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Be free
Epilim® takes care of epilepsy.
Life takes care of itself.
Bob Peter Okello
PAN AFRICAN ASSOCIATION OF NEUROLOGICAL SCIENCE CONGRESS
Aficana Hotel Kampala
7th June, 2016
SANOFI AND NEUROLOGY
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Belief that Epilepsy is still a public health concern
Epilepsy not well understood-stigma
Treatment areas not well understood.
Will not define epilepsy-share experiences with Epilim
Epilim-Gaba-transaminase inhibitor
Epilim satisfies most of the medical epilepsy treatment
goals
Achieve Seizure free status
Monotherapy preferably
Tolerability of treatment of choice
2008
CONSTANT PROOF OF
EFFICACY
Jedrzejczak J et.
al.
2007
Marson AG et. al.
Regardless of seizure type or aetiology
1996
De Silva et. al.
1994
Richen et. al.
1985
1967
Carraz et al.
First clinical trial
to demonstrate
VPA efficacy in
seizures1
*Valproate
Turnbull et. al.
First large randomized
study showing efficacy
of VPA in generalized
seizures2
Large randomized
Study showing equal
efficacy of VPA and
CBZ, irrespective of
seizure type3
Large long term RCT
Comparing VPA,CBZ
PHT&PB showed similar
Efficacy lower withdrawal
for VPA and CBZ4
SANAD study. E
effectiveness of
VPA, LTG or TPM
for
generalized seizures
and unclassifiable
epilepsy:
Unblinded RCT5
VIPE study: An
observational study
of first line VPA
monotherapy in
partial epilepsy6
VPA: valporate
CBZ: carbamazepine
LTG: lamotrigine
TPM: topiramate
PHT: phenytoin
PB: phenobarbital
Ref: 1. Carraz G, Fau Chateau R et al. Ann Med Psychol.(Paris) 1964;122(Tome 2):557-584
2. Turnbull DM, Howel D, Rawlins MD et al. Br. Med J(Clin Res Ed.) 1985;290(6471)815-819
3.Richens A, Davidson DL, Cartridge NE et al. J Neurol. Neurosurg. Psychiatry. 1994;57(6): 682-6
4. De Silva M,MacArdle B, McGowan M, et al. Lancet: 1996; 347 (9003): 709-713
5. Marson AG, Al-Kharusi AM, Alwaidh M et al. Lancet. 2007 Mar 24; 369 (9566): 1016-1026
6. Jedrzejczak J, Kunikova, M Magureanu S. Eur J Neurol 2008, 15:66-72
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Monotherapy allowed only after
previous treatment failure
Spectrum of indications of anti-epileptic drugs
Atonic
seizures
Myoclonic
seizures
Abscence
seizures
Epilim®: effective in all
types of seizures5,7
Clonic
seizures
Tonic
seizures
Tonic-clonic
seizures
Partial
seizures
lamotrigine9* topiramate10
≥2yrs
>4yrs
*Monotherapy
phenytoin11
carbamazepine12
in children under 12 years is not recommended9
Epilim® has a broad spectrum of activity across a wide range of
seizure types and epilepsy syndromes7
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
% of seizure-free adult patients at 2, 3
and 6 months in the intent-to-treat
population
N= 1192 adults
90
Adapted from Jedrzejczak J, et al. 2008
Epilim® effective first-line
in partial seizures6
Percentage of seizure-free patients
100
80
70
60
50
40
30
20
10
0
2 months
3 months
6 months
Epilim® provides patients the reassurance of seizure freedom as
early as 2 months6
Epilim® effective first-line in partial seizures6
Significant control of seizures6 High retention rate at 6 months6
72.7%
remission rate* at 6 months
* proportion of seizure-free
subjects during the last 3 months
of the study; age group >15yrs
88.7%
retention rate**
** proportion of subjects
remaining on treatment at 6
months of the study; age group
>15yrs
Favourable tolerance profile6
10.4%
reported side-effects (drug
related)
Epilim® first choice therapy
for generalised and
unclassified epilepsies5
100
EPILIM®
90
lamotrigine
topiramate
80
Adapted from Marson, et al. 2007
*The
SANAD
Study
Percentage of 12-month remission
% 12-month remission - per protocol population
