Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM.
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Transcript of Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM.
![Page 1: Barbara Lynne Phillips, M.D. Assistant Professor of Neurology WSU BSOM.](https://reader035.fdocuments.net/reader035/viewer/2022072114/56649d035503460f949d67d4/html5/thumbnails/1.jpg)
INTRODUCTION TO THE NEWEST
ANTICONVULSANTSBarbara Lynne Phillips, M.D.
Assistant Professor of NeurologyWSU BSOM
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Disclosures
Participated in Phase II and III trials of lacosamide
No other disclosures
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Anticonvulsants
Mainstay of treatment Two main targets
Ion channels (Na, K, Ca) GABA/Glutamate Other
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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
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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
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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
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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)
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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.
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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
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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
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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
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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
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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
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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
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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
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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.
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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.
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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)
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Questions