B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Matever 250 mg film-coated tablets Matever 500 mg film-coated tablets Matever 750 mg film-coated tablets Matever 1000 mg film-coated tablets

levetiracetam

Read all of this leaflet carefully before you or your child start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Matever is and what it is used for

• 2. What you need to know before you take Matever

• 3. How to take Matever

• 4. Possible side effects

• 5. How to store Matever

• 6. Contents of the pack and other information

1. What Matever is and what it is used for

Levetiracetam is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).

Matever is used:

• on its own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat a certain form of epilepsy. Epilepsy is a condition where the patients have repeated fits (seizures). Levetiracetam is used for the epilepsy form in which the fits initially affect only one side of the brain, but could thereafter extend to larger areas on both sides of the brain (partial onset seizure with or without secondary generalisation). Levetiracetam has been given to you by your doctor to reduce the number of fits.
• as an add-on to other antiepileptic medicines to treat:

• ■ partial onset seizures with or without generalisation in adults, adolescents, children and infants from one month of age

• ■ myoclonic seizures (short, shock-like jerks of a muscle or group of muscles) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy

• ■ primary generalised tonic-clonic seizures (major fits, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (the type of epilepsy that is thought to have a genetic cause).

2. What you need to know before you take Matever

Do not take Matever

• if you are allergic to levetiracetam, pyrrolidone derivatives or any of the other ingredients of

this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor before taking Matever

• If you suffer from kidney problems, follow your doctor’s instruc­tions. He/she may decide if your dose should be adjusted.
• If you notice any slowdown in the growth or unexpected puberty development of your child, please contact your doctor.
• A small number of people being treated with anti-epileptics such as Matever have had thoughts of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.
• If you have a family or medical history of irregular heart rhythm (visible on an electrocardiogram), or if you have a disease and/or take a treatment that make(s) you prone to heartbeat irregularities or salt imbalances.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually or if you or your family and friends notice important changes in mood or behaviour.
• Aggravation of epilepsy

Your seizures may rarely become worse or happen more often, mainly during the first month after the start of the treatment or increase of the dose. If you experience any of these new symptoms while taking Matever, see a doctor as soon as possible.

Children and adolescents

• Matever is not indicated in children and adolescents below 16 years on its own (monotherapy).

Other medicines and Matever

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take macrogol (a medicine used as laxative) for one hour before and one hour after taking levetiracetam as this may results in a loss of its effect.

Pregnancy and 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. Levetiracetam can be used during pregnancy, only if after careful assessment it is considered necessary by your doctor.

You should not stop your treatment without discussing this with your doctor.

A risk of birth defects for your unborn child cannot be completely excluded.

Breast-feeding is not recommended during treatment.

Driving and using machines

Matever may impair your ability to drive or operate any tools or machinery, as it may make you feel sleepy. This is more likely at the beginning of treatment or after an increase in the dose. You should not drive or use machines until it is established that your ability to perform such activities is not affected.

Matever 250 mg, 750 mg tablets contain Sunset Yellow FCF (E110)

Sunset Yellow FCF (E110) colouring agent may cause allergic reactions.

The other strengths of Matever tablets do not contain this ingredient.

Matever 1000 mg tablets contain lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

The other strengths of Matever tablets do not contain this ingredient.

3. How to take Matever

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

Take the number of tablets following your doctor’ s instructions.

Matever must be taken twice a day, once in the morning and once in the evening, at about the same time each day.

Adjunctive Therapy and monotherapy (from 16 years of age)

• Adults (>18 years) and adolescents (12 to 17 years) weighing 50 kg or more:

General dose: between 1,000 mg and 3,000 mg each day.

When you will first start taking Matever, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Example: if your daily dose is intended to be 1,000 mg, your reduced starting dose is 1 tablet of 250 mg in the morning and 1 tablet of 250 mg in the evening, and the dose will be gradually incremented to reach 1,000 mg daily after 2 weeks.

• Adolescents (12 to 17 years) weighing 50 kg or less:

Your doctor will prescribe the most appropriate pharmaceutical form of Matever according to weight and dose.

• Dose in infants (1 month to 23 months) and children (2 to 11 years) weighing less than 50 kg:

Your doctor will prescribe the most appropriate pharmaceutical form of Matever according to the age, weight and dose.

