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ANTI-EPILEPTIC DRUG CHART

DRUG MOA ANTI-EPILEPTIC- GENERAL DOSING MONITORING ADRS/BLACK BOX WARNINGS PHARMACOKINETICS
INDICATIONS
Phenytoin - Sodium - Simple partial Dosing: - Therapeutic Range: 10-20 mg/L Concentration Dependent: - Absorption: slow
(Dilantin) channel - Complex partial - Loading dose: 15-20 mg/kg - Ataxia - Vd=0.6-0.8 L/kg in adults
blocker - Generalized tonic- - Titrate dose by 300-600 mg daily in divided - Free drug: 1-2 mg/L - Blurred vision - Highly protein bound (~92%)
Fosphenytoin clonic doses - Dizziness - Altered binding in:
(Cerebyx) - Absence - Range: 200-1200 mg/day divided 3 times Monitoring Therapeutic Levels - Headache  Hypoalbuminemia
- Myoclonic daily - Adjust for albumin - Increased blood glucose  Uremia
Capsule - Prevention of sz - Lethargy  DM
IV following head Formulations: [PHT]/[(0.2 x albumin) +1] - Nystagmus (involuntary arm movements)  Competitive displacement via VPA, salicylates, naproxen,
Solution trauma/surgery - Oral Tablet (Phenytoin acid) *If CrCl <10 ml/min, use 0.1 x albumin - Slurred speech ibuprofen
Tablet Chew - Oral Liquid (Phenytoin acid) - Visual changes
- Oral Capsule (Phenytoin sodium) Phenytoin IV - Half-life: saturable metabolism, no true half-life
- Injectable (Phenytoin sodium) - Can ONLY be administered IV Idiosyncratic: - Metabolism: non-linear kinetics (Michaelis-Menten)
*Caution when switching products - Can ONLY be administered in NS - Blood dyscrasias - Excretion: urine
- Max rate is 50 mg/min - Stevens-Johnson
% Phenytoin acid (PA) - Immunologic reaction
- Capsules, Injectable= 92% Fosphenytoin - Liver failure
- Chewable tabs, susp= 100% - Dosed in phenytoin equivalents (PE)
- fosPHT =2/3 PHT labeled “phenytoin - Can be administered IV or IM Chronic Use:
equivalents=PE” - Can be administered in NS or D5W - Cognitive impairment
- Max rate is 150 mg/min - Decrease in folic acid and vitamin B12
- Gingival hyperplasia
- Hirsutism (coarsening of facial features)
- Osteomalacia
- Peripheral neuropathy
- Skin thickening
Phenobarbital - Potentiates - Simple partial - 50-100 mg BID-TID - Therapeutic Range: 15-40 mg/L Concentration Dependent: - Well absorbed from GI or IM
(Luminal) GABA - Complex partial - Titrate gradually by 30 mg every - Ataxia  Time to peak 2-6 hrs
- Generalized tonic- 2-4 weeks - Lower in range for generalized szs - Headache  BA: 95-100%
Primidone clonic - Higher in range for partial szs - Hyperactivity  No interference from meals
(Mysoline)— - Absence - Nausea - Vd=0.5-0.8 L/kg
prodrug form - Myoclonic - Toxic: >40 mg/L - Sedation - Protein binding: 20-50%
- Status epilepticus Slowness, ataxia (35-80 mg/L) - Unsteadiness - Metabolism: Hepatic via hydroxylation and glucuronide conjugation
IV Coma with reflexes (70-120 mg/L) - Conc:
Solution Coma w/o reflexes (>100 mg/L) Idiosyncratic:  Dose ratio lower in kids than adults
Tablet - Blood dyscrasias  T1/2=40-80 hrs in children
Monitoring: - Stevens-Johnson  T1/2=80-140 hrs in adults
- CBC with platelets  T1/2=100-400 hrs in neonates
- LTFs Chronic Use: - Excretion: Urine (20-40% as unchanged drug)
- Behavior changes
- Connective tissue disorders
- Decrease in folic acid and vitamin B12
- Intellectual blunting
- Mood change
- Osteomalacia
- Sedation
Carbamazepine - Sodium - Simple partial - 100 mg BID or TID - Therapeutic Range: 4-12 mg/L Concentration Dependent: - Absorption: slow
(Tegretol) channel - Complex partial - Titrate by 200 mg/day every 3 days (monotherapy) - Diplopia  Dissolution-rate-limited absorption
blocker - Generalized tonic- - Range is 400-1200 mg/day divided BID-TID - Combination therapy: 4-8 mg/L - Dizziness  Peak Cp at 4-8 hrs from regular tab (faster in kids)
Capsule XR clonic - XR form dosed BID - Toxic Range: >15 mg/L - Drowsiness  Solution & chewable tabs have a greater Cp peak-trough
Solution - Adjunct atonic - Nausea fluctuation
Tablet - Adjunct myoclonic Formulations: - Therapeutic range: Measure levels at - Unsteadiness  Enterohepatic recirculation
Tablet Chew - Chewable, IR Tablet (Tegretol) 2-4 weeks to allow for auto-induction - Lethargy - Protein binding: 70-90%
Tablet XR - XR Tablet (Tegretol XR) - Auto-induction: t1/2 will vary until - Vd=1-2 L/kg
- XR Capsule (Carbatrol) completion of auto-induction, 3-5 wks Idiosyncratic: - Metabolism: hepatic to epoxide metabolite
- Oral Suspension - Lower end for generalized tonic- - Blood dyscrasias - Excretion: urine
clonic szs - Stevens-Johnson
- Higher for partial complex szs Seen more in Han Chinese w/ HLA-B*1502
FDA recommends genetic testing
Monitoring:
- CBC with platelets Chronic Use:
- LFTs - Decreased bone density
- Na - Hyponatremia
- Renal function - Liver failure

