Antiseizure Medication Chart: Indications, Clearance, and Adverse Reactions
Based on the most recent guideline evidence, here is a comprehensive chart of commonly used antiseizure medications with their key clinical characteristics 1.
First-Generation Antiseizure Medications
| Medication | Primary Indications | Systemic Clearance | Major Adverse Reactions |
|---|---|---|---|
| Phenytoin (Dilantin) | Focal seizures, generalized tonic-clonic, status epilepticus | Hepatic metabolism (CYP450 enzyme inducer) | Hypotension, bradyarrhythmias, cardiac arrest, soft tissue injury with extravasation, purple glove syndrome, gingival hyperplasia [1] |
| Fosphenytoin (Cerebyx) | Focal seizures, generalized tonic-clonic, status epilepticus | Hepatic metabolism (converted to phenytoin) | Hypotension, cardiac dysrhythmias (fewer adverse events than IV phenytoin) [1] |
| Carbamazepine (Tegretol) | Focal seizures, generalized tonic-clonic | Hepatic metabolism (CYP450 enzyme inducer) | Drowsiness, nausea, dizziness, hyponatremia, aplastic anemia, Stevens-Johnson syndrome [1] |
| Valproate (Depacon) | Broad spectrum: focal, generalized, absence, myoclonic seizures, status epilepticus | Hepatic metabolism | Dizziness, thrombocytopenia, liver toxicity, hyperammonemia, weight gain, tremor, hair loss, teratogenicity [1] |
| Phenobarbital (Luminal) | Focal seizures, generalized tonic-clonic, status epilepticus | Hepatic metabolism (25%), renal excretion (75%) | Respiratory depression, hypotension, sedation, cognitive impairment [1] |
Second-Generation Antiseizure Medications
| Medication | Primary Indications | Systemic Clearance | Major Adverse Reactions |
|---|---|---|---|
| Levetiracetam (Keppra) | Focal seizures, generalized tonic-clonic, myoclonic seizures, status epilepticus | Renal excretion (66% unchanged), minimal hepatic metabolism | Fatigue, dizziness, behavioral changes, irritability, depression, rarely pain at infusion site [1,2] |
| Lamotrigine (Lamictal) | Focal seizures, generalized tonic-clonic, absence seizures, Lennox-Gastaut syndrome | Hepatic metabolism (glucuronidation) | Mild transient nausea, serious rashes including Stevens-Johnson syndrome (especially with rapid titration or concurrent valproate), dizziness [1] |
| Gabapentin (Neurontin) | Adjunct for focal seizures | Renal excretion (unchanged) | Somnolence, dizziness, ataxia, fatigue, weight gain [1] |
| Topiramate (Topamax) | Focal seizures, generalized tonic-clonic, Lennox-Gastaut syndrome | Renal excretion (70% unchanged), hepatic metabolism (30%) | Cognitive slowing, word-finding difficulty, paresthesias, weight loss, renal calculi, metabolic acidosis [2] |
| Oxcarbazepine (Trileptal) | Focal seizures | Hepatic metabolism to active metabolite, renal excretion | Somnolence, dizziness, headache, ataxia, nausea, vomiting, hyponatremia, diplopia [2] |
| Lacosamide (Vimpat) | Adjunct for focal seizures | Renal excretion (40% unchanged), hepatic metabolism (60%) | Mild to moderate dizziness, headache, back pain, somnolence, injection site pain, PR interval prolongation [1] |
| Zonisamide (Zonegran) | Adjunct for focal seizures | Renal excretion (35% unchanged), hepatic metabolism (65%) | Fatigue, dizziness, somnolence, anorexia, abnormal thinking, renal calculi, rash [2] |
Third-Generation Antiseizure Medications
| Medication | Primary Indications | Systemic Clearance | Major Adverse Reactions |
|---|---|---|---|
| Perampanel (Fycompa) | Adjunct for focal seizures, generalized tonic-clonic | Hepatic metabolism (CYP3A4/5) | Dizziness, somnolence, irritability, aggression, falls, weight gain [3] |