Levetiracetam 100 mg/ml oral solution is a formulation more appropriate to infants and children under the age of 6 years and to children and adolescents (from 6 to 17 years) weighing less than 50 kg and when tablets don’t allow accurate dose.

Method of administration

Swallow Matever tablets with a sufficient quantity of liquid (e.g. a glass of water). You may take Matever with or without food. After oral administration the bitter taste of levetiracetam may be experienced.

Duration of treatment

• Matever is used as a chronic treatment. You should continue Matever treatment for as long as your doctor has told you.
• Do not stop your treatment without your doctor’s advice as this could increase your seizures.

If you take more Matever than you should

The possible side effects of an overdose of Matever are sleepiness, agitation, aggression, decrease of alertness, inhibition of breathing and coma.

Contact your doctor if you took more tablets than you should. Your doctor will establish the best possible treatment of overdose.

If you forget to take Matever

Contact your doctor if you have missed one or more doses.

Do not take a double dose to make up for a forgotten tablet.

If you stop taking Matever

If stopping treatment Matever should be discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your Matever treatment, he/she will instruct you about the gradual withdrawal of Matever.

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.

Tell your doctor immediately, or go to your nearest emergency department, if you experience:

weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic (anaphylactic) reaction

swelling of the face, lips, tongue and throat (Quincke’s oedema)

flu-like symptoms and a rash on the face followed by an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS])

symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the legs, ankles or feet, as this may be a sign of sudden decrease of kidney function

a skin rash which may form blisters and look like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme )

a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome )

a more severe form of rash causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis )

signs of serious mental changes or if someone around you notices signs of confusion, somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These could be symptoms of an encephalopathy.

The most frequently reported side effects are nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like sleepiness, tiredness and dizziness may be more common. These effects should however decrease over time.

Very common: may affect more than 1 in 10 people

• nasopharyngitis;
• somnolence (sleepiness), headache.

Common: may affect up to 1 in 10 people

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness), lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);
• vertigo (sensation of rotation);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• rash;
• asthenia/fatigue (tiredness).

Uncommon: may affect up to 1 in 100 people

• decreased number of blood platelets, decreased number of white blood cells;
• weight decrease, weight increase;
• suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, an­ger,

confusion, panic attack, emotional instability/mood swings, agitation;

• amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia

(impaired coordinated movements), paraesthesia (tingling), disturbance in attention (loss of concentration);

• diplopia (double vision), vision blurred;

elevated/abnormal values in a liver function test;

hair loss, eczema, pruritus;

muscle weakness, myalgia (muscle pain);

injury.

Rare: may affect up to 1 in 1,000 people

• infection;
• decreased number of all blood cell types;
• severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction],

Quincke’s oedema [swelling of the face, lips, tongue and throat]);

• decreased blood sodium concentration;
• suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable

to concentrate);

• delirium;
• encephalopathy (see sub-section “Tell your doctor immediately” for a detailed description of

symptoms;

• seizures may become worse or happen more often;
• uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);
• change of the heart rhythm (Electrocardi­ogram);
• pancreatitis;
• liver failure, hepatitis;
• sudden decrease in kidney function;
• skin rash, which may form blisters and looks like small targets (central dark spots surrounded

by a paler area, with a dark ring around the edge) (erythema multiforme ), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome), and a more severe form causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis );

• rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase increase. Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.
• limp or difficulty walking.

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. Y ou can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Matever

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 carton box and blister after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Matever contains

The active substance is called levetiracetam.

One tablet of Matever 250 mg contains 250 mg of levetiracetam.

One tablet of Matever 500 mg contains 500 mg of levetiracetam.

One tablet of Matever 750 mg contains 750 mg of levetiracetam.

One tablet of Matever 1000 mg contains 1000 mg of levetiracetam.

The other ingredients are:

Tablet core: calcium hydrogen phosphate dihydrate, cellulose microcrystalline, crospovidone type A, hydroxypropyl­cellulose (L).

250 mg:

Film-coating: hypromellose (E464), titanium dioxide (E171), talc, propylene glycol (E1520) colourants*.