70
60
50
40
30
20
10
0
1
2
3
4
5
Time from randomisation (years)
Epilim® is more effective than lamotrigine and topiramate in patients
with generalised and unclassified epilepsy5
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
1.0
lamotrigine
p= 0.006
topiramate
0.8
Adapted from Marson, et al. 2007
Epilim® first choice therapy
for generalised and
unclassified epilepsies5
EPILIM®
Probability of remaining on drug
*The
SANAD
Study5
Time to treatment failure for any reason
0.6
0.4
0.2
0
1
2
3
4
5
6
Time from randomisation
“Epilim® should remain the drug of first choice for many
patients with generalised and unclassified epilepsies”5
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
*Standard And Newer Antepileptic Drugs
1st-line treatment
Endorsed first-line monotherapy14
For all seizure types and most
epilepsy syndromes
Epilim® is effective & shows acceptable
tolerability as first-line monotherapy
in partial epilepsy
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Drugs to be avoided
Seizure type
Generalised
Tonic-clonic
Absence
Recommended for first-line
treatment regardless
of seizure type
1st-line
(may worsen seizures)
Tiagabine
Vigabatrin
Carbamazepine
Gabapentin
Oxcarbazepine
Tiagabine
Vigabatrin
Myoclonic
Carbamazepine
Gabapentin
Oxcarbazepine
Tiagabine
Vigabatrin
Tonic
Carbamazepine
Oxcarbazepine
Atomic
Carbamazepine
Oxcarbazepine
Phenytoin
NICE Guidelines 201214
Focal
with/without
Secondary
generalisation
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Epilim® effective first-line
for the treatment of partial epilepsy
in children6
Demonstrates significant efficacy6
83.7%
remission rate* at 6 months
* proportion of seizure-free subjects during
the last 3 months of the study; age group ≥ 15yrs
High retention rate at 6 months6
92.0%
retention** rate
** proportion of subjects remaining on treatment
at 6 months of the study ; age group ≥ 15yrs
Epilim® is effective & shows acceptable
tolerability as first-line monotherapy in partial
epilepsy6
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Treatment selection for benign childhood
epilepsy with centro-temporal spikes13
95% Confidence Intervals (correlated to the length of rectangles)
Usually not appropriate
Equivocal
Usually appropriate
N
42
42
41
EPILIM®
Carbamazepine
oxcarbazepine
1
Epilim® is the gold standard
anti-epileptic drug for the
treatment of children7
* A survey on paediatric epilepsy and seizures
completed by 42 European physicians
specialising in paediatric epilepsy
2
3
4
5
6
7
8
9
Paediatric epilepsy survey rating evaluation scale
Treatment selection for cryptogenic
complex partial seizures
95% Confidence Intervals (correlated to the length of rectangles)
Usually not appropriate
Equivocal
Usually appropriate
N
41
41
42
42
carbamazepine
oxcarbazepine
EPILIM®
lamotrigine
1
2
3
4
5
6
7
8
9
Paediatric epilepsy survey rating evaluation scale
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Treatment selection for myoclonic and
generalised tonic-clonic Seizures13
95% Confidence Intervals (correlated to the length of rectangles)
Usually not appropriate
Equivocal
Usually appropriate
N
EPILIM®
Lamotrigine
Levetiracetam
Topiramate
clobazam
clonazepam
40
40
39
39
40
40
1
Epilim® is the gold standard
anti-epileptic drug for the
treatment of children7
•A survey on paediatric epilepsy and seizures completed by
42 European physicians specialising in paediatric epilepsy
2
3
4
5
6
7
8
9
Paediatric epilepsy survey rating evaluation scale
OpinionEuropean
13Dec 2007Expert
Treatment selection for absence epilepsy13
95% Confidence Intervals (correlated to the length of rectangles)
Usually not appropriate
Equivocal
Usually appropriate
