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Introduction to the newest anticonvulsants Introduction to the newest anticonvulsants

Introduction to the newest anticonvulsants - PowerPoint Presentation

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Introduction to the newest anticonvulsants - PPT Presentation

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

bid dosing renal potential dosing bid potential renal metabolism psych indication mechanism tablet hepatic adjunctive ataxia dose concerns pts

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Slide1

Introduction to the newest anticonvulsants

Barbara Lynne Phillips, M.D.

Assistant Professor of Neurology

WSU BSOM

Slide2

Disclosures

Participated in Phase II and III trials of

lacosamide

No other disclosures

Slide3

Anticonvulsants

Mainstay of treatment

Two main targets

Ion channels (Na, K, Ca)

GABA/Glutamate

Other

Slide4

Rationale 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

Slide5

Vimpat (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

Slide6

Vimpat (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

Slide7

Onfi (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

)

Slide8

Onfi (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.

Slide9

Aptiom (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

Slide10

Aptiom (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

Slide11

Fycompa (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

Slide12

Fycompa (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

Slide13

Sabril (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

Slide14

Sabril (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

Slide15

Banzel (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

Slide16

Banzel (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.

Slide17

Potiga (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.

Slide18

Potiga (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)

Slide19

Questions