Carbamazepine | Modulate sodium channels | Loading dose: Not recommended due to excessive dose-related toxicity Maintenance dose: Titrate dosage to target over 3-4 wk Adults: 10-20 mg/kg/d as a divided dose Children: 20-30 mg/kg/d as a divided dose | Half-life: 10-25 h with chronic dosing Apparent volume of distribution: 0.8-1.9 L/kg Protein binding: 67%-81% Primary elimination route: Hepatic | 4-12 mg/mL
(17-51 μmol/L) | Diplopia, drowsiness, nausea, sedation | Aplastic anemia, hyponatremia, leukopenia, osteoporosis, rash |
Clonazepam | Enhance GABA
activity | Loading dose:
Not recommended due to
increased adverse effects Maintenance dose:
Initiate at 0.5 mg one to three times
daily, titrate dose to effectiveness
usually 3-5 mg daily in 2-3
divided doses | Half-life: 30-40 h Apparent volume of distribution:
3.2 L/kg Protein binding: 47%-80% Primary elimination route:
Hepatic | Not established | Ataxia, memory
impairment, sedation, slowed
thinking | |
Ethosuximide | Modulate calcium
channels | Loading dose:
Not recommended due to increased adverse effects Maintenance dose:
Initiate at 250 mg twice daily and
titrate to 500-1000 mg twice
daily | Half-life: 60 h Apparent volume of distribution:
0.6-0.7 L/kg Protein binding: None Primary elimination route:
Hepatic | 40-100 mg/mL
(283-708 mmol/L) | Ataxia, sedation | Hepatotoxicity, neutropenia, rash |
Felbamate | Inhibit glutamate
activity | Loading dose:
Not recommended due to
increased adverse effects Maintenance dose:
1200-3600 mg/d in 3-4 divided
doses | Half-life: Monotherapy: 20 h Concurrent enzyme inducers:
11-16 h Apparent volume of distribution:
0.7-0.8 L/kg Protein binding: 25%-35% Primary elimination route:
Hepatic | Not established | Anxiety, insomnia, nausea | Anorexia, aplastic anemia, headache, hepatotoxicity, weight loss |
Gabapentin | Modulate calcium channels and enhance GABA activity | Loading dose: Not recommended due to short half-life Maintenance dose:
900-3600 mg/d in
3-4 divided doses (doses up to 10,000 mg/d have been tolerated) | Half-life: 5-7 h (proportional to creatinine clearance) Apparent volume of distribution: 0.6-0.8 L/kg Protein binding: >10% Primary elimination route:
Renal | Not established | Drowsiness, sedation | Peripheral edema, weight gain |
Lamotrigine | Modulate sodium channels | Loading dose: Not recommended due to increased risk of rash Maintenance dose: 150-800 mg/d in 2-3 divided doses. Doses should be initiated and titrated according to the manufacturer's recommendations to reduce the risk of rash | Half-life: Monotherapy: 24 h Concurrent enzyme inducers: 12-15 h Concurrent enzyme inhibitors: 55-60 h Apparent volume of distribution: 1.1 L/kg Protein binding: 55% Primary elimination route: Hepatic | Not established | Ataxia, drowsiness, headache, insomnia, sedation | Rash |
Levetiracetam | Unknown | Loading dose: Not recommended due to excessive adverse effects Maintenance dose: 1000-3000 mg/d Start at 1000 mg/d and titrate upward as indicated by response | Half-life: 6-8 h Apparent volume of distribution: 0.5-0.7 L/kg Protein binding: >10% Primary elimination route: 70% renal 30% hepatic | Not established | Somnolence, dizziness | Depression |
Oxcarbazepine | Modulate sodium channels | Loading dose: Not recommended due to excessive adverse effects Maintenance dose: 600–1200 mg/d Start at 300 mg twice daily and titrate upward as indicated by response | Half-life: Parent drug ∼2 h 10-monohydroxy metabolite ∼9 h Apparent volume of distribution: 0.5–0.7 L/kg Protein binding: 40% Primary elimination route: Hepatic | Not established | Diplopia, dizziness, somnolence | Hyponatremia, 25%-30% cross sensitivity in patients with hypersensitivity to carbamazepine |
