INTRODUCTION TO THE NEWEST

ANTICONVULSANTSBarbara Lynne Phillips, M.D.

Assistant Professor of NeurologyWSU BSOM

Disclosures

Participated in Phase II and III trials of lacosamide

No other disclosures

Anticonvulsants

Mainstay of treatment Two main targets

Ion channels (Na, K, Ca) GABA/Glutamate Other

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

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

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

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)

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.

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

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

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

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

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

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

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

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.

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.

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)

Questions