Exalief

1 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 400 mg tablets 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 400 mg of eslicarbazepine acetate. 
 
For a full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
 
White circular biconvex tablets, engraved ‘ESL 400’on one side and scored on the other side. The scoreline 
is only to facilitate breaking for ease of swallowing and not to divide into equal doses.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Exalief is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary 
generalisation. 
 
4.2 Posology and method of administration 
 
Posology 
 
Exalief must be added to existing anticonvulsant therapy. The recommended starting dose is 400 mg once 
daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, 
the dose may be increased to 1200 mg once daily (see section 5.1). 
 
Elderly (over 65 years of age) 
Caution should be exercised in the treatment of elderly patients as there is limited safety information on the 
use of Exalief in these patients. 
 
Paediatric population 
The safety and efficacy of Exalief in children below 18 years has not yet been established. No data are 
available. 
 
Patients with renal impairment 
Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (CLCR) as follows: 
- CLCR >60 ml/min: no dose adjustment required 
- CLCR 30-60 ml/min: initial dose of 400 mg every other day for 2 weeks followed by a once daily dose of 

400 mg. However, based on individual response, the dose may be increased. 
- CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient 

data 
 
Patients with hepatic impairment 
No dose adjustment is needed in patients with mild to moderate hepatic impairment.  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment 
(see section 4.4 and 5.2) and use in these patients is therefore not recommended. 
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Method of administration 
 
Exalief may be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other carboxamide derivatives (e.g. carbamazepine, 
oxcarbazepine) or to any of the excipients.  
 
Known second or third degree atrioventricular (AV) block. 
 
4.4 Special warnings and precautions for use 
 
Exalief has been associated with some central nervous system adverse reactions, such as dizziness and 
somnolence, which could increase the occurrence of accidental injury.  
 
Exalief may decrease the effectiveness of hormonal contraceptives. Additional non-hormonal forms of 
contraception are recommended when using Exalief (see section 4.5 and 4.6). 
 
As with other anti-epileptic medicinal products, if Exalief is to be discontinued it is recommended to 
withdraw it gradually to minimise the potential of increased seizure frequency.  
 
Concomitant use of Exalief with oxcarbazepine is not recommended because this may cause overexposure to 
the active metabolites. 
 
There is no experience regarding the withdrawal of concomitant use of anti-epileptic medicinal products 
during treatment with Exalief (switch to monotherapy). 
 
Rash developed as an adverse reaction in 1.1% of total population treated with Exalief in placebo-controlled 
add-on studies in epileptic patients. If signs or symptoms of hypersensitivity develop, Exalief must be 
discontinued. 
 
No cases of serious cutaneous reactions have been reported with eslicarbazepine acetate. Presence of 
HLA-B*1502 allele in individuals of Han Chinese and Thai origin has been shown to be strongly associated 
with the risk of developing Stevens-Johnson syndrome (SJS) when treated with carbamazepine. Therefore, 
whenever possible, subjects of Han Chinese and Thai origin should be screened for this allele before starting 
treatment with carbamazepine or chemically-related compounds. The presence of HLA-B*1502 allele in 
other ethnicities is negligible. The allele HLA-B*1502 is not associated to SJS in the Caucasian population. 
 
Hyponatraemia has been reported as an adverse reaction in less than 1% of patients treated with Exalief. 
Hyponatraemia is asymptomatic in most cases, however, it may be accompanied by clinical symptoms like 
worsening of seizures, confusion, decreased consciousness. Frequency of hyponatraemia increased with 
increasing eslicarbazepine acetate dose. In patients with pre-existing renal disease leading to hyponatraemia, 
or in patients concomitantly treated with medicinal products which may themselves lead to hyponatraemia 
(e.g. diuretics, desmopressin), serum sodium levels should be examined before and during treatment with 
eslicarbazepine acetate. Furthermore, serum sodium levels should be determined if clinical signs of 
hyponatraemia occur. Apart from this, sodium levels should be determined during routine laboratory 
examination. If clinically relevant hyponatraemia develops, Exalief should be discontinued. 
 
The influence of Exalief on primary generalised seizures has not been studied. Use is therefore not 
recommended in these patients. 
 
Prolongations in PR interval have been observed in clinical studies with eslicarbazepine acetate.  
Caution should be exercised in patients with medical conditions (e.g. low levels of thyroxine, cardiac 
conduction abnormalities), or when taking concomitant medicinal products known to be associated with PR 
prolongation. 

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Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (see section 4.2). In patients with CLCR <30 ml/min use is not 
recommended due to insufficient data. 
 
As clinical data are limited in patients with mild to moderate hepatic impairment and pharmacokinetic and 
clinical data are missing in patients with severe hepatic impairment, Exalief should be used with caution in 
patients with mild to moderate hepatic impairment and is not recommended in patients with severe hepatic 
impairment. 
 
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic active substances in 
several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic medicinal 
products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this 
risk is not known and the available data do not exclude the possibility of an increased risk for eslicarbazepine 
acetate. Therefore patients should be monitored for signs of 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 suicidal ideation or behaviour emerge. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Eslicarbazepine acetate is extensively converted to eslicarbazepine, which is mainly eliminated by 
glucuronidation. In vitro eslicarbazepine is a weak inducer of CYP3A4 and UDP-glucuronyl transferases. In 
vivo eslicarbazepine showed an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by metabolism through CYP3A4.Thus, an increase in the dose of the medicinal products that are 
mainly metabolised through CYP3A4 may be required, when used concomitantly with Exalief. 
Eslicarbazepine in vivo may have an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by conjugation through the UDP-glucuronyl transferases. When initiating or discontinuing 
treatment with Exalief or changing the dose, it may take 2 to 3 weeks to reach the new level of enzyme 
activity. This time delay must be taken into account when Exalief is being used just prior to or in 
combination with other medicines that require dose adjustment when co-administered with Exalief. 
Eslicarbazepine has inhibiting properties with respect to CYP2C19. Thus, interactions can arise when co-
administering high doses of eslicarbazepine acetate with medicinal products that are mainly metabolised by 
CYP2C19. 
 
Interactions with other antiepileptic medicinal products 
Carbamazepine 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 800 mg once daily and 
carbamazepine 400 mg twice daily resulted in an average decrease of 32% in exposure to the active 
metabolite eslicarbazepine, most likely caused by an induction of glucuronidation. No change in exposure to 
carbamazepine or its metabolite carbamazepine-epoxide was noted. Based on individual response, the dose 
of Exalief may need to be increased if used concomitantly with carbamazepine. Results from patient studies 
showed that concomitant treatment increased the risk of the following adverse reactions: diplopia (11.4% of 
subjects with concomitant carbamazepine, 2.4% of subjects without concomitant carbamazepine), abnormal 
coordination (6.7% with concomitant carbamazepine, 2.7% without concomitant carbamazepine), and 
dizziness (30.0% with concomitant carbamazepine, 11.5% without concomitant carbamazepine). The risk of 
increase of other specific adverse reactions caused by co-administration of carbamazepine and 
eslicarbazepine acetate cannot be excluded. 
  
Phenytoin 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
phenytoin resulted in an average decrease of 31-33% in exposure to the active metabolite, eslicarbazepine, 
most likely caused by an induction of glucuronidation, and an average increase of 31-35% in exposure to M

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phenytoin, most likely caused by an inhibition of CYP2C19. Based on individual response, the dose of 
Exalief may need to be increased and the dose of phenytoin may need to be decreased. 
 
Lamotrigine 
Glucuronidation is the major metabolic pathway for both eslicarbazepine and lamotrigine and therefore an 
interaction could be expected. A study in healthy subjects with eslicarbazepine acetate 1,200 mg once daily 
showed a minor average pharmacokinetic interaction (exposure of lamotrigine decreased 15%) between 
eslicarbazepine acetate and lamotrigine and consequently no dose adjustments are required. However, due to 
interindividual variability, the effect may be clinically relevant in some individuals. 
 
Topiramate 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
topiramate showed no significant change in exposure to eslicarbazepine but an 18% decrease in exposure to 
topiramate, most likely caused by a reduced bioavailability of topiramate. No dose adjustment is required.  
 
Valproate and levetiracetam 
A population pharmacokinetics analysis of phase III studies in epileptic adult patients indicated that 
concomitant administration with valproate or levetiracetam did not affect the exposure to eslicarbazepine but 
this has not been verified by conventional interaction studies.  
 
Other medicinal products 
Oral contraceptives 
Administration of eslicarbazepine acetate 1,200 mg once daily to female subjects using a combined oral 
contraceptive showed an average decrease of 37% and 42% in systemic exposure to levonorgestrel and 
ethinyloestradiol, respectively, most likely caused by an induction of CYP3A4. Therefore, women of 
childbearing potential must use adequate contraception during treatment with Exalief, and up to the end of 
the current menstruation cycle after the treatment has been discontinued (see section 4.4 and 4.6). 
 
Simvastatin 
A study in healthy subjects showed an average decrease of 50% in systemic exposure to simvastatin when 
co-administered with eslicarbazepine acetate 800 mg once daily, most likely caused by an induction of 
CYP3A4. An increase of the simvastatin dose may be required when used concomitantly with 
eslicarbazepine acetate. 
 
Warfarin 
Co-administration of eslicarbazepine acetate 1,200 mg once daily with warfarin showed a small (23%) but 
statistically significant decrease in exposure to S-warfarin. There was no effect on the R-warfarin 
pharmacokinetics or on coagulation. However, due to inter-individual variability in the interaction, special 
attention on monitoring of INR should be performed the first weeks after initiation or ending concomitant 
treatment of warfarin and eslicarbazepine acetate.  
 
Digoxin 
A study in healthy subjects showed no effect of eslicarbazepine acetate 1,200 mg once daily on digoxin 
pharmacokinetics, suggesting that eslicarbazepine acetate has no effect on the transporter P-glycoprotein. 
 
Monoamino Oxidase Inhibitors (MAOIs) 
Based on a structural relationship of eslicarbazepine acetate to tricyclic antidepressants, an interaction 
between eslicarbazepine acetate and MAOIs is theoretically possible.  
 
4.6 Fertility, pregnancy and lactation 
 
Risk related to epilepsy and antiepileptic medicinal products in general 
It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to 
three times greater than the rate of approximately 3 % in the general population. Most frequently reported are 
cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic medicinal product M

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therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is 
important that monotherapy is practised whenever possible. Specialist advice should be given to women who 
are likely to become pregnant or who are of child-bearing potential. The need for antiepileptic therapy 
should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of 
antiepileptic therapy should be undertaken as this may lead to breakthrough seizures which could have 
serious consequences for both mother and child. 
 
Pregnancy 
There are no data from the use of eslicarbazepine acetate in pregnant women. Studies in animals have shown 
reproductive toxicity (see Fertility). If women receiving eslicarbazepine acetate become pregnant or plan to 
become pregnant, the use of Exalief should be carefully re-evaluated. Minimum effective doses should be 
given, and monotherapy whenever possible should be preferred at least during the first three months of 
pregnancy. Patients should be counselled regarding the possibility of an increased risk of malformations and 
given the opportunity to antenatal screening. 
 
Monitoring and prevention 
Antiepileptic medicinal products may contribute to folic acid deficiency, a possible contributory cause of 
foetal abnormality. Folic acid supplementation is recommended before and during pregnancy. As the 
efficacy of this supplementation is not proven, a specific antenatal diagnosis can be offered even for women 
with a supplementary treatment of folic acid. 
 
In the newborn child 
Bleeding disorders in the newborn caused by antiepileptic medicinal products have been reported. As a 
precaution, vitamin K1 should be administered as a preventive measure in the last few weeks of pregnancy 
and to the newborn. 
 
Women of childbearing potential/contraception 
Eslicarbazepine acetate adversely interacts with oral contraceptives. Therefore, an alternative, effective and 
safe method of contraception should be used during treatment and up to the end of the current menstrual 
cycle after treatment has been stopped. 
 
Breastfeeding  
It is unknown whether eslicarbazepine acetate is excreted in human breast milk. Animal studies have shown 
excretion of eslicarbazepine in breast milk. As a risk to the breast-fed child cannot be excluded breast-
feeding should be discontinued during treatment with Exalief.  
 
Fertility 
Eslicarbazepine acetate was evaluated in rats and mice for potential adverse effects on fertility of the parental 
and F1 generation. In a fertility study in male and female rats, impairment of female fertility by 
eslicarbazepine acetate was shown. In a fertility study in mice, developmental effects were observed in 
embryos; however, effects could also result from lower corpora lutea count and thus show impairment 
of fertility. In the mouse, the overall incidence of major abnormalities and the incidence for major skeletal 
abnormalities were increased. No effects on F1 fertility parameters were observed in rats and mice.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Some patients might 
experience dizziness, somnolence or visual disorders, particularly on initiation of treatment. Therefore, 
patients should be advised that their physical and/ or mental abilities needed for operating machinery or 
driving may be impaired and they are recommended not to do so until it has been established that their ability 
to perform such activities is not affected. 
 
4.8 Undesirable effects 
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In placebo-controlled studies involving 1,192 adult patients with partial-onset seizures (856 patients treated 
with eslicarbazepine acetate and 336 treated with placebo), 45.3% of patients treated with eslicarbazepine 
acetate and 24.4% of patients treated with placebo experienced adverse reactions. 
 
Adverse reactions were usually mild to moderate in intensity and occurred predominantly during the first 
weeks of treatment with eslicarbazepine acetate.  
 
In the table below all adverse reactions, which occurred at an incidence greater than placebo and numerically 
present in more than 1 patient are listed by System Organ Class and frequency:  
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. 
Within each frequency category, adverse reactions are presented in order of decreasing seriousness. 
 