500 mg:

Film-coating: hypromellose (E464), titanium dioxide (E171), hydroxypropyl cellulose (E463), propylene glycol (E1520), sorbic acid (E200), sorbitan monooleate (E494), vanillin, colourants*.

750 mg:

Film-coating: hypromellose (E464), iron oxide red (E172), macrogol/PEG 4000, titanium dioxide (E171), colourants*.

1000 mg:

Film-coating: hypromellose (E464), lactose monohydrate,ma­crogol/PEG 4000, titanium dioxide (E171).

• * The colourants are:

250 mg tablet: indigo carmine aluminum lake (E132), sunset yellow FCF aluminum lake (E110), quinoline yellow aluminium lake (E104)

500 mg tablet: quinoline yellow aluminium lake (E104)

750 mg tablet: indigo carmine aluminum lake (E132), sunset yellow FCF aluminum lake (E110) 1000 mg tablet: (no additional colourant).

What Matever looks like and contents of the pack

Matever 250 mg: The film-coated tablets are blue, oblong, biconvex.

Matever 500 mg: The film-coated tablets are yellow, oblong, biconvex.

Matever 750 mg: The film-coated tablets are pink, oblong, biconvex.

Matever 1000 mg: The film-coated tablets are white, oblong, biconvex.

White opaque PVC/PE/PVDC-Aluminium foil blister in cardboard boxes.

Matever tablets are packaged in blister packs supplied in cardboard boxes containing:

• 250 mg: 20, 30, 50, 60, 100 and multipack of 200 (2 packs of 100) film-coated tablets.
• 500 mg: 10, 20, 30, 50, 60, 100, 120 and multipack of 200 (2 packs of 100) film-coated

tablets.

• 750 mg: 20, 30, 50, 60, 80, 100, 120 and multipack of 200 (2 packs of 100) film-coated

tablets.

• 1000 mg: 10, 20, 30, 50, 60, 100 and multipack of 200 (2 packs of 100) film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A., 6 Dervenakion Str., 15351 Pallini, Attiki, Greece

Manufacturer

Pharmathen S.A.

6 Dervenakion Str.

15351 Pallini, Attiki

Greece

or

Pharmathen International S.A.

Industrial Park Sapes,

Rodopi Prefecture, Block No 5,

Rodopi 69300,

Greece

For any information about this medicine, Marketing Authorisation Holder.

Belgie/Belgiqu­e/Belgien

Pharmathen S.A.

Tél/Tel: +30 210 66 04 300

Etnrapaa

Pharmathen S.A.

Ten.: +30 210 66 04 300

Česká republika

ARDEZ Pharma, spol. s r.o.

Tel.: +420 220 400 391

Danmark

Pharmathen S.A.

Tel.: +30 210 66 04 300

Deutschland

Pharmathen S.A.

Tel.: +30 210 66 04 300

Eesti (Estonia)

SIA ELVIM

Tel: +371 67808450

EZZáňa

INNOVIS PHARMA AEBE

Tnk +30 210 66 64 805–806

España

Pharmathen S.A.

Tel: +30 210 66 04 300

France

Pharmathen S.A.

Tél: +30 210 66 04 300

Hrvatska

Pharmathen S.A.

Tel: +30 210 66 04 300

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

Package leaflet: Information for the patient

Matever 100 mg/ml concentrate for solution for infusion levetiracetam

Read all of this leaflet carefully before you or your child start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Matever is and what it is used for

• 2. What you need to know before you are given Matever

• 3. How Matever is given

• 4. Possible side effects

• 5. How to store Matever

• 6. Contents of the pack and other information

1. What Matever is and what it is used for

Levetiracetam is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).

Matever is used:

• on its own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat a certain form of epilepsy. Epilepsy is a condition where the patients have repeated fits (seizures). Levetiracetam is used for the epilepsy form in which the fits initially affect only one side of the brain, but could thereafter extend to larger areas on both sides of the brain (partial onset seizure with or without secondary generalisation). Levetiracetam has been given to you by your doctor to reduce the number of fits.
• as an add-on to other antiepileptic medicines to treat:

• ■ partial onset seizures with or without generalisation in adults, adolescents and children from 4 years of age

• ■ myoclonic seizures (short, shock-like jerks of a muscle or group of muscles) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy.

