Zebinix 50 mg/ml oral suspension

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Zebinix 50 mg/ml oral suspension

eslicarbazepine acetate

Read this entire 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What Zebinix is and what it is used for

Zebinix contains the active substance eslicarbazepine acetate.

Zebinix belongs to a group of medicines called antiepileptic drugs, used to treat epilepsy, a condition in which affected individuals experience repeated seizures or convulsive fits.

Zebinix is used:

• as a single medicine (monotherapy) in adult patients with newly diagnosed epilepsy;
• together with other antiepileptic medicines (adjunctive therapy) in adult, adolescent, and pediatric patients over 6 years of age who have seizures (convulsions) originating in one part of the brain (partial seizures). These seizures may or may not be followed by a seizure affecting the entire brain (secondary generalization).

Your doctor has prescribed Zebinix to reduce the number of seizures.

2. What you need to know before taking Zebinix

Do not take Zebinix:

• if you are allergic to eslicarbazepine acetate, to other carboxamide derivatives (for example, 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 specific type of heart rhythm disorder (second- or third-degree atrioventricular (AV) block).

Warnings and precautions

Talk to your doctor or pharmacist before starting Zebinix.

Inform your doctor immediately:

• if you develop blisters or skin peeling, and/or mucous membrane involvement, rash, difficulty swallowing or breathing, or swelling of the lips, face, eyelids, throat, or tongue. These could be signs of an allergic reaction;
• if you experience confusion, worsening of seizures, or decreased level of consciousness, which could indicate low blood levels of salts.

Inform your doctor:

• if you have kidney problems. Your doctor may need to adjust your dose. Zebinix is not recommended in patients with severe renal disease;
• if you have liver problems. Zebinix is not recommended in patients with severe hepatic impairment;
• if you are taking any medicine that may cause an abnormality on the ECG (electrocardiogram) known as PR interval prolongation. If you are unsure whether your medicines may cause this effect, discuss it with your doctor;
• if you have any heart conditions such as heart failure or heart attack, or any disturbances in heart rhythm;
• if you have seizures that begin with a generalized electrical discharge affecting both sides of the brain.

A small number of people taking antiepileptic medicines have had thoughts about harming themselves or suicide. If this happens to you while taking Zebinix, contact your doctor immediately.

Zebinix may cause dizziness and/or drowsiness, especially at the beginning of treatment. Take special care while taking Zebinix to avoid accidental injuries such as falls.

Take special care with Zebinix

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

If you develop a severe rash or other skin symptoms (see section 4), stop taking Zebinix and consult your doctor or seek immediate medical attention.

In patients of Thai origin and the Han Chinese ethnic group, the risk of serious skin reactions associated with carbamazepine or chemically related compounds can be predicted by a blood test. Your doctor may advise you about the need for such a blood test before starting Zebinix.

Children

Zebinix must not be given to children aged 6 years or younger.

Taking Zebinix with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This is because some medicines may interfere with how Zebinix works, or Zebinix may interfere with the effect of other medicines. Inform your doctor if you are taking:

• phenytoin (a medicine used to treat epilepsy), as dose adjustment may be necessary;
• carbamazepine (a medicine used to treat epilepsy), as your dose may need to be adjusted, and the following side effects of Zebinix may occur more frequently: double vision, abnormal coordination, and dizziness;
• hormonal contraceptives (such as the contraceptive pill), as Zebinix may reduce their effectiveness;
• simvastatin (a medicine used to lower cholesterol levels), as dose adjustment may be required;
• rosuvastatin, a medicine used to lower cholesterol levels;
• the anticoagulant warfarin;
• monoamine oxidase inhibitor (MAOI) antidepressants;
• do not take oxcarbazepine (a medicine used to treat epilepsy) together with Zebinix, as it is unknown whether it is safe to take these two medicines together.

See section “Pregnancy and breastfeeding” for recommendations regarding contraception.

Pregnancy and breastfeeding

Use of Zebinix is not recommended during pregnancy, as the effects of Zebinix on pregnancy and the unborn child are unknown.

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

There are limited data on the use of eslicarbazepine acetate in pregnant women.

Studies have shown an increased risk of congenital malformations and neurological development problems (brain development) in children of women taking 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, inform your doctor immediately. You must not stop taking your medicine without first discussing it with your doctor. Stopping your medication without medical advice may cause seizures, which could be dangerous for you and your unborn child. Your doctor may decide to change your treatment.

