Levetiracetam Hospira

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ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 

  



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1. NAME OF THE MEDICINAL PRODUCT 

 

Levetiracetam Hospira 100 mg/ml concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each ml contains 100 mg of levetiracetam. 

 

Each 5 ml vial contains 500 mg of levetiracetam. 

 

Excipient with known effect: 

 

Each vial contains 19 mg of sodium. 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Concentrate for solution for infusion (sterile concentrate). 

 

Clear, colourless solution 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Levetiracetam Hospira 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. 

 

Levetiracetam Hospira 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. 

 

Levetiracetam Hospira concentrate is an alternative for patients when oral administration is 

temporarily not feasible. 

 

4.2 Posology and method of administration 

 

Posology 

 

Levetiracetam 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 



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twice daily every two weeks depending upon the clinical response. The maximum dose is 1,500 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. 

 

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 ≥ 80 500 to 1,500 mg twice daily 

Mild 50-79 500 to 1,000 mg twice daily 

Moderate 30-49 250 to 750 mg twice daily 

Severe < 30 250 to 500 mg twice daily 

End-stage renal disease 

patients undergoing dialysis(1) 

- 500 to 1,000 mg once daily(2) 



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(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 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/1.73 m2) 

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 levetiracetam 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. 



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

 

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 1,500 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 levetiracetam 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 

 

Levetiracetam Hospira 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 



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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. 

 

Worsening of seizures 

 

As with other types of antiepileptic drugs, levetiracetam may rarely exacerbate seizure frequency or 

severity. This paradoxical effect was mostly reported within the first month after levetiracetam 

initiation or increase of the dose, and was reversible upon drug discontinuation or dose decrease. 

Patients should be advised to consult their physician immediately in case of aggravation of epilepsy. 

 

Electrocardiogram QT interval prolongation 

 

Rare cases of ECG QT interval prolongation have been observed during the post-marketing 

surveillance. Levetiracetam should be used with caution in patients with QTc-interval prolongation, in 

patients concomitantly treated with drugs affecting the QTc-interval, or in patients with relevant pre-

existing cardiac disease or electrolyte disturbances. 

 

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 19 mg of sodium per vial. The maximum single dose (corresponding 

to 1,500 mg levetiracetam) contains 57 mg of sodium, equivalent to 2.85% of the WHO maximum 

recommended daily intake (RDI) of 2 g sodium for an adult. To be taken into consideration by patients 

on a controlled sodium diet. 

 

This medicinal product may be diluted with sodium-containing solutions (see section 4.2) and this 

should be considered in relation to the total sodium from all sources that will be administered to the 

patient. 

 

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. 



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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 drugs. 

 

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 child bearing 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 medicines, 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 

medicines AEDs could be associated with a higher risk of congenital malformations than 

monotherapy, depending on the associated antiepileptics. 

 

Pregnancy  

 

A large amount of postmarketing data on pregnant women exposed to levetiracetam monotherapy 

(more than 1800, among which in more than 1500 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.  

 



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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.  

 

Breastfeeding  

 

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

However, if levetiracetam treatment is needed during breastfeeding, the benefit/risk of the treatment 

should be weighed considering the importance of breastfeeding. 

 

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 

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 

Nasopharyngiti

s 

  Infection 

Blood and 

lymphatic 

system 

disorders 

  Thrombocytopeni

a, leukopenia 

Pancytopenia, 

neutropenia, 

agranulocytosis 



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MedDRA SOC 
Frequency category 

Very common Common Uncommon Rare 

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/irritabilit

y 

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, 

seizures 

aggravated 

Eye disorders   Diplopia, vision 

blurred 

 

Ear and 

labyrinth 

disorders 

 Vertigo   

Cardiac 

disorders 

   Electrocardiogra

m QT prolonged 

Respiratory, 

thoracic and 

mediastinal 

disorders 

 Cough   

Gastrointestina

l disorders 

 Abdominal pain, 

diarrhoea, dyspepsia, 

vomiting, nausea 

 Pancreatitis 

Hepatobiliary 

disorders 

  Liver function test 

abnormal 

Hepatic failure, 

hepatitis 

 

Renal and 

Urinary 

disorders 

   Acute kidney 

injury 

Skin and 

subcutaneous 

tissue disorders 

 Rash Alopecia, eczema, 

pruritus 

Toxic epidermal 

necrolysis, 

Stevens-Johnson 

syndrome, 



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MedDRA SOC 
Frequency category 

Very common Common Uncommon Rare 

erythema 

multiforme 

Musculoskeleta

l and 

connective 

tissue disorders 

  Muscular 

weakness, myalgia 

Rhabdomyolysis 

and blood 

creatine 

phosphokinase 

increased* 

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.  