System Organ 
Class 

Very  
common 

Common Uncommon Rare 

Blood and 
lymphatic system 
disorders 

  Anaemia Thrombocytopenia,
leukopenia 

Immune system 
disorders 

  Hypersensitivity  

Endocrine 
disorders 

  Hypothyroidism  

Metabolism and 
nutrition disorders 

  Increased appetite, 
decreased appetite, 
hyponatraemia, electrolyte 
imbalance, cachexia, 
dehydration, obesity 

 

Psychiatric 
disorders 

  Insomnia, apathy, 
depression, nervousness, 
agitation, irritability, 
attention deficit/ 
hyperactivity disorder, 
confusional state, mood 
swings, crying, 
psychomotor retardation, 
stress, psychotic disorder 

 

Nervous system 
disorders 

Dizziness*, 
somnolence 
 

Headache, 
abnormal 
coordination
*, 
disturbance 
in attention, 
tremor 

Memory impairment, 
balance disorder, amnesia, 
hypersomnia, sedation, 
aphasia, dysaesthesia, 
dystonia, lethargy, 
parosmia, autonomic 
nervous system imbalance, 
cerebellar ataxia, cerebellar 
syndrome, grand mal 
convulsion, neuropathy 
peripheral, sleep phase 
rhythm disturbance, 
nystagmus, speech 
disorder, dysarthria, 
hypoaesthesia, ageusia, 
burning sensation 

 

Eye disorders  Diplopia*, 
vision 
blurred 

Vision disturbance, 
oscillopsia, binocular eye 
movement disorder, ocular 
hyperaemia, saccadic eye 

 

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movement, eye pain 
Ear and labyrinth 
disorders 

 Vertigo 
 

Ear pain, hypoacusis, 
tinnitus 

 

Cardiac disorders   Palpitations, bradycardia, 
sinus bradycardia 

 

Vascular disorders   Hypertension, hypotension, 
orthostatic hypotension 

 

Respiratory, 
thoracic and 
mediastinal 
disorders 

  Dysphonia, epistaxis, chest 
pain 

 

Gastrointestinal 
disorders 

 Nausea, 
vomiting, 
diarrhoea 

Dyspepsia, gastritis, 
abdominal pain, dry mouth, 
abdominal discomfort, 
abdominal distension, 
duodenitis, epigastric 
discomfort, gingival 
hyperplasia, gingivitis , 
irritable bowel syndrome, 
melaena, odynophagia, 
stomach discomfort, 
stomatitis, toothache 

Pancreatitis 

Hepatobiliary 
disorders 

  Liver disorder  

Skin and 
subcutaneous tissue 
disorders 

 Rash 
 

Alopecia, dry skin, 
hyperhidrosis, erythema, 
nail disorder, skin disorder 

 

Musculoskeletal 
and connective 
tissue disorders 

  Myalgia, back pain, neck 
pain 

 

Renal and urinary 
disorders 

  Nocturia, urinary tract 
infection 

 

Reproductive 
system and breast 
disorders 

  Menstruation irregular  

General disorders 
and administration 
site conditions 

 Fatigue, gait 
disturbance 
 

Asthenia, malaise, chills, 
oedema peripheral, adverse 
drug reaction, peripheral 
coldness 

 

Investigations   Blood pressure decreased, 
weight decreased, blood 
pressure diastolic 
decreased, blood pressure 
increased, blood pressure 
systolic decreased, blood 
sodium decreased, 
haematocrit decreased, 
haemoglobin decreased, 
heart rate increased, 
transaminases increased, 
triglycerides increased, tri-
iodothyronine (T3) free 
decreased, thyroxine (T4) 
free decreased 

 

Injury, poisoning   Drug toxicity, fall, joint  M
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and procedural 
complications  

injury, poisoning, skin 
injury 

* In patients concomitantly treated with carbamazepine and eslicarbazepine acetate in placebo-controlled 
studies, diplopia, abnormal coordination and dizziness were reported more frequently. 
 
The use of eslicarbazepine acetate is associated with increase in the PR interval. Adverse reactions associated 
with PR interval prolongation (e.g. AV block, syncope, bradycardia) may occur. No second or higher degree 
AV block was seen in eslicarbazepine acetate treated patients. 
 
Rare adverse reactions such as bone marrow depression, anaphylactic reactions, severe cutaneous reactions 
(e.g. Stevens-Johnson Syndrome), systemic lupus erythematosus or serious cardiac arrhythmias did not occur 
during the placebo-controlled studies of the epilepsy program with eslicarbazepine acetate. However, they 
have been reported with oxcarbazepine. Therefore, their occurrence after treatment with Exalief cannot be 
excluded. 
 
4.9 Overdose 
 
Central nervous symptoms such as vertigo, walking instability and hemi-paresis have been observed with 
accidental Exalief overdose. There is no known specific antidote. Symptomatic and supportive treatment 
should be administered as appropriate. Eslicarbazepine acetate metabolites can effectively be cleared by 
haemodialysis, if necessary (see section 5.2). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiepileptics, Carboxamide derivatives, ATC code: N03AF04 
 
Mechanism of action 
The precise mechanisms of action of eslicarbazepine acetate are unknown. However, in vitro 
electrophysiological studies indicate that both eslicarbazepine acetate and its metabolites stabilise the 
inactivated state of voltage-gated sodium channels, preventing their return to the activated state and thereby 
sustaining repetitive neuronal firing.  
 
Pharmacodynamic effect 
Eslicarbazepine acetate and its active metabolites prevented the development of seizures in nonclinical 
models predictive of anticonvulsant efficacy in man. In humans, the pharmacological activity of 
eslicarbazepine acetate is primarily exerted through the active metabolite eslicarbazepine. 
 
Clinical efficacy and safety 
The efficacy and safety of eslicarbazepine acetate has been demonstrated in three phase III double-blind 
placebo-controlled studies in 1,049 adult patients with partial epilepsy refractory to treatment with one to 
three concomitant anti-epileptic medicinal products. Oxcarbazepine and felbamate were not allowed as 
concomitant medicinal products in these studies. Eslicarbazepine acetate was tested at doses of 400 mg, 
800 mg and 1200 mg, once daily. Eslicarbazepine acetate 800 mg once daily and 1200 mg once daily were 
significantly more effective than placebo in reducing seizure frequency over a 12-week maintenance period. 
The percentage of subjects with a 50% reduction in seizure frequency over all phase III studies was 19% for 
placebo, 21% for eslicarbazepine acetate 400 mg, 34% for eslicarbazepine acetate 800 mg and 36% for 
eslicarbazepine acetate 1200 mg daily.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
Eslicarbazepine acetate is extensively converted to eslicarbazepine. Plasma levels of eslicarbazepine acetate 
usually remain below the limit of quantification, following oral administration. Eslicarbazepine tmax is M

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attained at 2 to 3 h post-dose. Bioavailability may be assumed as high because the amount of metabolites 
recovered in urine corresponded to more than 90% of an eslicarbazepine acetate dose.  
 
Distribution 
The binding of eslicarbazepine to plasma proteins is relatively low (<40%) and independent from 
concentration. In vitro studies have shown that plasma protein binding was not relevantly affected by the 
presence of warfarin, diazepam, digoxin, phenytoin and tolbutamide. The binding of warfarin, diazepam, 
digoxin, phenytoin and tolbutamide was not significantly affected by the presence of eslicarbazepine.  
 
Biotransformation 
Eslicarbazepine acetate is rapidly and extensively biotransformed to its major active metabolite 
eslicarbazepine by hydrolytic first-pass metabolism. Peak plasma concentrations (Cmax) of eslicarbazepine 
are attained at 2-3 hours post-dose and steady state plasma concentrations are attained after 4 to 5 days of 
once daily dosing, consistent with an effective half-life in the order of 20-24 h. In studies in healthy subjects 
and epileptic adult patients, the apparent half-life of eslicarbazepine was 10-20 h and 13-20 h, respectively. 
Minor metabolites in plasma are R-licarbazepine and oxcarbazepine, which were shown to be active, and the 
glucuronic acid conjugates of eslicarbazepine acetate, eslicarbazepine, R-licarbazepine and oxcarbazepine.  
 
Eslicarbazepine acetate does not affect its own metabolism or clearance. 
 
In studies with eslicarbazepine in fresh human hepatocytes a mild activation of UGT1A1 mediated 
glucuronidation was observed. 
 
Excretion 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion, 
in the unchanged and glucuronide conjugate forms. In total, eslicarbazepine and its glucuronide correspond 
to more than 90% of total metabolites excreted in urine, approximately two thirds in the unchanged form and 
one third as glucuronide conjugate. 
 
Linearity / non-linearity 
The pharmacokinetics of eslicarbazepine is linear and dose-proportional in the range 400-1200 mg both in 
healthy subjects and patients. 
 
Elderly (over 65 years of age) 
The pharmacokinetic profile of eslicarbazepine acetate is unaffected in the elderly patients with creatinine 
clearance >60 ml/min (see section 4.2).  
 
Renal impairment 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion. 
A study in patients with mild to severe renal impairment showed that clearance is dependent on renal 
function. During treatment with Exalief dose adjustment is recommended in patients with creatinine 
clearance <60 ml/min (see section 4.2).  
Haemodialysis removes eslicarbazepine acetate metabolites from plasma.  
 
Hepatic impairment 
The pharmacokinetics and metabolism of eslicarbazepine acetate were evaluated in healthy subjects and 
moderately liver-impaired patients after multiple oral doses. Moderate hepatic impairment did not affect the 
pharmacokinetics of eslicarbazepine acetate. No dose adjustment is recommended in patients with mild to 
moderate liver impairment (see section 4.2).  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment.  
 
Gender 
Studies in healthy subjects and patients showed that pharmacokinetics of eslicarbazepine acetate were not 
affected by gender.  
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5.3 Preclinical safety data 
 
Adverse affects observed in animal studies occurred at exposure levels appreciably lower than the clinical 
exposure levels to eslicarbazepine (the principal and pharmacologically active metabolite of eslicarbazepine 
acetate). Safety margins based on comparative exposure have thus not been established. 
 
Evidence of nephrotoxicity was observed in repeated dose toxicity studies in the rat, but was not seen in 
studies in mice or dogs, and is consistent with an exacerbation of spontaneous chronic progressive 
nephropathy in this species.  
 
Liver centrilobular hypertrophy was seen in repeated dose toxicity studies in mice and rats and an increased 
incidence of liver tumours was observed in the carcinogenicity study in mice; these findings are consistent 
with an induction of hepatic microsomal enzymes, an effect which has not been observed in patients 
receiving eslicarbazepine acetate. 
 
Genotoxicity studies with eslicarbazepine acetate indicate no special hazards for humans.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Povidone K 29/32 
Croscarmellose sodium  
Magnesium stearate 
 
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 
 
Exalief 400 mg tablets are packaged in ALU/ALU or ALU/PVC blisters placed into cardboard boxes 
containing 7, 14 or 28 tablets. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
BIAL - Portela & Cª , SA 
À Av. da Siderurgia Nacional 4745-457 S. Mamede do Coronado - Portugal 
tel: +351 22 986 61 00 
fax: +351 22 986 61 99 M

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e-mail: info@bial.com  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/001-006 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21.04.2009 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/. 

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1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 600 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 600 mg of eslicarbazepine acetate. 
 

For a full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
 
White oblong tablets, engraved ‘ESL 600’on one side and scored on the other side. The tablet can be divided 
into equal halves.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Exalief is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary 
generalisation. 
 
4.2 Posology and method of administration 
 
Posology 
 
Exalief must be added to existing anticonvulsant therapy. The recommended starting dose is 400 mg once 
daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, 
the dose may be increased to 1200 mg once daily (see section 5.1). 
 
Elderly (over 65 years of age) 
Caution should be exercised in the treatment of elderly patients as there is limited safety information on the 
use of Exalief in these patients. 
 
Paediatric population 
The safety and efficacy of Exalief below 18 years has not yet been established. No data are available. 
 
Patients with renal impairment 
Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (CLCR) as follows: 
- CLCR >60 ml/min: no dose adjustment required 
- CLCR 30-60 ml/min: initial dose of 400 mg every other day for 2 weeks followed by a once daily dose of 

400 mg. However, based on individual response, the dose may be increased. 
- CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient 

data 
 
Patients with hepatic impairment 
No dose adjustment is needed in patients with mild to moderate hepatic impairment.  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment 
(see section 4.4 and 5.2) and use in these patients is therefore not recommended. M

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Method of administration 
 
Exalief may be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other carboxamide derivatives (e.g. carbamazepine, 
oxcarbazepine) or to any of the excipients.  
 
Known second or third degree atrioventricular (AV) block. 
 
4.4 Special warnings and precautions for use 
 
Exalief has been associated with some central nervous system adverse reactions, such as dizziness and 
somnolence, which could increase the occurrence of accidental injury.  
 
Exalief may decrease the effectiveness of hormonal contraceptives. Additional non-hormonal forms of 
contraception are recommended when using Exalief (see section 4.5 and 4.6). 
 
As with other anti-epileptic medicinal products, if Exalief is to be discontinued it is recommended to 
withdraw it gradually to minimise the potential of increased seizure frequency.  
 
Concomitant use of Exalief with oxcarbazepine is not recommended because this may cause overexposure to 
the active metabolites. 
 
There is no experience regarding the withdrawal of concomitant use of anti-epileptic medicinal products 
during treatment with Exalief (switch to monotherapy). 
 
Rash developed as an adverse reaction in 1.1% of total population treated with Exalief in placebo-controlled 
add-on studies in epileptic patients. If signs or symptoms of hypersensitivity develop, Exalief must be 
discontinued. 
 
No cases of serious cutaneous reactions have been reported with eslicarbazepine acetate. Presence of 
HLA-B*1502 allele in individuals of Han Chinese and Thai origin has been shown to be strongly associated 
with the risk of developing Stevens-Johnson syndrome (SJS) when treated with carbamazepine. Therefore, 
whenever possible, subjects of Han Chinese and Thai origin should be screened for this allele before starting 
treatment with carbamazepine or chemically-related compounds. The presence of HLA-B*1502 allele in 
other ethnicities is negligible. The allele HLA-B*1502 is not associated to SJS in the Caucasian population. 
 
Hyponatraemia has been reported as an adverse reaction in less than 1% of patients treated with Exalief. 
Hyponatraemia is asymptomatic in most cases, however, it may be accompanied by clinical symptoms like 
worsening of seizures, confusion, decreased consciousness. Frequency of hyponatraemia increased with 
increasing eslicarbazepine acetate dose. In patients with pre-existing renal disease leading to hyponatraemia, 
or in patients concomitantly treated with medicinal products which may themselves lead to hyponatraemia 
(e.g. diuretics, desmopressin), serum sodium levels should be examined before and during treatment with 
eslicarbazepine acetate. Furthermore, serum sodium levels should be determined if clinical signs of 
hyponatraemia occur. Apart from this, sodium levels should be determined during routine laboratory 
examination. If clinically relevant hyponatraemia develops, Exalief should be discontinued. 
 