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

Do not breast-feed while taking Zebinix. It is unknown whether Zebinix passes into breast milk.

Driving and using machines

Zebinix may cause dizziness, drowsiness, and affect your vision, particularly at the beginning of treatment. If this occurs, do not drive or operate tools or machines.

Zebinix contains methyl parahydroxybenzoate (E218) and sulphites

Zebinix oral suspension contains methyl parahydroxybenzoate (E218), which may cause allergic reactions (possibly delayed), and sulphites, which may rarely cause severe allergic reactions and bronchospasm (sudden sensation of suffocation).

3. How to take Zebinix

Follow exactly the instructions given by your doctor for taking this medicine. If you are unsure, consult your doctor or pharmacist again.

Adults

Starting dose

400 mg once daily for one or two weeks before increasing to the maintenance dose. Your doctor will decide whether you should take this dose for one or two weeks.

Maintenance dose

The usual maintenance dose is 800 mg once daily.

Depending on your response to Zebinix, the dose may be increased to 1,200 mg once daily. If you are taking Zebinix alone (monotherapy), your doctor may consider increasing your dose to 1,600 mg once daily.

Patients with kidney problems

If you have kidney problems, you will generally 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 problems.

Elderly patients (over 65 years of age)

If you are elderly and taking Zebinix as monotherapy, the 1,600 mg dose is not suitable for you.

Children over 6 years of age

Starting dose

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

Maintenance dose

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

Children ≥ 60 kg

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

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

Method and route of administration

Zebinix is administered orally.

Zebinix oral suspension can be taken with or without food.

Shake well before use.

Always use the oral syringe provided to take your medicine.

Instructions for use:

Step 1. Remove the bottle, oral syringe, and bottle adapter from the carton.

Step 2. Shake the bottle for at least 10 seconds and remove the child-resistant safety cap by pressing down and turning it counterclockwise (to the left).

Step 3. Insert the adapter into the neck of the open bottle. You may need to apply some pressure to secure it properly. Once inserted, the adapter should not be removed from the bottle. The bottle can be closed with the cap while the adapter remains in place.

Step 4. To facilitate the process, mark the desired volume by moving the plunger. Insert the tip of the oral syringe into the bottle adapter, keeping the bottle upright. Push the plunger fully down. This will create pressure inside the bottle, which helps dispense the suspension by forcing it into the syringe.

Step 5. Hold the syringe in place and turn the bottle upside down.

Gently pull the plunger of the oral syringe until the desired volume is reached.

Step 6. If you see any air bubbles in the syringe, push the plunger up sufficiently to expel large air bubbles. Then gently pull the plunger down to the dose prescribed by your doctor.

Step 7. Turn the bottle upright and remove the syringe from the bottle. Be careful not to push the plunger down while removing the syringe from the bottle.

Step 8. Replace the bottle cap by turning it clockwise (to the right).

Step 9. Place the syringe in the mouth against the inside of the cheek. Slowly press down the plunger to release the Zebinix into your mouth.

Step 10: Rinse the syringe after each use by drawing clean water into it from a glass. Repeat this rinsing process three times.

Store the bottle and oral syringe together in the carton until the next use.

If you take more Zebinix than you should

If you accidentally take more Zebinix than you should, you may be at risk of having more seizures, or you may feel that your heartbeat is irregular or faster than normal. Contact your doctor or go immediately to a hospital if you experience any of these symptoms. Take the medicine packaging with you so the doctor knows what you have taken.

If you forget to take Zebinix

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

If you stop taking Zebinix

Do not stop taking the oral suspension suddenly. If you do, you may be at risk of having more seizures. Your doctor will decide how long you should take Zebinix. If your doctor decides to stop your treatment with Zebinix, your dose will usually be gradually reduced. It is important that you complete the treatment as instructed by your doctor; otherwise, your symptoms may worsen.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

The following adverse effects can be very serious. If they occur, stop taking Zebinix immediately and contact a doctor or go to a hospital straight away, as you may require urgent medical treatment:

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

Very common adverse effects (may affect more than 1 in 10 people) are:

• dizziness or somnolence.

Common adverse effects (may affect up to 1 in 10 people) are:

• sensation of unsteadiness, spinning or floating;
• nausea or vomiting;
• headache;
• diarrhoea;
• double or blurred vision;
• difficulty concentrating;
• feeling tired or lack of energy;
• tremor;
• skin rash;
• blood tests showing low sodium levels;
• decreased appetite;
• difficulty sleeping;
• problems with coordination of movement (ataxia);
• weight gain.

