ZEBINIX 200 mg TABLETS

2. What you need to know before you take Zebinix

Do not take Zebinix:

• if you are allergic to eslicarbazepine acetate, to other carboxamide derivatives (e.g. carbamazepine or oxcarbazepine, medicines used to treat epilepsy), or to any of the other ingredients of this medicine (listed in section 6);
• if you have a certain type of heart rhythm disorder (second or third degree atrioventricular (AV) block).

Warnings and precautions

Tell your doctor or pharmacist before you start taking Zebinix

Tell your doctor immediately:

• if you get blisters or peeling of the skin and/or mucous membranes, rash, problems with swallowing or breathing, swelling of the lips, face, eyelids, throat or tongue. These could be signs of an allergic reaction;
• if you become confused, your seizures get worse or you lose consciousness, which could be signs of low blood levels of salts.

Tell your doctor:

• if you have kidney problems. Your doctor may need to adjust your dose. Zebinix is not recommended in patients with severe kidney disease;
• if you have liver problems. Zebinix is not recommended in patients with severe liver problems;
• if you are taking any medicine that may cause an abnormality in your ECG (electrocardiogram) called a prolonged PR interval. If you are not sure if the medicines you are taking may cause this effect, discuss this with your doctor;
• if you have any heart disease such as heart failure or heart attack, or have any heart rhythm problems;
• if you have seizures that start with a widespread electrical discharge that affects both sides of the brain.

A small number of people taking antiepileptics have had thoughts of harming themselves or suicide. If at any time you have these thoughts, contact your doctor immediately.

Zebinix may make you feel dizzy or drowsy, particularly at the start of treatment. Be extra careful when taking Zebinix to avoid accidental injury, such as falls.

Be extra careful with Zebinix

In the post-marketing experience, in patients treated with Zebinix, serious and potentially life-threatening skin reactions, including Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported.

If you develop a severe rash or other sign of skin reaction (see section 4), stop taking Zebinix and contact your doctor or seek medical attention immediately.

In patients of Thai and Chinese Han ethnicity, the risk of serious skin reactions associated with carbamazepine or chemically-related compounds can be predicted by a blood test. Your doctor will be able to advise you whether you need such a blood test before taking Zebinix.

Children

Zebinix must not be given to children under 6 years of age.

Taking Zebinix with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This is because some medicines may affect the way Zebinix works, or Zebinix may affect the way other medicines work. Tell your doctor if you are taking:

• phenytoin (a medicine used to treat epilepsy), as you may need to have your dose adjusted;
• carbamazepine (a medicine used to treat epilepsy), as you may need to have your dose adjusted, and the following side effects of Zebinix may occur more frequently: double vision, abnormal coordination and dizziness;
• hormonal contraceptives (such as the pill) as Zebinix may reduce their effectiveness;
• simvastatin (a medicine used to lower cholesterol levels), as you may need to have your dose adjusted;
• rosuvastatin, a medicine used to lower cholesterol levels;
• the anticoagulant warfarin;
• monoamine oxidase inhibitors (a type of antidepressant);
• do not take oxcarbazepine (a medicine used to treat epilepsy) with Zebinix, as it is not known if it is safe to take these two medicines together.

See the section “Pregnancy and breast-feeding” for advice on contraception.

Pregnancy and breast-feeding

Zebinix should not be used during pregnancy, as its effects on pregnancy and the unborn child are not known.

If you are planning to become pregnant, talk to your doctor before stopping your contraceptive and before becoming pregnant. Your doctor may decide to change your treatment.

There is limited information on the use of eslicarbazepine acetate in pregnant women.

Studies have shown an increased risk of congenital malformations and developmental delay (development of the brain) in the children of women who take antiepileptic medicines, particularly when more than one antiepileptic medicine is taken at the same time.

If you are pregnant or think you may be pregnant, tell your doctor immediately. Do not stop taking your medicine until you have talked to your doctor. Stopping your medicine suddenly may cause seizures, which could be harmful for you and your unborn child. Your doctor will discuss with you whether you should continue to take Zebinix.

If you are a woman of childbearing age and not planning to become pregnant, you must use an effective method of contraception during treatment with Zebinix. Zebinix may affect the way hormonal contraceptives work, making them less effective in preventing pregnancy. Therefore, you are advised to use other forms of safe and effective contraception while taking Zebinix. Talk to your doctor, who will discuss with you the most suitable type of contraception to use while you are taking Zebinix. If you stop taking Zebinix, you should continue to use an effective method of contraception until the end of your current menstrual cycle. If you take Zebinix during pregnancy, your baby is at risk of having bleeding problems immediately after birth. Your doctor may give you and your baby a medicine to prevent this.