The influence of Exalief on primary generalised seizures has not been studied. Use is therefore not 
recommended in these patients. 
 
Prolongations in PR interval have been observed in clinical studies with eslicarbazepine acetate.  M

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Caution should be exercised in patients with medical conditions (e.g. low levels of thyroxine, cardiac 
conduction abnormalities), or when taking concomitant medicinal products known to be associated with PR 
prolongation. 
 
Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (see section 4.2). In patients with CLCR <30 ml/min use is not 
recommended due to insufficient data. 
 
As clinical data are limited in patients with mild to moderate hepatic impairment and pharmacokinetic and 
clinical data are missing in patients with severe hepatic impairment, Exalief should be used with caution in 
patients with mild to moderate hepatic impairment and is not recommended in patients with severe hepatic 
impairment. 
 
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic active substances in 
several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic medicinal 
products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this 
risk is not known and the available data do not exclude the possibility of an increased risk for eslicarbazepine 
acetate. Therefore patients should be monitored for signs of 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 suicidal ideation or behaviour emerge. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Eslicarbazepine acetate is extensively converted to eslicarbazepine, which is mainly eliminated by 
glucuronidation. In vitro eslicarbazepine is a weak inducer of CYP3A4 and UDP-glucuronyl transferases. In 
vivo eslicarbazepine showed an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by metabolism through CYP3A4. Thus, an increase in the dose of the medicinal products that are 
mainly metabolised through CYP3A4 may be required, when used concomitantly with Exalief. 
Eslicarbazepine in vivo may have an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by conjugation through the UDP glucuronyl transferases. When initiating or discontinuing 
treatment with Exalief or changing the dose, it may take 2 to 3 weeks to reach the new level of enzyme 
activity. This time delay must be taken into account when Exalief is being used just prior to or in 
combination with other medicines that require dose adjustment when co-administered with Exalief. 
Eslicarbazepine has inhibiting properties with respect to CYP2C19. Thus, interactions can arise when co-
administering high doses of eslicarbazepine acetate with medicinal products that are mainly metabolised by 
CYP2C19. 
 
Interactions with other antiepileptic medicinal products 
Carbamazepine 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 800 mg once daily and 
carbamazepine 400 mg twice daily resulted in an average decrease of 32% in exposure to the active 
metabolite eslicarbazepine, most likely caused by an induction of glucuronidation. No change in exposure to 
carbamazepine or its metabolite carbamazepine-epoxide was noted. Based on individual response, the dose 
of Exalief may need to be increased if used concomitantly with carbamazepine. Results from patient studies 
showed that concomitant treatment increased the risk of the following adverse reactions: diplopia (11.4% of 
subjects with concomitant carbamazepine, 2.4% of subjects without concomitant carbamazepine), abnormal 
coordination (6.7% with concomitant carbamazepine, 2.7% without concomitant carbamazepine), and 
dizziness (30.0% with concomitant carbamazepine, 11.5% without concomitant carbamazepine). The risk of 
increase of other specific adverse reactions caused by co-administration of carbamazepine and 
eslicarbazepine acetate cannot be excluded.  
 
Phenytoin 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
phenytoin resulted in an average decrease of 31-33% in exposure to the active metabolite, eslicarbazepine, 

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most likely caused by an induction of glucuronidation, and an average increase of 31-35% in exposure to 
phenytoin, most likely caused by an inhibition of CYP2C19. Based on individual response, the dose of 
Exalief may need to be increased and the dose of phenytoin may need to be decreased. 
 
Lamotrigine 
Glucuronidation is the major metabolic pathway for both eslicarbazepine and lamotrigine and therefore an 
interaction could be expected. A study in healthy subjects with eslicarbazepine acetate 1,200 mg once daily 
showed a minor average pharmacokinetic interaction (exposure of lamotrigine decreased 15%) between 
eslicarbazepine acetate and lamotrigine and consequently no dose adjustments are required. However, due to 
interindividual variability, the effect may be clinically relevant in some individuals. 
 
Topiramate 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
topiramate showed no significant change in exposure to eslicarbazepine but an 18% decrease in exposure to 
topiramate, most likely caused by a reduced bioavailability of topiramate. No dose adjustment is required.  
 
Valproate and levetiracetam 
A population pharmacokinetics analysis of phase III studies in epileptic adult patients indicated that 
concomitant administration with valproate or levetiracetam did not affect the exposure to eslicarbazepine but 
this has not been verified by conventional interaction studies.  
 
Other medicinal products 
Oral contraceptives 
Administration of eslicarbazepine acetate 1,200 mg once daily to female subjects using a combined oral 
contraceptive showed an average decrease of 37% and 42% in systemic exposure to levonorgestrel and 
ethinyloestradiol, respectively, most likely caused by an induction of CYP3A4. Therefore, women of 
childbearing potential must use adequate contraception during treatment with Exalief, and up to the end of 
the current menstruation cycle after the treatment has been discontinued (see section 4.4 and 4.6). 
 
Simvastatin 
A study in healthy subjects showed an average decrease of 50% in systemic exposure to simvastatin when 
co-administered with eslicarbazepine acetate 800 mg once daily, most likely caused by an induction of 
CYP3A4. An increase of the simvastatin dose may be required when used concomitantly with 
eslicarbazepine acetate. 
 
Warfarin 
Co-administration of eslicarbazepine acetate 1,200 mg once daily with warfarin showed a small (23%) but 
statistically significant decrease in exposure to S-warfarin. There was no effect on the R-warfarin 
pharmacokinetics or on coagulation. However, due to inter-individual variability in the interaction, special 
attention on monitoring of INR should be performed the first weeks after initiation or ending concomitant 
treatment of warfarin and eslicarbazepine acetate.  
 
Digoxin 
A study in healthy subjects showed no effect of eslicarbazepine acetate 1,200 mg once daily on digoxin 
pharmacokinetics, suggesting that eslicarbazepine acetate has no effect on the transporter P-glycoprotein. 
 
Monoamino Oxidase Inhibitors (MAOIs) 
Based on a structural relationship of eslicarbazepine acetate to tricyclic antidepressants, an interaction 
between eslicarbazepine acetate and MAOIs is theoretically possible.  
 
4.6 Fertility, pregnancy and lactation 
 
Risk related to epilepsy and antiepileptic medicinal products in general 
It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to 
three times greater than the rate of approximately 3 % in the general population. Most frequently reported are M

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cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic medicinal product 
therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is 
important that monotherapy is practised whenever possible. Specialist advice should be given to women who 
are likely to become pregnant or who are of child-bearing potential. The need for antiepileptic therapy 
should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of 
antiepileptic therapy should be undertaken as this may lead to breakthrough seizures which could have 
serious consequences for both mother and child. 
 
Pregnancy 
There are no data from the use of eslicarbazepine acetate in pregnant women. Studies in animals have shown 
reproductive toxicity (see Fertility). If women receiving eslicarbazepine acetate become pregnant or plan to 
become pregnant, the use of Exalief should be carefully re-evaluated. Minimum effective doses should be 
given, and monotherapy whenever possible should be preferred at least during the first three months of 
pregnancy. Patients should be counselled regarding the possibility of an increased risk of malformations and 
given the opportunity to antenatal screening. 
 
Monitoring and prevention 
Antiepileptic medicinal products may contribute to folic acid deficiency, a possible contributory cause of 
foetal abnormality. Folic acid supplementation is recommended before and during pregnancy. As the 
efficacy of this supplementation is not proven, a specific antenatal diagnosis can be offered even for women 
with a supplementary treatment of folic acid. 
 
In the newborn child 
Bleeding disorders in the newborn caused by antiepileptic medicinal products have been reported. As a 
precaution, vitamin K1 should be administered as a preventive measure in the last few weeks of pregnancy 
and to the newborn. 
 
Women of childbearing potential/contraception 
Eslicarbazepine acetate adversely interacts with oral contraceptives. Therefore, an alternative, effective and 
safe method of contraception should be used during treatment and up to the end of the current menstrual 
cycle after treatment has been stopped. 
 
Breastfeeding 
It is unknown whether eslicarbazepine acetate is excreted in human breast milk. Animal studies have shown 
excretion of eslicarbazepine in breast milk. As a risk to the breast-fed child cannot be excluded breast-
feeding should be discontinued during treatment with Exalief.  
 
Fertility 
Eslicarbazepine acetate was evaluated in rats and mice for potential adverse effects on fertility of the parental 
and F1 generation. In a fertility study in male and female rats, impairment of female fertility by 
eslicarbazepine acetate was shown. In a fertility study in mice, developmental effects were observed in 
embryos; however, effects could also result from lower corpora lutea count and thus show impairment 
of fertility. In the mouse, the overall incidence of major abnormalities and the incidence for major skeletal 
abnormalities were increased. No effects on F1 fertility parameters were observed in rats and mice.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Some patients might 
experience dizziness, somnolence or visual disorders, particularly on initiation of treatment. Therefore, 
patients should be advised that their physical and/ or mental abilities needed for operating machinery or 
driving may be impaired and they are recommended not to do so until it has been established that their ability 
to perform such activities is not affected. 
 
4.8 Undesirable effects 
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In placebo-controlled studies involving 1,192 adult patients with partial-onset seizures (856 patients treated 
with eslicarbazepine acetate and 336 treated with placebo), 45.3% of patients treated with eslicarbazepine 
acetate and 24.4% of patients treated with placebo experienced adverse reactions. 
 
Adverse reactions were usually mild to moderate in intensity and occurred predominantly during the first 
weeks of treatment with eslicarbazepine acetate.  
 
In the table below all adverse reactions, which occurred at an incidence greater than placebo and numerically 
present in more than 1 patient are listed by System Organ Class and frequency:  
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. 
Within each frequency category, adverse reactions are presented in order of decreasing seriousness. 
 
System Organ 
Class 

Very  
common 

Common Uncommon Rare 

Blood and 
lymphatic system 
disorders 

  Anaemia Thrombocytopenia,
leukopenia 

Immune system 
disorders 

  Hypersensitivity  

Endocrine 
disorders 

  Hypothyroidism  

Metabolism and 
nutrition disorders 

  Increased appetite, 
decreased appetite, 
hyponatraemia, electrolyte 
imbalance, cachexia, 
dehydration, obesity 

 

Psychiatric 
disorders 

  Insomnia, apathy, 
depression, nervousness, 
agitation, irritability, 
attention deficit/ 
hyperactivity disorder, 
confusional state, mood 
swings, crying, 
psychomotor retardation, 
stress, psychotic disorder 

 

Nervous system 
disorders 

Dizziness*, 
somnolence 
 

Headache, 
abnormal 
coordination
*, 
disturbance 
in attention, 
tremor 

Memory impairment, 
balance disorder, amnesia, 
hypersomnia, sedation, 
aphasia, dysaesthesia, 
dystonia, lethargy, 
parosmia, autonomic 
nervous system imbalance, 
cerebellar ataxia, cerebellar 
syndrome, grand mal 
convulsion, neuropathy 
peripheral, sleep phase 
rhythm disturbance, 
nystagmus, speech 
disorder, dysarthria, 
hypoaesthesia, ageusia, 
burning sensation 

 

Eye disorders  Diplopia*, 
vision 
blurred 

Vision disturbance, 
oscillopsia, binocular eye 
movement disorder, ocular 
hyperaemia, saccadic eye 

 

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movement, eye pain 
Ear and labyrinth 
disorders 

 Vertigo 
 

Ear pain, hypoacusis, 
tinnitus 

 

Cardiac disorders   Palpitations, bradycardia, 
sinus bradycardia 

 

Vascular disorders   Hypertension, hypotension, 
orthostatic hypotension 

 

Respiratory, 
thoracic and 
mediastinal 
disorders 

  Dysphonia, epistaxis, chest 
pain 

 

Gastrointestinal 
disorders 

 Nausea, 
vomiting, 
diarrhoea 

Dyspepsia, gastritis, 
abdominal pain, dry mouth, 
abdominal discomfort, 
abdominal distension, 
duodenitis, epigastric 
discomfort, gingival 
hyperplasia, gingivitis , 
irritable bowel syndrome, 
melaena, odynophagia, 
stomach discomfort, 
stomatitis, toothache 

Pancreatitis 

Hepatobiliary 
disorders 

  Liver disorder  

Skin and 
subcutaneous tissue 
disorders 

 Rash 
 

Alopecia, dry skin, 
hyperhidrosis, erythema, 
nail disorder, skin disorder 

 

Musculoskeletal 
and connective 
tissue disorders 

  Myalgia, back pain, neck 
pain 

 

Renal and urinary 
disorders 

  Nocturia, urinary tract 
infection 

 

Reproductive 
system and breast 
disorders 

  Menstruation irregular  

General disorders 
and administration 
site conditions 

 Fatigue, gait 
disturbance 
 

Asthenia, malaise, chills, 
oedema peripheral, adverse 
drug reaction, peripheral 
coldness 

 

Investigations   Blood pressure decreased, 
weight decreased, blood 
pressure diastolic 
decreased, blood pressure 
increased, blood pressure 
systolic decreased, blood 
sodium decreased, 
haematocrit decreased, 
haemoglobin decreased, 
heart rate increased, 
transaminases increased, 
triglycerides increased, tri-
iodothyronine (T3) free 
decreased, thyroxine (T4) 
free decreased 

 

Injury, poisoning   Drug toxicity, fall, joint  M
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and procedural 
complications 

injury, poisoning, skin 
injury 

* In patients concomitantly treated with carbamazepine and eslicarbazepine acetate in placebo-controlled 
studies, diplopia, abnormal coordination and dizziness were reported more frequently. 
 
The use of eslicarbazepine acetate is associated with increase in the PR interval. Adverse reactions associated 
with PR interval prolongation (e.g. AV block, syncope, bradycardia) may occur. No second or higher degree 
AV block was seen in eslicarbazepine acetate treated patients. 
 
Rare adverse reactions such as bone marrow depression, anaphylactic reactions, severe cutaneous reactions 
(e.g. Stevens-Johnson Syndrome), systemic lupus erythematosus or serious cardiac arrhythmias did not occur 
during the placebo-controlled studies of the epilepsy program with eslicarbazepine acetate. However, they 
have been reported with oxcarbazepine. Therefore, their occurrence after treatment with Exalief cannot be 
excluded. 
 