• ■ primary generalised tonic-clonic seizures (major fits, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (the type of epilepsy that is thought to have a genetic cause).

Matever concentrate is an alternative for patients when administration of the antiepileptic oral Matever medicine is temporarily not feasible.

2. What you need to know before you are given Matever

Do not use Matever

• if you are allergic to levetiracetam, pyrrolidone derivatives or any of the other ingredients of this

medicine (listed in Section 6).

Warnings and precautions

Talk to your doctor before you are given Matever

• if you suffer from kidney problems, follow your doctor's instruc­tions. He/she may decide if

your dose should be adjusted.

• If you notice any slowdown in the growth or unexpected puberty development of your child,

please contact your doctor.

• A small number of people being treated with anti-epileptics such as Matever have had thoughts

of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.

• If you have a family or medical history of irregular heart rhythm (visible on an

electrocardiogram), or if you have a disease and/or take a treatment that make(s) you prone to heartbeat irregularities or salt imbalances.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually or if you or your family and friends notice important changes in mood or behaviour.
• Aggravation of epilepsy

Your seizures may rarely become worse or happen more often, mainly during the first month after the start of the treatment or increase of the dose. If you experience any of these new symptoms while taking Matever, see a doctor as soon as possible.

Children and adolescents

• Matever is not indicated in children and adolescents below 16 years on its own (monotherapy)

Other medicines and Matever

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take macrogol (a medicine used as laxative) for one hour before and one hour after taking levetiracetam as this may results in a reduction of its effect.

Pregnancy and 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. Levetiracetam can be used during pregnancy, only if after careful assessment it is considered necessary by your doctor.

You should not stop your treatment without discussing this with your doctor.

A risk of birth defects for your unborn child cannot be completely excluded.

Breast-feeding is not recommended during treatment.

Driving and using machines

Matever may impair your ability to drive or operate any tools or machinery, as it may make you feel sleepy. This is more likely at the beginning of treatment or after an increase in the dose. You should not drive or use machines until it is established that your ability to perform such activities is not affected.

Matever contains sodium

This medicine contains 57.21 mg sodium (main component of cooking/table salt) in each maximum single dose. This is equivalent to 2.86 % of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Matever is given

A doctor or a nurse will administer you Matever as an intravenous infusion.

Matever must be administered twice a day, once in the morning and once in the evening, at about the same time each day.

The intravenous formulation is an alternative to your oral administration. You can switch from the film-coated tablets or from the oral solution to the intravenous formulation or reverse directly without dose adaptation. Your total daily dose and frequency of administration remain identical.

Adjunctive therapy and Monotherapy (from 16 years of age).

Adults (>18 years) and adolescents (12 to 17 years) weighing 50 kg or more:

General dose: between 1000 mg and 3,000 mg each day.

When you will first start taking Matever, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Dose in children (4 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg:

General dose: between 20 mg per kg bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration

Matever is for intravenous use. The recommended dose must be diluted in at least 100 ml of a compatible diluent and infused over 15 minutes.

For doctors and nurses, more detailed direction for the proper use of Matever is provided in section 6.

Duration of treatment

• There is no experience with administration of intravenous levetiracetam for a longer period than

• 4 days.

If you stop using Matever

If stopping treatment, as with other antiepileptic medicines, Matever should be discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your Matever treatment, he/she will instruct you about the gradual withdrawal of Matever.

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.

Tell your doctor immediately, or go to your nearest emergency department, if you experience:

• weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic (anaphylactic) reaction
• swelling of the face, lips, tongue and throat (Quincke’s oedema)
• flu-like symptoms and a rash on the face followed by an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS])
• symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the legs, ankles or feet, as this may be a sign of sudden decrease of kidney function
• a skin rash which may form blisters and look like small targets (central dark spots surrounded

by a paler area, with a dark ring around the edge) (erythema multiforme )

• a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and

genitals (Stevens-Johnson syndrome )

• a more severe form of rash causing skin peeling in more than 30% of the body surface (toxic

epidermal necrolysis )

• signs of serious mental changes or if someone around you notices signs of confusion, somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These could be symptoms of an encephalopathy.

The most frequently reported adverse reactions were nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like sleepiness, tiredness and dizziness may be more common. These effects should however decrease over time.

