Matever

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

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1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 250 mg film-coated tablets  

Matever 500 mg film-coated tablets  

Matever 750 mg film-coated tablets  

Matever 1000 mg film-coated tablets  

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Matever 250 mg film-coated tablets  

 

Each film-coated tablet contains 250 mg levetiracetam. 

 

Excipients with known effect 

 

Each film-coated tablet contains 0.0025 mg sunset yellow FCF aluminum lake (E110). 

 

Matever 500 mg film-coated tablets  

 

Each film-coated tablet contains 500 mg levetiracetam. 

 

Matever 750 mg film-coated tablets  

 

Each film-coated tablet contains 750 mg levetiracetam. 

 

Excipients with known effect 

 

Each film-coated tablet contains 0.08 mg sunset yellow FCF aluminum lake (E110). 

 

Matever 1000 mg film-coated tablets  

 

Each film-coated tablet contains 1000 mg levetiracetam. 

 

Excipients with known effect 

 

Each film-coated tablet contains 3.8 mg lactose monohydrate. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Film-coated tablet.  

 

Matever 250 mg film-coated tablets  

 

Blue, oblong, biconvex film-coated tablets.  

 

Matever 500 mg film-coated tablets  

 

Yellow, oblong, biconvex film-coated tablets.  

 

Matever 750 mg film-coated tablets  

 

Pink, oblong, biconvex film-coated tablets.  



 

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Matever 1000 mg film-coated tablets  

 

White, oblong, biconvex film-coated tablets. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Matever is indicated as monotherapy in the treatment of partial onset seizures with or without 

secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed 

epilepsy.  

 

Matever is indicated as adjunctive therapy  

•  in the treatment of partial onset seizures with or without secondary generalisation in adults, 

adolescents, children and infants from 1 month of age with epilepsy.  

•  in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with 

Juvenile Myoclonic Epilepsy.  

•  in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 

years of age with Idiopathic Generalised Epilepsy. 

 

4.2 Posology and method of administration 

 

Posology 

 

Monotherapy for adults and adolescents from 16 years of age 

 

The recommended starting dose is 250 mg twice daily which should be increased to an initial 

therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg 

twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg 

twice daily. 

 

Add-on therapy for adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more 

 

The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of 

treatment. 

Depending upon the clinical response and tolerability, the daily dose can be increased up to 1,500 mg 

twice daily. Dose changes can be made in 500 mg twice daily increases or decreases every two to four 

weeks. 

 

Discontinuation 

 

If levetiracetam has to be discontinued it is recommended to withdraw it gradually (e.g. in adults and 

adolescents weighing more than 50 kg: 500 mg decreases twice daily every two to four weeks; in 

infants older than 6 months, children and adolescents weighting less than 50 kg: dose decrease should 

not exceed 10 mg/kg twice daily every two weeks; in infants (less than 6 months): dose decrease 

should not exceed 7 mg/kg twice daily every two weeks). 

 

Special populations 

 

Elderly (65 years and older) 

 

Adjustment of the dose is recommended in elderly patients with compromised renal function (see 

“Renal impairment” below). 

 

Renal impairment 



 

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The daily dose must be individualised according to renal function.  

 

For adult patients, refer to the following table and adjust the dose as indicated. To use this dosing 

table, an estimate of the patient's creatinine clearance (CLcr) in ml/min is needed. The CLcr in ml/min 

may be estimated from serum creatinine (mg/dl) determination, for adults and adolescents weighting 

50 kg or more, using the following formula:  

 

                               [140-age (years)] x weight (kg) 

CLcr (ml/min) = ----------------------------------------- (x 0.85 for women) 

                               72 x serum creatinine (mg/dl) 

 

Then CLcr is adjusted for body surface area (BSA) as follows: 

 

CLcr (ml/min) 

CLcr (ml/min/1.73 m2) = ---------------------------- x 1.73 

BSA subject (m2) 

 

Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal 

function 

 

Group 

 

Creatinine clearance 

(ml/min/1.73m2 ) 

Dose and frequency 

 

Normal 

Mild 

Moderate 

Severe 

End-stage renal disease patients 

undergoing dialysis (1) 

≥ 80 

50-79 

30-49 

< 30 

- 

 

500 to 1,500 mg twice daily 

500 to 1,000 mg twice daily 

250 to 750 mg twice daily 

250 to 500 mg twice daily 

500 to 1,000 mg once daily (2) 

 

(1)A 750 mg loading dose is recommended on the first day of treatment with levetiracetam.  

(2) Following dialysis, a 250 to 500 mg supplemental dose is recommended.  

 

For children with renal impairment, levetiracetam dose needs to be adjusted based on the renal 

function as levetiracetam clearance is related to renal function. This recommendation is based on a 

study in adult renally impaired patients.  

 

The CLcr in ml/min/1.73 m2 may be estimated from serum creatinine (mg/dl) determination, for young 

adolescents, children and infants, using the following formula (Schwartz formula):  

 

      Height (cm) x ks 

CLcr (ml/min/1.73 m2) =  ------------------------------------ 

      Serum Creatinine (mg/dl) 

 

ks= 0.45 in Term infants to 1 year old; ks= 0.55 in Children to less than 13 years and in adolescent 

female; ks= 0.7 in adolescent male 

 

Dosing adjustment for infants, children and adolescents patients weighing less than 50 kg with 

impaired renal function 

Group Creatinine 

clearance 

(ml/min/1.73 m2) 

Dose and frequency (1) 

Infants 1 to less than 6 

months 

Infants 6 to 23 months, 

children and adolescents 

weighing less than 50 kg 

Normal ≥ 80 7 to 21 mg/kg (0.07 to 

0.21 ml/kg) twice daily 

10 to 30 mg/kg (0.10 to 

0.30 ml/kg) twice daily 

Mild 50-79 7 to 14 mg/kg (0.07 to 

0.14 ml/kg) twice daily 

10 to 20 mg/kg (0.10 to 

0.20 ml/kg) twice daily 



 

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Moderate 30-49 3.5 to 10.5 mg/kg (0.035 

to 0.105 ml/kg) twice 

daily 

5 to 15 mg/kg (0.05 to 

0.15 ml/kg) twice daily 

Severe < 30 3.5 to 7 mg/kg (0.035 to 

0.07 ml/kg) twice daily 

5 to 10 mg/kg (0.05 to 

0.10 ml/kg) twice daily 

End-stage renal 

disease patients 

undergoing dialysis 

-- 7 to 14 mg/kg (0.07 to 

0.14 ml/kg)once daily 
(2) (4) 

10 to 20 mg/kg (0.10 to 

0.20 ml/kg) once daily (3) (5) 

(1) Levetiracetam oral solution should be used for doses under 250 mg, for doses not multiple of 

250 mg when dosing recommendation is not achievable by taking multiple tablets and for patients 

unable to swallow tablets.  
(2) A 10.5 mg/kg (0.105 ml/kg) loading dose is recommended on the first day of treatment with 

levetiracetam. 

 (3) A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with 

levetiracetam. 
(4) Following dialysis, a 3.5 to 7 mg/kg (0.035 to 0.07 ml/kg) supplemental dose is recommended. 
(5) Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 ml/kg) supplemental dose is recommended. 

 

Hepatic impairment  

 

No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with 

severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency. 

Therefore, a 50 % reduction of the daily maintenance dose is recommended when the creatinine 

clearance is < 60 ml/min/1.73 m2. 

 

Paediatric population 

 

The physician should prescribe the most appropriate pharmaceutical form, presentation and strength 

according to age, weight and dose. 

 

The tablet formulation is not adapted for use in infants and children under the age of 6 years.  An oral 

solution is the preferred formulation for use in this population. In addition, the available dose strengths 

of the tablets are not appropriate for initial treatment in children weighing less than 25 kg, for patients 

unable to swallow tablets or for the administration of doses below 250 mg. In all of the above cases an 

oral solution should be used. 

 

Monotherapy 

 

The safety and efficacy of Matever in children and adolescents below 16 years as monotherapy 

treatment have not been established. 

No data are available. 

 

Add-on therapy for infants aged from 6 to 23 months, children (2 to 11 years) and adolescents (12 to 

17 years) weighing less than 50 kg 

 

An oral solution is the preferred formulation for use in infants and children under the age of 6 years. 

 

For children 6 years and above, an oral solution should be used for doses under 250 mg, for doses not 

multiple of 250 mg when dosing recommendation is not achievable by taking multiple tablets and for 

patients unable to swallow tablets. 

The lowest effective dose should be used. The starting dose for a child or adolescent of 25 kg should 

be 250 mg twice daily with a maximum dose of 750 mg twice daily.  

Dose in children 50 kg or greater is the same as in adults. 

 

Add-on therapy for infants aged from 1 month to less than 6 months 

 

The oral solution is the formulation to use in infants. 



 

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Method of administration 

 

The film-coated tablets must be taken orally, swallowed with a sufficient quantity of liquid and may 

be taken with or without food. After oral administration the bitter taste of levetiracetam may be 

experienced. The daily dose is administered in two equally divided doses. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients 

listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

Renal impairment 

 

The administration of levetiracetam to patients with renal impairment may require dose adjustment. In 

patients with severely impaired hepatic function, assessment of renal function is recommended before 

dose selection (see section 4.2).  

 

Acute kidney injury 

 

The use of levetiracetam has been very rarely associated with acute kidney injury, with a time to onset 

ranging from a few days to several months. 

 

Blood cell counts 

 

Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, 

thrombocytopenia and pancytopenia) have been described in association with levetiracetam 

administration, generally at the beginning of the treatment. Complete blood cell counts are advised in 

patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders 

(section 4.8). 

 

Suicide 

 

Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with 

anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled 

trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and 

behaviour. The mechanism of this risk is not known.  

 

Therefore, patients should be monitored for signs of depression and/or suicidal ideation and 

behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) 

should be advised to seek medical advice should signs of depression and/or suicidal ideation or 

behaviour emerge. 

 

Abnormal and aggressive behaviours 

 

Levetiracetam may cause psychotic symptoms and behavioural abnormalities including irritability and 

aggressiveness. Patients treated with levetiracetam should be monitored for developing psychiatric 

signs suggesting important mood and/or personality changes. If such behaviours are noticed, treatment 

adaptation or gradual discontinuation should be considered. If discontinuation is considered, please 

refer to section 4.2. 

 

Paediatric population 

 

The tablet formulation is not adapted for use in infants and children under the age of 6 years.  

 



 

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Available data in children did not suggest impact on growth and puberty. However, long term effects 

on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children 

remain unknown. 

 

Excipients 

 

Matever 250 mg, 750 mg film-coated tablets contain E110 colouring agent which may cause allergic 

reactions. 

Matever 1000 mg film-coated tablets contain lactose. Patients with rare hereditary problems of 

galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this 

medicinal product. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Antiepileptic medicinal products 

 

Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not 

influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, 

carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these 

antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam.  

 

As in adults, there is no evidence of clinically significant medicinal product interactions in paediatric 

patients receiving up to 60 mg/kg/day levetiracetam.  

A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy 

(4 to 17 years) confirmed that adjunctive therapy with orally administered levetiracetam did not 

influence the steady-state serum concentrations of concomitantly administered carbamazepine and 

valproate. However, data suggested a 20 % higher levetiracetam clearance in children taking enzyme-

inducing antiepileptic medicinal products. Dose adjustment is not required.  

