Barbara Lynne Phillips MD Assistant Professor of Neurology WSU BSOM Disclosures Participated in Phase II and III trials of lacosamide No other disclosures Anticonvulsants Mainstay of treatment ID: 760640
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Slide1
Introduction to the newest anticonvulsants
Barbara Lynne Phillips, M.D.
Assistant Professor of Neurology
WSU BSOM
Slide2Disclosures
Participated in Phase II and III trials of
lacosamide
No other disclosures
Slide3Anticonvulsants
Mainstay of treatment
Two main targets
Ion channels (Na, K, Ca)
GABA/Glutamate
Other
Slide4Rationale for new AEDs
Despite more than 15 available agents, rate of
sz
control is still only about 60% for first drug tried and up to 75% overall
% of patients who are intractable remains the same at 25-30%
Multiple new agents available in last few years, some with unique mechanisms of action
Slide5Vimpat (lacosamide)
PO tablet, oral suspension and IV
Indication: first line, monotherapy and adjunctive, partial onset
sz
, 17+
Schedule V
Metabolism: Hepatic, CYP 3A4 2C9
Dosing: Start 50 mg bid, max rec 200 mg bid
Mechanism: Slow inactivation Na channel
Slide6Vimpat (lacosamide)
Potential SE: Dizziness most common. Others ataxia,
paresthesias
, headache, syncope, psych symptoms reported but rare.
No significant drug interactions
Concerns: Can increase PR interval, more likely in DM
neurop
or CV disease. Use with caution in dysrhythmia pts.
Adjust dose in hepatic and renal pts
Slide7Onfi (clobazam)
PO: tablet, oral suspension, considered orphan drug
Indication: Adjunctive in pts with LGS, 2
yo
+
Schedule IV
Metabolism: hepatic CYP 2C19,
wk
3A4
Dosing: 5 mg bid – 20 mg bid
Mechanism:
Benzo
, potentiates
GABAergic
neurotrans
, GABA A receptor, (1,5
benzo
)
Slide8Onfi (clobazam)
Potential SE: somnolence most common. Ataxia, confusion, psych (8%).SJS rare but reported. Withdrawal
sx
possible.
Weak inducer CYP 2C19 – may reduce effect of some BCPs
Concerns:
Etoh
raises CLB level by 50%, other CNS depressants potentiate sedation, caution with previous psych
hx
,
adj
dose in geriatric, hepatic and renal pts.
Slide9Aptiom (eslicarbazepine)
PO tablet, once daily dosing
Indication: adjunctive partial
sz
, 18+
Not scheduled
Metabolism: Drug is extensively metabolized to
Eslicarbazepine
, major active metabolite(?), no
autoinduction
. Renal excretion
Dosing: 400 mg
qd
– 600 mg
qd
Mechanism:
inhib
voltage gated Na channels
Slide10Aptiom (eslicarbazepine)
Potential SE: dizzy, drowsy, nausea, h/a, ataxia, diplopia, blurry vis. NO increase in psych
sx
over what is expected in this population.
Rare SJS, DRESS, rash
Concerns: can’t be given with OXC, dose
adj
with CBZ, don’t give if allergic to either. Mild inducer may affect BCP,
decr
dose with
decr
CrCl
. Reported
decr
T3/T4 only. Unknown sig
Slide11Fycompa (perampanil)
PO tablet, once daily dosing
Indication: Adjunctive, partial onset, 12
yo
+
Schedule III. Euphoria,
sim
to ketamine
Metabolism: hepatic CYP 3A4
Dosing: 2-4 mg/d – max 12 mg/d
Mechanism: non-competitive AMPA glutamate receptor ANTAGONIST on post-synaptic neurons
Slide12Fycompa (perampanil)
Potential SE: dizzy, ataxia, drowsy. Has black box warning for potential psych
sx
incl
hostile, aggression, anger, anxiety, agitation, suicidal
Psych SE: dose dependent 12% at 8 mg, 20% at 12 mg. (6% placebo). Most w/
i
6
wks
Other concerns: enzyme inducers reduce its effectiveness, may reduce BCP efficacy, possible euphoria, not rec in severe
hep
/renal
Slide13Sabril (vigabatrin)
PO (tablet and powder)
Indication: Refractory CPS, 10+ (not first line), infantile spasms 1 m-2
yr
, first line monotherapy
Not scheduled
Metabolism: renal excretion, min metabolized
Dosing: 500 mg bid – 1500 mg bid adults
Mechanism: irreversible inhibitor of GABA -transaminase
Slide14Sabril (vigabatrin)
Potential SE: Black box for vision loss (
periph
) which is gradual, progressive,
bilat
concentric field constriction. Higher risk with longer exposure. Permanent.
Req
serial VF testing.
Other SE: fatigue, memory,
wt
gain, coordination
prob
, confusion in 16+. 10-16 also URI. Infants – lethargy, bronchitis, ear infection
incl
acute otitis media
Extremely good efficacy, no cardiac or protein binding
Slide15Banzel (rufinamide)
PO tablet, oral suspension. Take with food.
Indication: adjunctive,
sz
in LGS 4+. Particularly effective in reducing Drop Attacks.
Not scheduled
Dosing: 400 bid- 1600 mg bid adults. 10/mg/kg/d up to 1600 mg bid, children
Metabolism: extensively hydrolyzed, renal
exc
Mechanism: modulation of Na channel, prolongs inactive state
Slide16Banzel (rufinamide)
Potential SE: dizzy, drowsy, ataxia, nausea,
infreq
mood problems and suicidality
Other: Prolongs QT interval, clinically without risk unless pre-existing. Contraindicated in Familial Short QT Syndrome.
May reduce efficacy of BCP. VPA
decr
its
metab
by 70% causing
incr
level. No change dosing for renal. Not rec for hepatic disease.
Slide17Potiga (ezogabine)
PO tablet
Indication:
Adj
partial onset, 18+, not first line
Schedule V
Dosing: 100 mg
tid
– 400 mg
tid
Metabolism:glucuronidated
, renal excretion
Mechanism: enhances transmembrane K currents mediated by KCNQ ion channels.
Slide18Potiga (ezogabine)
Potential SE: Black box for visual disturbance, retinal
pigmentary
abnormalities like pigment dystrophies. Urinary retention – some
req
prolonged self-cath. Skin discoloration (blue-grey, brown) nails, lips, mucous membranes, skin (1/4 with concomitant retinal pigment
abnl
)
Other: dizzy, psych (hallucinations, mood, psychosis)
Slide19Questions