Uncommon adverse effects (may affect up to 1 in 100 people) are:

• clumsiness of movement;
• allergy;
• constipation;
• seizures;
• underactive thyroid gland. Symptoms include low levels of thyroid hormones (detected in blood tests), intolerance to cold, enlarged tongue, brittle nails or hair, and low body temperature;
• liver problems (such as increased liver enzymes);
• high blood pressure or a marked increase in blood pressure;
• low blood pressure, or decreased blood pressure upon standing;
• blood tests showing low levels of salts (including chloride), or a reduction in the number of red blood cells;
• dehydration;
• changes in eye movements, blurred vision or red eyes;
• falls;
• thermal burns;
• memory problems or forgetfulness;
• crying, feeling depressed, nervousness or confusion, lack of interest or emotions;
• inability to speak, write or understand spoken or written language;
• agitation;
• attention deficit/hyperactivity;
• irritability;
• mood changes or hallucinations;
• difficulty speaking;
• nosebleeds;
• chest pain;
• tingling or numbness in any part of the body;
• migraine;
• burning sensation;
• abnormal sensation to touch;
• disturbances in smell;
• ringing in the ears;
• difficulty hearing;
• swelling of arms and legs;
• heartburn, stomach discomfort, abdominal pain, bloating and abdominal discomfort or dry mouth;
• • black stools;
  • swollen gums or toothache;
  • sweating or dry skin;
  • itching;
  • skin changes (e.g. skin redness);
  • hair loss;
  • urinary tract infection;
  • general malaise, weakness or chills;
  • weight loss;
  • muscle pain, limb pain, muscle weakness;
  • bone metabolism disorder;
  • increased bone proteins;
  • flushing, cold extremities;
  • slower or irregular heartbeat;
  • extreme drowsiness;
  • sedation;
  • motor neurological disorder involving muscle contractions causing twisting movements, repetitive movements or abnormal postures. Symptoms may include tremors, pain and cramps;
  • drug toxicity;
  • anxiety.

Adverse effects with unknown frequency (cannot be estimated from available data) are:

• Reduction in platelets, increasing the risk of bleeding or bruising;
• Severe back or stomach pain (caused by inflammation of the pancreas);
• Reduction in white blood cells, making infections more likely;
• Red spots or circular lesions, often with central blisters on the trunk, skin peeling, mouth, throat, nose, genital or eye ulcers, 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, facial rash, widespread rash, high body temperature, elevated liver enzymes, blood abnormalities (eosinophilia), enlarged lymph nodes and other body conditions (drug reaction with eosinophilia and systemic symptoms, also known as DRESS or drug hypersensitivity syndrome);
  • Severe allergic reaction causing swelling of the face, throat, hands, feet, ankles or lower legs;
  • Hives (itchy skin rash);
  • Lethargy, confusion, muscle spasms or a marked worsening of seizures (possible symptoms of low sodium levels in blood due to inappropriate antidiuretic hormone (ADH) secretion).

Use of Zebinix is associated with an ECG (electrocardiogram) abnormality known as PR interval prolongation. Adverse effects associated with this ECG abnormality may occur (e.g. fainting and slowed heart rate).

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse 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 bottle and the outer carton after the letters CAD. The expiry date refers to the last day of the month indicated.

After opening the bottle, do not use the medicine for longer than 2 months.

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 and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Zebinix

• The active substance is eslicarbazepine acetate. Each ml of oral suspension contains 50 mg of eslicarbazepine acetate.
• The other components are xanthan gum (E415), macrogol stearate 100, methyl parahydroxybenzoate (E218), sodium saccharin (E954), artificial Tutti-Frutti flavoring (containing maltodextrin, propylene glycol, natural and artificial flavoring, and gum arabic (E414)), flavor masking agent (containing propylene glycol, water, and natural and artificial flavoring), and purified water.

Appearance of the product and contents of the container

Zebinix 50 mg/ml is a white to off-white suspension.

The oral suspension is packaged in amber-colored glass bottles with a child-resistant HDPE closure, containing 200 ml of oral suspension, packed in cardboard boxes. Each cardboard box contains a 10 ml graduated polypropylene syringe with 0.2 ml graduations and a copolymer bottle adapter.

Marketing Authorization Holder and Manufacturer

BIAL - Portela & Cª, S.A.,
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]

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: <{MM YYYY}>

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