 

Probenecid 

 

Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to 

inhibit the renal clearance of the primary metabolite, but not of levetiracetam. Nevertheless, the 

concentration of this metabolite remains low.  

 

Methotrexate 

 

Concomitant administration of levetiracetam and methotrexate has been reported to decrease 

methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to 

potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in 

patients treated concomitantly with the two medicinal products. 

 

Oral contraceptives and other pharmacokinetics interactions 

 

Levetiracetam 1,000 mg daily did not influence the pharmacokinetics of oral contraceptives (ethinyl-

estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not 

modified. -Levetiracetam 2,000 mg daily did not influence the pharmacokinetics of digoxin and 

warfarin; prothrombin times were not modified. Co-administration with digoxin, oral contraceptives 

and warfarin did not influence the pharmacokinetics of levetiracetam.  

 

Laxatives 

 

There have been isolated reports of decreased levetiracetam efficacy when the osmotic laxative 

macrogol has been concomitantly administered with oral levetiracetam. Therefore, macrogol should 

not be taken orally for one hour before and for one hour after taking levetiracetam. 

 

Food and alcohol 



 

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The extent of absorption of levetiracetam was not altered by food, but the rate of absorption was 

slightly reduced.  

No data on the interaction of levetiracetam with alcohol are available. 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential  

Specialist advice should be given to women who are of childbearing potential. Treatment with 

levetiracetam should be reviewed when a woman is planning to become pregnant. As with all 

antiepileptic medicinal products, sudden discontinuation of levetiracetam should be avoided as this 

may lead to breakthrough seizures that could have serious consequences for the woman and the 

unborn child. Monotherapy should be preferred whenever possible because therapy with multiple 

antiepileptic medicinal products AEDs could be associated with a higher risk of congenital 

malformations than monotherapy, depending on the associated antiepileptics. 

 

Pregnancy 

A large amount of post-marketing data on pregnant women exposed to levetiracetam monotherapy 

(more than 1,800, among which in more than 1,500 exposure occurred during the 1st trimester) do not 

suggest an increase in the risk for major congenital malformations. Only limited evidence is available 

on the neurodevelopment of children exposed to levetiracetam monotherapy in utero. However, 

current epidemiological studies (on about 100 children) do not suggest an increased risk of 

neurodevelopmental disorders or delays.  

Levetiracetam can be used during pregnancy, if after careful assessment it is considered clinically 

needed. In such case, the lowest effective dose is recommended.  

Physiological changes during pregnancy may affect levetiracetam concentration. Decrease in 

levetiracetam plasma concentrations has been observed during pregnancy. This decrease is more 

pronounced during the third trimester (up to 60 % of baseline concentration before pregnancy). 

Appropriate clinical management of pregnant women treated with levetiracetam should be ensured.  

 

Breast-feeding 

Levetiracetam is excreted in human breast milk. Therefore, breast-feeding is not recommended. 

However, if levetiracetam treatment is needed during breast-feeding, the benefit/risk of the treatment 

should be weighed considering the importance of breast-feeding. 

 

Fertility 

No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, 

potential risk for human is unknown. 

 

4.7 Effects on ability to drive and use machines 

 

Levetiracetam has minor or moderate influence on the ability to drive and use machines. Due to 

possible different individual sensitivity, some patients might experience somnolence or other central 

nervous system related symptoms, especially at the beginning of treatment or following a dose 

increase. Therefore, caution is recommended in those patients when performing skilled tasks, e.g. 

driving vehicles or operating machinery. Patients are advised not to drive or use machines until it is 

established that their ability to perform such activities is not affected. 

 

4.8 Undesirable effects 
 

Summary of the safety profile 

 

The most frequently reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue 

and dizziness. The adverse reaction profile presented below is based on the analysis of pooled 

placebo-controlled clinical trials with all indications studied, with a total of 3,416 patients treated with 

levetiracetam. These data are supplemented with the use of levetiracetam in corresponding open-label 

extension studies, as well as post-marketing experience.  The safety profile of levetiracetam is 



 

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generally similar across age groups (adult and paediatric patients) and across the approved epilepsy 

indications.   

 

Tabulated list of adverse reactions 

 

Adverse reactions reported in clinical studies (adults, adolescents, children and infants > 1 month) and 

from post-marketing experience are listed in the following table per System Organ Class and per 

frequency. Adverse reactions are presented in the order of decreasing seriousness and their frequency 

is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 

to<1/100); rare (≥1/10,000 to<1/1,000) and very rare (<1/10,000) 

 

MedDRA SOC 
Frequency category 

Very common Common Uncommon  Rare 

Infections and 

infestations 

Nasopharyngitis    Infection 

Blood and 

lymphatic 

system 

disorders 

  Thrombocytopenia, 

leukopenia 

Pancytopenia, 

neutropenia, 

agranulocytosis 

Immune system 

disorders 

   Drug reaction 

with 

eosinophilia and 

systemic 

symptoms 

(DRESS), 

Hypersensitivity 

(including 

angioedema and 

anaphylaxis) 

Metabolism and 

nutrition 

disorders 

 Anorexia Weight decreased, 

weight increase 

Hyponatraemia 

Psychiatric 

disorders 

 Depression, hostility/ 

aggression, anxiety,  

insomnia, 

nervousness/irritability 

Suicide attempt, 

suicidal 

ideation,psychotic 

disorder, abnormal 

behaviour, 

hallucination, anger, 

confusional state, 

panic attack, affect 

lability/mood 

swings, agitation 

Completed 

suicide, 

personality 

disorder, 

thinking 

abnormal, 

delirium 

Nervous system 

disorders 

Somnolence, 

headache 

Convulsion, balance 

disorder, dizziness, 

lethargy, tremor 

Amnesia, memory 

impairment, 

coordination 

abnormal/ataxia, 

paraesthesia, 

disturbance in 

attention 

Choreoathetosis, 

dyskinesia, 

hyperkinesia, 

gait disturbance, 

encephalopathy 

Eye disorders   Diplopia, vision 

blurred 

 

Ear and 

labyrinth 

disorders 

 Vertigo   

Respiratory,  Cough   



 

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thoracic and 

mediastinal 

disorders 

Gastrointestinal 

disorders 

 Abdominal pain, 

diarrhoea, dyspepsia, 

vomiting, nausea 

 Pancreatitis 

Hepatobiliary 

disorders 

  Liver function test 

abnormal 

Hepatic failure, 

hepatitis 

Skin and 

subcutaneous 

tissue disorders 

 Rash Alopecia, eczema, 

pruritus,  

Toxic epidermal 

necrolysis, 

Stevens-Johnson 

syndrome, 

erythema 

multiforme 

Musculoskeletal 

and connective 

tissue disorders 

  Muscular weakness, 

myalgia 

Rhabdomyolysis 

and blood 

creatine 

phosphokinase 

increased* 

Renal and 

urinary 

disorders 

   Acute kidney 

injury 

General 

disorders and 

administration 

site conditions 

 Asthenia/fatigue   

Injury, 

poisoning and 

procedural 

complications 

  Injury  

 

* Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.  

 

Description of selected adverse reactions 

 

The risk of anorexia is higher when levetiracetam is co-administered with topiramate. 

In several cases of alopecia, recovery was observed when levetiracetam was discontinued. 

Bone marrow suppression was identified in some of the cases of pancytopenia. 

 

Cases of encephalopathy generally occurred at the beginning of the treatment (few days to a few 

months) and were reversible after treatment discontinuation. 

 

Paediatric population 

 

In patients aged 1 month to less than 4 years, a total of 190 patients have been treated with 

levetiracetam in placebo-controlled and open label extension studies.  Sixty of these patients were 

treated with levetiracetam in placebo-controlled studies.  In patients aged 4-16 years, a total of 645 

patients have been treated with levetiracetam in placebo-controlled and open label extension studies.  

233 of these patients were treated with levetiracetam in placebo-controlled studies. In both these 

paediatric age ranges, these data are supplemented with the post-marketing experience of the use of 

levetiracetam. 

 

In addition, 101 infants aged less than 12 months have been exposed in a post authorization safety 

study. No new safety concerns for levetiracetam were identified for infants less than 12 months of age 

with epilepsy. 



 

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The adverse reaction profile of levetiracetam is generally similar across age groups and across the 

approved epilepsy indications.  Safety results in paediatric patients in placebo-controlled clinical 

studies were consistent with the safety profile of levetiracetam in adults except for behavioural and 

psychiatric adverse reactions which were more common in children than in adults.  In children and 

adolescents aged 4 to 16 years, vomiting (very common, 11.2%), agitation (common, 3.4%), mood 

swings (common, 2.1%), affect lability (common, 1.7%), aggression (common, 8.2%), abnormal 

behaviour (common, 5.6%), and lethargy (common, 3.9%) were reported more frequently than in other 

age ranges or in the overall safety profile.  In infants and children aged 1 month to less than 4 years, 

irritability (very common, 11.7%) and coordination abnormal (common, 3.3%) were reported more 

frequently than in other age groups or in the overall safety profile.   

 

A double-blind, placebo-controlled paediatric safety study with a non-inferiority design has assessed 

the cognitive and neuropsychological effects of levetiracetam in children 4 to 16 years of age with 

partial onset seizures. It was concluded that levetiracetam was not different (non inferior) from 

placebo with regard to the change from baseline of the Leiter-R Attention and Memory, Memory 

Screen Composite score in the per-protocol population. Results related to behavioural and emotional 

functioning indicated a worsening in levetiracetam treated patients on aggressive behavior as 

measured in a standardised and systematic way using a validated instrument (CBCL – Achenbach 

Child Behavior Checklist). However, subjects who took levetiracetam in the long-term open label 

follow-up study, did not experience a worsening, on average, in their behavioural and emotional 

functioning; in particular measures of aggressive behavior were not worse than baseline. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

Symptoms 

 

Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma 

were observed with Matever overdoses.  

 

Management of overdose 

 

After an acute overdose, the stomach may be emptied by gastric lavage or by induction of emesis. 

There is no specific antidote for levetiracetam. Treatment of an overdose will be symptomatic and may 

include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74 % for the 

primary metabolite. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: antiepileptics, other antiepileptics, ATC code: N03AX14.  

 

The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of α-ethyl-2-oxo-1-

pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances.  

 

Mechanism of action 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

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The mechanism of action of levetiracetam still remains to be fully elucidated. In vitro and in vivo 

experiments suggest that levetiracetam does not alter basic cell characteristics and normal 

neurotransmission.  

In vitro studies show that levetiracetam affects intraneuronal Ca2+ levels by partial inhibition of N-type 

Ca2+ currents and by reducing the release of Ca2+ from intraneuronal stores. In addition it partially 

reverses the reductions in GABA- and glycine-gated currents induced by zinc and β-carbolines. 

Furthermore, levetiracetam has been shown in in vitro studies to bind to a specific site in rodent brain 

tissue. This binding site is the synaptic vesicle protein 2A, believed to be involved in vesicle fusion 

and neurotransmitter exocytosis. Levetiracetam and related analogs show a rank order of affinity for 

binding to the synaptic vesicle protein 2A which correlates with the potency of their anti-seizure 

protection in the mouse audiogenic model of epilepsy. This finding suggests that the interaction 

between levetiracetam and the synaptic vesicle protein 2A seems to contribute to the antiepileptic 

mechanism of action of the medicinal product.  