N
Childhood
EPILIM®
ethosuximide
lamotrigine
42
42
42
1
2
3
4
5
6
7
8
9
Paediatric epilepsy survey rating evaluation scale
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Epilepsy/syndrome
Usual first-line drug
Infantile spasms-west syndrome
Vigabatrin, corticosteroids
Severe myoclonic epilepsy of infancy
- Dravet syndrome
Epilim®
is recommended
as first-line treatment of
epilepsy syndromes7
IGE with absences
Epilepsy with CSWS
Lennox-Gastut and related syndrome
IGE with myoclonus with or without
GTCS IGE with myoclonus with GTCS
Epilim®, topiramate
Epilim®, ethosuximide
Epilim®, ethosuximide
Epilim®, Epilim® + lamotrigine
Epilim®
Epilim®
Focal epilepsy
Epilim®, carbamazepine
Undetermined epilepsy
Epilim®
CSWS= Continous Spikes and Waves during Sleep; GTCS=Generalised
Tonic-Clonic Seizures; IGE= Idiopathic Generalised Epilepsy
* except Status epilepticus
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Epilim® IV vs. phenytoin IV
Indicated for all seizure types*
Does not cause clinically significant
cardiac or respiratory depression
Does not cause irritation at site of
injection
Injectable in less than 5 minutes
Generally linear pharmacokinetics,
offering a more predictable stable profile
Continuous infusion may be used,
when repeated doses are needed
* except Status epilepticus
Percentage of pts with termination of
seizures
Epilim® IV is effective
therapy in seizure
Emergency situations15
100
90
96.0%
85.3%
80
70
60
50
40
30
20
10
0
Series of
seizures
Change of
medication/IV
switch
N = 102 patients; initial Epilim® IV bolus dose varied between 4-16 mg/kg, depending on
the severity of the condition, with 74% of patients receiving 15-16 mg/kg, admin. 5-10 mins
followed by a continuous infusion of 0.5-4.0 mg/kg/h maintenance dose within 2 hrs to 10
days
Epilim® IV represents an effective alternative to phenytoin in all seizure
emergency situations with no evidence of sedation,
cardiorespiratory disturbances and hypotension15
 Epilim® has over 45 years of clinical experience in millions of
patients worldwide1

 Epilim® is distinguished by its broad spectrum of efficacy
against seizures7

 Epilim® remains the mainstay for treatment of epilepsy in all
age groups7

 Epilim® is the gold standard AED for the treatment of children7

 Epilim® has a low risk of causing paradoxical seizure
aggravation7
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Epilim® Adult Dosing Guidelines8
Epilim® Adult Dosing Guidelines8
Starting dose
*
600 mg/day*
*Increasing by 200 mg/day at 3 day intervals until control is achieved.
Maximum dose is 2500mg /day
• Epilim® should preferably be taken with or after food
• The tablets should be swallowed whole and not crushed
or chewed, and not taken with aerated mineral water
• Epilim® Chrono is a controlled-release formulation and may
be given once or twice daily
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
Children under 20 kg
• 20 mg/kg/day given in divided doses
Epilim® Paediatric
Dosing Guidelines8
Weight (kg)
5
10
Average Daily Dose
100 mg
In mg
2.5 ml
In ml
200 mg
5 ml
15
20
300 mg
7.5 ml
400 mg
10 ml
Children 20 kg and over
• 20-30 mg/kg/day given in divided doses
Weight (kg)
Average Daily
Dose In mg
20
400 to 600 mg
40
800 to 1200 mg
• Initial dose: 400 mg/day, irrespective of body mass
Epilim® IV
Dosage Guidelines8
1. Reconstitute with the solvent provided
2. Loading Dose: 400-800 mg IV over 3-5 minutes
3. Maintenance Dose: continuous or repeated infusion up to a
maximum of 2 500 mg/day
*Valproate
should not be prescribed to female children, female adolescents, women of childbearing potential or pregnant women unless other
treatments are ineffective or not tolerated.