BBW
- Aplastic anemia
- Agranulocytosis

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DRUG MOA ANTI-EPILEPTIC- GENERAL DOSING MONITORING ADRS/BLACK BOX WARNINGS PHARMACOKINETICS
INDICATIONS
Oxcarbazepine - Sodium - Simple partial - 150 mg BID - No established therapeutic plasma Concentration Dependent: - Well absorbed
(Trileptal) channel - Complex partial - Titrate gradually up to 600 mg BID concentration - Ataxia - Protein binding: ~40%
blocker - Generalized tonic- - Max: 2400 mg daily - Dizziness - Vd=0.2 L/kg
Keto-analogue clonic - Take without regard to meals Monitoring: - Nausea - Metabolism: 10-monoydroxy metabolite (MHD)
of CBZ - Atonic - Na - Sedation - Excretion: 90-95% renal
- Myoclonic - 200 CBZ ~300 OXCBZ - May induce hepatic enzymes at higher doses
Solution Idiosyncratic: - Weaker inducer than CBZ
Tablet - Stevens Johnson
Tablet XR
Chronic Use:
- Hyponatremia (higher than CBZ)
Valproic Acid - Sodium - Simple partial - 250 mg BID (5-10 mg/kg/day) - Therapeutic Range: 50-100 mg/L Concentration Dependent: - Absorption: rapid (1-2 hours without food, 4 hours with food)
(Depakene) channel - Complex partial - Administer >250 mg/day in div doses - GI upset - Vd small=0.1-0.4 L/kg
blocker - Generalized tonic- - Titrate by 250 mg BID every 3-4 days (5-10 - Timing to steady state: 2-5 days - Nystagmus - Conc-dependent protein binding:
Divalproex - Enhance clonic mg/kg/day) - Toxic range: >150 mg/L - Sedation  ↓’d w/ hypoalbuminemia, pregnancy, head trauma, renal failure
Sodium GABA activity - Absence - Range: 1000-1500 mg/day divided BID-TID - Thrombocytopenia  Displaces other bound drugs (e.g. phenytoin, warfarin)
(Depakote) - T-type Ca2+ - Atonic - XR dosed once daily - Pharmacodynamic effects may be - Tremor - Metabolic pathways: extensive hepatic metabolism
channel - Myoclonic delayed by several wks (metabolites) - Unsteadiness  3-ene, 4-ene and diene unsaturated metabolites
Valproate blocker - Status epilepticus Formulations: - Unsaturated –ene metabolites may be pharmacologically active and accumulate
sodium - Valproic acid (Depakene, Stavzor) Monitoring: Idiosyncratic: in CNS:
(Depacon) - Divalproex (Depkote, ER) - CBC with platelets - Alopecia  4-ene metabolite responsible for idiosyncratic fatal hepatotoxicity
- Valproate sodium (Depacon) - LFTs - Hepatic failure - Seen in kids <2 yo or w/ inborn errors of metabolism
Capsule - Serum amylase - Pancreatitis (β-oxidation), mitochondrial dzs, or poly-AED
Capsule DR Depakote to Depakote ER: therapy.
Cap Sprinkle - ↑ER by ~20% b/c ER is less bioavailable Chronic Use: - Excretion: urine
IV - ER ↓s tremor, wt gain, GI upset more than - Hyperammonemia - Most important influenced on wt-normalized clearance of VPA:
Solution delayed release - Polycystic ovary-like syndrome  Age
Syrup - Weight gain  Daily dose
Tablet DR  AED polytherapy
Tablet XR BBW
- Hepatic failure
- Pancreatitis
Gabapentin - Modulates - Simple partial - 100 mg TID - No established therapeutic plasma Common: - Absorption: dose-dependent
(Neurontin) Ca2+ channels - Complex partial - Titrate by 300 mg/day every 3-7 days concentration - Dizziness - Vd=0.65-1 L/kg
on cortical - Adjunct - Range: 900-4800 mg divided TID-QID - Somnolence - Protein binding: none
Capsule neurons generalized tonic- - Max: 3600 mg/day Monitoring: - Metabolism: not metabolized, no liver enzyme induction
Solution - GABA clonic - No routine labs recommended Less common: - Excretion: urine
Tablet analog but no *Adjust for renal function - Edema
direct activity - Weight gain
on GABA
receptor