4.9 Overdose 
 
Central nervous symptoms such as vertigo, walking instability and hemi-paresis have been observed with 
accidental Exalief overdose. There is no known specific antidote. Symptomatic and supportive treatment 
should be administered as appropriate. Eslicarbazepine acetate metabolites can effectively be cleared by 
haemodialysis, if necessary (see section 5.2). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiepileptics, Carboxamide derivatives, ATC code: N03AF04 
 
Mechanism of action 
The precise mechanisms of action of eslicarbazepine acetate are unknown. However, in vitro 
electrophysiological studies indicate that both eslicarbazepine acetate and its metabolites stabilise the 
inactivated state of voltage-gated sodium channels, preventing their return to the activated state and thereby 
sustaining repetitive neuronal firing.  
 
Pharmacodynamic effect 
Eslicarbazepine acetate and its active metabolites prevented the development of seizures in nonclinical 
models predictive of anticonvulsant efficacy in man. In humans, the pharmacological activity of 
eslicarbazepine acetate is primarily exerted through the active metabolite eslicarbazepine. 
 
Clinical efficacy and safety 
The efficacy and safety of eslicarbazepine acetate has been demonstrated in three phase III double-blind 
placebo-controlled studies in 1,049 adult patients with partial epilepsy refractory to treatment with one to 
three concomitant anti-epileptic medicinal products. Oxcarbazepine and felbamate were not allowed as 
concomitant medicinal products in these studies. Eslicarbazepine acetate was tested at doses of 400 mg, 
800 mg and 1200 mg, once daily. Eslicarbazepine acetate 800 mg once daily and 1200 mg once daily were 
significantly more effective than placebo in reducing seizure frequency over a 12-week maintenance period. 
The percentage of subjects with a 50% reduction in seizure frequency over all phase III studies was 19% for 
placebo, 21% for eslicarbazepine acetate 400 mg, 34% for eslicarbazepine acetate 800 mg and 36% for 
eslicarbazepine acetate 1200 mg daily.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
Eslicarbazepine acetate is extensively converted to eslicarbazepine. Plasma levels of eslicarbazepine acetate 
usually remain below the limit of quantification, following oral administration. Eslicarbazepine tmax is M

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attained at 2 to 3 h post-dose. Bioavailability may be assumed as high because the amount of metabolites 
recovered in urine corresponded to more than 90% of an eslicarbazepine acetate dose.  
 
Distribution 
The binding of eslicarbazepine to plasma proteins is relatively low (<40%) and independent from 
concentration. In vitro studies have shown that plasma protein binding was not relevantly affected by the 
presence of warfarin, diazepam, digoxin, phenytoin and tolbutamide. The binding of warfarin, diazepam, 
digoxin, phenytoin and tolbutamide was not significantly affected by the presence of eslicarbazepine.  
 
Biotransformation 
Eslicarbazepine acetate is rapidly and extensively biotransformed to its major active metabolite 
eslicarbazepine by hydrolytic first-pass metabolism. Peak plasma concentrations (Cmax) of eslicarbazepine 
are attained at 2-3 hours post-dose and steady state plasma concentrations are attained after 4 to 5 days of 
once daily dosing, consistent with an effective half-life in the order of 20-24 h. In studies in healthy subjects 
and epileptic adult patients, the apparent half-life of eslicarbazepine was 10-20 h and 13-20 h, respectively. 
Minor metabolites in plasma are R-licarbazepine and oxcarbazepine, which were shown to be active, and the 
glucuronic acid conjugates of eslicarbazepine acetate, eslicarbazepine, R-licarbazepine and oxcarbazepine.  
 
Eslicarbazepine acetate does not affect its own metabolism or clearance. 
 
In studies with eslicarbazepine in fresh human hepatocytes a mild activation of UGT1A1 mediated 
glucuronidation was observed. 
 
Excretion 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion, 
in the unchanged and glucuronide conjugate forms. In total, eslicarbazepine and its glucuronide correspond 
to more than 90% of total metabolites excreted in urine, approximately two thirds in the unchanged form and 
one third as glucuronide conjugate. 
 
Linearity / non-linearity 
The pharmacokinetics of eslicarbazepine is linear and dose-proportional in the range 400-1200 mg both in 
healthy subjects and patients. 
 
Elderly (over 65 years of age) 
The pharmacokinetic profile of eslicarbazepine acetate is unaffected in the elderly patients with creatinine 
clearance >60 ml/min (see section 4.2).  
 
Renal impairment 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion. 
A study in patients with mild to severe renal impairment showed that clearance is dependent on renal 
function. During treatment with Exalief dose adjustment is recommended in patients with creatinine 
clearance <60 ml/min (see section 4.2).  
Haemodialysis removes eslicarbazepine acetate metabolites from plasma.  
 
Hepatic impairment 
The pharmacokinetics and metabolism of eslicarbazepine acetate were evaluated in healthy subjects and 
moderately liver-impaired patients after multiple oral doses. Moderate hepatic impairment did not affect the 
pharmacokinetics of eslicarbazepine acetate. No dose adjustment is recommended in patients with mild to 
moderate liver impairment (see section 4.2).  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment.  
 
Gender 
Studies in healthy subjects and patients showed that pharmacokinetics of eslicarbazepine acetate were not 
affected by gender.  
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5.3 Preclinical safety data 
 
Adverse affects observed in animal studies occurred at exposure levels appreciably lower than the clinical 
exposure levels to eslicarbazepine (the principal and pharmacologically active metabolite of eslicarbazepine 
acetate). Safety margins based on comparative exposure have thus not been established. 
 
Evidence of nephrotoxicity was observed in repeated dose toxicity studies in the rat, but was not seen in 
studies in mice or dogs, and is consistent with an exacerbation of spontaneous chronic progressive 
nephropathy in this species.  
 
Liver centrilobular hypertrophy was seen in repeated dose toxicity studies in mice and rats and an increased 
incidence of liver tumours was observed in the carcinogenicity study in mice; these findings are consistent 
with an induction of hepatic microsomal enzymes, an effect which has not been observed in patients 
receiving eslicarbazepine acetate. 
 
Genotoxicity studies with eslicarbazepine acetate indicate no special hazards for humans.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Povidone K 29/32 
Croscarmellose sodium  
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5  Nature and contents of container 
 
Exalief 600 mg tablets are packed in ALU/ALU or ALU/PVC blisters placed into cardboard boxes 
containing 30 or 60 tablets.  
 
Exalief 600 mg tablets are packed in HDPE bottles with polypropylene child resistant closure, placed into 
cardboard boxes, containing 90 tablets. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
BIAL - Portela & Cª , SA M

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À Av. da Siderurgia Nacional 4745-457 S. Mamede do Coronado - Portugal 
tel: +351 22 986 61 00 
fax: +351 22 986 61 99 
e-mail: info@bial.com  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/007-011 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21.04.2009 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/. 

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24 

1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 800 mg tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each tablet contains 800 mg of eslicarbazepine acetate. 
 
For a full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Tablet. 
 
White oblong tablets, engraved ‘ESL 800’on one side and scored on the other side. The tablet can be divided 
into equal halves.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Exalief is indicated as adjunctive therapy in adults with partial-onset seizures with or without secondary 
generalisation. 
 
4.2 Posology and method of administration 
 
Posology 
 
Exalief must be added to existing anticonvulsant therapy. The recommended starting dose is 400 mg once 
daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, 
the dose may be increased to 1200 mg once daily (see section 5.1). 
 
Elderly (over 65 years of age) 
Caution should be exercised in the treatment of elderly patients as there is limited safety information on the 
use of Exalief in these patients. 
 
Paediatric population 
The safety and efficacy of Exalief in children below 18 years has not yet been established.  No data are 
available. 
 
Patients with renal impairment 
Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (CLCR) as follows: 
- CLCR >60 ml/min: no dose adjustment required 
- CLCR 30-60 ml/min: initial dose of 400 mg every other day for 2 weeks followed by a once daily dose of 

400 mg. However, based on individual response, the dose may be increased. 
- CLCR <30 ml/min: use is not recommended in patients with severe renal impairment due to insufficient 

data 
 
Patients with hepatic impairment 
No dose adjustment is needed in patients with mild to moderate hepatic impairment.  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment 
(see section 4.4 and 5.2) and use in these patients is therefore not recommended. M

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Method of administration 
 
Exalief may be taken with or without food. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance, to other carboxamide derivatives (e.g. carbamazepine, 
oxcarbazepine) or to any of the excipients.  
 
Known second or third degree atrioventricular (AV) block. 
 
4.4 Special warnings and precautions for use 
 
Exalief has been associated with some central nervous system adverse reactions, such as dizziness and 
somnolence, which could increase the occurrence of accidental injury.  
 
Exalief may decrease the effectiveness of hormonal contraceptives. Additional non-hormonal forms of 
contraception are recommended when using Exalief (see section 4.5 and 4.6). 
 
As with other anti-epileptic medicinal products, if Exalief is to be discontinued it is recommended to 
withdraw it gradually to minimise the potential of increased seizure frequency.  
 
Concomitant use of Exalief with oxcarbazepine is not recommended because this may cause overexposure to 
the active metabolites. 
 
There is no experience regarding the withdrawal of concomitant use of anti-epileptic medicinal products 
during treatment with Exalief (switch to monotherapy). 
 
Rash developed as an adverse reaction in 1.1% of total population treated with Exalief in placebo-controlled 
add-on studies in epileptic patients. If signs or symptoms of hypersensitivity develop, Exalief must be 
discontinued. 
 
No cases of serious cutaneous reactions have been reported with eslicarbazepine acetate. Presence of 
HLA-B*1502 allele in individuals of Han Chinese and Thai origin has been shown to be strongly associated 
with the risk of developing Stevens-Johnson syndrome (SJS) when treated with carbamazepine. Therefore, 
whenever possible, subjects of Han Chinese and Thai origin should be screened for this allele before starting 
treatment with carbamazepine or chemically-related compounds. The presence of HLA-B*1502 allele in 
other ethnicities is negligible. The allele HLA-B*1502 is not associated to SJS in the Caucasian population. 
 
Hyponatraemia has been reported as an adverse reaction in less than 1% of patients treated with Exalief. 
Hyponatraemia is asymptomatic in most cases, however, it may be accompanied by clinical symptoms like 
worsening of seizures, confusion, decreased consciousness. Frequency of hyponatraemia increased with 
increasing eslicarbazepine acetate dose. In patients with pre-existing renal disease leading to hyponatraemia, 
or in patients concomitantly treated with medicinal products which may themselves lead to hyponatraemia 
(e.g. diuretics, desmopressin), serum sodium levels should be examined before and during treatment with 
eslicarbazepine acetate. Furthermore, serum sodium levels should be determined if clinical signs of 
hyponatraemia occur. Apart from this, sodium levels should be determined during routine laboratory 
examination. If clinically relevant hyponatraemia develops, Exalief should be discontinued. 
 
The influence of Exalief on primary generalised seizures has not been studied. Use is therefore not 
recommended in these patients. 
 
Prolongations in PR interval have been observed in clinical studies with eslicarbazepine acetate.  M

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Caution should be exercised in patients with medical conditions (e.g. low levels of thyroxine, cardiac 
conduction abnormalities), or when taking concomitant medicinal products known to be associated with PR 
prolongation. 
 
Caution should be exercised in the treatment of patients with renal impairment and the dose should be 
adjusted according to creatinine clearance (see section 4.2). In patients with CLCR <30 ml/min use is not 
recommended due to insufficient data. 
 
As clinical data are limited in patients with mild to moderate hepatic impairment and pharmacokinetic and 
clinical data are missing in patients with severe hepatic impairment, Exalief should be used with caution in 
patients with mild to moderate hepatic impairment and is not recommended in patients with severe hepatic 
impairment. 
 
Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic active substances in 
several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic medicinal 
products has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this 
risk is not known and the available data do not exclude the possibility of an increased risk for eslicarbazepine 
acetate. Therefore patients should be monitored for signs of 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 suicidal ideation or behaviour emerge. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Interaction studies have only been performed in adults. 
 
Eslicarbazepine acetate is extensively converted to eslicarbazepine, which is mainly eliminated by 
glucuronidation. In vitro eslicarbazepine is a weak inducer of CYP3A4 and UDP-glucuronyl transferases. In 
vivo eslicarbazepine showed an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by metabolism through CYP3A4. Thus, an increase in the dose of the medicinal products that are 
mainly metabolised through CYP3A4 may be required, when used concomitantly with Exalief. 
Eslicarbazepine in vivo may have an inducing effect on the metabolism of medicinal products that are mainly 
eliminated by conjugation through the UDP-glucuronyl transferases. When initiating or discontinuing 
treatment with Exalief or changing the dose, it may take 2 to 3 weeks to reach the new level of enzyme 
activity. This time delay must be taken into account when Exalief is being used just prior to or in 
combination with other medicines that require dose adjustment when co-administered with Exalief. 
Eslicarbazepine has inhibiting properties with respect to CYP2C19. Thus, interactions can arise when co-
administering high doses of eslicarbazepine acetate with medicinal products that are mainly metabolised by 
CYP2C19. 
 
Interactions with other antiepileptic medicinal products 
Carbamazepine 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 800 mg once daily and 
carbamazepine 400 mg twice daily resulted in an average decrease of 32% in exposure to the active 
metabolite eslicarbazepine, most likely caused by an induction of glucuronidation. No change in exposure to 
carbamazepine or its metabolite carbamazepine-epoxide was noted. Based on individual response, the dose 
of Exalief may need to be increased if used concomitantly with carbamazepine. Results from patient studies 
showed that concomitant treatment increased the risk of the following adverse reactions: diplopia (11.4% of 
subjects with concomitant carbamazepine, 2.4% of subjects without concomitant carbamazepine), abnormal 
coordination (6.7% with concomitant carbamazepine, 2.7% without concomitant carbamazepine), and 
dizziness (30.0% with concomitant carbamazepine, 11.5% without concomitant carbamazepine). The risk of 
increase of other specific adverse reactions caused by co-administration of carbamazepine and 
eslicarbazepine acetate cannot be excluded.  
 
Phenytoin 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
phenytoin resulted in an average decrease of 31-33% in exposure to the active metabolite, eslicarbazepine, 

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most likely caused by an induction of glucuronidation, and an average increase of 31-35% in exposure to 
phenytoin, most likely caused by an inhibition of CYP2C19. Based on individual response, the dose of 
Exalief may need to be increased and the dose of phenytoin may need to be decreased. 
 