| Brivaracetam (Briviact) | Adjunct for focal seizures | Hepatic metabolism (95%), renal excretion (minimal) | Somnolence, dizziness, fatigue, nausea [3] |
| Eslicarbazepine (Aptiom) | Focal seizures | Hepatic metabolism to active metabolite, renal excretion | Dizziness, somnolence, nausea, headache, diplopia, hyponatremia [3] |
| Cenobamate (Xcopri) | Focal seizures | Hepatic metabolism (CYP2E1, CYP2A6, CYP2B6) | Somnolence, dizziness, fatigue, diplopia, ataxia, DRESS syndrome (requires slow titration) [3] |
Specialized Antiseizure Medications
| Medication | Primary Indications | Systemic Clearance | Major Adverse Reactions |
|---|---|---|---|
| Cannabidiol (Epidiolex) | Lennox-Gastaut syndrome, Dravet syndrome, tuberous sclerosis complex | Hepatic metabolism (CYP3A4, CYP2C19) | Somnolence, decreased appetite, diarrhea, elevated liver enzymes, drug interactions [3] |
| Ganaxolone (Ztalmy) | Seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder | Hepatic metabolism (CYP3A4) | Somnolence, pyrexia, salivary hypersecretion [3] |
| Fenfluramine (Fintepla) | Dravet syndrome, Lennox-Gastaut syndrome | Hepatic metabolism (CYP2D6, CYP1A2) | Decreased appetite, somnolence, diarrhea, constipation, cardiac valvulopathy (requires echocardiographic monitoring) [3] |
Critical Dosing Adjustments by Organ Function
Renal Impairment Adjustments 3:
- Require dose reduction: Levetiracetam, gabapentin, lacosamide, topiramate, zonisamide, eslicarbazepine
- Minimal adjustment needed: Brivaracetam, rufinamide, cannabidiol, carbamazepine, valproate, lamotrigine
Hepatic Impairment Adjustments 3:
- Require dose reduction or avoidance: Cenobamate (avoid in severe), perampanel (strict dose caps in severe), stiripentol (contraindicated in any hepatic impairment)
- Minimal adjustment needed: Brivaracetam, rufinamide, eslicarbazepine (mild-moderate only)
Status Epilepticus Treatment Hierarchy 1
After benzodiazepine failure, second-line options include:
| Agent | Dose | Administration Rate | Key Advantages |
|---|---|---|---|
| Valproate | 20-30 mg/kg IV | 40 mg/min (max 10 mg/kg/min) | Faster administration, fewer cardiovascular adverse effects than phenytoin [1] |
| Fosphenytoin | 18-20 PE/kg IV | 150 PE/min max | Fewer adverse events than phenytoin, IM option available [1] |
| Levetiracetam | 30-60 mg/kg IV | 100 mg/min | Low incidence of hypotension/respiratory depression [1] |
| Phenytoin | 18-20 mg/kg IV | 50 mg/min max | Effective but higher cardiovascular risk [1] |
For refractory status epilepticus (third-line):
- Propofol: 2 mg/kg bolus, 3-7 mg/kg/hr infusion (requires intubation) 1
- Pentobarbital: 13 mg/kg bolus, 2-3 mg/kg/hr infusion (high hypotension risk) 1
- Midazolam: 0.15-0.20 mg/kg load, 1-5 mg/kg/min infusion 4
Key Clinical Pearls
Enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital) accelerate metabolism of oral contraceptives, warfarin, and other medications, and worsen cardiovascular risk through hyperlipidemia 5.
Lamotrigine rash risk is dramatically increased with concurrent valproate use or rapid titration; never load lamotrigine unless patient has been on it >6 months without rash 1.
Hyponatremia is common with carbamazepine, oxcarbazepine, and eslicarbazepine—monitor sodium levels regularly 2.
Renal stones occur with topiramate and zonisamide due to carbonic anhydrase inhibition 2.
Behavioral/psychiatric effects are most prominent with levetiracetam (irritability, depression) and perampanel (aggression)—avoid in patients with psychiatric history 2, 5.