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Transcript
The New Antiepileptic Drugs:
Where Do They Belong in
Our Armamentarium?
Madhu Jasti, MD
University of Alabama at Birmingham School of Medicine,
Birmingham, Alabama
A REPORT FROM THE 68th ANNUAL MEETING OF THE AMERICAN EPILEPSY SOCIETY
© 2015 Direct One Communications, Inc. All rights reserved.
1
Overview

Selection of an antiepileptic drug (AED) is based
primarily on efficacy for specific seizure types and
epileptic syndromes.

Because different AEDs may be similarly effective,
the choice of one AED over another often rests on
other properties, such as their side-effect profile and
tolerability, potential for drug interactions,
pharmacokinetic properties, and cost.

Over the past decade, many new drugs have been
added to the therapeutic armamentarium for
epilepsy; many more are clinically useful even
though their mode of action may not have been
completely elucidated.
© 2015 Direct One Communications, Inc. All rights reserved.
2
Ezogabine

Broad-spectrum AED

First-in-class KCNQ agonist

Daily dose: 600–1,200 mg PO in 3 divided doses

May cause skin discoloration and/or retinal
pigmentation (FDA black-box warning)

Overall assessment: Third/fourth-line AED reserved
for patients ≥ 18 years of age with focal seizures
refractory to other drugs
Wuttke TV et al. Mol Pharmacol. 2005;67:1009; Stephen LJ, Brodie MJ. CNS Drugs. 2011;25:89; French JA et
al. Neurology. 2011;76:1555; Brodie MJ et al. Neurology. 2010;75:1817
© 2015 Direct One Communications, Inc. All rights reserved.
3
Eslicarbazepine Acetate

Narrow-spectrum AED

Structurally related to carbamazepine and
oxcarbazepine and equally efficacious

Daily dose: 800–1,200 mg PO in a single dose

Tends to be well tolerated

Overall assessment: Useful first-line AED for adults
≥ 18 years of age with focal seizures; similar to
carbamazepine and oxcarbazepine but offering
simpler dosage titration and once-daily dosing
Singh RP, Asconapé JJ. J Cent Nerv Syst Dis. 2011;3:179; Almeida L, Soares-da-Silva P. Neurotherapeutics.
2007;4:88; Bonifácio MJ et al. Epilepsia. 2001;42:600; Hebeisen S et al. Epilepsia. 2011;52(suppl 6):257;
Almeida L et al. J Clin Pharmacol. 2005;45:1062; Falcão A et al. CNS Drugs. 2012;26:79; Keating GM. CNS
Drugs. 2014;28:583; Chung S et al. AAN 2014, Poster 3.329; Benbadis S et al. AAN 2014, Poster 3.237; Gil-Nagel
A et al. Acta Neurol Scand. 2009;120:281
© 2015 Direct One Communications, Inc. All rights reserved.
4
Stiripentol

Not FDA approved; orphan drug status in the US

GABA receptor modulator

Daily dose: 50–100 mg/kg (maximum, 4 g) PO in
2–3 divided doses

Overall assessment: Niche drug for use with
clobazam and valproate as adjunctive therapy of
refractory generalized tonic-clonic seizures in
patients with severe myoclonic epilepsy in infancy
(Dravet syndrome) whose seizures are not
adequately controlled
Poisson M et al. Arzneimittelforschung. 1984;34:199; Fisher JL. Eur J Pharmacol. 2011;654:160; Tran A et al.
Clin Pharmacol Ther. 1997;62:490; Chiron C et al. Lancet. 2000;356:1638; Levy RH et al. Clin Pharmacol Ther.
1984;36:661; Kassaï B et al. Epilepsia. 2008;49:343; Wirrell EC et al. Epilepsia. 2013;54:1595; Peigné S et al.
Epilepsy Res. 2014;108:909
© 2015 Direct One Communications, Inc. All rights reserved.
5
Vigabatrin

Broad-spectrum AED

GABA transaminase inhibitor

Daily dose: for infantile spasms, up to 150 mg/kg PO
in 2 divided doses; for refractory complex partial
seizures, 1,000 mg PO twice daily for patients 10–16
years old and 1,500 mg PO twice daily for those > 16
years of age or weighing > 60 kg

May cause permanent vision loss (FDA black-box
warning)

Overall assessment: Drug of choice for patients with
epileptic spasms and tuberous sclerosis
Ben-Menachem E. Acta Neurol Scand Suppl. 2011;192:5; Appleton RE et al. Epilepsia. 1999;40:1627; BenMenachem E, Sander JW. Acta Neurol Scand Suppl. 2011;192:16; Wild JM et al. CNS Drugs. 2009;23:965
© 2015 Direct One Communications, Inc. All rights reserved.
6
Perampanel

Broad-spectrum AED

First-in-class AMPA glutamate receptor antagonist

Daily dose: 4–12 mg PO in a single dose

Use with caution in patients with hepatic or renal
failure

May cause aggression and hostility (FDA black-box
warning)

Overall assessment: Useful adjunctive therapy for
patients ≥ 12 years of age with partial-onset seizures,
with or without generalized seizures, particularly for
those who are refractory to other AEDs
Faulkner MA. Am J Health Syst Pharm. 2014;71:191; Steinhoff BJ et al. Epilepsia. 2013;54:1481; Michael A.
Epilepsy Curr. 2011;11:56
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7
Lacosamide

Narrow-spectrum AED

Enhances slow inactivation of sodium channels

Daily dose: 150–200 mg PO twice daily

Overall assessment: Useful as monotherapy
or adjunctive therapy for patients ≥ 17 years of age
with partial-onset seizures, with or without
secondary generalization; IV formulation is useful in
inpatient/emergency department settings; possible
role in status epilepticus
Chung S et al. Epilepsia. 2010;51:958; Hoy SM. CNS Drugs. 2013;27:1125; Italiano D, Perucca E. Clin
Pharmacokinet. 2013;52:627; Cawello W et al. Epilepsia. 2013;54:530; Grosso S et al. Acta Neurol Scand.
2014;129:420; Höfler J, Trinka E. Epilepsia. 2013;54:393; Stephen LJ et al. Epilepsy Behav. 2011;22:499; Sake
JK et al. CNS Drugs. 2010;24:1055
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8
Rufinamide

Broad-spectrum AED

Prolongs inactive state of sodium channels

Daily dose: 45 mg/kg (maximum, 3,200 mg) PO in
2 divided doses

Overall assessment: Indicated for adjunctive
treatment of Lennox-Gastaut syndrome in patients
≥ 4 years of age; possibly useful as a third-line AED
for treating focal epilepsy
Grosso S et al. Eur J Paediatr Neurol. 2014;18:641; Thome-Souza S et al. Epilepsia. 2014;55:1235; Cusmai R et
al. Epilepsy Res. 2014;108:542
© 2015 Direct One Communications, Inc. All rights reserved.
9
Clobazam

Broad-spectrum AED

Potentiation of GABAergic neurotransmission

Daily dose: for patients weighing ≤ 30 kg, 5–20 mg
PO in 2 divided doses; for those weighing > 30 kg,
10–40 mg PO in 2 divided doses

Overall assessment: Currently approved only for
treatment of Lennox-Gastaut syndrome in patients
≥ 2 years of age but also may be useful as adjunctive
therapy of Dravet syndrome and as second- or thirdline therapy of focal epilepsy
Conry JA et al. Epilepsia. 2014;55:558; Ogungbenro K, Aarons L. Pharm Res. 2015;32:144; Tolbert D et al.
Epilepsy Behav. 2014;37:11
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10