• Very common: may affect more than 1 in 10 people nasopharyngitis;
• somnolence (sleepiness), headache.

Common: may affect up to 1 in 10 people

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness),

lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);

• vertigo (sensation of rotation);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• rash;
• asthenia/fatigue (tiredness).

Uncommon: may affect up to 1 in 100 people

• decreased number of blood platelets, decreased number of white blood cells;
• weight decrease, weight increase;
• suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, an­ger,

confusion, panic attack, emotional instability/mood swings, agitation;

• amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia

(impaired coordinated movements), paraesthesia (tingling), disturbance in attention (loss of concentration);

• diplopia (double vision), vision blurred;
• elevated/abnormal values in a liver function test;
• hair loss, eczema, pruritus;
• muscle weakness, myalgia (muscle pain);
• injury.

Rare: may affect up to 1 in 1,000 people

• infection;
• decreased number of all blood cell types;
• severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction],

Quincke’s oedema [swelling of the face, lips, tongue and throat]);

• decreased blood sodium concentration;
• suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable

to concentrate);

• delirium;
• encephalopathy (see sub-section “Tell your doctor immediately” for a detailed description of

symptoms);

• seizures may become worse or happen more often;
• uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);
• change of the heart rhythm (Electrocardi­ogram);
• pancreatitis;
• liver failure, hepatitis;
• sudden decrease in kidney function;
• skin rash, which may form blisters and looks like small targets (central dark spots surrounded

by a paler area, with a dark ring around the edge) (erythema multiforme ), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome ), and a more severe form causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis );

• rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase increase. Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.
• limp or difficulty walking.

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 By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Matever

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 vial and carton box after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

6. Contents of the pack and other information

What Matever contains

The active substance is called levetiracetam. Each ml of solution for infusion contains 100 mg of levetiracetam.

The other ingredients are: sodium acetate trihydrate, glacial acetic acid, sodium chloride, water for injections.

What Matever looks like and contents of the pack

Matever 250 mg: The film-coated tablets are blue, oblong, biconvex.

Matever 500 mg: The film-coated tablets are yellow, oblong, biconvex.

Matever 750 mg: The film-coated tablets are pink, oblong, biconvex.

Matever 1000 mg: The film-coated tablets are white, oblong, biconvex.

White opaque PVC/PE/PVDC-Aluminium foil blister in cardboard boxes.

Matever tablets are packaged in blister packs supplied in cardboard boxes containing:

• 250 mg: 20, 30, 50, 60, 100 and multipack of 200 (2 packs of 100) film-coated tablets.
• 500 mg: 10, 20, 30, 50, 60, 100, 120 and multipack of 200 (2 packs of 100) film-coated

tablets.

• 750 mg: 20, 30, 50, 60, 80, 100, 120 and multipack of 200 (2 packs of 100) film-coated

tablets.

• 1000 mg: 10, 20, 30, 50, 60, 100 and multipack of 200 (2 packs of 100) film-coated tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Pharmathen S.A., 6 Dervenakion Str., 15351 Pallini, Attiki, Greece

Manufacturer

Pharmathen S.A.

6 Dervenakion Str.

15351 Pallini, Attiki

Greece

or

Pharmathen International S.A.

Industrial Park Sapes,

Rodopi Prefecture, Block No 5,

Rodopi 69300,

Greece

For any information about this medicine, Marketing Authorisation Holder.

Belgie/Belgiqu­e/Belgien

Pharmathen S.A.

Tél/Tel: +30 210 66 04 300

Etnrapaa

Pharmathen S.A.

Ten.: +30 210 66 04 300

Česká republika

ARDEZ Pharma, spol. s r.o.

Tel.: +420 220 400 391

Danmark

Pharmathen S.A.

Tel.: +30 210 66 04 300

Deutschland

Pharmathen S.A.

Tel.: +30 210 66 04 300

Eesti (Estonia)

SIA ELVIM

Tel: +371 67808450

EZZáňa

INNOVIS PHARMA AEBE

Tnk +30 210 66 64 805–806

España

Pharmathen S.A.

Tel: +30 210 66 04 300

France

Pharmathen S.A.

Tél: +30 210 66 04 300

Hrvatska

Pharmathen S.A.

