymer, microcrystalline cellulose, sodium hydroxide, titanium dioxide, and carnauba wax.

Depending on the tablet strength, the coating also contains:

375 mg tablet: macrogol, polysorbate 80, aluminum lake of indigo carmine (E132)

500 mg tablet: macrogol, talc, partially hydrolyzed polyvinyl alcohol, yellow iron oxide (E172), red iron oxide (E172).

750 mg tablet: glycerol triacetate, lactose monohydrate, aluminum lake of brilliant blue FCF (E133) and tartrazine (E102)

Appearance of Ranexa and pack contents

Ranexa prolonged-release tablets are oval in shape.

The 375 mg tablets are pale blue in color and have 375 engraved on one side.

The 500 mg tablets are light orange in color and have 500 engraved on one side.

The 750 mg tablets are pale green in color and have 750 engraved on one side.

Ranexa is supplied in boxes of 30, 60 or 100 tablets in blisters or 60 tablets in plastic bottles. Not all pack sizes may be marketed.

Marketing authorisation holder

Menarini International Operations Luxembourg S.A.

1, Avenue de la Gare, L-1611 Luxembourg, Luxembourg

Manufacturer

Menarini - Von Heyden GmbH

Leipziger Straße 7-13

01097 Dresden

Germany

or

Berlin Chemie AG

Glienicker Weg 125

12489 Berlin

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder.

Date of last revision of this leaflet {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.