 

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 



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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 behaviour as 

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

Child Behaviour 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 behaviour 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 levetiracetam 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. 

 

 

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 

 

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. 

 



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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 1,000 mg, 2,000 mg, or 3,000 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 1,000, 2,000 or 3,000 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. 

 

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 400-1,200 mg/day or levetiracetam 1,000-3,000 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 



13 

 

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

epilepsy. 

 

In this study, levetiracetam, dose was 3,000 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 3,000 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 

1,500 mg levetiracetam diluted in 100 ml of a compatible diluent and infused intravenously over 

15 minutes is bioequivalent to 1,500 mg levetiracetam oral intake, given as three 500 mg tablets. 

 

The intravenous administration of doses up to 4,000 mg diluted in 100 ml of 0.9% sodium chloride 

infused over 15 minutes and doses up to 2,500 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 1,500 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 

1,500 mg infused over 15 minutes was 51 ± 19 micrograms/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. 

 



14 

 

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 levetiracetam 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. 

 

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 

levetiracetam, 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. 



15 

 

 

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. 

 

Adverse effects 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 for 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 1,800 mg/kg/day (x 6 the MRHD on a mg/m2 or exposure basis) in parents and F1 

generation. 

 

Two embryo-foetal development (EFD) studies were performed in rats at 400, 1,200 and 

3,600 mg/kg/day. At 3,600 mg/kg/day, in only one of the 2 EFD studies, there was a slight decrease in 

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

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

Adverse Effect Level) was 3 600 mg/kg/day for pregnant female rats (x 12 the MRHD on a mg/m2 

basis) and 1,200 mg/kg/day for foetuses. 

 

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

1,200 and 1,800 mg/kg/day. The dose level of 1,800 mg/kg/day induced a marked maternal toxicity 

and a decrease in foetal weight associated with increased incidence of foetuses with 

cardiovascular/skeletal anomalies. The NOAEL was < 200 mg/kg/day for the dams and 200 mg/kg/day 

for the foetuses (equal to the MRHD on a mg/m2 basis). 

 



16 

 

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

and 1,800 mg/kg/day. The NOAEL was ≥1,800 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 effects 

seen in any of the standard developmental or maturation endpoints at doses up to 1,800 mg/kg/day 

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

 

 

6. PHARMACEUTICAL PARTICULARS 

 

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 

 

Chemical and physical in-use stability of the diluted product stored in PVC bags has been 

demonstrated for 24 hours at 30 °C and at 2-8 °C. From a microbiological point of view, unless the 

method of dilution precludes the risk of microbial contamination, the product should be used 

immediately. If not used immediately, in-use storage time and conditions are the responsibility of the 

user. 

 

6.4 Special precautions for storage 

 

This medicinal product does not require any special storage conditions. 

 

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

 

6.5 Nature and contents of container 

 

5 ml glass vial (type I) with bromobutyl coated rubber stoppers and an aluminium flip-off seal. 

 

Each carton contains 10 or 25 vials. 

 

Not all pack sizes may be marketed 

 

6.6 Special precautions for disposal and other handling 

 

See Table 1 for the recommended preparation and administration of Levetiracetam Hospira 

concentrate for solution for infusion to achieve a total daily dose of 500 mg, 1,000 mg, 2,000 mg, or 

3,000 mg in two divided doses. 

 

Table 1. Preparation and administration of Levetiracetam Hospira concentrate for solution for infusion 

 



17 

 

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 1,000 mg/day 

1,000 mg 10 ml (two 

5 ml vials) 

100 ml 15 minutes Twice daily 2,000 mg/day 

1,500 mg 15 ml (three 

5 ml vials) 

100 ml 15 minutes Twice daily 3,000 mg/day 

 

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

 

Levetiracetam concentrate for solution for infusion was found to be physically compatible and 

chemically stable when mixed with the following diluents: 

 

• Sodium chloride 9 mg/ml (0.9%) solution for injection 

• Lactated Ringer’s solution for injection 

• Dextrose 50 mg/ml (5%) solution for 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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/13/889/001 

EU/1/13/889/002 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 08 January 2014 

Date of latest renewal: 20 November 2018 

 

 

10 DATE OF REVISION OF THE TEXT 

 

{MM/YYYY} 

 

 

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

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

  



18 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX II 

 

A. MANUFACTURER(S) 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 

 

 



19 

 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer(s) responsible for batch release 

 

Hospira UK Limited 

Horizon 

Honey Lane 

Hurley 

Maidenhead 

SL6 6RJ 

United Kingdom 

 

Pfizer Service Company BVBA 

Hoge Wei 10 

1930 Zaventem 

Belgium 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

 

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) 

 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 

and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 

and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

• At the request of the European Medicines Agency; 

• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached. 

