Ranexa 500 mg prolonged-release tablets

 

What is it and how is it used?

Ranexa is a medicine used in combination with other medicines to treat angina pectoris, which is a chest pain or discomfort that you feel anywhere along the upper part of your body between your neck and upper abdomen, often brought on by exercise or too much activity.

What do you have to consider before using it?

Do not take Ranexa

  • if you are allergic (hypersensitive) to ranolazine or any of the other ingredients of Ranexa listed in section 6 of this leaflet.
  • if you have severe kidney problems.
  • if you have moderate or severe liver problems.
  • if you are using certain medicines to treat bacterial infections (clarithromycin, telithromycin), fungal infections (itraconazole, ketoconazole, voriconazol, posaconazol), HIV infection (protease inhibitors), depression (nefazodone) or heart rhythm disorders (e.g. quinidine, dofetilide, or sotalol).

Take special care with Ranexa
Speak to 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 abnormal electrocardiogram (ECG).
  • if you are elderly.
  • if you have low weight (60 kg or less).
  • if you have heart failure.

Your doctor may decide to give you a lower dose or take other precautions if any of these apply to you.

Using other medicines
Do not use the following medicines if you take Ranexa:

  • certain medicines to treat 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 you take Ranexa if you use:

  • certain medicines to treat a bacterial infection (erythromycin), or a fungal infection (fluconazole), a medicine used to prevent rejection of a transplanted organ (ciclosporin), or if you are taking some heart tablets such as diltiazem or verapamil. These medicines may cause an increase in the number of side effects, such as dizziness, nausea, or vomiting, which are possible side effects of Ranexa (see section 4). Your doctor may decide to give you a lower dose.
  • medicines to treat epilepsy or another neurologic disorder (e.g. phenytoin, carbamazepine, or phenobarbital); are taking rifampicin for an infection (e.g. tuberculosis); or are taking the herbal remedy St. John's Wort, as these medicines may cause Ranexa to be less effective.
  • heart medicines containing digoxin or metoprolol, as your doctor may want to change the dose of this medicine whilst you are taking Ranexa.
  • certain medicines to treat allergies (e.g. terfenadine, astemizole, mizolastine), heart rhythm disorders (e.g. disopyramide, procainamide), and depression (e.g. imipramine, doxepin, amitriptyline), as these medicines may affect your ECG.
  • certain medicines to treat depression (bupropion), psychosis, HIV infection (efavirenz), or cancer (cyclophosphamide).

Please tell your doctor or pharmacist if you are using or have recently used any other medicines, including medicines obtained without a prescription.

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

Pregnancy
You should not take Ranexa if you are pregnant unless your doctor has advised you to do so.

Breast-feeding
You should not take Ranexa if you are breast-feeding. Ask your doctor for advice if you are breast-feeding.

Ask your doctor for advice before using any 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 for advice about driving or using machines.

Ranexa may cause side effects such as dizziness (common) and blurred vision (uncommon) that may affect your ability to drive or use machinery. If you experience these symptoms, do not drive or operate machinery until they have resolved completely.

Important information about some of the ingredients of Ranexa
The 750 mg prolonged-release tablets contain the azo colouring agent E102. This colouring agent- may cause allergic reactions.

The 750 mg prolonged-release tablets contain lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

How is it used?

Always take Ranexa exactly as your doctor has told you to. You should check with your doctor or pharmacist if you are not sure.

Always swallow the tablets whole with water. Do not crush, suck, or chew the tablets or break them in half, as this might affect the way the medicine is released from the tablets into your body.

The starting dose for adults is one 375 mg tablet twice a day. After 2−4 weeks, your doctor may increase the dose to get the right effect. The maximum dose of Ranexa is 750 mg twice a day.

It is important that you tell your doctor if you get side effects such as dizziness or feeling or being sick. Your doctor may lower your dose or, if this is not sufficient, stop treatment with Ranexa.

Children and adolescents under 18 years old should not take Ranexa.

If you take more Ranexa than you should
If you accidentally take too many Ranexa tablets or take a higher dose than recommended by your doctor, it is important that you tell your doctor at once. If you cannot contact your doctor, go to the nearest accident and emergency department. Take along any tablets that are left, including the container and the carton, so that the hospital staff can easily tell 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 nearly time to take your next dose. Do not take a double dose to make up for a forgotten dose.

What are possible side effects?

Like all medicines, Ranexa can cause side effects, although not everybody gets them. These are usually mild or moderate.

You should stop taking Ranexa and see your doctor immediately if you experience the following symptoms of angioedema, which is a rare condition but can be severe:

  • swollen face, tongue, or throat
  • difficulty swallowing
  • hives or difficulty breathing

Tell your doctor if you experience common side effects such as dizziness or feeling sick or vomiting. Your doctor may lower your dose or stop treatment with Ranexa.

