Major antiepileptic medications
| Antiepileptic Drug (AED), Trade Name, Manufacturer, Year Released | Mechanism | Metabolism | Common Dosages | Therapeutic Level, Half-Life | Common or Significant Side Effects |
|---|---|---|---|---|---|
| Phenobarbital , generic by various manufacturers, 1912 | Prolongs opening of GABA-ergic Cl − channels, increases GABA inhibition. | Hepatic > renal. Enzyme inducing. 20%-45% protein bound. | For status epilepticus: 20-mg/kg loading dose. Neonates: 2-5 mg/kg/day divided bid. Adults: 100-300 mg divided bid. Children: 3-7 mg/kg/day divided bid. | Therapeutic range: 15-40 mg/L. Half-life: 24-168 hours. Takes 2-3 weeks to achieve steady state if no loading dose given. | Sedation, depression, cognitive slowing, respiratory depression, hepatic dysfunction, lupus-like syndrome, erythema multiforme, osteomalacia. |
| Phenytoin , Dilantin by Parke-Davis, 1938 | Blocks voltage-dependent Na + and Ca 2+ channels, reduces high-frequency firing. | Hepatic > renal. Enzyme inducing. 90% protein bound. Nonlinear kinetics. | Loading dose 20 mg/kg. Maintenance 5 mg/kg/day, may divide bid. Adjust dose based on level (nonlinear kinetics). For level 7-10 mg/L, increase dose by 50 mg/day. Level <7 increase dose by 100 mg/day. | Therapeutic range: 10-20 mg/L. Check unbound level (0.5-3 mg/L) if creatinine clearance <10, albumin <3.2 mg/dL, on valproate, pregnant, or suspected toxicity. Half-life: average 22 hours (range 7-42 hours, nonlinear kinetics). | Cerebellar atrophy, ataxia, megaloblastic anemia, neuropathy, gingival hyperplasia, nystagmus, osteomalacia. |
| Primidone , Mysoline by Athena Neurosciences, 1954 | Enhances GABA inhibition, essentially as phenobarbital, but may also have additional activity. | Renal > hepatic. Enzyme inducing. Protein bound. | Adults: start 100-125 mg qhs, increase by 100-125 mg/day every 3 days to initial target of 250 mg tid. Children: start 50-60 mg/day, increase by 50 mg/day every 3 days to initial target of 10-25 mg/kg/day divided tid. | Therapeutic range: Primidone: 5-12 mg/L. Phenobarbital: 15-40 mg/L. Half-life: Primidone: 8-22 hours. Phenobarbital: 56-140 hours. Phenylethylmalonamide: 10-25 hours. | Sedation, depression, cognitive slowing, respiratory depression, hepatic dysfunction, lupus-like syndrome, erythema multiforme, osteomalacia. |
| Ethosuximide , Zarontin by Parke-Davis, 1960 | Blocks T-type calcium channels, reduces thalamocortical excitability. | Hepatic > renal. | Adults: 1000 mg/day in divided doses tid. Children: 20 mg/kg/day | Therapeutic range: 40-100 mg/L. Half-life: 30-60 hours. | Sedation, nausea/vomiting, headache, personality changes, psychosis. |
| Carbamazepine , Tegretol, Tegretol XR by Novartis, Carbatrol by Shire, 1974 | Blocks voltage-dependent Na + and Ca 2+ channels, reduces high-frequency firing. | Hepatic > renal. Active metabolite: carbamazepine 10-11 epoxide. Enzyme inducing. | Adults: 200-400 mg tid. Children <12: start 10-20 mg/kg/day divided bid or tid, increase by 5-10 mg/kg/day weekly, target 20-35 mg/kg/day divided bid or tid. Take with food. | Therapeutic range: 4-12 mg/L. Half-life: initially 25-65 hours with induction, 12-17 hours. | Sedation, ataxia, nausea, diplopia/blurred vision, nausea, hyponatremia, SIADH, elevated LFTs, osteomalacia, photosensitivity. |
| Valproic acid , Depakote, Depakote ER, Depakene by Abbott, 1978 | Blocks voltage-dependent Na + and Ca 2+ channels, reduces high-frequency firing. Potentiates GABA. | Hepatic N -glucuronidation and beta-oxidation CYP450 . >90% protein bound. | Adults and children: start 10-15 mg/kg/day bid or tid. Increase by 5-10 mg/kg/day weekly. Max 60 mg/kg/day. | Therapeutic range: 50-125 mg/L. Half-life: 9-12 hours, children, 5-13 hours, 20 hours with extended-release preparation. | Tremor, weight gain, elevated LFTs, increased bleeding, thrombocytopenia, hyperammonemia, polycystic ovary syndrome, fragile hair, osteomalacia. |