  



20 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 

  



21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

  



22 

 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

Box of 10 or 25 vials 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Levetiracetam Hospira 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 levetiracetam. 

 

 

3. LIST OF EXCIPIENTS 

 

Other ingredients include sodium acetate trihydrate, glacial acetic acid, sodium chloride, water for 

injections. See the package leaflet for further information. 

 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Concentrate for solution for infusion 

 

500 mg/5 ml 

 

10 vials  

25 vials  

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

Dilute before 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. 

 

 



23 

 

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 

 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium  

 

 

12. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/13/889/001 

EU/1/13/889/002 

 

 

13. BATCH NUMBER 

 

BN 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 

 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER – HUMAN READABLE DATA 

 

PC 

SN 

NN 

 

  



24 

 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

Vial of 5 ml 

 

 

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

 

Levetiracetam Hospira 100 mg/ml sterile concentrate 

levetiracetam 

IV  

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

Use immediately after dilution. 

 

 

4. BATCH NUMBER 

 

BN 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

500 mg/5 ml 

 

 

6. OTHER 

 

 

  



25 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 

  



26 

 

 

 

Package leaflet: Information for the patient 

 

Levetiracetam Hospira 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 Levetiracetam Hospira is and what it is used for 

2. What you need to know before you are given Levetiracetam Hospira 

3. How Levetiracetam Hospira is given 

4. Possible side effects 

5. How to store Levetiracetam Hospira 

6. Contents of the pack and other information 

 

 

1. What Levetiracetam Hospira is and what it is used for 

 

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

 

Levetiracetam Hospira 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). 

 

Levetiracetam Hospira concentrate for solution for infusion is an alternative for patients when 

administration of the antiepileptic levetiracetam medicine by mouth is temporarily not feasible. 

 

 

2. What you need to know before you are given Levetiracetam Hospira 

 

Do not use Levetiracetam Hospira 

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

medicine (listed in section 6). 

 



27 

 

Warnings and precautions 

Talk to your doctor before you are given Levetiracetam Hospira 

• 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 Levetiracetam Hospira have 

had thoughts of harming or killing themselves. If you have any symptoms of depression and/or 

suicidal ideation, please contact your doctor. 

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

electrocardiogram), or if you have a disease and/or take a treatment that make(s) you prone to 

heartbeat irregularities or salt imbalances. 

 

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

days: 

• Abnormal thoughts, feeling irritable or reacting more aggressively than usually, or if you or 

your family and friends notice important changes in mood or behaviour. 

• Aggravation of epilepsy  

Your seizures may rarely become worse or happen more often, mainly during the first month 

after the start of the treatment or increase of the dose. If you experience any of these new 

symptoms while taking Levetiracetam Hospira, see a doctor as soon as possible. 

 

Children and adolescents 

• Levetiracetam Hospira is not indicated in children and adolescents below 16 years on it’s own 

(monotherapy). 

 

Other medicines and Levetiracetam Hospira 

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

medicines, including medicines obtained without a prescription. 

 

Do not take macrogol (a drug 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 breastfeeding, 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 

Levetiracetam Hospira 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. 

 

Levetiracetam Hospira contains sodium 

One maximum single dose of Levetiracetam Hospira concentrate contains 57 mg of sodium (19 mg of 

sodium per vial) equivalent to 2.85% of the recommended maximum daily dietary intake of sodium for 

an adult. This should be taken into consideration if you are on a controlled sodium diet. 

 



28 

 

 

3. How Levetiracetam Hospira is given 

 

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

Levetiracetam Hospira 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 1,000 mg and 3,000 mg each day. 

When you first start taking Levetiracetam Hospira, your doctor will prescribe you a lower dose for 

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: 

Levetiracetam Hospira 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 Levetiracetam Hospira 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 Levetiracetam Hospira: 

If stopping treatment, as with other antiepileptic medicines, Levetiracetam Hospira should be 

discontinued gradually to avoid an increase of seizures. Should your doctor decide to stop your 

Levetiracetam Hospira treatment, he/she will instruct you about the gradual withdrawal of 

Levetiracetam Hospira. 