 

Pharmacodynamic effects 

 

Levetiracetam induces seizure protection in a broad range of animal models of partial and primary 

generalised seizures without having a pro-convulsant effect. The primary metabolite is inactive.  

In man, an activity in both partial and generalised epilepsy conditions (epileptiform 

discharge/photoparoxysmal response) has confirmed the broad spectrum pharmacological profile of 

levetiracetam.  

 

Clinical efficacy and safety 

 

Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation 

in adults, adolescents, children and infants from 1 month of age with epilepsy: 

 

In adults, levetiracetam efficacy has been demonstrated in 3 double-blind, placebo-controlled studies 

at 1000 mg, 2000 mg, or 3000 mg/day, given in 2 divided doses, with a treatment duration of up to 

18 weeks. In a pooled analysis, the percentage of patients who achieved 50 % or greater reduction 

from baseline in the partial onset seizure frequency per week at stable dose (12/14 weeks) was of 

27.7 %, 31.6 % and 41.3 % for patients on 1000, 2000 or 3000 mg levetiracetam respectively and of 

12.6 % for patients on placebo.  

 

Paediatric population 

 

In paediatric patients (4 to 16 years of age), levetiracetam efficacy was established in a double-blind, 

placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks. In 

this study, the patients received levetiracetam as a fixed dose of 60 mg/kg/day (with twice a day 

dosing).  

44.6 % of the levetiracetam treated patients and 19.6 % of the patients on placebo had a 50 % or 

greater reduction from baseline in the partial onset seizure frequency per week. With continued long-

term treatment, 11.4 % of the patients were seizure-free for at least 6 months and 7.2 % were seizure-

free for at least 1 year.  

 

In paediatric patients (1 month to less than 4 years of age), levetiracetam efficacy was established in a 

double-blind, placebo-controlled study, which included 116 patients and had a treatment duration of 

5 days. In this study, patients were prescribed 20 mg/kg, 25 mg/kg, 40 mg/kg or 50 mg/kg daily dose 

of oral solution based on their age titration schedule. A dose of 20 mg/kg/day titrating to 40 mg/kg/day 

for infants one month to less than six months and a dose of 25 mg/kg/day titrating to 50 mg/kg/day for 

infants and children 6 months to less than 4 years old, was use in this study. The total daily dose was 

administered twice daily. 

The primary measure of effectiveness was the responder rate (percent of patients with ≥ 50 % 

reduction from baseline in average daily partial onset seizure frequency) assessed by a blinded central 

reader using a 48-hour video EEG.  The efficacy analysis consisted of 109 patients who had at least 24 

hours of video EEG in both baseline and evaluation periods. 43.6 % of the levetiracetam treated 

patients and 19.6 % of the patients on placebo were considered as responders. The results are 



 

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consistent across age group. With continued long-term treatment, 8.6 % of the patients were seizure-

free for at least 6 months and 7.8 % were seizure-free for at least 1 year.35 infants aged less than 1 

year with partial onset seizures have been exposed in placebo-control clinical studies of which only 13 

were aged < 6 months. 

 

Monotherapy in the treatment of partial onset seizures with or without secondary generalisation in 

patients from 16 years of age with newly diagnosed epilepsy.  

 

Efficacy of levetiracetam as monotherapy was established in a double-blind, parallel group, non-

inferiority comparison to carbamazepine controlled release (CR) in 576 patients 16 years of age or 

older with newly or recently diagnosed epilepsy. The patients had to present with unprovoked partial 

seizures or with generalized tonic-clonic seizures only. The patients were randomized to 

carbamazepine CR 400 -1200 mg/day or levetiracetam 1000 -3000 mg/day, the duration of the 

treatment was up to 121 weeks depending on the response.  

Six-month seizure freedom was achieved in 73.0 % of levetiracetam-treated patients and 72.8 % of 

carbamazepine-CR treated patients; the adjusted absolute difference between treatments was 0.2 % 

(95 % CI: -7.8 8.2). More than half of the subjects remained seizure free for 12 months (56.6 % and 

58.5 % of subjects on levetiracetam and on carbamazepine CR respectively).  

 

In a study reflecting clinical practice, the concomitant antiepileptic medication could be withdrawn in 

a limited number of patients who responded to levetiracetam adjunctive therapy (36 adult patients out 

of 69).  

 

Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of 

age with Juvenile Myoclonic Epilepsy. 

 

Levetiracetam efficacy was established in a double-blind, placebo-controlled study of 16 weeks 

duration, in patients 12 years of age and older suffering from idiopathic generalized epilepsy with 

myoclonic seizures in different syndromes. The majority of patients presented with juvenile myoclonic 

epilepsy.  

In this study, levetiracetam, dose was 3000 mg/day given in 2 divided doses.  

58.3 % of the levetiracetam treated patients and 23.3 % of the patients on placebo had at least a 50 % 

reduction in myoclonic seizure days per week. With continued long-term treatment, 28.6 % of the 

patients were free of myoclonic seizures for at least 6 months and 21.0 % were free of myoclonic 

seizures for at least 1 year.  

 

Adjunctive therapy in the treatment of primary generalised tonic-clonic seizures in adults and 

adolescents from 12 years of age with idiopathic generalised epilepsy. 

 

Levetiracetam efficacy was established in a 24-week double-blind, placebo-controlled study which 

included adults, adolescents and a limited number of children suffering from idiopathic generalized 

epilepsy with primary generalized tonic-clonic (PGTC) seizures in different syndromes (juvenile 

myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand 

Mal seizures on awakening). In this study, levetiracetam dose was 3000 mg/day for adults and 

adolescents or 60 mg/kg/day for children, given in 2 divided doses.  

72.2 % of the levetiracetam treated patients and 45.2 % of the patients on placebo had a 50 % or 

greater decrease in the frequency of PGTC seizures per week. With continued long-term treatment, 

47.4 % of the patients were free of tonic-clonic seizures for at least 6 months and 31.5 % were free of 

tonic-clonic seizures for at least 1 year. 

 

5.2 Pharmacokinetic properties 

 

Levetiracetam is a highly soluble and permeable compound. The pharmacokinetic profile is linear with 

low intra- and inter-subject variability. There is no modification of the clearance after repeated 

administration. There is no evidence for any relevant gender, race or circadian variability. The 

pharmacokinetic profile is comparable in healthy volunteers and in patients with epilepsy. 

 



 

14 

Due to its complete and linear absorption, plasma levels can be predicted from the oral dose of 

levetiracetam expressed as mg/kg bodyweight. Therefore, there is no need for plasma level monitoring 

of levetiracetam.  

 

A significant correlation between saliva and plasma concentrations has been shown in adults and 

children (ratio of saliva/plasma concentrations ranged from 1 to 1.7 for oral tablet formulation and 

after 4 hours post-dose for oral solution formulation). 

 

Adults and adolescents 

 

Absorption 

 

Levetiracetam is rapidly absorbed after oral administration. Oral absolute bioavailability is close to 

100 %.  

Peak plasma concentrations (Cmax) are achieved at 1.3 hours after dosing. Steady-state is achieved after 

two days of a twice daily administration schedule.  

Peak concentrations (Cmax) are typically 31 and 43 µg/ml following a single 1,000 mg dose and 

repeated 1,000 mg twice daily dose, respectively.  

The extent of absorption is dose-independent and is not altered by food.  

 

Distribution 

 

No tissue distribution data are available in humans.  

Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins(< 10 %).  

The volume of distribution of levetiracetam is approximately 0.5 to 0.7 l/kg, a value close to the total 

body water volume.  

 

Biotransformation 

 

Levetiracetam is not extensively metabolised in humans. The major metabolic pathway (24 % of the 

dose) is an enzymatic hydrolysis of the acetamide group. Production of the primary metabolite, 

ucb L057, is not supported by liver cytochrome P450 isoforms. Hydrolysis of the acetamide group was 

measurable in a large number of tissues including blood cells. The metabolite ucb L057 is 

pharmacologically inactive.  

 

Two minor metabolites were also identified. One was obtained by hydroxylation of the pyrrolidone 

ring (1.6 % of the dose) and the other one by opening of the pyrrolidone ring (0.9 % of the dose).  

Other unidentified components accounted only for 0.6 % of the dose.  

 

No enantiomeric interconversion was evidenced in vivo for either levetiracetam or its primary 

metabolite.  

 

In vitro, levetiracetam and its primary metabolite have been shown not to inhibit the major human 

liver cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl 

transferase (UGT1A1 and UGT1A6) and epoxide hydroxylase activities. In addition, levetiracetam 

does not affect the in vitro glucuronidation of valproic acid.  

In human hepatocytes in culture, levetiracetam had little or no effect on CYP1A2, SULT1E1 or 

UGT1A1. Levetiracetam caused mild induction of CYP2B6 and CYP3A4. The in vitro data and in 

vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme 

induction is expected in vivo. Therefore, the interaction of Matever with other substances, or vice 

versa, is unlikely.  

 

Elimination 

 

The plasma half-life in adults was 71 hours and did not vary either with dose, route of administration 

or repeated administration. The mean total body clearance was 0.96 ml/min/kg.  

 



 

15 

The major route of excretion was via urine, accounting for a mean 95 % of the dose (approximately 

93 % of the dose was excreted within 48 hours). Excretion via faeces accounted for only 0.3 % of the 

dose.  

The cumulative urinary excretion of levetiracetam and its primary metabolite accounted for 66 % and 

24 % of the dose, respectively during the first 48 hours.  

The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 ml/min/kg respectively indicating 

that levetiracetam is excreted by glomerular filtration with subsequent tubular reabsorption and that 

the primary metabolite is also excreted by active tubular secretion in addition to glomerular filtration. 

Levetiracetam elimination is correlated to creatinine clearance.  

 

Elderly 

 

In the elderly, the half-life is increased by about 40 % (10 to 11 hours). This is related to the decrease 

in renal function in this population (see section 4.2). 

 

Renal impairment 

 

The apparent body clearance of both levetiracetam and of its primary metabolite is correlated to the 

creatinine clearance. It is therefore recommended to adjust the maintenance daily dose of Matever, 

based on creatinine clearance in patients with moderate and severe renal impairment (see section 4.2).  

 

In anuric end-stage renal disease adult subjects the half-life was approximately 25 and 3.1 hours 

during interdialytic and intradialytic periods, respectively.  

The fractional removal of levetiracetam was 51 % during a typical 4-hour dialysis session.  

 

Hepatic impairment 

 

In subjects with mild and moderate hepatic impairment, there was no relevant modification of the 

clearance of levetiracetam. In most subjects with severe hepatic impairment, the clearance of 

levetiracetam was reduced by more than 50 % due to a concomitant renal impairment (see section 4.2). 

 

Paediatric population 

 

Children (4 to 12 years) 

 

Following single oral dose administration (20 mg/kg) to epileptic children (6 to 12 years), the half-life 

of levetiracetam was 6.0 hours. The apparent body weight adjusted clearance was approximately 30 % 

higher than in epileptic adults. 

 

Following repeated oral dose administration (20 to 60 mg/kg/day) to epileptic children (4 to 12 years), 

levetiracetam was rapidly absorbed. Peak plasma concentration was observed 0.5 to 1.0 hour after 

dosing. Linear and dose proportional increases were observed for peak plasma concentrations and area 

under the curve. The elimination half-life was approximately 5 hours. The apparent body clearance 

was 1.1 ml/min/kg. 