Tel: +30 210 66 04 300

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

Package leaflet: Information for the patient

Matever 100 mg/ml concentrate for solution for infusion levetiracetam

Read all of this leaflet carefully before you or your child start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

• 1. What Matever is and what it is used for

• 2. What you need to know before you are given Matever

• 3. How Matever is given

• 4. Possible side effects

• 5. How to store Matever

• 6. Contents of the pack and other information

1. What Matever is and what it is used for

Levetiracetam is an antiepileptic medicine (a medicine used to treat seizures in epilepsy).

Matever is used:

• on its own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat a certain form of epilepsy. Epilepsy is a condition where the patients have repeated fits (seizures). Levetiracetam is used for the epilepsy form in which the fits initially affect only one side of the brain, but could thereafter extend to larger areas on both sides of the brain (partial onset seizure with or without secondary generalisation). Levetiracetam has been given to you by your doctor to reduce the number of fits.
• as an add-on to other antiepileptic medicines to treat:

• ■ partial onset seizures with or without generalisation in adults, adolescents and children from 4 years of age

• ■ myoclonic seizures (short, shock-like jerks of a muscle or group of muscles) in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy.

• ■ primary generalised tonic-clonic seizures (major fits, including loss of consciousness) in adults and adolescents from 12 years of age with idiopathic generalised epilepsy (the type of epilepsy that is thought to have a genetic cause).

Matever concentrate is an alternative for patients when administration of the antiepileptic oral Matever medicine is temporarily not feasible.

2. What you need to know before you are given Matever

Do not use Matever

• if you are allergic to levetiracetam, pyrrolidone derivatives or any of the other ingredients of this

medicine (listed in Section 6).

Warnings and precautions

Talk to your doctor before you are given Matever

• if you suffer from kidney problems, follow your doctor's instruc­tions. He/she may decide if

your dose should be adjusted.

• If you notice any slowdown in the growth or unexpected puberty development of your child,

please contact your doctor.

• A small number of people being treated with anti-epileptics such as Matever have had thoughts

of harming or killing themselves. If you have any symptoms of depression and/or suicidal ideation, please contact your doctor.

• If you have a family or medical history of irregular heart rhythm (visible on an

electrocardiogram), or if you have a disease and/or take a treatment that make(s) you prone to heartbeat irregularities or salt imbalances.

Tell your doctor or pharmacist if any of the following side effects gets serious or lasts longer than a few days:

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually or if you or your family and friends notice important changes in mood or behaviour.
• Aggravation of epilepsy

Your seizures may rarely become worse or happen more often, mainly during the first month after the start of the treatment or increase of the dose. If you experience any of these new symptoms while taking Matever, see a doctor as soon as possible.

Children and adolescents

• Matever is not indicated in children and adolescents below 16 years on its own (monotherapy)

Other medicines and Matever

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take macrogol (a medicine used as laxative) for one hour before and one hour after taking levetiracetam as this may results in a reduction of its effect.

Pregnancy and 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. Levetiracetam can be used during pregnancy, only if after careful assessment it is considered necessary by your doctor.

You should not stop your treatment without discussing this with your doctor.

A risk of birth defects for your unborn child cannot be completely excluded.

Breast-feeding is not recommended during treatment.

Driving and using machines

Matever may impair your ability to drive or operate any tools or machinery, as it may make you feel sleepy. This is more likely at the beginning of treatment or after an increase in the dose. You should not drive or use machines until it is established that your ability to perform such activities is not affected.

Matever contains sodium

This medicine contains 57.21 mg sodium (main component of cooking/table salt) in each maximum single dose. This is equivalent to 2.86 % of the recommended maximum daily dietary intake of sodium for an adult.

• 3. How Matever is given

A doctor or a nurse will administer you Matever as an intravenous infusion.

Matever must be administered twice a day, once in the morning and once in the evening, at about the same time each day.

The intravenous formulation is an alternative to your oral administration. You can switch from the film-coated tablets or from the oral solution to the intravenous formulation or reverse directly without dose adaptation. Your total daily dose and frequency of administration remain identical.

Adjunctive therapy and Monotherapy (from 16 years of age).

Adults (>18 years) and adolescents (12 to 17 years) weighing 50 kg or more:

General dose: between 1000 mg and 3,000 mg each day.