| Felbamate , Felbatol by Wallace, 1993 | N -methyl- d -aspartate blocker (glycine site), enhances GABA inhibition, blocks Na + channels. | Renal > hepatic. | Adults: start 1200 mg/day divided tid or qid. Increase by 1200 mg/day weekly. Max 3600 mg/day. Children: start 15 mg/kg/day divided tid, increase by 15 mg/kg/day weekly. Max 3600 mg/day. | Therapeutic range: 30-80 mg/L. Half-life: 20-23 hours. | Requires informed consent regarding idiosyncratic reactions—aplastic anemia and hepatic failure. Headache, drowsiness, agitation, weight loss, nausea/vomiting, tachycardia. |
| Gabapentin , Neurontin by Parke-Davis, 1993 | Increases brain GABA levels, may work at Ca 2+ channels. | Renal >95% unchanged | Adults: start 300 mg qhs, increase by 300 mg/day every 1-3 days. Max 3600 mg/day divided tid. Children: start 10-20 mg/kg/day divided tid, increase by 10-20 mg/kg/day. Max 50 mg/kg/day divided tid. | Therapeutic range: 2-12 mg/L. Half-life: 4-6 hours. | Somnolence, fatigue, ataxia, weight gain, edema, TTP, leukopenia, tinnitus. |
| Lamotrigine , Lamictal by Glaxo Wellcome, 1994 | Voltage-dependent Na + channel blocker. Decreases release of excitatory neurotransmitters. | Hepatic > renal. | Starting titration varies if on other drugs. Adults (with valproate): start 25 mg/day, increase by 25 mg bid every 1-2 weeks, initial target 100 mg bid. Monotherapy or enzyme-inducing AEDs: start 25 mg bid, increase by 50 mg every week, target 200 mg bid. Children (with valproate): 0.15 mg/kg/day for 2 weeks, then 0.3 mg/kg/day for weeks 3-4. Children on monotherapy or enzyme-inducing AEDs: 0.6 mg/kg/day for first 2 weeks, then 1.2 mg/kg/day for weeks 3-4, target 5-15 mg/kg/day. | Therapeutic range: 4-15 mg/L. Half-life: 11-60 hours (depending if on inducer or inhibitor). | Rash or Stevens–Johnson syndrome more likely if increased rapidly. Nausea, lethargy, dizziness, headache. |
| Topiramate , Topamax by Ortho Biotech, 1996 | Blocks repetitive neuron firing. Blocks kainate and AMPA receptors. Improves GABA inhibition, carbonic anhydrase inhibitor. | Predominantly renal, but has enzyme-inducing effects. | Adults: start 25 mg daily, increase by 25-50 mg divided bid weekly, target 100-200 mg divided bid. Children: 1-3 mg/kg/day, increase by 1-3 mg/kg/day every 1-2 weeks divided bid, target 5-9 mg/kg/day | Therapeutic range: 4-10 mg/L. Half-life: 18-30 hours. | Nephrolithiasis, acute angle closure glaucoma, metabolic acidosis, hyperthermia, tingling, altered taste, anorexia/weight loss, lethargy, word finding problems, diarrhea, dizziness. |
| Tiagabine , Gabitril by Cephalon, 1997 | Potentiates GABA by blocking glial uptake. | Hepatic >90%. Protein bound. | Adults: start 4 mg daily, increase to 4 mg bid in 2 weeks, then increase by 4 mg day, divided bid weekly, target 32-56 mg divided bid. Children: (12-16 years): start same as adult, but target 20-32 mg. | Therapeutic range: 0.1-0.3 mg/L. Half-life: 4-9 hours. | Fatigue, weakness, poor attention, ataxia, nausea, tremor. |
| Levetiracetam , Keppra by UCB Pharma, 1999 | Decreased high-voltage N + -type Ca 2+ channel current, reduces effects of Zn and beta-carbolines at GABA A and glycine receptors. | Renal > hepatic. Not enzyme inducing. <10% protein bound. | Adults: start 250 mg bid for 1 week, then target 500 mg bid. May increase to 1500 bid. | Therapeutic range: 5-40 mg/L. Half-life: 6-8 hours. | Personality changes, irritability, sedation, hallucinations. |