Lamotrigine 
Glucuronidation is the major metabolic pathway for both eslicarbazepine and lamotrigine and therefore an 
interaction could be expected. A study in healthy subjects with eslicarbazepine acetate 1,200 mg once daily 
showed a minor average pharmacokinetic interaction (exposure of lamotrigine decreased 15%) between 
eslicarbazepine acetate and lamotrigine and consequently no dose adjustments are required. However, due to 
interindividual variability, the effect may be clinically relevant in some individuals. 
 
Topiramate 
In a study in healthy subjects, concomitant administration of eslicarbazepine acetate 1,200 mg once daily and 
topiramate showed no significant change in exposure to eslicarbazepine but an 18% decrease in exposure to 
topiramate, most likely caused by a reduced bioavailability of topiramate. No dose adjustment is required.  
 
Valproate and levetiracetam 
A population pharmacokinetics analysis of phase III studies in epileptic adult patients indicated that 
concomitant administration with valproate or levetiracetam did not affect the exposure to eslicarbazepine but 
this has not been verified by conventional interaction studies.  
 
Other medicinal products 
Oral contraceptives 
Administration of eslicarbazepine acetate 1,200 mg once daily to female subjects using a combined oral 
contraceptive showed an average decrease of 37% and 42% in systemic exposure to levonorgestrel and 
ethinyloestradiol, respectively, most likely caused by an induction of CYP3A4. Therefore, women of 
childbearing potential must use adequate contraception during treatment with Exalief, and up to the end of 
the current menstruation cycle after the treatment has been discontinued (see section 4.4 and 4.6). 
 
Simvastatin 
A study in healthy subjects showed an average decrease of 50% in systemic exposure to simvastatin when 
co-administered with eslicarbazepine acetate 800 mg once daily, most likely caused by an induction of 
CYP3A4. An increase of the simvastatin dose may be required when used concomitantly with 
eslicarbazepine acetate. 
 
Warfarin 
Co-administration of eslicarbazepine acetate 1,200 mg once daily with warfarin showed a small (23%) but 
statistically significant decrease in exposure to S-warfarin. There was no effect on the R-warfarin 
pharmacokinetics or on coagulation. However, due to inter-individual variability in the interaction, special 
attention on monitoring of INR should be performed the first weeks after initiation or ending concomitant 
treatment of warfarin and eslicarbazepine acetate.  
 
Digoxin 
A study in healthy subjects showed no effect of eslicarbazepine acetate 1,200 mg once daily on digoxin 
pharmacokinetics, suggesting that eslicarbazepine acetate has no effect on the transporter P-glycoprotein. 
 
Monoamino Oxidase Inhibitors (MAOIs) 
Based on a structural relationship of eslicarbazepine acetate to tricyclic antidepressants, an interaction 
between eslicarbazepine acetate and MAOIs is theoretically possible.  
 
4.6 Fertility, pregnancy and lactation 
 
Risk related to epilepsy and antiepileptic medicinal products in general 
It has been shown that in the offspring of women with epilepsy, the prevalence of malformations is two to 
three times greater than the rate of approximately 3 % in the general population. Most frequently reported are M

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cleft lip, cardiovascular malformations and neural tube defects. Multiple antiepileptic medicinal product 
therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is 
important that monotherapy is practised whenever possible. Specialist advice should be given to women who 
are likely to become pregnant or who are of child-bearing potential. The need for antiepileptic therapy 
should be reviewed when a woman is planning to become pregnant. No sudden discontinuation of 
antiepileptic therapy should be undertaken as this may lead to breakthrough seizures which could have 
serious consequences for both mother and child. 
 
Pregnancy 
There are no data from the use of eslicarbazepine acetate in pregnant women. Studies in animals have shown 
reproductive toxicity (see Fertility). If women receiving eslicarbazepine acetate become pregnant or plan to 
become pregnant, the use of Exalief should be carefully re-evaluated. Minimum effective doses should be 
given, and monotherapy whenever possible should be preferred at least during the first three months of 
pregnancy. Patients should be counselled regarding the possibility of an increased risk of malformations and 
given the opportunity to antenatal screening. 
 
Monitoring and prevention 
Antiepileptic medicinal products may contribute to folic acid deficiency, a possible contributory cause of 
foetal abnormality. Folic acid supplementation is recommended before and during pregnancy. As the 
efficacy of this supplementation is not proven, a specific antenatal diagnosis can be offered even for women 
with a supplementary treatment of folic acid. 
 
In the newborn child 
Bleeding disorders in the newborn caused by antiepileptic medicinal products have been reported. As a 
precaution, vitamin K1 should be administered as a preventive measure in the last few weeks of pregnancy 
and to the newborn. 
 
Women of childbearing potential/contraception 
Eslicarbazepine acetate adversely interacts with oral contraceptives. Therefore, an alternative, effective and 
safe method of contraception should be used during treatment and up to the end of the current menstrual 
cycle after treatment has been stopped. 
 
Breastfeeding  
It is unknown whether eslicarbazepine acetate is excreted in human breast milk. Animal studies have shown 
excretion of eslicarbazepine in breast milk. As a risk to the breast-fed child cannot be excluded breast-
feeding should be discontinued during treatment with Exalief.  
 
Fertility 
Eslicarbazepine acetate was evaluated in rats and mice for potential adverse effects on fertility of the parental 
and F1 generation. In a fertility study in male and female rats, impairment of female fertility by 
eslicarbazepine acetate was shown. In a fertility study in mice, developmental effects were observed in 
embryos; however, effects could also result from lower corpora lutea count and thus show impairment 
of fertility. In the mouse, the overall incidence of major abnormalities and the incidence for major skeletal 
abnormalities were increased. No effects on F1 fertility parameters were observed in rats and mice.  
 
4.7 Effects on ability to drive and use machines 
 
No studies on the effects on the ability to drive and use machines have been performed. Some patients might 
experience dizziness, somnolence or visual disorders, particularly on initiation of treatment. Therefore, 
patients should be advised that their physical and/ or mental abilities needed for operating machinery or 
driving may be impaired and they are recommended not to do so until it has been established that their ability 
to perform such activities is not affected. 
 
4.8 Undesirable effects 
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In placebo-controlled studies involving 1,192 adult patients with partial-onset seizures (856 patients treated 
with eslicarbazepine acetate and 336 treated with placebo), 45.3% of patients treated with eslicarbazepine 
acetate and 24.4% of patients treated with placebo experienced adverse reactions. 
 
Adverse reactions were usually mild to moderate in intensity and occurred predominantly during the first 
weeks of treatment with eslicarbazepine acetate.  
 
In the table below all adverse reactions, which occurred at an incidence greater than placebo and numerically 
present in more than 1 patient are listed by System Organ Class and frequency:  
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. 
Within each frequency category, adverse reactions are presented in order of decreasing seriousness. 
 
System Organ 
Class 

Very  
common 

Common Uncommon Rare 

Blood and 
lymphatic system 
disorders 

  Anaemia Thrombocytopenia,
leukopenia 

Immune system 
disorders 

  Hypersensitivity  

Endocrine 
disorders 

  Hypothyroidism  

Metabolism and 
nutrition disorders 

  Increased appetite, 
decreased appetite, 
hyponatraemia, electrolyte 
imbalance, cachexia, 
dehydration, obesity 

 

Psychiatric 
disorders 

  Insomnia, apathy, 
depression, nervousness, 
agitation, irritability, 
attention deficit/ 
hyperactivity disorder, 
confusional state, mood 
swings, crying, 
psychomotor retardation, 
stress, psychotic disorder 

 

Nervous system 
disorders 

Dizziness*, 
somnolence 
 

Headache, 
abnormal 
coordination
*, 
disturbance 
in attention, 
tremor 

Memory impairment, 
balance disorder, amnesia, 
hypersomnia, sedation, 
aphasia, dysaesthesia, 
dystonia, lethargy, 
parosmia, autonomic 
nervous system imbalance, 
cerebellar ataxia, cerebellar 
syndrome, grand mal 
convulsion, neuropathy 
peripheral, sleep phase 
rhythm disturbance, 
nystagmus, speech 
disorder, dysarthria, 
hypoaesthesia, ageusia, 
burning sensation 

 

Eye disorders  Diplopia*, 
vision 
blurred 

Vision disturbance, 
oscillopsia, binocular eye 
movement disorder, ocular 
hyperaemia, saccadic eye 

 

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movement, eye pain 
Ear and labyrinth 
disorders 

 Vertigo 
 

Ear pain, hypoacusis, 
tinnitus 

 

Cardiac disorders   Palpitations, bradycardia, 
sinus bradycardia 

 

Vascular disorders   Hypertension, hypotension, 
orthostatic hypotension 

 

Respiratory, 
thoracic and 
mediastinal 
disorders 

  Dysphonia, epistaxis, chest 
pain 

 

Gastrointestinal 
disorders 

 Nausea, 
vomiting, 
diarrhoea 

Dyspepsia, gastritis, 
abdominal pain, dry mouth, 
abdominal discomfort, 
abdominal distension, 
duodenitis, epigastric 
discomfort, gingival 
hyperplasia, gingivitis , 
irritable bowel syndrome, 
melaena, odynophagia, 
stomach discomfort, 
stomatitis, toothache 

Pancreatitis 

Hepatobiliary 
disorders 

  Liver disorder  

Skin and 
subcutaneous tissue 
disorders 

 Rash 
 

Alopecia, dry skin, 
hyperhidrosis, erythema, 
nail disorder, skin disorder 

 

Musculoskeletal 
and connective 
tissue disorders 

  Myalgia, back pain, neck 
pain 

 

Renal and urinary 
disorders 

  Nocturia, urinary tract 
infection 

 

Reproductive 
system and breast 
disorders 

  Menstruation irregular  

General disorders 
and administration 
site conditions 

 Fatigue, gait 
disturbance 
 

Asthenia, malaise, chills, 
oedema peripheral, adverse 
drug reaction, peripheral 
coldness 

 

Investigations   Blood pressure decreased, 
weight decreased, blood 
pressure diastolic 
decreased, blood pressure 
increased, blood pressure 
systolic decreased, blood 
sodium decreased, 
haematocrit decreased, 
haemoglobin decreased, 
heart rate increased, 
transaminases increased, 
triglycerides increased, tri-
iodothyronine (T3) free 
decreased, thyroxine (T4) 
free decreased 

 

Injury, poisoning   Drug toxicity, fall, joint  M
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and procedural 
complications  

injury, poisoning, skin 
injury 

* In patients concomitantly treated with carbamazepine and eslicarbazepine acetate in placebo-controlled 
studies, diplopia, abnormal coordination and dizziness were reported more frequently. 
 
The use of eslicarbazepine acetate is associated with increase in the PR interval. Adverse reactions associated 
with PR interval prolongation (e.g. AV block, syncope, bradycardia) may occur. No second or higher degree 
AV block was seen in eslicarbazepine acetate treated patients. 
 
Rare adverse reactions such as bone marrow depression, anaphylactic reactions, severe cutaneous reactions 
(e.g. Stevens-Johnson Syndrome), systemic lupus erythematosus or serious cardiac arrhythmias did not occur 
during the placebo-controlled studies of the epilepsy program with eslicarbazepine acetate. However, they 
have been reported with oxcarbazepine. Therefore, their occurrence after treatment with Exalief cannot be 
excluded. 
 
4.9 Overdose 
 
Central nervous symptoms such as vertigo, walking instability and hemi-paresis have been observed with 
accidental Exalief overdose. There is no known specific antidote. Symptomatic and supportive treatment 
should be administered as appropriate. Eslicarbazepine acetate metabolites can effectively be cleared by 
haemodialysis, if necessary (see section 5.2). 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Antiepileptics, Carboxamide derivatives, ATC code: N03AF04 
 
Mechanism of action 
The precise mechanisms of action of eslicarbazepine acetate are unknown. However, in vitro 
electrophysiological studies indicate that both eslicarbazepine acetate and its metabolites stabilise the 
inactivated state of voltage-gated sodium channels, preventing their return to the activated state and thereby 
sustaining repetitive neuronal firing.  
 
Pharmacodynamic effect 
Eslicarbazepine acetate and its active metabolites prevented the development of seizures in nonclinical 
models predictive of anticonvulsant efficacy in man. In humans, the pharmacological activity of 
eslicarbazepine acetate is primarily exerted through the active metabolite eslicarbazepine. 
 
Clinical efficacy and safety 
The efficacy and safety of eslicarbazepine acetate has been demonstrated in three phase III double-blind 
placebo-controlled studies in 1,049 adult patients with partial epilepsy refractory to treatment with one to 
three concomitant anti-epileptic medicinal products. Oxcarbazepine and felbamate were not allowed as 
concomitant medicinal products in these studies. Eslicarbazepine acetate was tested at doses of 400 mg, 
800 mg and 1200 mg, once daily. Eslicarbazepine acetate 800 mg once daily and 1200 mg once daily were 
significantly more effective than placebo in reducing seizure frequency over a 12-week maintenance period. 
The percentage of subjects with a 50% reduction in seizure frequency over all phase III studies was 19% for 
placebo, 21% for eslicarbazepine acetate 400 mg, 34% for eslicarbazepine acetate 800 mg and 36% for 
eslicarbazepine acetate 1200 mg daily.  
 
5.2 Pharmacokinetic properties 
 
Absorption 
Eslicarbazepine acetate is extensively converted to eslicarbazepine. Plasma levels of eslicarbazepine acetate 
usually remain below the limit of quantification, following oral administration. Eslicarbazepine tmax is M

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attained at 2 to 3 h post-dose. Bioavailability may be assumed as high because the amount of metabolites 
recovered in urine corresponded to more than 90% of an eslicarbazepine acetate dose.  
 
Distribution 
The binding of eslicarbazepine to plasma proteins is relatively low (<40%) and independent from 
concentration. In vitro studies have shown that plasma protein binding was not relevantly affected by the 
presence of warfarin, diazepam, digoxin, phenytoin and tolbutamide. The binding of warfarin, diazepam, 
digoxin, phenytoin and tolbutamide was not significantly affected by the presence of eslicarbazepine.  
 