When you will first start taking Matever, your doctor will prescribe you a lower dose during 2 weeks before giving you the lowest general dose.

Dose in children (4 to 11 years) and adolescents (12 to 17 years) weighing less than 50 kg:

General dose: between 20 mg per kg bodyweight and 60 mg per kg bodyweight each day.

Method and route of administration

Matever is for intravenous use. The recommended dose must be diluted in at least 100 ml of a compatible diluent and infused over 15 minutes.

For doctors and nurses, more detailed direction for the proper use of Matever is provided in section 6.

Duration of treatment

• There is no experience with administration of intravenous levetiracetam for a longer period than

• 4 days.

If you stop using Matever

If stopping treatment, as with other antiepileptic medicines, Matever should be discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your Matever treatment, he/she will instruct you about the gradual withdrawal of Matever.

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.

Tell your doctor immediately, or go to your nearest emergency department, if you experience:

• weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic (anaphylactic) reaction
• swelling of the face, lips, tongue and throat (Quincke’s oedema)
• flu-like symptoms and a rash on the face followed by an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS])
• symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the legs, ankles or feet, as this may be a sign of sudden decrease of kidney function
• a skin rash which may form blisters and look like small targets (central dark spots surrounded

by a paler area, with a dark ring around the edge) (erythema multiforme )

• a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and

genitals (Stevens-Johnson syndrome )

• a more severe form of rash causing skin peeling in more than 30% of the body surface (toxic

epidermal necrolysis )

• signs of serious mental changes or if someone around you notices signs of confusion, somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), abnormal behaviour or other neurological signs including involuntary or uncontrolled movements. These could be symptoms of an encephalopathy.

The most frequently reported adverse reactions were nasopharyngitis, somnolence (sleepiness), headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like sleepiness, tiredness and dizziness may be more common. These effects should however decrease over time.

• Very common: may affect more than 1 in 10 people nasopharyngitis;
• somnolence (sleepiness), headache.

Common: may affect up to 1 in 10 people

• anorexia (loss of appetite);
• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability;
• convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness),

lethargy (lack of energy and enthusiasm), tremor (involuntary trembling);

• vertigo (sensation of rotation);
• cough;
• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea;
• rash;
• asthenia/fatigue (tiredness).

Uncommon: may affect up to 1 in 100 people

• decreased number of blood platelets, decreased number of white blood cells;
• weight decrease, weight increase;
• suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, an­ger,

confusion, panic attack, emotional instability/mood swings, agitation;

• amnesia (loss of memory), memory impairment (forgetfulness), abnormal coordination/ataxia

(impaired coordinated movements), paraesthesia (tingling), disturbance in attention (loss of concentration);

• diplopia (double vision), vision blurred;
• elevated/abnormal values in a liver function test;
• hair loss, eczema, pruritus;
• muscle weakness, myalgia (muscle pain);
• injury.

Rare: may affect up to 1 in 1,000 people

• infection;
• decreased number of all blood cell types;
• severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction],

Quincke’s oedema [swelling of the face, lips, tongue and throat]);

• decreased blood sodium concentration;
• suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable

to concentrate);

• delirium;
• encephalopathy (see sub-section “Tell your doctor immediately” for a detailed description of

symptoms);

• seizures may become worse or happen more often;
• uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling movements, hyperkinesia (hyperactivity);
• change of the heart rhythm (Electrocardi­ogram);
• pancreatitis;
• liver failure, hepatitis;
• sudden decrease in kidney function;
• skin rash, which may form blisters and looks like small targets (central dark spots surrounded

by a paler area, with a dark ring around the edge) (erythema multiforme ), a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome ), and a more severe form causing skin peeling in more than 30% of the body surface (toxic epidermal necrolysis );

• rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase increase. Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.
• limp or difficulty walking.

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 By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Matever

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 vial and carton box after “EXP”. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

6. Contents of the pack and other information

What Matever contains

The active substance is called levetiracetam. Each ml of solution for infusion contains 100 mg of levetiracetam.

The other ingredients are: sodium acetate trihydrate, glacial acetic acid, sodium chloride, water for injections.

What Matever looks like and contents of the pack

Matever concentrate for solution for infusion (Matever concentrate) is a clear, colorless, sterile liquid.