 

Infants and children (1 month to 4 years) 

 

Following single dose administration (20 mg/kg) of a 100 mg/ml oral solution to epileptic children 

(1 month to 4 years), levetiracetam was rapidly absorbed and peak plasma concentrations were 

observed approximately 1 hour after dosing.  The pharmacokinetic results indicated that half-life was 

shorter (5.3 h) than for adults (7.2 h) and apparent clearance was faster (1.5 ml/min/kg) than for adults 

(0.96 ml/min/kg). 

 

In the population pharmacokinetic analysis conducted in patients from 1 month to 16 years of age, 

body weight was significantly correlated to apparent clearance (clearance increased with an increase in 

body weight) and apparent volume of distribution. Age also had an influence on both parameters. This 



 

16 

effect was pronounced for the younger infants, and subsided as age increased, to become negligible 

around 4 years of age. 

 

In both population pharmacokinetic analyses, there was about a 20 % increase of apparent clearance of 

levetiracetam when it was co-administered with an enzyme-inducing antiepileptic medicinal product. 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, genotoxicity and carcinogenic potential.  

Adverse reactions not observed in clinical studies, but seen in the rat and to a lesser extent in the 

mouse at exposure levels similar to human exposure levels and with possible relevance to clinical use 

were liver changes, indicating an adaptive response such as increased weight and centrilobular 

hypertrophy, fatty infiltration and increased liver enzymes in plasma.  

 

No adverse reactions on male or female fertility or reproduction performance were observed in rats at 

doses up to 1800 mg/kg/day (x 6 the MRHD on a mg/m2 or exposure basis) in parents and F1 

generation. 

 

Two embryo-fetal development (EFD) studies were performed in rats at 400, 1200 and 

3600 mg/kg/day. At 3600 mg/kg/day, in only one of the 2 EFD studies, there was a slight decrease in 

fetal weight associated with a marginal increase in skeletal variations/minor anomalies. There was no 

effect on embryomortality and no increased incidence of malformations. The NOAEL (No Observed 

Adverse Effect Level) was 3600 mg/kg/day for pregnant female rats (x 12 the MRHD on a mg/m2 

basis) and 1200 mg/kg/day for fetuses.  

 

Four embryo-fetal development studies were performed in rabbits covering doses of 200, 600, 800, 

1200 and 1800 mg/kg/day. The dose level of 1800 mg/kg/day induced a marked maternal toxicity and 

a decrease in fetal weight associated with increased incidence of fetuses with cardiovascular/skeletal 

anomalies. The NOAEL was < 200 mg/kg/day for the dams and 200 mg/kg/day for the fetuses (equal 

to the MRHD on a mg/m2 basis).  

A peri- and post-natal development study was performed in rats with levetiracetam doses of 70, 350 

and 1800 mg/kg/day. The NOAEL was ≥ 1800 mg/kg/day for the F0 females, and for the survival, 

growth and development of the F1 offspring up to weaning (x 6 the MRHD on a mg/m2 basis). 

 

Neonatal and juvenile animal studies in rats and dogs demonstrated that there were no adverse 

reactions seen in any of the standard developmental or maturation endpoints at doses up to 

1800 mg/kg/day (x 6 – 17 the MRHD on a mg/m2 basis). 

 

Environmental Risk Assessment (ERA) 

 

The use of Matever in accordance with the product information is not likely to result in an 

unacceptable environmental impact (see section 6.6). 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Core 

 

Calcium hydrogen phosphate dihydrate 

Microcrystalline cellulose 

Crospovidone type A 

Hydroxypropylcellulose (L) 

 

Film-coating 



 

17 

 

Matever 250 mg film-coated tablets  

 

Coating agent (blue) consisting of:  

Hypromellose (E464) 

Titanium dioxide (E171) 

Talc 

Propylene glycol (E1520) 

Indigo carmine aluminum lake (E132) 

Sunset yellow FCF aluminum lake (E110) 

Quinoline yellow aluminium lake (E104).  

 

Matever 500 mg film-coated tablets  

 

Coating agent (yellow) consisting of:  

Hydroxypropylcellulose (E463) 

Hypromellose (E464) 

Propylene glycol (E1520) 

Quinoline yellow aluminium lake (E104) 

Sorbic acid (E200) 

Sorbitan monooleate (E494) 

Titanium dioxide (E171) 

Vanillin. 

 

Matever 750 mg film-coated tablets  

 

Coating agent (orange) consisting of:  

Hypromellose (E464) 

Indigo carmine aluminum lake (E132) 

Sunset yellow FCF aluminum lake (E110) 

Iron oxide red (E172) 

Macrogol/PEG 4000  

Titanium dioxide (E171). 

 

Matever 1000 mg film-coated tablets  

 

Coating agent (white) consisting of:  

Hypromellose (E464) 

Lactose monohydrate 

Macrogol/PEG 4000 

Titanium dioxide (E171). 

 

6.2 Incompatibilities 

 

Not applicable. 

 

6.3 Shelf life 

 

3 years. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

6.5 Nature and contents of container 
 

Matever 250 mg film-coated tablets  



 

18 

 

Aluminium/PVC/PE/PVDC blisters placed into cardboard boxes containing 20, 30, 50, 60, 100 and 

multipack containing 200 (2 packs of 100) film-coated tablets. 

 

Matever 500 mg film-coated tablets  

 

Aluminium/PVC/PE/PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 100, 

120 and multipack containing 200 (2 packs of 100) film-coated tablets. 

 

Matever 750 mg film-coated tablets  

 

Aluminium/PVC/PE/PVDC blisters placed into cardboard boxes containing 20, 30, 50, 60, 80, 100, 

120 and multipack containing 200 (2 packs of 100) film-coated tablets. 

 

Matever 1000 mg film-coated tablets  

 

Aluminium/PVC/PE/PVDC blisters placed into cardboard boxes containing 10, 20, 30, 50, 60, 100 

and multipack containing 200 (2 packs of 100) film-coated tablets. 

 

Not all pack sizes may be marketed. 

 

6.6 Special precautions for disposal 

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A.  

6, Dervenakion str.,  

153 51 Pallini  

Attiki, Greece  

Tel.: +30 210 66 04 300 

Fax: +30 210 66 66 749 

 

 

8. MARKETING AUTHORISATION NUMBER(S)  

 

Matever 250 mg film-coated tablets  

 

EU/1/11/711/001 

EU/1/11/711/002 

EU/1/11/711/003 

EU/1/11/711/004 

EU/1/11/711/005 

EU/1/11/711/006 

 

Matever 500 mg film-coated tablets  

 

EU/1/11/711/007 

EU/1/11/711/008 

EU/1/11/711/009 

EU/1/11/711/010 

EU/1/11/711/011 

EU/1/11/711/012 

EU/1/11/711/013 



 

19 

EU/1/11/711/014 

 

Matever 750 mg film-coated tablets  

 

EU/1/11/711/015 

EU/1/11/711/016 

EU/1/11/711/017 

EU/1/11/711/018 

EU/1/11/711/019 

EU/1/11/711/020 

EU/1/11/711/021 

EU/1/11/711/022 

 

Matever 1000 mg film-coated tablets  

 

EU/1/11/711/023 

EU/1/11/711/024 

EU/1/11/711/025 

EU/1/11/711/026 

EU/1/11/711/027 

EU/1/11/711/028 

EU/1/11/711/029 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 03 October 2011 

Date of latest renewal: 29 June 2016 

 

 

10. DATE OF REVISION OF THE TEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu 

http://www.ema.europa.eu/


 

20 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 100 mg/ml concentrate for solution for infusion. 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each ml contains 100 mg of levetiracetam. 

The 5 ml vial contains 500 mg of levetiracetam. 

 

Excipient with known effect 

 

Each ml contains 3.81 mg sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Concentrate for solution for infusion (sterile concentrate). 

 

Clear, colourless concentrate. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Matever is indicated as monotherapy in the treatment of partial onset seizures with or without 

secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed 

epilepsy.  

 

Matever is indicated as adjunctive therapy 

• in the treatment of partial onset seizures with or without secondary generalisation in adults, 

adolescents and children from 4 years of age with epilepsy. 

• in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with 

Juvenile Myoclonic Epilepsy. 

• in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 

12 years of age with Idiopathic Generalised Epilepsy. 

 

Matever concentrate is an alternative for patients when oral administration is temporarily not feasible. 

 

4.2 Posology and method of administration 

 

Posology 

 

Matever therapy can be initiated with either intravenous or oral administration. 

Conversion to or from oral to intravenous administration can be done directly without titration. The 

total daily dose and frequency of administration should be maintained. 

 

Monotherapy for adults and adolescents from 16 years of age 

 

The recommended starting dose is 250 mg twice daily which should be increased to an initial 

therapeutic dose of 500 mg twice daily after two weeks. The dose can be further increased by 250 mg 

twice daily every two weeks depending upon the clinical response. The maximum dose is 1500 mg 

twice daily. 



 

21 

Add-on therapy for adults (≥18 years) and adolescents (12 to 17 years) weighing 50 kg or more 

 

The initial therapeutic dose is 500 mg twice daily. This dose can be started on the first day of 

treatment. Depending upon the clinical response and tolerability, the daily dose can be increased up to 

1,500 mg twice daily. Dose changes can be made in 500 mg twice daily increases or decreases every 

two to four weeks. 

 

Duration of treatment 

 

There is no experience with administration of intravenous levetiracetam for longer period than 4 days. 

 

Discontinuation 

 

If levetiracetam has to be discontinued it is recommended to withdraw it gradually (e.g. in adults and 

adolescents weighing more than 50 kg: 500 mg decreases twice daily every two to four weeks; in 

children and adolescents weighting less than 50 kg: dose decrease should not exceed 10 mg/kg twice 

daily every two weeks). 

 

Special populations 

 

Elderly (65 years and older) 

 

Adjustment of the dose is recommended in elderly patients with compromised renal function (see 

“Renal impairment” below). 

 

Renal impairment 

 

The daily dose must be individualised according to renal function.  

 

For adult patients, refer to the following table and adjust the dose as indicated. To use this dosing 

table, an estimate of the patient's creatinine clearance (CLcr) in ml/min is needed. The CLcr in ml/min 

may be estimated from serum creatinine (mg/dl) determination, for adults and adolescents weighting 

50 kg or more, the following formula: 

 

   [140-age (years)] x weight (kg) 

CLcr (ml/min)=   -----------------------------------------  (x 0.85 for women) 

   72 x serum creatinine (mg/dl) 

 

Then CLcr is adjusted for body surface area (BSA) as follows: 

 

     CLcr (ml/min) 

CLcr (ml/min/1.73 m2) =    ----------------------------  x 1.73  

     BSA subject (m2) 

 

Dosing adjustment for adult and adolescents patients weighing more than 50 kg with impaired renal 

function: 

 

Group Creatinine clearance 

(ml/min/1.73m2) 

Dose and frequency 

Normal 

Mild 

Moderate 

Severe 

End-stage renal disease patients 

undergoing dialysis (1) 

≥ 80 

50-79 

30-49 

< 30 

- 

500 to 1,500 mg twice daily 

500 to 1,000  mg twice daily 

250 to 750 mg twice daily 

250 to 500 mg twice daily 

500 to 1,000 mg once daily (2) 

(1) A 750 mg loading dose is recommended on the first day of treatment with levetiracetam. 
(2) Following dialysis, a 250 to 500 mg supplemental dose is recommended. 



