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

 Participated in Phase II and III trials of lacosamide  No other disclosures

 Mainstay of treatment  Two main targets  Ion channels (Na, K, Ca)  GABA/Glutamate  Other

 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

 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

 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

 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)

 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.

 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

 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

 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

 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

 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

 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 also URI. Infants – lethargy, bronchitis, ear infection incl acute otitis media  Extremely good efficacy, no cardiac or protein binding

 PO tablet, oral suspension. Take with food.  Indication: adjunctive, sz in LGS 4+. Particularly effective in reducing Drop Attacks.  Not scheduled  Dosing: 400 bid 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

 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.

 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.

 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)