Do not breast-feed while you are taking Zebinix. It is not known if Zebinix passes into breast milk.

Driving and using machines

Zebinix may cause dizziness, drowsiness and affect your vision, particularly at the start of treatment. If this happens to you, do not drive or use any tools or machines.

3. How to take Zebinix

Take this medicine exactly as your doctor has told you. If you are not sure, check with your doctor or pharmacist.

Adults

Dose at the start of treatment

400 mg once a day for one or two weeks, before increasing to the maintenance dose. Your doctor will decide whether you should be given this dose for one or two weeks.

Maintenance dose

The usual maintenance dose is 800 mg once a day.

Depending on how you respond to Zebinix, the dose may be increased to 1,200 mg once a day. If you are taking Zebinix on its own (monotherapy), your doctor may consider increasing your dose to 1,600 mg once a day.

Patient with kidney problems

If you have kidney problems, you will usually be given a lower dose of Zebinix. Your doctor will determine the correct dose for you. Zebinix is not recommended if you have severe kidney disease.

Elderly patients (65 years or older)

If you are an elderly patient and are taking Zebinix on its own (monotherapy), the dose of 1,600 mg is not suitable for you.

Children aged 6 years and older

Dose at the start of treatment

The starting dose is 10 mg per kilogram of body weight once a day for one or two weeks, before increasing to the maintenance dose.

Maintenance dose

Depending on the response to Zebinix, the dose may be increased by 10 mg per kilogram of body weight, at intervals of one or two weeks, up to 30 mg per kilogram of body weight. The maximum dose is 1,200 mg once a day.

Children ≥ 60 kg

Children with a body weight of 60 kg or more should take the same dose as adults.

The oral suspension, another form of the medicine, may be more suitable for administration in children. Talk to your doctor or pharmacist.

Form and route of administration

Zebinix is taken by mouth. Swallow the tablet with a glass of water.

Zebinix can be taken with or without food.

If you have difficulty swallowing the tablet whole, you can crush it and add it to a small amount of water or apple sauce to take immediately.

The tablet can be divided into equal doses.

If you take more Zebinix than you should

If you accidentally take more Zebinix than you should, you are at risk of having more seizures; or you may feel that your heart is beating irregularly or faster. Contact your doctor or go immediately to a hospital if you experience any of these symptoms. Take the medicine pack with you, so that the doctor knows what you have taken.

If you forget to take Zebinix

If you forget to take a tablet, take it as soon as you remember and then continue as normal. Do not take a double dose to make up for a forgotten dose.

If you stop taking Zebinix

Do not stop taking Zebinix suddenly. If you do, you may have more seizures. Your doctor will decide for how long you need to take Zebinix. If your doctor decides to stop your treatment with Zebinix, your dose will usually be reduced gradually. It is important that you complete the treatment as instructed by your doctor; otherwise, your symptoms may get worse.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

The following side effects may be very serious. If they happen, stop taking Zebinix and tell a doctor or go to a hospital straight away, as you may need urgent medical treatment:

• blistering or peeling of the skin and/or mucous membranes, rash, problems with swallowing or breathing, swelling of the lips, face, eyelids, throat or tongue. These could be signs of an allergic reaction.

The following side effects are very common(may affect more than 1 in 10 people)

• dizziness or drowsiness.

The following side effects are common(may affect up to 1 in 10 people)

• feeling unsteady, or as if you are spinning or floating;
• nausea or vomiting;
• headache;
• diarrhoea;
• double vision or blurred vision;
• difficulty concentrating;
• feeling tired or lacking energy;
• shaking;
• skin rash;
• blood tests showing low levels of sodium;
• loss of appetite;
• difficulty sleeping;
• difficulty with coordination of movements (ataxia);
• weight gain.