 

22 

 

For children with renal impairment, levetiracetam dose needs to be adjusted based on the renal 

function as levetiracetam clearance is related to renal function. This recommendation is based on a 

study in adult renally impaired patients. 

 

The CLcr in ml/min/1.73 m2 may be estimated from serum creatinine (mg/dl) determination, for young 

adolescents and children using the following formula (Schwartz formula):  

 

      Height (cm) x ks 

CLcr (ml/min/1.73 m2) =  ------------------------------------ 

      Serum Creatinine (mg/dl) 

ks= 0.55 in Children to less than 13 years and in adolescent female; ks= 0.7 in adolescent male 

 

Dosing adjustment for children and adolescents patients weighing less than 50 kg with impaired renal 

function 

 

Group Creatinine 

clearance 

(ml/min/1.73m2) 

Dose and frequency 

Children from 4 years and adolescents weighing less than 

50 kg 

Normal ≥ 80 10 to 30 mg/kg (0.10 to 0.30 ml/kg) twice daily 

Mild 50-79 10 to 20 mg/kg (0.10 to 0.20 ml/kg) twice daily 

Moderate 30-49 5 to 15 mg/kg (0.05 to 0.15 ml/kg) twice daily 

Severe < 30 5 to 10 mg/kg (0.05 to 0.10 ml/kg) twice daily  

End-stage renal 

disease patients 

undergoing dialysis  

-- 10 to 20 mg/kg (0.10 to 0.20 ml/kg) once daily (1) (2) 

(1) A 15 mg/kg (0.15 ml/kg) loading dose is recommended on the first day of treatment with 

levetiracetam. 
(2) Following dialysis, a 5 to 10 mg/kg (0.05 to 0.10 ml/kg) supplemental dose is recommended. 

 

Hepatic impairment  

 

No dose adjustment is needed in patients with mild to moderate hepatic impairment. In patients with 

severe hepatic impairment, the creatinine clearance may underestimate the renal insufficiency. 

Therefore a 50 % reduction of the daily maintenance dose is recommended when the creatinine 

clearance is < 60 ml/min/1.73 m2. 

 

Paediatric population 

 

The physician should prescribe the most appropriate pharmaceutical form, presentation and strength 

according to age, weight and dose. 

 

Monotherapy 

 

The safety and efficacy of Matever in children below and adolescents 16 years as monotherapy 

treatment have not been established. 

No data are available. 

 

Add-on therapy for children aged 4 to 11 years and adolescents (12 to 17 years) weighing less than 

50 kg 

 

The initial therapeutic dose is 10 mg/kg twice daily.  

Depending upon the clinical response and tolerability, the dose can be increased up to 30 mg/kg twice 

daily. Dose changes should not exceed increases or decreases of 10 mg/kg twice daily every two 

weeks. The lowest effective dose should be used. 

Dose in children 50 kg or greater is the same as in adults. 

 



 

23 

Dose recommendations for children and adolescents: 

 

Weight Starting dose:  

10 mg/kg twice daily 

Maximum dose:  

30 mg/kg twice daily 

15 kg (1) 150 mg twice daily 450 mg twice daily 

20 kg (1) 200 mg twice daily 600 mg twice daily 

25 kg 250 mg twice daily 750 mg twice daily 

From 50 kg (2) 500 mg twice daily 1500 mg twice daily 
(1) Children 25 kg or less should preferably start the treatment with levetiracetam 100 mg/ml oral 

solution. 
(2) Dose in children and adolescents 50 kg or more is the same as in adults. 

 

Add-on therapy for infants and children less than 4 years  

 

The safety and efficacy of Matever concentrate for solution for infusion in infants and children less 

than 4 years have not been established. 

Currently available data are described in sections 4.8, 5.1, and 5.2 but no recommendation on a 

posology can be made. 

 

Method of administration 

 

Matever concentrate is for intravenous use only and the recommended dose must be diluted in at least 

100 ml of a compatible diluent and administered intravenously as a 15-minute intravenous infusion 

(see section 6.6). 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or other pyrrolidone derivatives or to any of the excipients 

listed in section 6.1. 

 

4.4 Special warnings and precautions for use 

 

Renal impairment 

 

The administration of levetiracetam to patients with renal impairment may require dose adjustment. In 

patients with severely impaired hepatic function, assessment of renal function is recommended before 

dose selection (see section 4.2). 

 

Acute kidney injury 

 

The use of levetiracetam has been very rarely associated with acute kidney injury, with a time to onset 

ranging from a few days to several months. 

 

Blood cell counts 

 

Rare cases of decreased blood cell counts (neutropenia, agranulocytosis, leucopenia, 

thrombocytopenia and pancytopenia) have been described in association with levetiracetam 

administration, generally at the beginning of the treatment. Complete blood cell counts are advised in 

patients experiencing important weakness, pyrexia, recurrent infections or coagulation disorders 

(section 4.8). 

 

Suicide 

 

Suicide, suicide attempt, suicidal ideation and behaviour have been reported in patients treated with 

anti-epileptic agents (including levetiracetam). A meta-analysis of randomized placebo-controlled 



 

24 

trials of anti-epileptic medicinal products has shown a small increased risk of suicidal thoughts and 

behaviour. The mechanism of this risk is not known.  

 

Therefore patients should be monitored for signs of depression and/or suicidal ideation and behaviours 

and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised 

to seek medical advice should signs of depression and/or suicidal ideation or behaviour emerge. 

 

Abnormal and aggressive behaviours 

 

Levetiracetam may cause psychotic symptoms and behavioural abnormalities including irritability and 

aggressiveness. Patients treated with levetiracetam should be monitored for developing psychiatric 

signs suggesting important mood and/or personality changes. If such behaviours are noticed, treatment 

adaptation or gradual discontinuation should be considered. If discontinuation is considered, please 

refer to section 4.2. 

 

Paediatric population 

 

Available data in children did not suggest impact on growth and puberty. However, long term effects 

on learning, intelligence, growth, endocrine function, puberty and childbearing potential in children 

remain unknown. 

 

Excipients 

 

This medicinal product contains 57.21 mg sodium per maximum single dose, equivalent to 2.86 % of 

the WHO recommended maximum daily intake of 2 g sodium for an adult.  

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Antiepileptic medicinal products 

 

Pre-marketing data from clinical studies conducted in adults indicate that levetiracetam did not 

influence the serum concentrations of existing antiepileptic medicinal products (phenytoin, 

carbamazepine, valproic acid, phenobarbital, lamotrigine, gabapentin and primidone) and that these 

antiepileptic medicinal products did not influence the pharmacokinetics of levetiracetam. 

 

As in adults, there is no evidence of clinically significant medicinal product interactions in paediatric 

patients receiving up to 60 mg/kg/day levetiracetam. 

A retrospective assessment of pharmacokinetic interactions in children and adolescents with epilepsy 

(4 to 17 years) confirmed that adjunctive therapy with orally administered levetiracetam did not 

influence the steady-state serum concentrations of concomitantly administered carbamazepine and 

valproate. However, data suggested a 20 % higher levetiracetam clearance in children taking enzyme-

inducing antiepileptic medicinal products. Dose adjustment is not required.  

 

Probenecid 

 

Probenecid (500 mg four times daily), a renal tubular secretion blocking agent, has been shown to 

inhibit the renal clearance of the primary metabolite, but not of levetiracetam. Nevertheless, the 

concentration of this metabolite remains low.  

 

Methotrexate 

 

Concomitant administration of levetiracetam and methotrexate has been reported to decrease 

methotrexate clearance, resulting in increased/prolonged blood methotrexate concentration to 

potentially toxic levels. Blood methotrexate and levetiracetam levels should be carefully monitored in 

patients treated concomitantly with the two medicinal products. 

 



 

25 

Oral contraceptives and other pharmacokinetics interactions 

 

Levetiracetam 1,000 mg daily did not influence the pharmacokinetics of oral contraceptives (ethinyl-

estradiol and levonorgestrel); endocrine parameters (luteinizing hormone and progesterone) were not 

modified. Levetiracetam 2,000 mg daily did not influence the pharmacokinetics of digoxin and 

warfarin; prothrombin times were not modified. Co-administration with digoxin, oral contraceptives 

and warfarin did not influence the pharmacokinetics of levetiracetam. 

 

Alcohol 

 

No data on the interaction of levetiracetam with alcohol are available. 

 

4.6 Fertility, pregnancy and lactation 

 

Women of childbearing potential  

Specialist advice should be given to women who are of childbearing potential. Treatment with 

levetiracetam should be reviewed when a woman is planning to become pregnant. As with all 

antiepileptic medicinal products, sudden discontinuation of levetiracetam should be avoided as this 

may lead to breakthrough seizures that could have serious consequences for the woman and the 

unborn child. Monotherapy should be preferred whenever possible because therapy with multiple 

antiepileptic medicinal products AEDs could be associated with a higher risk of congenital 

malformations than monotherapy, depending on the associated antiepileptics. 

 

Pregnancy 

A large amount of post-marketing data on pregnant women exposed to levetiracetam monotherapy 

(more than 1,800, among which in more than 1,500 exposure occurred during the 1st trimester) do not 

suggest an increase in the risk for major congenital malformations. Only limited evidence is available 

on the neurodevelopment of children exposed to levetiracetam monotherapy in utero. However, 

current epidemiological studies (on about 100 children) do not suggest an increased risk of 

neurodevelopmental disorders or delays.  

Levetiracetam can be used during pregnancy, if after careful assessment it is considered clinically 

needed. In such case, the lowest effective dose is recommended. 

Physiological changes during pregnancy may affect levetiracetam concentration.  Decrease in 

levetiracetam plasma concentrations has been observed during pregnancy. This decrease is more 

pronounced during the third trimester (up to 60% of baseline concentration before pregnancy). 

Appropriate clinical management of pregnant women treated with levetiracetam should be ensured.  

 

Breast-feeding 

Levetiracetam is excreted in human breast milk. Therefore, breast-feeding is not recommended.  

However, if levetiracetam treatment is needed during breast-feeding, the benefit/risk of the treatment 

should be weighed considering the importance of breast-feeding. 

 

Fertility 

No impact on fertility was detected in animal studies (see section 5.3). No clinical data are available, 

potential risk for human is unknown. 

 

4.7 Effects on ability to drive and use machines 

 

Levetiracetam has minor or moderate influence on the ability to drive and use machines. Due to 

possible different individual sensitivity, some patients might experience somnolence or other central 

nervous system related symptoms, especially at the beginning of treatment or following a dose 

increase. Therefore, caution is recommended in those patients when performing skilled tasks, e.g. 

driving vehicles or operating machinery. Patients are advised not to drive or use machines until it is 

established that their ability to perform such activities is not affected. 

 

4.8 Undesirable effects 



 

26 

 

Summary of the safety profile 

 

The most frequently reported adverse reactions were nasopharyngitis, somnolence, headache, fatigue 

and dizziness. The adverse reaction profile presented below is based on the analysis of pooled 

placebo-controlled clinical trials with all indications studied, with a total of 3,416 patients treated with 

levetiracetam. These data are supplemented with the use of levetiracetam in corresponding open-label 

extension studies, as well as post-marketing experience.  The safety profile of levetiracetam is 

generally similar across age groups (adult and paediatric patients) and across the approved epilepsy 

indications.  Since there was limited exposure for levetiracetam intravenous use and since oral and 

intravenous formulations are bioequivalent, the safety information of levetiracetam intravenous will 

rely on levetiracetam oral use. 