Biotransformation 
Eslicarbazepine acetate is rapidly and extensively biotransformed to its major active metabolite 
eslicarbazepine by hydrolytic first-pass metabolism. Peak plasma concentrations (Cmax) of eslicarbazepine 
are attained at 2-3 hours post-dose and steady state plasma concentrations are attained after 4 to 5 days of 
once daily dosing, consistent with an effective half-life in the order of 20-24 h. In studies in healthy subjects 
and epileptic adult patients, the apparent half-life of eslicarbazepine was 10-20 h and 13-20 h, respectively. 
Minor metabolites in plasma are R-licarbazepine and oxcarbazepine, which were shown to be active, and the 
glucuronic acid conjugates of eslicarbazepine acetate, eslicarbazepine, R-licarbazepine and oxcarbazepine.  
 
Eslicarbazepine acetate does not affect its own metabolism or clearance. 
 
In studies with eslicarbazepine in fresh human hepatocytes a mild activation of UGT1A1 mediated 
glucuronidation was observed. 
 
Excretion 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion, 
in the unchanged and glucuronide conjugate forms. In total, eslicarbazepine and its glucuronide correspond 
to more than 90% of total metabolites excreted in urine, approximately two thirds in the unchanged form and 
one third as glucuronide conjugate. 
 
Linearity / non-linearity 
The pharmacokinetics of eslicarbazepine is linear and dose-proportional in the range 400-1200 mg both in 
healthy subjects and patients. 
 
Elderly (over 65 years of age) 
The pharmacokinetic profile of eslicarbazepine acetate is unaffected in the elderly patients with creatinine 
clearance >60 ml/min (see section 4.2).  
 
Renal impairment 
Eslicarbazepine acetate metabolites are eliminated from the systemic circulation primarily by renal excretion. 
A study in patients with mild to severe renal impairment showed that clearance is dependent on renal 
function. During treatment with Exalief dose adjustment is recommended in patients with creatinine 
clearance <60 ml/min (see section 4.2).  
Haemodialysis removes eslicarbazepine acetate metabolites from plasma.  
 
Hepatic impairment 
The pharmacokinetics and metabolism of eslicarbazepine acetate were evaluated in healthy subjects and 
moderately liver-impaired patients after multiple oral doses. Moderate hepatic impairment did not affect the 
pharmacokinetics of eslicarbazepine acetate. No dose adjustment is recommended in patients with mild to 
moderate liver impairment (see section 4.2).  
The pharmacokinetics of eslicarbazepine has not been evaluated in patients with severe hepatic impairment.  
 
Gender 
Studies in healthy subjects and patients showed that pharmacokinetics of eslicarbazepine acetate were not 
affected by gender.  
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5.3 Preclinical safety data 
 
Adverse affects observed in animal studies occurred at exposure levels appreciably lower than the clinical 
exposure levels to eslicarbazepine (the principal and pharmacologically active metabolite of eslicarbazepine 
acetate). Safety margins based on comparative exposure have thus not been established. 
 
Evidence of nephrotoxicity was observed in repeated dose toxicity studies in the rat, but was not seen in 
studies in mice or dogs, and is consistent with an exacerbation of spontaneous chronic progressive 
nephropathy in this species.  
 
Liver centrilobular hypertrophy was seen in repeated dose toxicity studies in mice and rats and an increased 
incidence of liver tumours was observed in the carcinogenicity study in mice; these findings are consistent 
with an induction of hepatic microsomal enzymes, an effect which has not been observed in patients 
receiving eslicarbazepine acetate. 
 
Genotoxicity studies with eslicarbazepine acetate indicate no special hazards for humans.  
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Povidone K 29/32 
Croscarmellose sodium  
Magnesium stearate 
 
6.2 Incompatibilities 
 
Not applicable. 
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special storage conditions. 
 
6.5  Nature and contents of container 
 
Exalief 800 mg tablets are packed in ALU/ALU or ALU/PVC blisters placed into cardboard boxes 
containing 20, 30, 60 or 90 tablets. 
 
Exalief 800 mg tablets are packed in HDPE bottles with polypropylene child resistant closure, placed into 
cardboard boxes, containing 90 tablets. 
 
Not all pack sizes may be marketed.  
 
6.6 Special precautions for disposal  
 
No special requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
BIAL - Portela & Cª , SA M

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34 

À Av. da Siderurgia Nacional 4745-457 S. Mamede do Coronado - Portugal 
tel: +351 22 986 61 00 
fax: +351 22 986 61 99 
e-mail: info@bial.com  
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/012-020 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 21.04.2009 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu/. 

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http://www.ema.europa.eu/�


35 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURING AUTHORISATION HOLDER 
RESPONSIBLE FOR BATCH RELEASE 

 
B. CONDITIONS OF THE MARKETING AUTHORISATION 

 
 

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A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
BIAL - Portela & Cª , S.A. 
À Av. da Siderurgia Nacional  
4745-457 S. Mamede do Coronado 
Portugal 
 
 
 
B. CONDITIONS OF THE MARKETING AUTHORISATION 
 
• CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON THE 

MARKETING AUTHORISATION HOLDER 
 
Medicinal product subject to medical prescription. 
 
• CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE 

OF THE MEDICINAL PRODUCT 
 
Not applicable. 
 
• OTHER CONDITIONS 
 
Pharmacovigilance system 
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the Marketing 
Authorisation, is in place and functioning before and whilst the product is on the market. 
 
Risk Management plan 
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the 
Pharmacovigilance Plan, as agreed in version 4.0 of the Risk Management Plan (RMP) presented in Module 
1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the 
CHMP. 
 
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the 
updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR). 
 
In addition, an updated RMP should be submitted 

• When new information is received that may impact on the current Safety Specification, 
Pharmacovigilance Plan or risk minimisation activities 

• Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached 
• At the request of the European Medicines Agency

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37 

 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 

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A. LABELLING 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Box of 7, 14 or 28 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 400 mg tablets 
Eslicarbazepine acetate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 400 mg of eslicarbazepine acetate. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
7 tablets 
14 tablets 
28 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight 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 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER M

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BIAL-Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/001   7 tablets - ALU/ALU blister 
EU/1/09/520/002   14 tablets - ALU/ALU blister 
EU/1/09/520/003   28 tablets - ALU/ALU blister 
EU/1/09/520/004   7 tablets - PVC/ALU blister 
EU/1/09/520/005   14 tablets - PVC/ALU blister 
EU/1/09/520/006   28 tablets - PVC/ALU blister 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Exalief 400 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS  
 
ALU/ALU blister 
PVC/ALU blister 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 400 mg tablets 
Eslicarbazepine acetate 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Box of 30 or 60 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 600 mg tablets 
Eslicarbazepine acetate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 600 mg of eslicarbazepine acetate. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
30 tablets 
60 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight 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 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL-Portela & Cª, S.A. M

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À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/007   30 tablets - ALU/ALU blister 
EU/1/09/520/008   60 tablets - ALU/ALU blister 
EU/1/09/520/009   30 tablets - PVC/ALU blister 
EU/1/09/520/010   60 tablets - PVC/ALU blister 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Exalief 600 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS  
 
ALU/ALU blister 
PVC/ALU blister 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 600 mg tablets 
Eslicarbazepine acetate 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND ON THE IMMEDIATE 
PACKAGING 
 
HPDE bottles carton and HPDE bottles of 90 tablets 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 600 mg tablets 
Eslicarbazepine acetate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 600 mg of eslicarbazepine acetate. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 tablets 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight 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 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
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BIAL-Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/011 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Exalief 600 mg 
 
(outer pack only) 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING  
 
Box of 20, 30, 60 or 90 tablets 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 800 mg tablets 
Eslicarbazepine acetate 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet contains 800 mg of eslicarbazepine acetate. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
20 tablets 
30 tablets 
60 tablets 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight 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 
 
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11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL-Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/012   20 tablets - ALU/ALU blister 
EU/1/09/520/013   30 tablets - ALU/ALU blister 
EU/1/09/520/014   60 tablets - ALU/ALU blister 
EU/1/09/520/015   90 tablets - ALU/ALU blister 
EU/1/09/520/016   20 tablets - PVC/ALU blister 
EU/1/09/520/017   30 tablets - PVC/ALU blister 
EU/1/09/520/018   60 tablets - PVC/ALU blister 
EU/1/09/520/019   90 tablets - PVC/ALU blister 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Exalief 800 mg 

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MINIMUM PARTICULARS TO APPEAR ON BLISTERS  
 
ALU/ALU blister 
PVC/ALU blister 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 800 mg tablets 
Eslicarbazepine acetate 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
BIAL 
 
 
3. EXPIRY DATE 
 
EXP 
  
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND ON THE IMMEDIATE 
PACKAGING 
 
HPDE bottles carton and HPDE bottles of 90 tablets  
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Exalief 800 mg tablets 
Eslicarbazepine acetate  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each tablet constains 800 mg of eslicarbazepine acetate. 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
90 tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF 

THE REACH AND SIGHT OF CHILDREN 
 
Keep out of the reach and sight 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 
 
 
11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER M

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BIAL-Portela & Cª, S.A. 
À Av. da Siderurgia Nacional 
4745-457 S. Mamede do Coronado 
Portugal 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/520/020 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Exalief 800 mg 
 
(outer pack only) 
 
 
 
 
 

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B. PACKAGE LEAFLET 
 

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PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Exalief 400 mg tablets 
 

Eslicarbazepine acetate 
 

Read all of this leaflet carefully before you start taking this medicine. 
- 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. Do not pass it on to others. It may harm them, even if their 

symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell 

your doctor or pharmacist. 
 
In this leaflet:  
1. What Exalief is and what it is used for 
2. Before you take Exalief 
3. How to take Exalief 
4. Possible side effects 
5. How to store Exalief 
6. Further information 
 
 
1. WHAT EXALIEF IS AND WHAT IT IS USED FOR 
 
Exalief belongs to a group of medicines called anti-epileptics used to treat epilepsy, a condition where 
someone has repeated seizures or fits.  
 
Exalief is used in adult patients who are already taking other anti-epileptic medicines and are still 
experiencing seizures that affect one part of the brain (partial seizure). These seizures may or may not be 
followed by a seizure affecting all of the brain (secondary generalisation). 
 
Exalief has been given to you by your doctor to reduce your number of seizures. 
 
 
2. BEFORE YOU TAKE EXALIEF 
 
Do not take Exalief if: 

• you are allergic (hypersensitive) to the active substance (eslicarbazepine acetate), to other 
carboxamide derivatives (e.g. carbamazepine or oxcarbazepine, medicines used to treat epilepsy) or to 
any of the other ingredients 

• you suffer from a certain type of heart rhythm disorder (second or third degree atrioventricular (AV) 
block) 

 
Take special care with Exalief 
Contact your doctor immediately if: 

• you have rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These 
could be signs of an allergic reaction.  

• you suffer from confusion, worsening of seizures or decreased consciousness which can be signs of 
low blood salt levels 

 
Please tell your doctor if:  

• you have kidney problems. Your doctor may need to adjust the dose. Exalief is not recommended in 
patients with severe renal disease. 

• you have liver problems. Exalief is not recommended in patients with severe liver problems. M
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• you are taking any medicine which can cause an abnormality on the ECG (electrocardiogram) called 
increased PR interval. If you are not sure if the medicines you are taking could have this effect, discuss 
with your doctor. 

• you suffer from a heart disease such as heart failure or heart attack. 
• you suffer from seizures that begin with a widespread electric discharge that involves both sides of the 

brain  
 

Exalief may make you feel dizzy and/or drowsy, particularly at the beginning of treatment. Take special care 
when taking Exalief to avoid accidental injury (fall). 
 
A small number of people being treated with anti-epileptics have had thoughts of harming or killing 
themselves. If at any time you have these thoughts, when taking Exalief, contact your doctor immediately. 
 
Children 
Exalief is not to be given to children and adolescents. 
 
Taking other medicines 
• Tell your doctor if you are taking phenytoin (a medicine used to treat epilepsy) since your dose may 

need to be adjusted. 
• Tell your doctor if you are taking carbamazepine (a medicine used to treat epilepsy) since your dose may 

have to be adjusted and the following side effects of Exalief may occur in higher frequency: seeing 
double, abnormal coordination and dizziness.  

• Tell your doctor if you are taking simvastatin (a medicine used to lower cholesterol levels) since your 
dose may have to be adjusted. 

• Tell your doctor if you are taking the blood thinner - warfarin. 
• Tell your doctor if you are taking tricyclic antidepressants e.g. amitriptyline. 
• Tell your doctor if you are taking hormonal/oral contraceptives. Exalief may make hormonal 

contraceptives such as the contraceptive pill less effective. Therefore it is recommended that you use 
other forms of safe and effective contraception, when taking Exalief up to the end of the current 
menstrual cycle after stopping treatment. 

• Do not take oxcarbazepine (a medicine used to treat epilepsy) with Exalief, as it is not known whether it 
is safe to take these medicines together. 

 
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. This is just in case any of them interfere with how Exalief works 
or how Exalief interferes with their effect. 
 
Taking Exalief with food and drink 
Exalief tablets may be taken with or without food. 
 
Pregnancy and breast-feeding 
Tell your doctor immediately if you are pregnant or planning to become pregnant. You must only take 
Exalief during pregnancy if your doctor tells you. 
 
Research has shown an increased risk of birth defects in children of women taking anti-epileptic medicines. 
On the other hand effective anti-epileptic therapy must not be interrupted since the worsening of the disease 
is harmful to both the mother and the unborn child.  
 
Do not breast-feed while you are taking Exalief. It is not known whether it passes into breast milk. 
 
See ‘Taking other medicines’ section for advice about contraception. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
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Exalief may make you feel dizzy, drowsy and affect your vision, particularly at the beginning of treatment. If 
this happens to you, do not drive or use any tools or machines. 
 
 
3. HOW TO TAKE EXALIEF 
 
Always take Exalief exactly as your doctor has told you. You should check with your doctor or pharmacist if 
you are not sure. 
 
Adults 
There are two dosing regimes for adults: 
 
Dose when you start treatment 
400 mg dose once daily for one or two weeks, before increasing to the maintenance dose. Your doctor will 
decide whether you will be given this dose for one or two weeks.  
 
Maintenance dose 
The usual maintenance dose is 800 mg once daily. 
Depending on how you respond to Exalief, your dose may be increased to 1200 mg once daily. 
 