 

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 



29 

 

cell (eosinophilia) and enlarged lymph nodes (Drug Reaction with Eosinophilia and Systemic 

Symptoms [DRESS])  

• symptoms such as low urine volume, tiredness, nausea, vomiting, confusion and swelling in the 

legs, ankles or feet, as this may be a sign of sudden decrease of kidney function 

• a skin rash which may form blisters and look like small targets (central dark spots surrounded by 

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

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

genitals (Stevens-Johnson syndrome) 

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

epidermal necrolysis) 

• signs of serious mental changes or if someone around you notices signs of confusion, 

somnolence (sleepiness), amnesia (loss of memory), memory impairment (forgetfulness), 

abnormal behaviour or other neurological signs including involuntary or uncontrolled 

movements. These could be symptoms of an encephalopathy. 

 

The most frequently reported adverse reactions were nasopharyngitis, somnolence (sleepiness), 

headache, fatigue and dizziness. At the beginning of the treatment or at dose increase side effects like 

sleepiness, tiredness and dizziness may be more common. These effects should however decrease over 

time. 

 

Very common: may affect more than 1 in 10 people 

• nasopharyngitis; 

• somnolence (sleepiness), headache. 

 

Common: may affect up to 1 in 10 people 

• anorexia (loss of appetite); 

• depression, hostility or aggression, anxiety, insomnia, nervousness or irritability; 

• convulsion, balance disorder (equilibrium disorder), dizziness (sensation of unsteadiness), 

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

• vertigo (sensation of rotation); 

• cough; 

• abdominal pain, diarrhoea, dyspepsia (indigestion), vomiting, nausea; 

• rash; 

• asthenia/fatigue (tiredness). 

 

Uncommon: may affect up to 1 in 100 people 

• decreased number of blood platelets, decreased number of white blood cells; 

• weight decrease, weight increase; 

• suicide attempt and suicidal ideation, mental disorder, abnormal behaviour, hallucination, anger, 

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

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

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

concentration); 

• diplopia (double vision), vision blurred; 

• elevated/abnormal values in a liver function test; 

• hair loss, eczema, pruritus; 

• muscle weakness, myalgia (muscle pain); 

• injury. 

 

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

• infection; 

• decreased number of all blood cell types; 

• severe allergic reactions (DRESS, anaphylactic reaction [severe and important allergic reaction], 

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

• decreased blood sodium concentration; 



30 

 

• suicide, personality disorders (behavioural problems), thinking abnormal (slow thinking, unable 

to concentrate); 

• delirium; 

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

symptoms); 

• seizures may become worse or happen more often; 

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

movements, hyperkinesia (hyperactivity); 

• change of the heart rhythm (Electrocardiogram); 

• pancreatitis 

• liver failure, hepatitis; 

• sudden decrease in kidney function; 

• skin rash, which may form blisters and looks like small targets (central dark spots surrounded by 

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

blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-

Johnson syndrome), and a more severe form causing skin peeling in more than 30% of the body 

surface (toxic epidermal necrolysis); 

• rhabdomyolysis (breakdown of muscle tissue) and associated blood creatine phosphokinase 

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

patients; 

• limp or difficulty walking. 

 

Reporting of side effects 

If you get any side effects talk to your doctor, pharmacist or nurse. 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 Levetiracetam Hospira 

 

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

 

Do not use this medicine after the expiry date stated on the vial and carton box after EXP: 

The expiry date refers to the last day of the month. 

 

This medicine does not require any special storage conditions. 

 

 

6. Contents of the pack and other information 

 

What Levetiracetam Hospira contains 

- The active substance is called levetiracetam. Each ml contains 100 mg of levetiracetam. 

- The other ingredients are: sodium acetate trihydrate, glacial acetic acid, sodium chloride, water 

for injections (see section 2 Levetiracetam Hospira contains sodium). 

 

What Levetiracetam Hospira looks like and contents of the pack 

Levetiracetam Hospira concentrate for solution for infusion (sterile concentrate) is a clear, colourless 

solution. 

 

Levetiracetam Hospira concentrate for solution for infusion is packed in a cardboard box containing 10 

or 25 vials of 5 ml. 

 

Not all pack sizes may be marketed.  

 



31 

 

Marketing Authorisation Holder 

Pfizer Europe MA EEIG 

Boulevard de la Plaine 17 

1050 Bruxelles 

Belgium 

 

Manufacturers 

Pfizer Service Company BVBA 

Hoge Wei 10 

1930 Zaventem 

Belgium 

 

Hospira UK Limited  

Horizon 

Honey Lane 

Hurley 

Maidenhead 

SL6 6RJ 

United Kingdom 



32 

 

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

Authorisation Holder. 