Lamotrigine - Inhibits - Simple partial - Dose depends on concomitant AEDs - Therapeutic Range: 4-20 mg/L Concentration Dependent: - Absorption: rapid and complete
(Lamictal) presynaptic - Complex partial - Ataxia - Vd=0.9-1.3 L/kg
glutamate & - Generalized tonic- - Adding lamotrigine to valproate Monitoring: - Blurred vision - Protein binding: ~55%
ODT aspartate tonic Initiate 25 mg every other day - No routine labs recommended - Drowsiness - Metabolism: hepatic and renal
Tablet release, by - Absence Titrate every 2 weeks by 25 mg - Headache - Enterohepatic recirculation 2nd peak 4-6 hrs
Tablet Chew blocking Na+ - Atonic Range: 100-200 mg/day divided BID - Unsteadiness - Excretion: urine
Tablet XR channels - Myoclonic
- Possible - Adding lamotrigine to enzyme inducers Idiosyncratic:
presynaptic Initiate 50 mg daily - Stevens Johnson (more common in children &
N-type Ca2+ Titrate every 1-2 weeks by 50-100 mg/day with concomitant valproate)
channel Range: 300-500 mg/day divided BID
inhibition. Chronic Use:
- Anemia
- Hepatic failure
- Leukopenia
- Thrombocytopenia

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DRUG MOA ANTI-EPILEPTIC- GENERAL DOSING MONITORING ADRS/BLACK BOX WARNINGS PHARMACOKINETICS
INDICATIONS
Topiramate - Sodium - Simple partial - 25-50 mg daily - No established therapeutic plasma Concentration Dependent: - Absorption: rapid and almost complete
(Topamax) channel - Complex partial - Titrate 25-50 mg/day every week concentration - Confusion - Vd=0.6-0.8 L/kg
blocker - Generalized tonic- - Range: 100-200 mg BID - Drowsiness - Protein binding: 15-40%
Capsule XR - Enhance clonic - Max: 200-1600 mg/day Monitoring: - Headache - Metabolism: minor amounts by liver vi hydroxylation, hydrolysis,
Cap Sprinkle GABA - Absence - CBC with platelets - Memory problems glucuronidation
Tablet - Antagonize - Myoclonic - LFTs - Paresthesia - Excretion: urine
AMPA activity - Serum electrolytes - Taste perversion
- Weak - Weight - Weight loss
carbonic
anhydrase Idiosyncratic:
inhibitor - Glaucoma
- Oligohydrosis
- Metabolic acidosis

Chronic Use:
- Nephrolithiasis
- Weight loss
Ethosuximide - T-type Ca2+ - Absence - 250 mg BID - Therapeutic Range: 40-100 mg/L Concentration Dependent: - Absorption: rapid and complete
(Zarontin) channel - Titrate by 250 mg every 4-7 days - Ataxia - Vd=0.6-0.7 L/kg
blocker - Max: 1500 mg daily Monitoring: - Drowsiness - Metabolism: hepatic
Capsule - Take with food/milk to minimize GI side - CBC with platelets - GI distress - Excretion: Urine
Solution effects - LFTs - Unsteadiness