 

Tabulated list of adverse reactions 

 

Adverse reactions reported in clinical studies (adults, adolescents, children and infants > 1 month) and 

from post-marketing experience are listed in the following table per System Organ Class and per 

frequency. Adverse reactions are presented in the order of decreasing seriousness and their frequency 

is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to 

<1/100); rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). 

 

MedDRA 

SOC 

Frequency category 

Very common Common Uncommon  Rare 

Infections and 

infestations 

Nasopharyngit

is  

  Infection 

Blood and 

lymphatic 

system 

disorders 

  Thrombocytopeni

a, leukopenia 

Pancytopenia,neutropen

ia, agranulocytosis 

Immune 

system 

disorders 

   Drug reaction with 

eosinophilia and 

systemic symptoms 

(DRESS), 

Hypersensitivity 

(including 

angioedema and 

anaphylaxis) 

Metabolism 

and nutrition 

disorders 

 Anorexia Weight 

decreased, weight 

increase 

Hyponatraemia 

Psychiatric 

disorders 

 Depression, 

hostility/ aggression, 

anxiety,  

insomnia, 

nervousness/irritabil

ity 

Suicide attempt, 

suicidal ideation, 

psychotic 

disorder, 

abnormal 

behaviour, 

hallucination, 

anger, 

confusional state, 

panic attack, 

affect 

lability/mood 

swings, agitation 

Completed suicide, 

personality disorder, 

thinking abnormal, 

delirium 

Nervous 

system 

Somnolence, 

headache 

Convulsion, balance 

disorder, dizziness, 

Amnesia, 

memory 

Choreoathetosis, 

dyskinesia, 



 

27 

MedDRA 

SOC 

Frequency category 

Very common Common Uncommon  Rare 

disorders lethargy, tremor impairment, 

coordination 

abnormal/ataxia, 

paraesthesia, 

disturbance in 

attention 

hyperkinesia, gait 

disturbance, 

encephalopathy 

Eye disorders   Diplopia, vision 

blurred 

 

Ear and 

labyrinth 

disorders 

 Vertigo   

Respiratory, 

thoracic and 

mediastinal 

disorders 

 Cough   

Gastrointestin

al disorders 

 Abdominal pain, 

diarrhoea, 

dyspepsia, vomiting, 

nausea 

 Pancreatitis 

Hepatobiliary 

disorders 

  Liver function 

test abnormal 

Hepatic failure, 

hepatitis 

Skin and 

subcutaneous 

tissue 

disorders 

 Rash Alopecia, 

eczema, pruritus,  

Toxic epidermal 

necrolysis, Stevens-

Johnson syndrome, 

erythema multiforme 

Musculoskelet

al and 

connective 

tissue 

disorders 

  Muscular 

weakness, 

myalgia 

Rhabdomyolysis and 

blood creatine 

phosphokinase 

increased* 

Renal and 

urinary 

disorders 

   Acute kidney injury 

General 

disorders and 

administration 

site conditions 

 Asthenia/fatigue   

Injury, 

poisoning and 

procedural 

complications 

  Injury  

 

* Prevalence is significantly higher in Japanese patients when compared to non-Japanese patients.  

 

Description of selected adverse reactions 

 

The risk of anorexia is higher when levetiracetam is co-administered with topiramate. 

In several cases of alopecia, recovery was observed when levetiracetam was discontinued. 

Bone marrow suppression was identified in some of the cases of pancytopenia. 

 

Cases of encephalopathy generally occurred at the beginning of the treatment (few days to a few 

months) and were reversible after treatment discontinuation. 

 



 

28 

Paediatric population 

 

In patients aged 1 month to less than 4 years, a total of 190 patients have been treated with 

levetiracetam in placebo-controlled and open label extension studies.  Sixty of these patients were 

treated with levetiracetam in placebo-controlled studies.  In patients aged 4-16 years, a total of 645 

patients have been treated with levetiracetam in placebo-controlled and open label extension studies.  

233 of these patients were treated with levetiracetam in placebo-controlled studies. In both these 

paediatric age ranges, these data are supplemented with the post-marketing experience of the use of 

levetiracetam. 

 

In addition, 101 infants aged less than 12 months have been exposed in a post authorization safety 

study. No new safety concerns for levetiracetam were identified for infants less than 12 months of age 

with epilepsy. 

 

The adverse reaction profile of levetiracetam is generally similar across age groups and across the 

approved epilepsy indications.  Safety results in paediatric patients in placebo-controlled clinical 

studies were consistent with the safety profile of levetiracetam in adults except for behavioural and 

psychiatric adverse reactions which were more common in children than in adults.  In children and 

adolescents aged 4 to 16 years, vomiting (very common, 11.2%), agitation (common, 3.4%), mood 

swings (common, 2.1%), affect lability (common, 1.7%), aggression (common, 8.2%), abnormal 

behaviour (common, 5.6%), and lethargy (common, 3.9%) were reported more frequently than in other 

age ranges or in the overall safety profile.  In infants and children aged 1 month to less than 4 years, 

irritability (very common, 11.7%) and coordination abnormal (common, 3.3%) were reported more 

frequently than in other age groups or in the overall safety profile.   

 

A double-blind, placebo-controlled paediatric safety study with a non-inferiority design has assessed 

the cognitive and neuropsychological effects of levetiracetam in children 4 to 16 years of age with 

partial onset seizures. It was concluded that levetiracetam was not different (non inferior) from 

placebo with regard to the change from baseline of the Leiter-R Attention and Memory, Memory 

Screen Composite score in the per-protocol population. Results related to behavioural and emotional 

functioning indicated a worsening in levetiracetam treated patients on aggressive behavior as 

measured in a standardized and systematic way using a validated instrument (CBCL – Achenbach 

Child Behavior Checklist). However subjects, who took levetiracetam in the long-term open label 

follow-up study, did not experience a worsening, on average, in their behavioural and emotional 

functioning; in particular measures of aggressive behavior were not worse than baseline. 

 

Reporting of suspected adverse reactions 

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

Symptoms 

 

Somnolence, agitation, aggression, depressed level of consciousness, respiratory depression and coma 

were observed with Matever overdoses. 

 

Management of overdose 

 

There is no specific antidote for levetiracetam. Treatment of an overdose will be symptomatic and may 

include haemodialysis. The dialyser extraction efficiency is 60 % for levetiracetam and 74 % for the 

primary metabolite. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

29 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1 Pharmacodynamic properties 

 

Pharmacotherapeutic group: antiepileptics, other antiepileptics, ATC code: N03AX14. 

 

The active substance, levetiracetam, is a pyrrolidone derivative (S-enantiomer of -ethyl-2-oxo-1-

pyrrolidine acetamide), chemically unrelated to existing antiepileptic active substances. 

 

Mechanism of action 

 

The mechanism of action of levetiracetam still remains to be fully elucidated.  In vitro and in vivo 

experiments suggest that levetiracetam does not alter basic cell characteristics and normal 

neurotransmission. 

 

In vitro studies show that levetiracetam affects intraneuronal Ca2+ levels by partial inhibition of N-type 

Ca2+ currents and by reducing the release of Ca2+ from intraneuronal stores.  In addition, it partially 

reverses the reductions in GABA- and glycine-gated currents induced by zinc and β-carbolines.  

Furthermore, levetiracetam has been shown in in vitro studies to bind to a specific site in rodent brain 

tissue.  This binding site is the synaptic vesicle protein 2A, believed to be involved in vesicle fusion 

and neurotransmitter exocytosis. Levetiracetam and related analogues show a rank order of affinity for 

binding to the synaptic vesicle protein 2A which correlates with the potency of their anti-seizure 

protection in the mouse audiogenic model of epilepsy.  This finding suggests that the interaction 

between levetiracetam and the synaptic vesicle protein 2A seems to contribute to the antiepileptic 

mechanism of action of the medicinal product. 

 

Pharmacodynamic effects 

 

Levetiracetam induces seizure protection in a broad range of animal models of partial and primary 

generalised seizures without having a pro-convulsant effect. The primary metabolite is inactive. 

In man, an activity in both partial and generalised epilepsy conditions (epileptiform 

discharge/photoparoxysmal response) has confirmed the broad spectrum pharmacological profile of 

levetiracetam. 

 

Clinical efficacy and safety 

 

Adjunctive therapy in the treatment of partial onset seizures with or without secondary generalisation 

in adults, adolescents and children from 4 years of age with epilepsy: 

 

In adults, levetiracetam efficacy has been demonstrated in 3 double-blind, placebo-controlled studies 

at 1000 mg, 2000 mg, or 3000 mg/day, given in 2 divided doses, with a treatment duration of  up to 

18 weeks. In a pooled analysis, the percentage of patients who achieved 50 % or greater reduction 

from baseline in the partial onset seizure frequency per week at stable dose (12/14 weeks) was of 

27.7 %, 31.6 % and 41.3 % for patients on 1000, 2000 or 3000 mg levetiracetam respectively and of 

12.6 % for patients on placebo. 

 

Paediatric population 

 

In paediatric patients (4 to 16 years of age), levetiracetam efficacy was established in a double-blind, 

placebo-controlled study, which included 198 patients and had a treatment duration of 14 weeks. In 

this study, the patients received levetiracetam as a fixed dose of 60 mg/kg/day (with twice a day 

dosing). 

44.6 % of the levetiracetam treated patients and 19.6 % of the patients on placebo had a 50 % or 

greater reduction from baseline in the partial onset seizure frequency per week. With continued long-



 

30 

term treatment, 11.4 % of the patients were seizure-free for at least 6 months and 7.2 % were seizure-

free for at least 1 year. 

35 infants aged less than 1 year with partial onset seizures have been exposed in placebo-control 

clinical studies of which only 13 were aged < 6 months. 

 

Monotherapy in the treatment of partial onset seizures with or without secondary generalisation in 

patients from 16 years of age with newly diagnosed epilepsy.  

 

Efficacy of levetiracetam as monotherapy was established in a double-blind, parallel group, non-

inferiority comparison to carbamazepine controlled release (CR) in 576 patients 16 years of age or 

older with newly or recently diagnosed epilepsy.  The patients had to present with unprovoked partial 

seizures or with generalized tonic-clonic seizures only. The patients were randomized to 

carbamazepine CR 400 – 1200 mg/day or levetiracetam 1000 – 3000 mg/day, the duration of the 

treatment was up to 121 weeks depending on the response.   

Six-month seizure freedom was achieved in 73.0 % of levetiracetam-treated patients and 72.8 % of 

carbamazepine-CR treated patients; the adjusted absolute difference between treatments was 0.2%  

(95 % CI: -7.8 8.2). More than half of the subjects remained seizure free for 12 months (56.6 % and 

58.5 % of subjects on levetiracetam and on carbamazepine CR respectively). 

 

In a study reflecting clinical practice, the concomitant antiepileptic medication could be withdrawn in 

a limited number of patients who responded to levetiracetam adjunctive therapy (36 adult patients out 

of 69).  

 

Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents from 12 years of 

age with Juvenile Myoclonic Epilepsy. 