 

België/Belgique/Belgien 

Pfizer SA/NV 

Tél/Tel: +32 2 554 62 11 

 

Lietuva 

Pfizer Luxembourg SARL filialas Lietuvoje 

Tel. + 370 52 51 4000 

 

България 

Пфайзер Люксембург САРЛ, Клон България 

Тел.: +359 2 970 4333 

 

Luxembourg/Luxemburg 

Pfizer SA/NV 

Tél/Tel: +32 2 554 62 11 

 

Česká republika 

Pfizer, spol. s r.o. 

Tel: +420-283-004-111 

 

Magyarország 

Pfizer Kft. 

Tel: + 36 1 488 37 00 

 

Danmark 

Pfizer ApS 

Tlf: + 45 44 20 11 00 

 

Malta 

Drugsales Ltd  

Tel: + 356 21 419 070/1/2 

Deutschland 

Pfizer Pharma PFE GmbH 

Tel: + 49 (0)800 8535555 

 

Nederland 

Pfizer bv 

Tel: +31 (0)10 406 43 01 

 

Eesti 

Pfizer Luxembourg SARL Eesti filiaal 

Tel: +372 666 7500 

 

Norge 

Pfizer AS 

Tlf: +47 67 52 61 00 

 

Ελλάδα 

Pfizer ΕΛΛΑΣ A.E. 

Τηλ.: +30 210 6785 800 

 

Österreich 

Pfizer Corporation Austria Ges.m.b.H. 

Tel: +43 (0)1 521 15-0 

 

España 

Pfizer, S.L. 

Tel: +34 91 490 99 00 

 

Polska  

Pfizer Polska Sp. z o.o. 

Tel: +48 22 335 61 00 

 

France 

Pfizer  

Tél: + 33 (0)1 58 07 34 40 

 

Portugal  

Laboratórios Pfizer, Lda. 

Tel: +351 21 423 55 00 

 

Hrvatska 

Pfizer Croatia d.o.o. 

Tel: +385 1 3908 777 

 

România 

Pfizer România S.R.L. 

Tel: +40 (0)21 207 28 00 

Ireland 

Pfizer Healthcare Ireland 

Tel: 1800 633 363 (toll free) 

+44 (0) 1304 616161 

 

Slovenija  

Pfizer Luxembourg SARL 

Pfizer, podružnica za svetovanje s področja 

farmacevtske dejavnosti, Ljubljana 

Tel: +386 (0)1 52 11 400 

 



33 

 

Ísland 

Icepharma hf. 

Sími: +354 540 8000 

 

Slovenská republika 

Pfizer Luxembourg SARL, organizačná zložka 

Tel: +421–2–3355 5500 

 

Italia 

Pfizer S.r.l. 

Tel: +39 06 33 18 21 

 

Suomi/Finland 

Pfizer Oy 

Puh/Tel: +358 (0)9 430 040 

 

Κύπρος 

Pharmaceutical Trading Co Ltd 

Τηλ: 24656165 

 

Sverige  

Pfizer AB 

Tel: +46 (0)8 550 520 00 

 

Latvija  

Pfizer Luxembourg SARL filiāle Latvijā 

Tel.: + 371 670 35 775 

 

United Kingdom 

Hospira UK Limited  

Tel: + 44 (0) 1628 515500 

 

 

This leaflet was last revised in month YYYY. 

 

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: 

 

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

 

One vial of Levetiracetam Hospira concentrate contains 500 mg levetiracetam (5 ml concentrate of 

100 mg/ml). See Table 1 for the recommended preparation and administration of Levetiracetam 

Hospira 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 Levetiracetam Hospira 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 1,000 mg/day 

1,000 mg 10 ml (two 5 ml 

vials) 

100 ml 15 minutes Twice daily 2,000 mg/day 

1,500 mg 15 ml (three 5 ml 

vials) 

100 ml 15 minutes Twice daily 3,000 mg/day 

 

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

 

In use shelf life:  

 

Chemical and physical in-use stability of the diluted product stored in PVC bags has been demonstrated 

for 24 hours at 30 °C and at 2-8 °C. From a microbiological point of view, unless the method of dilution 

precludes the risk of microbial contamination, the product should be used immediately. If not used 

immediately, in-use storage time and conditions are the responsibility of the user.  

 



34 

 

Levetiracetam Hospira concentrate was found to be physically compatible and chemically stable when 

mixed with the following diluents: 

 

• Sodium chloride 9 mg/ml (0.9%) solution for injection 

• Lactated Ringer’s solution for injection 

• Dextrose 50 mg/ml (5%) solution for injection


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) 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
	A. LABELLING
	B. PACKAGE LEAFLET