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INTRODUCTION TO THE NEWEST ANTICONVULSANTS Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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Page 1: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

INTRODUCTION TO THE NEWEST

ANTICONVULSANTSBarbara Lynne Phillips, M.D.

Assistant Professor of NeurologyWSU BSOM

Page 2: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

Disclosures

Participated in Phase II and III trials of lacosamide

No other disclosures

Page 3: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

Anticonvulsants

Mainstay of treatment Two main targets

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

Page 4: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 5: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 6: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 7: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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)

Page 8: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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.

Page 9: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 10: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 11: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 12: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 13: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 14: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 15: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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

Page 16: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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.

Page 17: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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.

Page 18: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

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)

Page 19: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM

Questions