 

Levetiracetam efficacy was established in a double-blind, placebo-controlled study of 16 weeks 

duration, in patients 12 years of age and older suffering from idiopathic generalized epilepsy with 

myoclonic seizures in different syndromes. The majority of patients presented with juvenile myoclonic 

epilepsy. 

In this study, levetiracetam, dose was 3000 mg/day given in 2 divided doses.  

58.3 % of the levetiracetam treated patients and 23.3 % of the patients on placebo had at least a 50 % 

reduction in myoclonic seizure days per week. With continued long-term treatment, 28.6 % of the 

patients were free of myoclonic seizures for at least 6 months and 21.0 % were free of myoclonic 

seizures for at least 1 year. 

 

Adjunctive therapy in the treatment of primary generalised tonic-clonic seizures in adults and 

adolescents from 12 years of age with idiopathic generalised epilepsy. 

 

Levetiracetam efficacy was established in a 24-week double-blind, placebo-controlled study which 

included adults, adolescents and a limited number of children suffering from idiopathic generalized 

epilepsy with primary generalized tonic-clonic (PGTC) seizures in different syndromes (juvenile 

myoclonic epilepsy, juvenile absence epilepsy, childhood absence epilepsy, or epilepsy with Grand 

Mal seizures on awakening).  In this study, levetiracetam dose was 3000 mg/day for adults and 

adolescents or 60 mg/kg/day for children, given in 2 divided doses. 

72.2 % of the levetiracetam treated patients and 45.2 % of the patients on placebo had a 50 % or 

greater decrease in the frequency of PGTC seizures per week. With continued long-term treatment, 

47.4 % of the patients were free of tonic-clonic seizures for at least 6 months and 31.5 % were free of 

tonic-clonic seizures for at least 1 year. 

 

5.2 Pharmacokinetic properties 

 

The pharmacokinetic profile has been characterized following oral administration. A single dose of 

1500 mg levetiracetam diluted in 100 ml of a compatible diluent and infused intravenously over 

15 minutes is bioequivalent to 1500 mg levetiracetam oral intake, given as three 500 mg tablets. 

 



 

31 

The intravenous administration of doses up to 4000 mg diluted in 100 ml of 0.9 % sodium chloride 

infused over 15 minutes and doses up to 2500 mg diluted in 100 ml of 0.9 % sodium chloride infused 

over 5 minutes was evaluated. The pharmacokinetic and safety profiles did not identify any safety 

concerns. 

 

Levetiracetam is a highly soluble and permeable compound. The pharmacokinetic profile is linear with 

low intra- and inter-subject variability. There is no modification of the clearance after repeated 

administration. The time independent pharmacokinetic profile of levetiracetam was also confirmed 

following 1500 mg intravenous infusion for 4 days with twice daily dosing.  

There is no evidence for any relevant gender, race or circadian variability. The pharmacokinetic 

profile is comparable in healthy volunteers and in patients with epilepsy. 

 

Adults and adolescents 

 

Distribution 

 

Peak plasma concentration (Cmax) observed in 17 subjects following a single intravenous dose of 

1500 mg infused over 15 minutes was 51 ± 19 µg/ml (arithmetic average ± standard deviation). 

 

No tissue distribution data are available in humans. 

Neither levetiracetam nor its primary metabolite are significantly bound to plasma proteins ( 10 %). 

The volume of distribution of levetiracetam is approximately 0.5 to 0.7 l/kg, a value close to the total 

body water volume. 

 

Biotransformation 

 

Levetiracetam is not extensively metabolised in humans. The major metabolic pathway (24 % of the 

dose) is an enzymatic hydrolysis of the acetamide group. Production of the primary metabolite, 

ucb L057, is not supported by liver cytochrome P450 isoforms. Hydrolysis of the acetamide group was 

measurable in a large number of tissues including blood cells. The metabolite ucb L057 is 

pharmacologically inactive. 

 

Two minor metabolites were also identified. One was obtained by hydroxylation of the pyrrolidone 

ring (1.6 % of the dose) and the other one by opening of the pyrrolidone ring (0.9 % of the dose).  

Other unidentified components accounted only for 0.6 % of the dose. 

 

No enantiomeric interconversion was evidenced in vivo for either levetiracetam or its primary 

metabolite. 

 

In vitro, levetiracetam and its primary metabolite have been shown not to inhibit the major human 

liver cytochrome P450 isoforms (CYP3A4, 2A6, 2C9, 2C19, 2D6, 2E1 and 1A2), glucuronyl 

transferase (UGT1A1 and UGT1A6) and epoxide hydroxylase activities. In addition, levetiracetam 

does not affect the in vitro glucuronidation of valproic acid. 

In human hepatocytes in culture, levetiracetam had little or no effect on CYP1A2, SULT1E1 or 

UGT1A1. Levetiracetam caused mild induction of CYP2B6 and CYP3A4. The in vitro data and in 

vivo interaction data on oral contraceptives, digoxin and warfarin indicate that no significant enzyme 

induction is expected in vivo. Therefore, the interaction of Matever with other substances, or vice 

versa, is unlikely 

 

Elimination 

 

The plasma half-life in adults was 71 hours and did not vary either with dose, route of administration 

or repeated administration. The mean total body clearance was 0.96 ml/min/kg. 

 



 

32 

The major route of excretion was via urine, accounting for a mean 95 % of the dose (approximately 

93 % of the dose was excreted within 48 hours). Excretion via faeces accounted for only 0.3 % of the 

dose. 

The cumulative urinary excretion of levetiracetam and its primary metabolite accounted for 66 % and 

24 % of the dose, respectively during the first 48 hours. 

The renal clearance of levetiracetam and ucb L057 is 0.6 and 4.2 ml/min/kg respectively indicating 

that levetiracetam is excreted by glomerular filtration with subsequent tubular reabsorption and that 

the primary metabolite is also excreted by active tubular secretion in addition to glomerular filtration. 

Levetiracetam elimination is correlated to creatinine clearance. 

 

Elderly 

 

In the elderly, the half-life is increased by about 40 % (10 to 11 hours). This is related to the decrease 

in renal function in this population (see section 4.2). 

 

Renal impairment 

 

The apparent body clearance of both levetiracetam and of its primary metabolite is correlated to the 

creatinine clearance. It is therefore recommended to adjust the maintenance daily dose of Matever, 

based on creatinine clearance in patients with moderate and severe renal impairment (see section 4.2). 

 

In anuric end-stage renal disease adult subjects the half-life was approximately 25 and 3.1 hours 

during interdialytic and intradialytic periods, respectively.  

The fractional removal of levetiracetam was 51 % during a typical 4-hour dialysis session. 

 

Hepatic impairment 

 

In subjects with mild and moderate hepatic impairment, there was no relevant modification of the 

clearance of levetiracetam. In most subjects with severe hepatic impairment, the clearance of 

levetiracetam was reduced by more than 50 % due to a concomitant renal impairment (see section 4.2). 

 

Paediatric population 

 

Children (4 to 12 years) 

 

The pharmacokinetics in paediatric patients has not been investigated after intravenous administration. 

However, based on the pharmacokinetic characteristics of levetiracetam, the pharmacokinetics in 

adults after intravenous administration and the pharmacokinetics in children after oral administration, 

the exposure (AUC) of levetiracetam is expected to be similar in paediatric patients aged 4 to 12 years 

after intravenous and oral administration. 

 

Following single oral dose administration (20 mg/kg) to epileptic children (6 to 12 years), the half-life 

of levetiracetam was 6.0 hours. The apparent body weight adjusted clearance was approximately 30 % 

higher than in epileptic adults. 

 

Following repeated oral dose administration (20 to 60 mg/kg/day) to epileptic children (4 to 12 years), 

levetiracetam was rapidly absorbed. Peak plasma concentration was observed 0.5 to 1.0 hour after 

dosing. Linear and dose proportional increases were observed for peak plasma concentrations and area 

under the curve. The elimination half-life was approximately 5 hours. The apparent body clearance 

was 1.1 ml/min/kg. 

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, genotoxicity and carcinogenic potential.  



 

33 

Adverse reactions not observed in clinical studies but seen in the rat and to a lesser extent in the mouse 

at exposure levels similar to human exposure levels and with possible relevance to clinical use were 

liver changes, indicating an adaptive response such as increased weight and centrilobular hypertrophy, 

fatty infiltration and increased liver enzymes in plasma. 

 

No adverse reactions on male or female fertility or reproduction performance were observed in rats at 

doses up to 1800 mg/kg/day (x 6 the MRHD on a mg/m2 or exposure basis) in parents and F1 

generation. 

 

Two embryo-fetal development (EFD) studies were performed in rats at 400, 1200 and 

3600 mg/kg/day. At 3600 mg/kg/day, in only one of the 2 EFD studies, there was a slight decrease in 

fetal weight associated with a marginal increase in skeletal variations/minor anomalies. There was no 

effect on embryomortality and no increased incidence of malformations. The NOAEL (No Observed 

Adverse Effect Level) was 3600 mg/kg/day for pregnant female rats (x 12 the MRHD on a mg/m2 

basis) and 1200 mg/kg/day for fetuses.  

 

Four embryo-fetal development studies were performed in rabbits covering doses of 200, 600, 800, 

1200 and 1800 mg/kg/day. The dose level of 1800 mg/kg/day induced a marked maternal toxicity and 

a decrease in fetal weight associated with increased incidence of fetuses with cardiovascular/skeletal 

anomalies. The NOAEL was <200 mg/kg/day for the dams and 200 mg/kg/day for the fetuses (equal 

to the MRHD on a mg/m2 basis).  

A peri- and post-natal development study was performed in rats with levetiracetam doses of 70, 350 

and 1800 mg/kg/day. The NOAEL was ≥ 1800 mg/kg/day for the F0 females, and for the survival, 

growth and development of the F1 offspring up to weaning.(x 6 the MRHD on a mg/m2 basis). 

 

Neonatal and juvenile animal studies in rats and dogs demonstrated that there were no adverse 

reactions seen in any of the standard developmental or maturation endpoints at doses up to 

1800 mg/kg/day (x 6-17 the MRHD on a mg/m2 basis) 

 

Environmental Risk Assessment (ERA) 

 

The use of Matever in accordance with the product information is not likely to result in an 

unacceptable environmental impact (see section 6.6). 

 

 

6. PHARMACEUTICALPARTICULARS 

 

6.1 List of excipients 

 

Sodium acetate trihydrate 

Glacial acetic acid  

Sodium chloride  

Water for injections 

 

6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

6.3 Shelf life 

 

2 years. 

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. 



 

34 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions.  

For storage conditions after dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

5 ml glass vial (type I) with bromobutyl stoppers and sealed with an aluminium flip off cap. Each 

cartoncontains10 vials. 

 

6.6 Special precautions for disposal and other handling 

 

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 medicinal product is for single use only, any unused solution should be discarded. 

 

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 

15-25 °C. 

 

Diluents: 

•Sodium chloride (0.9 %) injection 

•Lactated Ringer’s injection 

•Dextrose 5 % injection 

 

Medicinal product with particulate matter or discoloration should not be used. 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Fax: +30 210 66 66 749 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/030 

 

 

9. DATE OF FIRST AUTHORISATION/ RENEWAL OF THE AUTHORISATION 



 

35 

 

Date of first authorisation: 03 October 2011 

Date of latest renewal: 29 June 2016 

 

 

10. DATE OF REVISION OF THETEXT 

 

 

Detailed information on this medicinal product is available on the website of the European Medicines 

Agency http://www.ema.europa.eu. 