Other side effects you may experience include the following:

Common side effects (occur in 1 to 10 users in 100) are:
Constipation
Dizziness
Headache
Feeling sick, vomiting
Feeling weak

Uncommon side effects (occur in 1 to 10 users in 1,000) are:
Anxiety, difficulty sleeping
Blurred vision, visual disturbance
Changes in sensation (touch or taste), tremor, feeling tired or sluggish, sleepiness or drowsiness, faint or fainting, dizziness upon standing
Dark urine, blood in urine, difficulty urinating
Dehydration
Difficulty breathing, cough, nose bleed
Excessive sweating, itching
Feeling swollen or bloated
Hot flushes, low blood pressure
Increases in a substance called creatinine or increases in urea in your blood, increase in blood platelets or white blood cells, changes in ECG heart tracing
Joint swelling, pain in extremity
Loss of appetite and/or weight loss
Muscle cramp
Ringing in the ears and/or feeling a spinning sensation
Stomach pain or discomfort, indigestion, dry mouth, or wind

Rare side effects (occur in 1 to 10 users in 10,000) are:
Abnormal laboratory values for liver
Change in sense of smell, numbness in mouth or lips, impaired hearing
Cold sweat, rash
Decrease in blood pressure upon standing
Decreased or loss of consciousness
Disorientation
Feeling of coldness in hands and legs
Hives, allergic skin reaction
Impotence
Inflammation of pancreas or intestine
Loss of memory
Throat tightness

In some isolated cases, acute kidney failure has been reported with the use of Ranexa.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How should it be stored?

Keep out of the reach and sight of children.

Do not use Ranexa after the expiry date which is stated on each blister strip of tablets and on the outside of the carton and bottle.

This medicinal product 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 to protect the environment.

What is it?

Ranexa is a medicine that contains the active substance ranolazine. It is available as oval prolonged-release tablets (blue: 375 mg; orange: 500 mg; green: 750 mg). ‘Prolonged release’ means that ranolazine is released slowly from the tablet over a few hours.

What is it used for?

Ranexa is used to treat the symptoms of stable angina pectoris (chest pain caused by reduced blood flow to the heart). It is used as an add-on to existing treatment in patients whose disease is not adequately controlled by other medicines for angina pectoris, such as beta-blockers or calcium antagonists, or in patients who cannot take these medicines.
The medicine can only be obtained with a prescription.

How is it used?

The recommended starting dose of Ranexa is 375 mg twice a day. After two to four weeks, the dose should be increased to 500 mg twice a day, and then to 750 mg twice a day, depending on the patient’s response. The maximum dose is 750 mg twice a day. Doses may need to be lower in patients who have certain side effects. Dose increases should be carried out carefully in the elderly, in patients who weigh less than 60 kg, and in patients who have problems with their kidneys, liver or heart. Ranexa tablets should be swallowed whole and should not be broken, crushed or chewed. They can be taken with or without food.
Patients who take Ranexa must be given a ‘patient alert card’ that summarises the key safety information on the medicine.

How does it work?

The active substance in Ranexa, ranolazine, is thought to work by reducing the flow of sodium ions into the heart muscle cells. This interferes with the activity of special channels on the cell surface called ‘sodium-dependent calcium channels’ through which calcium ions normally enter the cells. This reduces the number of calcium ions that enter the cells. Calcium ions normally cause the heart muscle to contract. By reducing the flow of calcium into the cells, ranolazine is thought to help the heart to relax, improving blood flow to the heart muscle and relieving the symptoms of angina pectoris.

1 Previously known as Latixa.

How has it been studied?

Ranexa has been studied in one main study including a total of 823 patients with an average age of 64 years who had had angina pectoris for at least three months. Two doses of Ranexa (750 and 1000 mg twice a day) were compared with placebo (a dummy treatment) as an add-on to commonly used medicines for angina pectoris (atenolol, amlodipine or diltiazem). The main measure of effectiveness was how long patients could exercise after 12 weeks of treatment, compared with before treatment.

What benefits has it shown during the studies?

Ranexa was more effective than placebo at increasing the length of time the patients could exercise. At the start of the study, the patients could exercise for about 7 minutes. After 12 weeks, this increased by an average of 1 minute 56 seconds in the patients adding either dose of Ranexa, and by an average of 1 minute 32 seconds in those adding placebo.

What is the risk associated?

The most common side effects with Ranexa (seen in between 1 and 10 patients in 100) are dizziness, headache, constipation, vomiting, nausea (feeling sick) and asthenia (weakness). For the full list of all side effects reported with Ranexa, see the Package Leaflet.
Ranexa should not be used in people who may be hypersensitive (allergic) to ranolazine or any of the other ingredients. It must not be used in patients who have severe problems with their kidneys or moderate or severe problems with their liver. It must also not be used in patients who are taking other medicines that are broken down in the same way as ranolazine, or certain other medicines that are used to correct the heart rhythm. For the full list of these medicines, see the Package Leaflet.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that the effectiveness of Ranexa in improving the symptoms of patients with stable angina pectoris is modest but that it could be of value in patients who have not responded fully to other medicines. The Committee decided that Ranexa’s benefits are greater than its risks as an add-on treatment of the symptoms of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line anti-anginal medicines (such as beta-blockers and/or calcium antagonists). The Committee recommended that Ranexa be given marketing authorisation.

How has it been studied?

The company that makes Ranexa will agree on the wording of the patient alert card in each Member State. The card will be inserted in the boxes containing the tablets and will include information for patients and healthcare workers explaining how to use the medicine safely.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Latixa on 9 July 2008. The name of the medicine was changed to Ranexa on 11 August 2008. The marketing authorisation holder is Menarini International Operations Luxembourg S.A.