Phenobarbital | Modulate sodium channels | Loading dose: 10-20 mg/kg as single or divided intravenous infusions or orally in divided doses over 24-48 h Maintenance dose: Adults: 1-4 mg/kg/d as a single or divided dose Children: 3-6 mg/kg/d as divided dose Neonates: 1-3 mg/kg/d as divided dose | Half–life: Adults: 49-120 h Children: 37-73 h Neonates: ∼115 h Volume of distribution: 0.7-1 L/kg Protein binding: ∼50% Primary elimination route: Hepatic | 15-40 mg/mL
(65-172 μmol/L) | Ataxia, drowsiness, sedation | Attention deficit, cognitive impairment, hyperactivity, osteoporosis, passive-aggressive behavior |
Phenytoin | Modulate sodium channels | Loading dose: Adults: 15-20 mg/kg single intravenous dose or divided oral dose Infants > 3 mo: 10-15 mg/kg single intravenous dose Neonates: 15-20 mg/kg single intravenous dose Maintenance dose: Adults: 5-7 mg/kg/d as single or divided dose Children: 6-15 mg/kg/d as divided dose Neonates: 3-8 mg/kg/d as divided dose | Half-life: Follows capacity-limited or Michaelis-Menten pharmacokinetics Half-life increases as the dose and serum concentration increases Volume of distribution: Adults: 0.7 L/kg Children: 0.8 L/kg Neonates: 1.2 L/kg Protein binding: Adults, children: 88%-92% Neonates: 65% Primary elimination route: Hepatic | 10-20 mg/mL (40-79 mmol/L) total concentration 1-2 mg/mL (4-8 mmol/L) unbound concentration | Ataxia, diplopia, drowsiness, sedation | Anemia, gingival hyperplasia, hirsutism, lymphadenopathy, osteoporosis, rash |
Pregabalin | Modulate calcium channels | Loading dose: Not recommended due to increased adverse effects Maintenance dose: Initiate at 150 mg/d in 2-3 divided doses and titrate to a maximum dose of 600 mg/d | Half-life: 6.3 h, proportional to creatinine clearance Apparent volume of distribution: 0.5 L/kg Protein binding: Negligible Primary elimination route: Renal | Not established | Ataxia, blurred vision, dizziness, dry mouth, somnolence | Edema, weight gain |
Tiagabine | Enhance GABA activity | Loading dose: Not recommended due to excessive adverse effects Maintenance dose: 32-56 mg/d in four divided doses Doses should be titrated upward over 6 wk, starting at 4 mg/d | Half-life: Monotherapy: 7-9 h Concurrent enzyme inducers: 2.5-4.5 h Apparent volume of distribution: 0.6-0.8 L/kg Protein binding: 96% Primary elimination route: Hepatic | Not established | Dizziness, somnolence, irritability, slowed thinking | |
Topiramate | Modulate sodium channels; inhibit glutamate activity; enhance GABA activity | Loading dose: Not recommended due to excessive adverse effects Maintenance dose: 100-400 mg/d in 2-3 divided doses Doses should be started at 25-50 mg/d and gradually titrated upward over 3-6 wk to avoid excessive adverse effects | Half-life: Monotherapy: 21 h Concurrent enzyme inducers: 11-16 h Apparent volume of distribution: 0.55-0.8 L/kg Protein binding: 13%-17% Primary elimination route: 60% renal 40% hepatic | Not established | Ataxia, dizziness, drowsiness, slowed thinking | Acute glaucoma, metabolic acidosis, oligohidrosis, paresthesias, renal calculi, weight loss |
Valproic acid/divalproex sodium | Modulate sodium channels | Loading dose: 20-40 mg/kg Maintenance dose: Adults: 15-45 mg/kg/d in 2-4 divided doses Children: 5-60 mg/kg/d in 2-4 divided doses | Half-life: Adults: 8-15 h Children: 4-15 h Infants > 2 mo: 65 h Volume of distribution: 0.1-0.5 L/kg Protein binding: 90% (decreases with increasing serum concentrations) Primary elimination route: Hepatic | 50-100 mg/mL (346-693 μmol/L); children may require concentrations up to 150 mg/mL (1040 mmol/L) | Drowsiness, nausea, sedation, tremor | Hepatotoxicity, osteoporosis, pancreatitis, weight gain |
Zonisamide | Modulate sodium and calcium channels | Loading dose: Not recommended due to excessive adverse effects Maintenance dose: 100-600 mg/d; start at 100 mg/d and titrate upward as indicated by response | Half-life: ∼63 h Apparent volume of distribution: 1.45 L/kg Protein binding: 40% Primary elimination route: Hepatic | Not established | Dizziness, somnolence | Metabolic acidosis, oligohidrosis, paresthesias, renal calculi |