 

http://www.ema.europa.eu/
http://www.ema.europa.eu/


 

36 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURERS RESPONSIBLE FOR BATCH 

RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 

 



 

37 

A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

Pharmathen S.A. 

6, Dervenakion 

EL-15351 Pallini Attiki 

Greece 

 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to medical prescription. 

 

 

C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 

 

• Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal.  

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

• Risk management plan (RMP)  
 

Not applicable. 



 

38 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

39 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 

40 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 20, 30, 50, 60, 100 multipack containing 200 (2 x 100) [with Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 250 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 250 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains sunset yellow FCF aluminum lake (E110). See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

20 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

60 film-coated tablets 

100 film-coated tablets 

Multipack: 200 (2 packs of 100) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 

41 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTEMATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/001 

EU/1/11/711/002 

EU/1/11/711/003 

EU/1/11/711/004 

EU/1/11/711/005 

EU/1/11/711/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 250 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

mailto:info@pharmathen.com


 

42 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

Intermediate packaging containing 100 tablets for multipack of 200 (2 x 100) tablets [without 

Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 250 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 250 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains sunset yellow FCF aluminum lake (E110). See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 film-coated tablets.  

Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 



 

43 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/006 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 250 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

Not applicable.  

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

Not applicable.  

mailto:info@pharmathen.com


 

44 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Aluminium/ PVC/PE/PVDC blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 250 mg film-coated tablets 

levetiracetam 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 



 

45 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 10, 20, 30, 50, 60, 100, 120 multipack containing 200 (2 x 100) [with Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 500 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 500 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

10 film-coated tablets 

20 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

60 film-coated tablets 

100 film-coated tablets 

120 film-coated tablets 

Multipack: 200 (2 packs of 100) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 

46 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/007 

EU/1/11/711/008 

EU/1/11/711/009 

EU/1/11/711/010 

EU/1/11/711/011 

EU/1/11/711/012 

EU/1/11/711/013 

EU/1/11/711/014 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 500 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

mailto:info@pharmathen.com


 

47 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING  

 

Intermediate packaging containing 100 tablets for multipack of 200 (2 x 100) tablets [without 

Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 500 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 500 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 film-coated tablets.  

Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 



 

48 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/014 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 500 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

Not applicable.  

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

Not applicable.  

mailto:info@pharmathen.com


 

49 

 

 

MINIMUM PARTICULARS TOAPPEAR ON BLISTERS OR STRIPS 

 

Aluminium/ PVC/PE/PVDC blisters 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 500 mg film-coated tablets 

levetiracetam 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 



 

50 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 20, 30, 50, 60, 80, 100, 120 multipack containing 200 (2 x 100) [with Blue Box] 

 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 750 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 750 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains sunset yellow FCF aluminum lake (E110). See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

20 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

60 film-coated tablets 

80 film-coated tablets 

100 film-coated tablets 

120 film-coated tablets 

Multipack: 200 (2 packs of 100) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIALWARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 



 

51 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/015 

EU/1/11/711/016 

EU/1/11/711/017 

EU/1/11/711/018 

EU/1/11/711/019 

EU/1/11/711/020 

EU/1/11/711/021 

EU/1/11/711/022 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 750 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

mailto:info@pharmathen.com


 

52 

SN 

NN 



 

53 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Intermediate packaging containing 100 tablets for multipack of 200 (2 x 100) tablets [without 

Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 750 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 750 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains sunset yellow FCF aluminum lake (E110). See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 film-coated tablets.  

Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach and of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 



 

54 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/022 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 750 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

Not applicable.  

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

Not applicable.  

 

mailto:info@pharmathen.com


 

55 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Aluminium/ PVC/PE/PVDC blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 750 mg film-coated tablets 

levetiracetam 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 

 



 

56 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 10, 20, 30, 50, 60, 100 multipack containing 200 (2 x 100) [with Blue Box] 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 1000 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 1,000 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

10 film-coated tablets 

20 film-coated tablets 

30 film-coated tablets 

50 film-coated tablets 

60 film-coated tablets 

100 film-coated tablets 

Multipack: 200 (2 packs of 100) film-coated tablets 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 



 

57 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/023 

EU/1/11/711/024 

EU/1/11/711/025 

EU/1/11/711/026 

EU/1/11/711/027 

EU/1/11/711/028 

EU/1/11/711/029 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 1000 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

mailto:info@pharmathen.com


 

58 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Intermediate packaging containing 100 tablets for multipack of 200 (2 x 100) tablets [without 

Blue Box] 

 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 1000 mg film-coated tablets 

levetiracetam 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each film-coated tablet contains 1,000 mg levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains lactose. See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

100 film-coated tablets.  

Component of a multipack, can’t be sold separately. 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Oral use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

 

 



 

59 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini Attiki 

153 51 Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/11/711/029 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 1000 mg 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

Not applicable.  

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

Not applicable.  

mailto:info@pharmathen.com


 

60 

 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 

 

Aluminium/ PVC/PE/PVDC blister 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Matever 1000 mg film-coated tablets 

levetiracetam 

 

 

2. NAME OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. OTHER 

 



 

61 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 10 vials 

 

 

 

1.  NAME OF THE MEDICINAL PRODUCT 

 

Matever 100 mg/ml concentrate for solution for infusion 

levetiracetam 

 

 

2.  STATEMENT OF ACTIVE SUBSTANCE(S) 

 

One vial contains 500 mg/5 ml levetiracetam. 

Each ml contains 100 mg of levetiracetam. 

 

 

3.  LIST OF EXCIPIENTS 

 

Contains glacial acetic acid, water for injections, sodium acetate trihydrate, sodium chloride - see 

leaflet for further information. 

 

 

4.  PHARMACEUTICAL FORM AND CONTENTS 

 

500 mg/5 ml 

 

10 vials of concentrate for solution for infusion 

 

 

5.  METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

Use immediately after dilution. 

 

 

9. SPECIAL STORAGE CONDITIONS 

 



 

62 

No special precautions for storage prior to reconstitution. After dilution the infusion is stable for 24 

hours at 2 °C - 8 °C (in a refrigerator). 

 

 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Pharmathen S.A. 

6, Dervenakion str. 

Pallini 15351, Attiki, Greece 

Tel.: +30 210 66 04 300 

Email: info@pharmathen.com 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/11/711/030 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

Medicinal product subject to medical prescription. 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Matever 100 mg/ml concentrate for solution for infusion 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

mailto:info@pharmathen.com


 

63 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

Vial of 5 ml 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Matever 100 mg/ml concentrate for solution for infusion 

levetiracetam 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP  

Use immediately after dilution. 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

500 mg/5 ml  

 

 

6. OTHER 

 



 

64 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

 



 

65 

 

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 



 

66 

• 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 slow down 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. 

 

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 

 

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. 

 



 

67 

Monotherapy 

 

• Dose in adults and adolescents (from 16 years of age): 
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 1,000 mg, your reduced starting dose is 2 tablets of 250 mg in the 

morning and 2 tablets of 250 mg in the evening. 

 

Add-on therapy 

 

• Dose in adults and adolescents (12 to 17 years) weighing 50 kg or more: 

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

Example: if your daily dose is 1,000 mg, you might take 2 tablets of 250 mg in the morning and 

2 tablets of 250 mg in the evening. 

 

• Dose in infants (1 month to 23 months), children (2 to 11 years) and adolescents (12 to 17 
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 100mg/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. 



 

68 

 

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. 

 



 

69 

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; 

• uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling 

movements, hyperkinesia (hyperactivity); 

• 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 Appendix V. 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. 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

70 

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 

 

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 

Pharmathen S.A. 

Tél/Tel: +30 210 66 04 300 

Lietuva 

SIA ELVIM 

Tel: +371 67808450 



 

71 

 

България 

ACEpharma Ltd. 

Teл.: +359 2862 9152 

 

Luxembourg/Luxemburg 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

Česká republika 

ARDEZ Pharma, spol. s.r.o. 

Tel.: +420 220 400 391 

 

Magyarország  

Pharmathen S.A. 

Tel.: +30 210 66 04 300 

 

Danmark 

Pharmathen S.A. 

Tel.: +30 210 66 04 300 

 

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) 

SIA ELVIM 

Tel: +371 67808450 

 

Norge 

Pharmathen S.A. 

Tlf: +30 210 66 04 300 

 

Ελλάδα 

INNOVIS PHARMA ΑΕΒΕ 

Τηλ: +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 

 

Hrvatska 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

Portugal 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

România 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

Ireland 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

Slovenija 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

Ísland 

Alvogen ehf. 

Tel: +354 522 2900 

 

Slovenská republika  

ARDEZ Pharma, spol. s.r.o. 

Tel: +420 220 400 391 

Italia 

Ecupharma S.r.l 

Tel : +39-02-38238790 

 

Suomi/Finland 

Pharmathen S.A. 

Puh/Tel: +30 210 66 04 300 

Κύπρος 

The Star Medicines Importers Co. Ltd 

Τηλ: +357 25371056 

Sverige  

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

Latvija  

SIA ELVIM 

Tel: +371 67808450 

 

United Kingdom 

Pharmathen S.A. 

Tel: +30 210 66 04 300 



 

72 

This leaflet was last revised in  

 

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

http://www.ema.europa.eu 

 



 

73 

 

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  



 

74 

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 slow down 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. 

 

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 

 

Children and adolescents 

• Matever is not indicated in children and adolescents below 16 years on it’s 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. 

 

Monotherapy 

 

Dose in adults and adolescents (from 16 years of age): 

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



 

75 

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. 

 

Add-on therapy 

 

Dose in adults and adolescents (12 to 17 years) weighing 50 kg or more: 

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

 

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 



 

76 

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; 

• uncontrollable muscle spasms affecting the head, torso and limbs, difficulty in controlling 

movements, hyperkinesia (hyperactivity); 

• 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. 



 

77 

• 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 Appendix V. 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 

Pharmathen S.A. 

Tél/Tel: +30 210 66 04 300 

 

Lietuva 

Pharmathen S.A. 

Tel: +30 210 66 04 300 

 

България  

Pharmathen S.A. 

Teл.: +30 210 66 04 300 

 

Luxembourg/Luxemburg 

Pharmathen S.A. 

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 

Malta 

Pharmathen S.A. 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

78 

Tlf:  +45 49 12 66 00 

 

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 

 

Ελλάδα 

INNOVIS PHARMA ΑΕΒΕ 

Τηλ: +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 

 

Hrvatska 

Makpharm d.o.o. 

Tel: +385 1 4840 342 

 

Portugal 

Pharmathen S.A. 

Tel.: +30 210 66 04 300 

 

România 

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 Pharma. 

Puh/Tel:  +358 10 4261 

 

Κύπρος 

The Star Medicines Importers Co. Ltd 

Τηλ: +357 25371056 

Sverige  

Orion PharmaAB  

 Tel: 08- 623 64 40 

 

Latvija  

Pharmathen S.A. 

Tel: +30 210 66 04 300 

United Kingdom 

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: 

http://www.ema.europa.eu/. 

 

 

 

 

The following information is intended for healthcare professionals only: 

http://www.ema.europa.eu/


 

79 

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 15-

25°C.  

Diluents: 

• Sodium chloride (0.9 %) injection 

• Lactated Ringer's injection 

• Dextrose 5 % injection 
 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURERS RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
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