IMPORTANT
 Children exposed in utero to valproate are at a high risk of serious developmental
disorders (in up to 30-40% of cases) and/or congenital malformations (in
approximately 10% of cases).
 Valproate should not be prescribed to female children, female adolescents, women
of childbearing potential or pregnant women unless other treatments are ineffective
or not tolerated.
 Valproate treatment must be started and supervised by a doctor experienced in
managing epilepsy or bipolar disorder.
 Carefully balance the benets of valproate treatment against the risks when
prescribing valproate for the rst time, at routine treatment reviews, when a female
child reaches puberty and when a woman plans a pregnancy or becomes pregnant.
 Prescriber must ensure that all female patients are informed of and understand:
- risks associated with valproate during pregnancy;
- need to use eective contraception;
- need for regular review of treatment;
- the need to rapidly consult if she is planning a pregnancy or becomes pregnant.
REFERENCES:
1. Carraz G, Fau R, Chateau R, et al. Ann Med Psychol (Paris) 1964;122(Tome
2):577-584.2. Turnbull DM, Howel D, Rawlins MD, et al. Br Med J (Clin Res Ed) 1985; 290(6471): 815819.
3). Richens A, Davidson DL, Cartlidge NE, et al. J Neurol Neurosurg Psychiatry 1994; 57(6): 682-687.
4. De Silva M, MacArdle B, McGowan M, et al. Lancet 1996;347(9003):709-713.
5. Marson AG, et al. The SANAD Study of Effectiveness of Valproate, Lamotrigine, or Topiramate for
Generalised & UnclassifiableEpilepsy: An Unblinded Randomised Controlled Trial. The Lancet
2007;369:1016-26.
6. Jedrzejczak J, et al. An Observational Study of First-line Valproate Monotherapy in Focal Epilepsy. Eur
Jnl of Neurology 2008(15): 66-72.
7. Guerrini R, et al. Paediatric Drugs. 2006;8(2):113-129.
8. Epilim® Package Insert; sanofi-aventis south africa (Pty) Ltd.
9. Lamotrigine Package Insert; GlaxoSmithKline South Africa (Pty) Ltd.
10. Topiramate Package Insert; Janssen Pharmaceutica (Pty) Ltd.
11. Phenytoin Package Insert; Pfizer Laboratories (Pty) Ltd.
12. Carbamazepine Package Insert; Novartis South Africa (Pty) Ltd.
13. Wheless JW, et al. Treatment of Paediatric Epilepsy: European Expert Opinion 2007. Epileptic
Disorders 2007;9:S1-S62.
14. National Institute for Clinical Excellence (NICE) Clinical Guideline 20. The Epilepsies: The Diagnosis
and Management of Epilepsies in Adults and Children in Primary and Secondary care. October 2004.
(www.nice.org.uk/CG020NICEguideline).
15. Peters CNA, et al. IV Valproate as an Innovative Therapy in Seizure Emergency Situations Including
Status Epilepticus Experience in 102 Adult Patients. Seizure 2005(1):164-169.
16. Morton LD, et al.Treatment Options for Acute Seizure Acre. CNS Drugs 1998;10(6)405-416.
Abbreviated Prescribing Information. Please read full package insert carefully before prescribing.
Epilim® REGISTRATION NUMBERS: Epilim® Liquid Sugar-free: J/2.5/148; Epilim® CR 200: 27/2.5/0322;
Epilim® CR 300: Y/2.5/286; Epilim® CR 500: 27/2.5/0323; Epilim® 100 Crushable: 27/2.5/0500. Epilim®
Intravenous: Y/2.5/43;Water for Injection - Epilim®: Y/34/156. NAME AND BUSINESS ADDRESS OF
THE HOLDER OF THE CERTIFICATE OF REGISTRATION: sanofi-aventis south africa (pty) ltd., sanofiaventis House, 2 Bond Street, Midrand, 1685. ZASE.VPA.13.10.02