Elderly (over 65 years of age) 
If you are elderly your doctor will decide the suitable dose for you. 
 
Patients with kidney problems 
If you have kidney problems you will usually be given a lower dose of Exalief. Your doctor will work out 
the correct dose for you. Exalief is not recommended if you have severe kidney problems. 
 
Patients with liver problems 
The dose is the same as for adults. However, Exalief is not recommended if you have severe liver problems. 
Please talk to your doctor if you are unsure about the dose you should be taking. 
 
Method and route of administration 
Swallow the tablet with a glass of water.  
 
If you take more Exalief than you should 
If you accidently take more Exalief than you should, tell a doctor or go to a hospital accident and emergency 
department immediately. Take the medicine pack with you. This is so the doctor knows what you have taken. 
 
If you forget to take Exalief 
If you forget to take a tablet, take it as soon as you remember and carry on as usual. Do not take a double 
dose to make up for the one you have missed. 
 
If you stop taking Exalief 
Do not stop taking your tablets suddenly. If you do, you are at risk of having more seizures. Your doctor will 
decide how long you should take Exalief for. Should your doctor decide to stop your treatment with Exalief 
your dose will usually be reduced gradually. It is important that your treatment is completed as advised by 
your doctor or your symptoms may get worse. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Exalief can cause side effects, although not everybody gets them. 
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The following side effects can be very serious. If they happen to you stop taking Exalief and tell a doctor or 
go to a hospital immediately, as you may need urgent medical treatment: 
• Rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These could be 

signs of an allergic reaction  
 
The frequency of possible side effects listed below is defined as using the following convention: 
very common (affects more than 1 user in 10) 
common (affects 1 to 10 users in 100) 
uncommon (affects 1 to 10 users in 1,000) 
rare (affects 1 to 10 users in 10,000) 
very rare (affects less than 1 user in 10,000) 
 
Very common side effects are: 
• Feeling dizzy or sleepy  
 
Common side effects are: 
• Feeling unsteady or having a sensation of spinning or floating 
• Feeling sick or vomiting 
• Headache 
• Diarrhoea  
• Seeing double or blurred vision 
• Difficulty in concentration 
• Feeling low in energy or tired 
• Shaking 
• Clumsiness 
• Skin rash 
• Numbness and tingling in hands and feet 
 
Uncommon side effects are: 
• Hypersensitivity 
• Worsening of seizures 
• Underactive thyroid gland. Symptoms include cold intolerance, large tongue, thin and brittle fingernails 

or hair and low body temperature.  
• Increased levels of circulating fats in your blood 
• Difficulty in sleeping 
• Liver problems 
• High or low blood pressure or a fall in blood pressure on standing up  
• Blood tests showing that you have low levels of salts or sodium in your blood or a reduction in red blood 

cells 
• Dehydration 
• Eye movement changes, fuzzy vision, red eye or eye pain 
• Having falls 
• Poor memory or forgetfulness 
• Crying, feeling depressed, nervous or confused, lack of interest or emotion 
• Inability to speak or write or understand spoken or written language 
• Agitated 
• Irritability 
• Mood changes or hallucinations 
• Difficulty in speaking 
• Nosebleed 
• Chest pain 
• Weight loss and general ill health (Cachexia) 
• Feeling numb in any part of your body 
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• Disturbances in the sense of smell and/or tasting 
• Ear pain or ringing in the ears 
• Swelling in your legs and arms 
• Heart burn, stomach upset, abdominal pain, abdominal bloating and discomfort or dry mouth 
• Blood in faeces 
• Inflamed gums, mouth inflammation or toothache 
• Painful swallowing 
• Sweating or having dry skin 
• Nail or skin changes (e.g. red skin) 
• Hair loss 
• Having irregular periods 
• Increased urine production during night time 
• Urinary tract infection 
• Feeling generally unwell or having chills 
• Increased or decreased appetite 
• Weight loss or extreme weight gain 
• Muscle pain 
• Back pain or neck pain 
• Cold limbs 
• Faster, slower or irregular heart beat  
• Feeling sleepy 
• Neurological movement disorder where your muscles contract causing twisting and repetitive 

movements or abnormal postures. Symptoms include tremors, pain, cramping. 
• Irritable Bowel Syndrome (IBS). Symptoms include chronic abdominal cramps and diarrhoea or 

constipation. 
 
Rare side effects are: 
• Reduction in blood platelets which increases risk of bleeding or bruising 
• Severe pain in the back and stomach 
• Reduction in white blood cells which makes infections more likely 
 
The use of Exalief is associated with an abnormality in ECG (electrocardiogram) called increase in 
PR interval. Side effects associated with this ECG abnormality (e.g. fainting and slowing of heart beat) may 
occur. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your 
doctor or pharmacist. 
 
 
5. HOW TO STORE EXALIEF 
 
Keep out of the reach and sight of children. 
 
Do not use Exalief after the expiry date, which is stated on the blister package and the carton after EXP. The 
expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
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• The active substance is eslicarbazepine acetate. Each tablet contains 400 mg of eslicarbazepine acetate. 
• The other ingredients are povidone K29/32, croscarmellose sodium and magnesium stearate. 
 
What Exalief looks like and contents of the pack 
Exalief 400 mg tablets are white, circular and biconvex. The tablets have ‘ESL 400’engraved on one side and 
are scored on the other side. The scoreline is only to facilitate breaking the tablet into two for ease of 
swallowing, and it does not divide the tablet into two equal doses. 
 
The tablets are packaged in blisters in cardboard boxes containing 7, 14 or 28 tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
BIAL - Portela & Cª , S.A., À Av. da Siderurgia Nacional  
4745-457 S. Mamede do Coronado 
Portugal  
tel: +351 22 986 61 00  
fax: +351 22 986 61 99  
e-mail: info@bial.com  
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last approved in MMM/YYYY 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

M
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http://www.ema.europa.eu/�


59 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Exalief 600 mg tablets 
 

Eslicarbazepine acetate 
 

Read all of this leaflet carefully before you start taking this medicine. 
- 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. Do not pass it on to others. It may harm them, even if their 

symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell 

your doctor or pharmacist. 
 
In this leaflet:  
1. What Exalief is and what it is used for 
2. Before you take Exalief 
3. How to take Exalief 
4. Possible side effects 
5. How to store Exalief 
6. Further information 
 
 
1. WHAT EXALIEF IS AND WHAT IT IS USED FOR 
 
Exalief belongs to a group of medicines called anti-epileptics used to treat epilepsy, a condition where 
someone has repeated seizures or fits.  
 
Exalief is used in adult patients who are already taking other anti-epileptic medicines and are still 
experiencing seizures that affect one part of the brain (partial seizure). These seizures may or may not be 
followed by a seizure affecting all of the brain (secondary generalisation). 
 
Exalief has been given to you by your doctor to reduce your number of seizures. 
 
 
2. BEFORE YOU TAKE EXALIEF 
 
Do not take Exalief if: 

• you are allergic (hypersensitive) to the active substance (eslicarbazepine acetate), to other 
carboxamide derivatives (e.g. carbamazepine or oxcarbazepine, medicines used to treat epilepsy) or to 
any of the other ingredients 

• you suffer from a certain type of heart rhythm disorder (second or third degree atrioventricular (AV) 
block) 

 
Take special care with Exalief 
Contact your doctor immediately if: 

• you have rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These 
could be signs of an allergic reaction.  

• you suffer from confusion, worsening of seizures or decreased consciousness which can be signs of 
low blood salt levels 

 
Please tell your doctor if:  

• you have kidney problems. Your doctor may need to adjust the dose. Exalief is not recommended in 
patients with severe renal disease. 

• you have liver problems. Exalief is not recommended in patients with severe liver problems. M
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• you are taking any medicine which can cause an abnormality on the ECG (electrocardiogram) called 
increased PR interval. If you are not sure if the medicines you are taking could have this effect, discuss 
with your doctor. 

• you suffer from a heart disease such as heart failure or heart attack. 
• you suffer from seizures that begin with a widespread electric discharge that involves both sides of the 

brain  
 

Exalief may make you feel dizzy and/or drowsy, particularly at the beginning of treatment. Take special care 
when taking Exalief to avoid accidental injury (fall). 
 
A small number of people being treated with anti-epileptics have had thoughts of harming or killing 
themselves. If at any time you have these thoughts, when taking Exalief, contact your doctor immediately. 
 
Children 
Exalief is not to be given to children and adolescents. 
 
Taking other medicines 
• Tell your doctor if you are taking phenytoin (a medicine used to treat epilepsy) since your dose may 

need to be adjusted. 
• Tell your doctor if you are taking carbamazepine (a medicine used to treat epilepsy) since your dose may 

have to be adjusted and the following side effects of Exalief may occur in higher frequency: seeing 
double, abnormal coordination and dizziness.  

• Tell your doctor if you are taking simvastatin (a medicine used to lower cholesterol levels) since your 
dose may have to be adjusted. 

• Tell your doctor if you are taking the blood thinner - warfarin. 
• Tell your doctor if you are taking tricyclic antidepressants e.g. amitriptyline. 
• Tell your doctor if you are taking hormonal/oral contraceptives. Exalief may make hormonal 

contraceptives such as the contraceptive pill less effective. Therefore it is recommended that you use 
other forms of safe and effective contraception, when taking Exalief up to the end of the current 
menstrual cycle after stopping treatment. 

• Do not take oxcarbazepine (a medicine used to treat epilepsy) with Exalief, as it is not known whether it 
is safe to take these medicines together. 

 
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. This is just in case any of them interfere with how Exalief works 
or how Exalief interferes with their effect. 
 
Taking Exalief with food and drink 
Exalief tablets may be taken with or without food. 
 
Pregnancy and breast-feeding 
Tell your doctor immediately if you are pregnant or planning to become pregnant. You must only take 
Exalief during pregnancy if your doctor tells you. 
 
Research has shown an increased risk of birth defects in children of women taking anti-epileptic medicines. 
On the other hand effective anti-epileptic therapy must not be interrupted since the worsening of the disease 
is harmful to both the mother and the unborn child.  
 
Do not breast-feed while you are taking Exalief. It is not known whether it passes into breast milk. 
 
See ‘Taking other medicines’ section for advice about contraception. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines M

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Exalief may make you feel dizzy, drowsy and affect your vision, particularly at the beginning of treatment. If 
this happens to you, do not drive or use any tools or machines. 
 
 
3. HOW TO TAKE EXALIEF 
 
Always take Exalief exactly as your doctor has told you. You should check with your doctor or pharmacist if 
you are not sure. 
 
Adults 
There are two dosing regimes for adults: 
 
Dose when you start treatment 
400 mg dose once daily for one or two weeks, before increasing to the maintenance dose. Your doctor will 
decide whether you will be given this dose for one or two weeks.  
 
Maintenance dose 
The usual maintenance dose is 800 mg once daily. 
Depending on how you respond to Exalief, your dose may be increased to 1200 mg once daily. 
 
Elderly (over 65 years of age) 
If you are elderly your doctor will decide the suitable dose for you. 
 
Patients with kidney problems 
If you have kidney problems you will usually be given a lower dose of Exalief. Your doctor will work out 
the correct dose for you. Exalief is not recommended if you have severe kidney problems. 
 
Patients with liver problems 
The dose is the same as for adults. However, Exalief is not recommended if you have severe liver problems. 
Please talk to your doctor if you are unsure about the dose you should be taking. 
 
Method and route of administration 
Swallow the tablet with a glass of water.  
 
If you take more Exalief than you should 
If you accidently take more Exalief than you should, tell a doctor or go to a hospital accident and emergency 
department immediately. Take the medicine pack with you. This is so the doctor knows what you have taken. 
 
If you forget to take Exalief 
If you forget to take a tablet, take it as soon as you remember and carry on as usual. Do not take a double 
dose to make up for the one you have missed. 
 
If you stop taking Exalief 
Do not stop taking your tablets suddenly. If you do, you are at risk of having more seizures. Your doctor will 
decide how long you should take Exalief for. Should your doctor decide to stop your treatment with Exalief 
your dose will usually be reduced gradually. It is important that your treatment is completed as advised by 
your doctor or your symptoms may get worse. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Exalief can cause side effects, although not everybody gets them. 
 M

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The following side effects can be very serious. If they happen to you stop taking Exalief and tell a doctor or 
go to a hospital immediately, as you may need urgent medical treatment: 
• Rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These could be 

signs of an allergic reaction  
 
The frequency of possible side effects listed below is defined as using the following convention: 
very common (affects more than 1 user in 10) 
common (affects 1 to 10 users in 100) 
uncommon (affects 1 to 10 users in 1,000) 
rare (affects 1 to 10 users in 10,000) 
very rare (affects less than 1 user in 10,000) 
 
Very common side effects are: 
• Feeling dizzy or sleepy  
 
Common side effects are: 
• Feeling unsteady or having a sensation of spinning or floating 
• Feeling sick or vomiting 
• Headache 
• Diarrhoea  
• Seeing double or blurred vision 
• Difficulty in concentration 
• Feeling low in energy or tired 
• Shaking 
• Clumsiness 
• Skin rash 
• Numbness and tingling in hands and feet 
 
Uncommon side effects are: 
• Hypersensitivity 
• Worsening of seizures 
• Underactive thyroid gland. Symptoms include cold intolerance, large tongue, thin and brittle fingernails 

or hair and low body temperature.  
• Increased levels of circulating fats in your blood 
• Difficulty in sleeping 
• Liver problems 
• High or low blood pressure or a fall in blood pressure on standing up  
• Blood tests showing that you have low levels of salts or sodium in your blood or a reduction in red blood 

cells 
• Dehydration 
• Eye movement changes, fuzzy vision, red eye or eye pain 
• Having falls 
• Poor memory or forgetfulness 
• Crying, feeling depressed, nervous or confused, lack of interest or emotion 
• Inability to speak or write or understand spoken or written language 
• Agitated 
• Irritability 
• Mood changes or hallucinations 
• Difficulty in speaking 
• Nosebleed 
• Chest pain 
• Weight loss and general ill health (Cachexia) 
• Feeling numb in any part of your body 
• Burning sensation M

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• Disturbances in the sense of smell and/or tasting 
• Ear pain or ringing in the ears 
• Swelling in your legs and arms 
• Heart burn, stomach upset, abdominal pain, abdominal bloating and discomfort or dry mouth 
• Blood in faeces 
• Inflamed gums, mouth inflammation or toothache 
• Painful swallowing 
• Sweating or having dry skin 
• Nail or skin changes (e.g. red skin) 
• Hair loss 
• Having irregular periods 
• Increased urine production during night time 
• Urinary tract infection 
• Feeling generally unwell or having chills 
• Increased or decreased appetite 
• Weight loss or extreme weight gain 
• Muscle pain 
• Back pain or neck pain 
• Cold limbs 
• Faster, slower or irregular heart beat  
• Feeling sleepy 
• Neurological movement disorder where your muscles contract causing twisting and repetitive 

movements or abnormal postures. Symptoms include tremors, pain, cramping. 
• Irritable Bowel Syndrome (IBS). Symptoms include chronic abdominal cramps and diarrhoea or 

constipation. 
 
