Broad spectrum antiepileptics

BROAD SPECTRUM ANTIEPILEPTICS

Valproate
Pharmacokinetics: Nearly complete (>90%) absorption; peak levels formulation dependent; highly (90%) bound to plasma proteins; extensively metabolized in liver; t1/2 5–16h
Clinical uses: Generalized tonic-clonic seizures, partial seizures, absence seizures, myoclonic seizures, other generalized seizure; migraine prophylaxis
Toxicity: Nausea, tremor, weight gain, hair loss, teratogenic, hepatotoxic
Interactions: Phenobarbital, phenytoin, carbamazepine, lamotrigine, felbamate, rifampin, ethosuximide, primidone

Levetiracetam
MOA: SV2A ligand
Pharmacokinetics: Nearly complete (~95%) absorption; peak levels in 1–2h; not bound to plasma proteins; minimal metabolism in blood to inactive metabolite; ~66% excreted unchanged in urine; t1/2 6–11 h
Clinical uses: Focal seizures, generalized tonic-clonic seizures, myoclonic seizures
Toxicity: Nervousness, dizziness, depression, seizures
Interactions: Rare
Brivaracetam: Similar to levetiracetam but interaction with carbamazepine

Topiramate
MOA: Multiple actions
Pharmacokinetics: Bioavailability ~80%; peak levels in 2–4h; minimal (15%) plasma protein binding; variable metabolism; no active metabolites; 20–70% excreted unchanged in the urine; t ½ 20–30 h, but decreases with concomitant drugs
Clinical uses: Focal seizures, primary generalized seizures, Lennox-Gastaut syndrome; migraine prophylaxis
Toxicity: Somnolence, cognitive slowing, confusion, paresthesias
Interactions: Phenytoin, carbamazepine, oral contraceptives, lamotrigine

Zonisamide
Pharmacokinetics: Nearly complete (>90%) absorption; peak concentrations in 2–6h; modest (40–60%) plasma protein binding; moderate (>50%) metabolism in liver; 30% excreted unchanged in urine; t ½ 50-70h
Clinical uses: Focal seizures, generalized tonic-clonic seizures, myoclonic seizures
Toxicity: Drowsiness, cognitive impairment, confusion, skin rashes
Interactions: Minimal

Rufinamide
MOA: Sodium channel blocker and other mechanisms
Pharmacokinetics: Well absorbed orally; peak concentrations in 4–6h; low (35%) plasma protein binding; t ½ 6–10h; no active metabolites; mostly excreted in urine
Clinical uses: Lennox-Gastaut syndrome; focal seizures
Toxicity: Somnolence, vomiting, pyrexia, diarrhea
Interactions: Not metabolized via P450 enzymes, but antiseizure drug interactions may be present