The following side effects are uncommon(may affect up to 1 in 100 people)

• clumsiness;
• allergic reaction;
• constipation;
• seizures;
• underactive thyroid gland. Symptoms include decreased levels of thyroid hormones (detected in blood tests), intolerance to cold, increased size of the tongue, brittle or fragile nails and hair, and low body temperature;
• liver problems (such as increased liver enzymes);
• high blood pressure or a sudden increase in blood pressure;
• low blood pressure, or decreased blood pressure when standing up;
• blood tests showing low levels of salts (including chloride), or a decrease in the number of red blood cells;
• dehydration;
• changes in eye movements, blurred vision or red eyes;
• falls;
• heat burn;
• poor memory or forgetfulness;
• crying, feeling depressed, nervous or confused, lack of interest or emotions;
• inability to speak, write or understand spoken or written language;

• agitation;
• attention deficit/hyperactivity disorder;
• irritability;
• changes in mood or hallucinations;
• difficulty speaking;
• nosebleeds;
• chest pain;
• tingling or numbness in any part of the body;
• migraine;
• burning sensation;
• abnormal sensation to touch;
• changes in sense of smell;
• ringing in the ears;
• difficulty hearing;
• swelling of the legs and arms;
• heartburn, stomach upset, abdominal pain, bloating and stomach discomfort or dry mouth;
• black stools;
• gum inflammation or toothache;
• sweating or dry skin;
• itching;
• changes in skin (e.g. redness of the skin);
• hair loss;
• urinary tract infection;
• general feeling of being unwell, weakness or chills;
• weight loss;
• muscle pain, pain in the limbs, muscle weakness;
• bone metabolism disorder;
• increased bone protein;
• flushing, cold hands and feet;
• slow or irregular heartbeat;
• extreme drowsiness;
• sedation;
• neuromotor disorder where the muscles contract, causing twisting and repetitive movements or abnormal postures. Symptoms include tremors, pain and cramps;
• drug toxicity;
• anxiety.

The following side effects have unknown frequency(cannot be estimated from the available data)

• reduction in platelets which can increase the risk of bleeding or bruising;
• severe pain in the back or stomach (caused by inflammation of the pancreas);
• reduction in white blood cells which can make infections more likely;
• red patches or spots, often with blisters in the centre, on the trunk, peeling of the skin, ulcers in the mouth, throat, nose, genitals and eyes, red and inflamed eyes, which may be preceded by fever and/or flu-like symptoms (Stevens-Johnson syndrome/toxic epidermal necrolysis);
• initially flu-like symptoms, rash on the face, widespread rash, high body temperature, increased liver enzymes, blood abnormalities (eosinophilia), swollen lymph nodes and other body conditions (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or hypersensitivity syndrome);
• severe allergic reaction which causes swelling of the face, throat, hands, feet, ankles or lower legs;
• hives (itchy rash);
• lethargy, confusion, muscle spasms or a significant worsening of seizures (possible symptoms of low sodium levels in the blood due to inadequate secretion of antidiuretic hormone (ADH)).

The use of Zebinix is associated with an abnormality in the ECG (electrocardiogram) called a prolonged PR interval. Side effects associated with this ECG abnormality (e.g. fainting and slow heart beats) may occur.

Bone disorders including osteopenia and osteoporosis (thinning of the bones) and fractures have been reported with antiepileptic medicines structurally related to carbamazepine and oxcarbazepine. Talk to your doctor or pharmacist if you are on long-term treatment with antiepileptics, have a history of osteoporosis or are taking steroids.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zebinix

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

Do not use this medicine after the expiry date which is stated on the blister, bottle, and carton after the letters CAD. The expiry date is the last day of the month indicated.

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. This will help protect the environment.

6. Package contents and additional information

Composition of Zebinix

• The active substance is eslicarbazepine acetate. Each tablet contains 200 mg of eslicarbazepine acetate.
• The other ingredients are povidone K29/32, sodium croscarmellose, and magnesium stearate.

Appearance of the product and package contents

Zebinix 200 mg tablets are white and oblong, 11 mm in length. The tablets have the inscription “ESL 200” engraved on one side and are scored on the opposite side. The tablet can be divided into equal doses.

The tablets are packaged in blisters, in cardboard boxes of 20 or 60 tablets, and in HDPE bottles with a child-resistant closure, in cardboard boxes of 60 tablets.

Only certain pack sizes may be marketed.

Marketing authorisation holder and manufacturer

BIAL - Portela & Cª, S.A., À Av. da Siderurgia Nacional,

4745-457 S. Mamede do Coronado

Portugal

telephone: +351 22 986 61 00

fax: +351 22 986 61 99

email: [email protected]

You can request more information about this medicine by contacting 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 web site http://www.ema.europa.eu.