Rare side effects are: 
• Reduction in blood platelets which increases risk of bleeding or bruising 
• Severe pain in the back and stomach 
• Reduction in white blood cells which makes infections more likely 
 
The use of Exalief is associated with an abnormality in ECG (electrocardiogram) called increase in 
PR interval. Side effects associated with this ECG abnormality (e.g. fainting and slowing of heart beat) may 
occur. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your 
doctor or pharmacist. 
 
 
5. HOW TO STORE EXALIEF 
 
Keep out of the reach and sight of children. 
 
Do not use Exalief after the expiry date, which is stated on the blister package, bottle and the carton after 
EXP. The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Exalief contains M

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• The active substance is eslicarbazepine acetate. Each tablet contains 600 mg of eslicarbazepine acetate. 
• The other ingredients are povidone K29/32, croscarmellose sodium and magnesium stearate. 
 
What Exalief looks like and contents of the pack 
Exalief 600 mg tablets are white and oblong. The tablets have ‘ESL 600’engraved on one side and are scored 
on the other side, enabling the tablets to be divided into equal halves. 
 
The tablets are packaged in blisters in cardboard boxes containing 30 or 60 tablets, and in HDPE bottles with 
child resistant closure in cardboard boxes containing 90 tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
BIAL - Portela & Cª , S.A., À Av. da Siderurgia Nacional  
4745-457 S. Mamede do Coronado 
Portugal  
tel: +351 22 986 61 00  
fax: +351 22 986 61 99  
e-mail: info@bial.com  
 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last approved in MMM/YYYY 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

M
ed

ici
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l p
ro

du
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no
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http://www.ema.europa.eu/�


65 

PACKAGE LEAFLET: INFORMATION FOR THE USER 
 

Exalief 800 mg tablets 
 

Eslicarbazepine acetate 
 

Read all of this leaflet carefully before you start taking this medicine. 
- 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. Do not pass it on to others. It may harm them, even if their 

symptoms are the same as yours. 
- If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell 

your doctor or pharmacist. 
 
In this leaflet:  
1. What Exalief is and what it is used for 
2. Before you take Exalief 
3. How to take Exalief 
4. Possible side effects 
5. How to store Exalief 
6. Further information 
 
 
1. WHAT EXALIEF IS AND WHAT IT IS USED FOR 
 
Exalief belongs to a group of medicines called anti-epileptics used to treat epilepsy, a condition where 
someone has repeated seizures or fits.  
 
Exalief is used in adult patients who are already taking other anti-epileptic medicines and are still 
experiencing seizures that affect one part of the brain (partial seizure). These seizures may or may not be 
followed by a seizure affecting all of the brain (secondary generalisation). 
 
Exalief has been given to you by your doctor to reduce your number of seizures. 
 
 
2. BEFORE YOU TAKE EXALIEF 
 
Do not take Exalief if: 

• you are allergic (hypersensitive) to the active substance (eslicarbazepine acetate), to other 
carboxamide derivatives (e.g. carbamazepine or oxcarbazepine, medicines used to treat epilepsy) or to 
any of the other ingredients 

• you suffer from a certain type of heart rhythm disorder (second or third degree atrioventricular (AV) 
block) 

 
Take special care with Exalief 
Contact your doctor immediately if: 

• you have rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These 
could be signs of an allergic reaction.  

• you suffer from confusion, worsening of seizures or decreased consciousness which can be signs of 
low blood salt levels 

 
Please tell your doctor if:  

• you have kidney problems. Your doctor may need to adjust the dose. Exalief is not recommended in 
patients with severe renal disease. 

• you have liver problems. Exalief is not recommended in patients with severe liver problems. M
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• you are taking any medicine which can cause an abnormality on the ECG (electrocardiogram) called 
increased PR interval. If you are not sure if the medicines you are taking could have this effect, discuss 
with your doctor. 

• you suffer from a heart disease such as heart failure or heart attack. 
• you suffer from seizures that begin with a widespread electric discharge that involves both sides of the 

brain  
 

Exalief may make you feel dizzy and/or drowsy, particularly at the beginning of treatment. Take special care 
when taking Exalief to avoid accidental injury (fall). 
 
A small number of people being treated with anti-epileptics have had thoughts of harming or killing 
themselves. If at any time you have these thoughts, when taking Exalief, contact your doctor immediately. 
 
Children 
Exalief is not to be given to children and adolescents. 
 
Taking other medicines 
• Tell your doctor if you are taking phenytoin (a medicine used to treat epilepsy) since your dose may 

need to be adjusted. 
• Tell your doctor if you are taking carbamazepine (a medicine used to treat epilepsy) since your dose may 

have to be adjusted and the following side effects of Exalief may occur in higher frequency: seeing 
double, abnormal coordination and dizziness.  

• Tell your doctor if you are taking simvastatin (a medicine used to lower cholesterol levels) since your 
dose may have to be adjusted 

• Tell your doctor if you are taking the blood thinner - warfarin. 
• Tell your doctor if you are taking tricyclic antidepressants e.g. amitriptyline. 
• Tell your doctor if you are taking hormonal/oral contraceptives. Exalief may make hormonal 

contraceptives such as the contraceptive pill less effective. Therefore it is recommended that you use 
other forms of safe and effective contraception, when taking Exalief up to the end of the current 
menstrual cycle after stopping treatment. 

• Do not take oxcarbazepine (a medicine used to treat epilepsy) with Exalief, as it is not known whether it 
is safe to take these medicines together. 

 
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including 
medicines obtained without a prescription. This is just in case any of them interfere with how Exalief works 
or how Exalief interferes with their effect. 
 
Taking Exalief with food and drink 
Exalief tablets may be taken with or without food. 
 
Pregnancy and breast-feeding 
Tell your doctor immediately if you are pregnant or planning to become pregnant. You must only take 
Exalief during pregnancy if your doctor tells you. 
 
Research has shown an increased risk of birth defects in children of women taking anti-epileptic medicines. 
On the other hand effective anti-epileptic therapy must not be interrupted since the worsening of the disease 
is harmful to both the mother and the unborn child.  
 
Do not breast-feed while you are taking Exalief. It is not known whether it passes into breast milk. 
 
See ‘Taking other medicines’ section for advice about contraception. 
 
Ask your doctor or pharmacist for advice before taking any medicine. 
 
Driving and using machines M

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67 

Exalief may make you feel dizzy, drowsy and affect your vision, particularly at the beginning of treatment. If 
this happens to you, do not drive or use any tools or machines. 
 
 
3. HOW TO TAKE EXALIEF 
 
Always take Exalief exactly as your doctor has told you. You should check with your doctor or pharmacist if 
you are not sure. 
 
Adults 
There are two dosing regimes for adults: 
 
Dose when you start treatment 
400 mg dose once daily for one or two weeks, before increasing to the maintenance dose. Your doctor will 
decide whether you will be given this dose for one or two weeks.  
 
Maintenance dose 
The usual maintenance dose is 800 mg once daily. 
Depending on how you respond to Exalief, your dose may be increased to 1200 mg once daily. 
 
Elderly (over 65 years of age) 
If you are elderly your doctor will decide the suitable dose for you. 
 
Patients with kidney problems 
If you have kidney problems you will usually be given a lower dose of Exalief. Your doctor will work out 
the correct dose for you. Exalief is not recommended if you have severe kidney problems. 
 
Patients with liver problems 
The dose is the same as for adults. However, Exalief is not recommended if you have severe liver problems. 
Please talk to your doctor if you are unsure about the dose you should be taking. 
 
Method and route of administration 
Swallow the tablet with a glass of water.  
 
If you take more Exalief than you should 
If you accidently take more Exalief than you should, tell a doctor or go to a hospital accident and emergency 
department immediately. Take the medicine pack with you. This is so the doctor knows what you have taken. 
 
If you forget to take Exalief 
If you forget to take a tablet, take it as soon as you remember and carry on as usual. Do not take a double 
dose to make up for the one you have missed. 
 
If you stop taking Exalief 
Do not stop taking your tablets suddenly. If you do, you are at risk of having more seizures. Your doctor will 
decide how long you should take Exalief for. Should your doctor decide to stop your treatment with Exalief 
your dose will usually be reduced gradually. It is important that your treatment is completed as advised by 
your doctor or your symptoms may get worse. 
 
If you have any further questions on the use of this product, ask your doctor or pharmacist. 
 
 
4. POSSIBLE SIDE EFFECTS 
 
Like all medicines, Exalief can cause side effects, although not everybody gets them. 
 M

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68 

The following side effects can be very serious. If they happen to you stop taking Exalief and tell a doctor or 
go to a hospital immediately, as you may need urgent medical treatment: 
• Rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue. These could be 

signs of an allergic reaction  
 
The frequency of possible side effects listed below is defined as using the following convention: 
very common (affects more than 1 user in 10) 
common (affects 1 to 10 users in 100) 
uncommon (affects 1 to 10 users in 1,000) 
rare (affects 1 to 10 users in 10,000) 
very rare (affects less than 1 user in 10,000) 
 
Very common side effects are: 
• Feeling dizzy or sleepy  
 
Common side effects are: 
• Feeling unsteady or having a sensation of spinning or floating 
• Feeling sick or vomiting 
• Headache 
• Diarrhoea  
• Seeing double or blurred vision 
• Difficulty in concentration 
• Feeling low in energy or tired 
• Shaking 
• Clumsiness 
• Skin rash 
• Numbness and tingling in hands and feet 
 
Uncommon side effects are: 
• Hypersensitivity 
• Worsening of seizures 
• Underactive thyroid gland. Symptoms include cold intolerance, large tongue, thin and brittle fingernails 

or hair and low body temperature.  
• Increased levels of circulating fats in your blood 
• Difficulty in sleeping 
• Liver problems 
• High or low blood pressure or a fall in blood pressure on standing up  
• Blood tests showing that you have low levels of salts or sodium in your blood or a reduction in red blood 

cells 
• Dehydration 
• Eye movement changes, fuzzy vision, red eye or eye pain 
• Having falls 
• Poor memory or forgetfulness 
• Crying, feeling depressed, nervous or confused, lack of interest or emotion 
• Inability to speak or write or understand spoken or written language 
• Agitated 
• Irritability 
• Mood changes or hallucinations 
• Difficulty in speaking 
• Nosebleed 
• Chest pain 
• Weight loss and general ill health (Cachexia) 
• Feeling numb in any part of your body 
• Burning sensation M

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• Disturbances in the sense of smell and/or tasting 
• Ear pain or ringing in the ears 
• Swelling in your legs and arms 
• Heart burn, stomach upset, abdominal pain, abdominal bloating and discomfort or dry mouth 
• Blood in faeces 
• Inflamed gums, mouth inflammation or toothache 
• Painful swallowing 
• Sweating or having dry skin 
• Nail or skin changes (e.g. red skin) 
• Hair loss 
• Having irregular periods 
• Increased urine production during night time 
• Urinary tract infection 
• Feeling generally unwell or having chills 
• Increased or decreased appetite 
• Weight loss or extreme weight gain 
• Muscle pain 
• Back pain or neck pain 
• Cold limbs 
• Faster, slower or irregular heart beat  
• Feeling sleepy 
• Neurological movement disorder where your muscles contract causing twisting and repetitive 

movements or abnormal postures. Symptoms include tremors, pain, cramping. 
• Irritable Bowel Syndrome (IBS). Symptoms include chronic abdominal cramps and diarrhoea or 

constipation. 
 
Rare side effects are: 
• Reduction in blood platelets which increases risk of bleeding or bruising 
• Severe pain in the back and stomach 
• Reduction in white blood cells which makes infections more likely 
 
The use of Exalief is associated with an abnormality in ECG (electrocardiogram) called increase in 
PR interval. Side effects associated with this ECG abnormality (e.g. fainting and slowing of heart beat) may 
occur. 
 
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your 
doctor or pharmacist. 
 
 
5. HOW TO STORE EXALIEF 
 
Keep out of the reach and sight of children. 
 
Do not use Exalief after the expiry date, which is stated on the blister package, bottle and the carton after 
EXP. The expiry date refers to the last day of that month. 
 
This medicine does not require any special storage conditions. 
 
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to 
dispose of medicines no longer required. These measures will help to protect the environment. 
 
 
6. FURTHER INFORMATION 
 
What Exalief contains M

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70 

• The active substance is eslicarbazepine acetate. Each tablet contains 800 mg of eslicarbazepine acetate. 
• The other ingredients are povidone K29/32, croscarmellose sodium and magnesium stearate. 
 
What Exalief looks like and contents of the pack 
Exalief 800 mg tablets are white and oblong. The tablets have ‘ESL 800’engraved on one side and are scored 
on the other side, enabling the tablets to be divided into equal halves. 
 
The tablets are packaged in blisters in cardboard boxes containing 20, 30, 60 or 90 tablets, and in HDPE 
bottles with child resistant closure in cardboard boxes containing 90 tablets. 
 
Not all pack sizes may be marketed. 
 
Marketing Authorisation Holder and Manufacturer 
BIAL - Portela & Cª , S.A., À Av. da Siderurgia Nacional  
4745-457 S. Mamede do Coronado 
Portugal  
tel: +351 22 986 61 00  
fax: +351 22 986 61 99  
e-mail: info@bial.com  
 
 
For any information about this medicine, please contact the Marketing Authorisation Holder. 
 
This leaflet was last approved in MMM/YYYY 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/. 

  
 

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	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OF THE MARKETING AUTHORISATION
	A. LABELLING
	B. PACKAGE LEAFLET