Idiosyncratic:
- Blood dyscrasias
- Stevens Johnson

Chronic Use:
- Behavior changes
- Headache

Felbamate - Blocks - Adjunct simple - 400 mg TID - No established therapeutic plasma Concentration Dependent: - Absorption: rapid and almost complete
(Felbatol) glycine site partial - Titrate by 400-600 mg/day every 1-2 weeks concentration - Abdominal pain - Vd=0.7-0.8 L/kg
on N-methyl- - Adjunct complex - Range: 1200-3600 mg/day divided TID-QID - Ataxia - Protein binding: 22-25%
Solution D-aspartate partial Monitoring: - Constipation - Excretion: urine
Tablet receptor - Adjunct - CBC with platelets - Dizziness
. generalized tonic- - LFTs and bilirubin - Insomnia
clonic - Photosensitivity
- Adjunct absence *Patient must sign an informed - Weight loss
- Adjunct myoclonic consent due to the risk of aplastic
- Lennox-Gastaut anemia and hepatic failure Idiosyncratic:
Syndrome - Aplastic anemia
- Liver failure
- Stevens Johnson
- Thrombocytopenia

BBW
- Aplastic anemia
- Hepatic failure
Zonisamide - Sodium - Adjunct simple - 100 mg daily - Therapeutic Range: 10-40 mg/L Concentration Dependent: - Absorption: good
(Zonegran) channel partial - Titrate by 100 mg/day every 2 weeks - Cognitive impairment - Vd=1.45 L/kg
blocker - Adjunct complex - Range: 100-600 mg/day divided daily-BID Monitoring: - Dizziness - Protein binding: 40%
Capsule - T-type Ca2+ partial - CBC with platelets - Paresthesia - Metabolism: hepatic
channel - Adjunct myoclonic *Avoid in Sulfa Allergy - Renal function - Somnolence - Excretion: urine
blocker - Taste perversion
- Weak
carbonic Idiosyncratic:
anhydrase - Metabolic acidosis
inhibitor - Oligohydrosis
- Stevens Johnson

Chronic Use:
- Nephrolithiasis
- Weight loss

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DRUG MOA ANTI-EPILEPTIC- GENERAL DOSING MONITORING ADRS/BLACK BOX WARNINGS PHARMACOKINETICS
INDICATIONS
Tiagabine - Enhances - Adjunct simple - 4 mg daily - No established therapeutic plasma Concentration Dependent: - Absorption: rapid and almost complete
(Gabitril) GABA partial - Titrate by 4 mg BID every week concentration - Dizziness - Vd=1.2 L/kg
- Adjunct complex - Range: 32-56 mg/day divided BID-QID - Fatigue - Protein binding: 96%
Tablet partial Monitoring: - Slowed thinking - Metabolism: hepatic
- Adjunct atonic *Do not stop abruptly - No routine labs recommended - Tremor - Excretion: feces (60%) and urine (25%)
- Adjunct myoclonic
Idiosyncratic:
- Spike wave stupor
- Stevens Johnson
Levetiracetam - Inhibits Ca2+ - Adjunct simple - 250-500 mg BID - Therapeutic Range: 5-40 mg/L Concentration Dependent: - Absorption: rapid and complete
(Keppra) channels partial - Titrate by 250-500 mg BID every 2 weeks (not routinely performed) - Behavioral disturbance - Vd=0.7 L/kg
- Enhances - Adjunct complex - Range: 500-3000 mg/day divided BID - Sedation - Protein binding: <10%
IV GABA partial Monitoring: - Metabolism: not extensive, primarily by enzymatic hydrolysis
Solution - Adjunct - No routine labs recommended Idiosyncratic/Chronic: - Excretion: urine
Tablet generalized tonic- - Not established
cloinc - No CYP 450 metabolism
- Adjunct abscence - No significant DDIs
- Adjunct myoclonic

Pregabalin - Modulates - Adjunct partial - 75 mg BID - No established therapeutic plasma Concentration Dependent: - Absorption: rapid and almost complete
(Lyrica) Ca2+ channels - Adjunct complex - Titrate by 75 mg BID every week concentration - Blurred vision - Vd=0.5 L/kg
- Increases partial - Max: 600 mg/day divided BID-TID - Dizziness - Protein binding: none
Capsule neuronal Monitoring: - Somnolence - Metabolism: negligible
Tablet GABA *Schedule V controlled substance - No routine labs recommended - Excretion: urine
Idiosyncratic:
- Edema
- Creatine kinase elevation
- Thrombocytopenia