Matever concentrate 5 ml vial is packed in a cardboard box of 10 vials.

Marketing Authorisation Holder and Manufacturer

Pharmathen S.A.

6, Dervenakion str.

15351 Pallini, Attiki

Greece

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

België/Belgiqu­e/Belgien	Lietuva
Pharmathen S.A.	Pharmathen S.A.
Tél/Tel: +30 210 66 04 300	Tel: +30 210 66 04 300
Et^rapun	Luxembourg/Lu­xemburg
Pharmathen S.A.	Pharmathen S.A.

Ten.: +30 210 66 04 300	Tél/Tel: +30 210 66 04 300
Česká republika ARDEZ Pharma, spol. s r.o. Tel: +420 220 400 391	Magyarország Onkogen Kft. Tel.: +36 70 310 1163
Danmark Orion Pharma A/S Tlf: +45 49 12 66 00	Malta Pharmathen S.A. Tel: +30 210 66 04 300
Deutschland Pharmathen S.A. Tel.: +30 210 66 04 300	Nederland Pharmathen S.A. Tel: +30 210 66 04 300
Eesti (Estonia) Pharmathen S.A. Tel: +30 210 66 04 300	Norge Pharmathen S.A. Tlf: +30 210 66 04 300
EXXáSa INNOVIS PHARMA AEBE Tiy/ +30 210 66 64 805–806	Österreich Pharmathen S.A. Tel: +30 210 66 04 300
España Pharmathen S.A. Tel: +30 210 66 04 300	Polska Pharmathen S.A. Tel.: +30 210 66 04 300
France Pharmathen S.A. Tél: +30 210 66 04 300	Portugal Pharmathen S.A. Tel.: +30 210 66 04 300
Hrvatska Makpharm d.o.o. Tel: +385 1 4840 342	Romania Pharmathen S.A. Tel: +30 210 66 04 300
Ireland Pharmathen S.A. Tel: +30 210 66 04 300	Slovenija Lenis farmacevtika d.o.o Tel.: +386 1 235 07 00
Ísland Pharmathen S.A. Sími: +30 210 66 04 300	Slovenská republika ARDEZ Pharma, spol. s r.o. Tel: +420 220 400 391
Italia Ecupharma S.r.l Tel : +39–02–38238790	Suomi/Finland Orion Corporation Puh/Tel: +358 10 4261
Kúnpog The Star Medicines Importers Co. Ltd Tiy/ +357 25371056	Sverige Orion Pharma AB Tel: +46 8 623 6440
Latvija Pharmathen S.A. Tel: +30 210 66 04 300	United Kingdom (Northern Ireland) Pharmathen S.A. Tel: +30 210 66 04 300

This leaflet was last revised in

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site:.

The following information is intended for healthcare professionals only:

Directions for the proper use of Matever is provided in section 3.

One vial of Matever concentrate contains 500 mg levetiracetam (5 ml concentrate of 100 mg/ml). See Table 1 for the recommended preparation and administration of Matever concentrate to achieve a total daily dose of 500 mg, 1000 mg, 2000 mg, or 3000 mg in two divided doses.

Table 1. Preparation and administration of Matever concentrate

Dose	Withdrawal Volume	Volume of Diluent	Infusion Time	Frequency of administration	Total Daily Dose
250 mg	2.5 ml (half 5 ml vial)	100 ml	15 minutes	Twice daily	500 mg/day
500 mg	5 ml (one 5 ml vial)	100 ml	15 minutes	Twice daily	1000 mg/day
1000 mg	10 ml (two 5 ml vials)	100 ml	15 minutes	Twice daily	2000 mg/day
1500 mg	15 ml (three 5 ml vials)	100 ml	15 minutes	Twice daily	3000 mg/day

This medicine is for single use only any unused solution should be discarded.

In use shelf life: from a microbiological point of view, the product should be used immediately after dilution. If not used immediately, in-use storage time and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.

Matever concentrate was found to be physically compatible and chemically stable when mixed with the following diluents for at least 24 hours and stored in PVC bags at controlled room temperature 1525°C.

Diluents:

• Sodium chloride (0.9 %) inj ection
• Lactated Ringer's injection
• Dextrose 5 % injection