| Oxcarbazepine , Trileptal by Novartis, 2000 | Blocks Na + and Ca 2+ channels, stops high-frequency firing. | Hepatic = renal. Metabolized to active monohydroxy metabolite by cytosolic liver enzymes, then further glucuronidation and oxidation to other less active metabolites, then renal excretion. 40% protein bound. | Adults: start 300 mg bid, increase by 300 mg every 3 days, to initial target 600 mg bid. Max 2400 mg/day. Children (4-16 years): start 8-10 mg/kg every 2 weeks to target (all divided bid). 20-29 kg: 900 mg/day, 29-39 kg: 1200 mg/day, >39 kg: 1800 mg/day. | Therapeutic range: 10-monohydroxymetabolite 12-30 mg/L. Half-life: 8-12 hours. | Hyponatremia, fatigue, somnolence, ataxia, nausea, vomiting, diplopia, nystagmus. |
| Zonisamide , Zonegran by Elan, 2000 | Blocks Na + and Ca 2+ channels, stops high-frequency firing, interacts with GABA A A channels, carbonic anhydrase inhibitor. | Hepatic > renal. | Adults: start 100 mg/day, increase by 100 mg every 2 weeks, target of 400 mg once daily (may divide bid). Children: start 1.2 mg/kg/day, increase by 0.5-1 mg/kg/day every 2 weeks to target of 5-8 mg/kg/day. | Therapeutic range: 15-40 mg/L. Half-life: 63 hours. | Nephrolithiasis, tingling, altered taste, anorexia/weight loss, lethargy, word finding problems, visual field defects, dizziness. |
| Pregabalin , Lyrica by Pfizer, 2005 | Increases GABA and decreases glutamate, decreases influx through voltage-dependent Ca 2+ channels. | Renal. | Start 75 mg bid, increase to 300 mg bid. | Therapeutic range: variable. Half-life: 6 hours. | Dizziness, drowsiness. |
| Vigabatrin , Sabril by Ovaron Pharma, under FDA consideration in 2009 | Inhibits GABA transaminase to increase brain levels of GABA. | Renal. | Adults: start 500 mg bid, increase by 500 mg/day every week up to 3 gm/day bid. Infantile spasms: 50 mg/kg/day bid, titrate by 25-50 mg/kg/day every 3 days to max of 150 mg/kg/day. | Therapeutic range: unknown. Half-life: 5-12 hours. | Peripheral visual field defects, behavioral changes. Requires informed consent because of the visual field effects. |
| Lacosamide , Vimpat by Eisai, 2009 | Enhances slow inactivation of Na + channel. | Renal and hepatic. | Begin 25-50 mg bid and titrate by 50-100 mg/week to dose of 200 mg bid. | 13 hours, therapeutic levels not established. | Dizziness, headache, nausea, diplopia. May be increased with other AEDS that block sodium channels. |
| Rufinamide , Banzel by Eisai, 2009 | Sodium channel. | Hepatic. | Begin with 200-400 mg bid and increase weekly by 400-800 mg/day to target of 1600 mg bid. | 6-10 hours, therapeutic levels not established. | Somnolence, vomiting, headache, can shorten QT interval at higher doses and contraindicated in individuals with short QT interval. |
| Ezogabine , Potiga by GlaxoSmithKline, 2011 | Potassium channel (KCNQ) enhancer. | Hepatic. | Begin with 100 tid and increase weekly by 100-200 mg/day to target dose of 400 tid. | 13-20 hours, therapeutic levels not established. | Retinal/scleral pigment change, blue skin discoloration, urinary retention. |
| Clobazam , Onfi by Lundbeck, 2012 | GABA agonist (1,5-benzodiazepine). | Hepatic. | Begin with 5 mg bid and increase weekly by 10-20 mg/day to target of 40 mg bid. | 36-42 hours, therapeutic levels not established. | Sedation (less than other benzodiazepines), tolerance/withdrawal. |
| Eslicarbazepine , Aptiom by Sunovion, 2014 | Sodium channel blocker. | Hepatic. | Begin at 400 mg qhs and increase weekly by 400 mg to target of 1200 qhs. | 13-20 hours, therapeutic levels not established. | Diplopia, hyponatremia. |
| Perampanel , Fycompa by Eisai, 2014 | AMPA receptor blocker. | Hepatic. | Begin at 2 mg qhs and increase weekly by 2-4 mg weekly to target of 12 mg qhs. | 105 hours, therapeutic levels not established. | Irritability. |
SIADH , Syndrome of inappropriate antidiuretic hormone; LFT , liver function tests; AED , antiepileptic drug; TTP , thrombotic thrombocytopenic purpura; AMPA , α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; GABA , gamma aminobutyric acid.