Chronic Use:
- Weight gain
Lacosamide - Enhances - Adjunctive partial - 50 mg BID - No established therapeutic plasma Concentration Dependent: - Absorption: rapid and complete
(Vimpat) slow - Titrate by 100 mg/day every week concentration - Dizziness - Vd=0.6 L/kg
inactivation - Max: 600 mg/day divided BID - Headache - Protein binding: <15%
IV of Na+ Monitoring: - Nausea/Vomiting - Metabolism: hepatic
Solution channels *Schedule V controlled substance - LFTs - Excretion: urine
Tablet Idiosyncratic:
- Liver enzyme elevation
Rufinamide - Prolongs - Adjunctive Lennox- - 200-400 mg Bid - No established therapeutic plasma Common: - Absorption: slow and almost complete
(Banzel) inactive state Gastaut syndrome - Titrate by 400-800 mg/day every other day concentration - Dizziness - Vd ~50 L
of Na+ - Max: 3200 mg/day divided BID - Headache - Protein binding: 35%
Solution channels Monitoring: - Shortened QT interval - Metabolism: extensive via carboxylesterase-mediated hydrolysis
Tablet - No routine labs recommended - Somnolence - Excretion: urine

Less common:
- Leukopenia
Vigabatrin - Inhibits - Infantile spasms - 500 mg BID - No established therapeutic plasma Common: - Absorption: rapid and complete
(Sabril) GABA - Refractory complex - Titrate by 500 mg/day every week concentration - Dizziness - Vd=1.1 L/kg
transaminase partial - Max: 3000 mg/day divided BID - Headache - Protein binding: none
Powder packet Monitoring: - Nystagmus - Metabolism: negligible
Tablet - Ophthalmologic exams - Tremor - Excretion: urine
- Renal function - Weight gain

Less common:
- Hepatic failure

BBW:
- Permanent vision loss
Clobazam - May - Adjunct Lennox- - 5 mg daily for ≥1 week - No established therapeutic plasma Common: - Absorption: good
(Onfi) potentiate Gastaut syndrome - Increase to 5 mg BID for ≥1 week concentration - Aggressive behavior - Vd ~100 L
GABA via - Then increase to 10 mg BID thereafter - Fever - Protein binding: 80-90%
Solution benzodiazepi Monitoring: - Insomnia - Metabolism: hepatic
Tablet ne site *Schedule IV controlled substance - No routine labs recommended - Somnolence - Excretion: urine

Less common:
- Stevens Johnson

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DRUG MOA ANTI-EPILEPTIC- GENERAL DOSING MONITORING ADRS/BLACK BOX WARNINGS PHARMACOKINETICS
INDICATIONS
Eslicarbazepine - Prodrug that - Adjunct partial - 400 mg daily for 1 week - No established therapeutic plasma Common: - Absorption: good
acetate inhibits Na+ - Titrate by 400 mg/day every week concentration - Elevated LFTs - Vd=0.9 L/kg
(Aptiom) channels - Range: 800-1200 mg daily - Hyponatremia - Protein binding: <40%
Monitoring: - Hypothyroidism - Metabolism: rapid and extensive hydrolytic first-pass metabolism to major and
Tablet - LFTs - Somnolence minor active metabolite
- Excretion: urine
Less common:
- Stevens Johnson
Perampanel - AMPA - Adjunctive partial - 2 mg daily at bedtime - No established therapeutic plasma Common: - Absorption: rapid and complete
(Fycompa) glutamate - Titrate by 2 mg/day every week concentration - Backache - Protein binding: 95%
receptor - Range: 8-12 mg daily - Dizziness - Metabolism: extensive via primary oxidation
Tablet inhibitor Monitoring: - Headache - Excretion: feces (50%), urine (20%)
*Schedule III controlled substance - No routine labs recommended - Somnolence

Less common:
- Aggressive behavior

BBW:
- Serious or life-threatening psychiatric and
behavioral adverse reactions including aggression,
hostility, irritability, anger
Ezogabine - Enhance K+ - Adjunctive partial - 100 mg TID - No established therapeutic plasma Common: - Absorption: rapid and almost complete
(Potiga) currents to - Titrate by 50-150 mg/day every week concentration - Confusion - Vd=2-3 L/kg
reduce brain - Range: 300-1200 mg/day divided TID - Dizziness - Protein binding: 80%
Tablet excitability Monitoring: - Memory impairment - Metabolism: glucuronidation and acetylation
*Schedule V controlled substance - No routine labs recommended - Tremor - Excretion: urine
- Vertigo

Less common:
- Hallucinations
- Prolonged QT interval
- Syncope

BBW:
- Permanent vision loss
Benzodiazepine - Enhance - Adjunctive therapy
GABA - Short-term therapy
Clonazepam
Lorazepam

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