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Table 181-5

Dosage and Adverse Effects of Commonly Used Antiepileptic Drugs

Generic NameTrade NamePrincipal UsesTypical Dose; Dose IntervalHalf-LifeTherapeutic RangeAdverse EffectsDrug Interactionsa
NeurologicSystemic
CarbamazepineTegretolc

Tonic-clonic

Focal-onset

600-1800 mg/d (15-35 mg/kg, child); bid (capsules or tablets), tid-qid (oral suspension)10-17 h (variable due to autoinduction: complete 3-5 wk after initiation)4-12 µg/mL

Ataxia

Dizziness

Diplopia

Vertigo

Aplastic anemia

Leukopenia

Gastrointestinal irritation

Hepatotoxicity

Hyponatremia

Level decreased by enzyme-inducing drugsb

Level increased by erythromycin, propoxyphene, isoniazid, cimetidine, fluoxetine

ClobazamOnfiLennox-Gastaut syndrome10-40 mg/d (5-20 mg/d for patients <30 kg body weight); bid36-42 h (71-82 h for less active metabolite)Not established

Fatigue

Sedation

Ataxia

Aggression

Insomnia

Constipation

Anorexia

Skin rash

Level increased by CYP2C19 inhibitors
ClonazepamKlonopin

Absence

Atypical absence

Myoclonic

1-12 mg/d; qd-tid24-48 h10-70 ng/mL

Ataxia

Sedation

Lethargy

AnorexiaLevel decreased by enzyme-inducing drugsb
EthosuximideZarontinAbsence750-1250 mg/d (20-40 mg/kg); qd-bid

60 h, adult

30 h, child

40-100 µg/mL

Ataxia

Lethargy

Headache

Gastrointestinal irritation

Skin rash

Bone marrow suppression

Level decreased by enzyme-inducing drugsb

Level increased by valproic acid

EzogabinePotigaFocal-onset800-1200 mg/d; tid7-11 hNot established

Dizziness

Fatigue

Sedation

Confusion

Vertigo

Tremor

Retinal abnormalities

Skin discoloration

Cardiac conduction (QT interval prolongation)

Urinary retention

Level decreased by enzyme-inducing drugsb
FelbamateFelbatol

Focal-onset

Lennox-Gastaut syndrome

Tonic-clonic

2400-3600 mg/d, tid-qid16-22 h30-60 µg/mL

Insomnia

Dizziness

Sedation

Headache

Aplastic anemia

Hepatic failure

Weight loss

Gastrointestinal irritation

Increases phenytoin, valproic acid, active carbamazepine metabolite
GabapentinNeurontinFocal-onset900-2400 mg/d; tid-qid5-9 h2-20 µg/mL

Sedation

Dizziness

Ataxia

Fatigue

Gastrointestinal irritation

Weight gain

Edema

No known significant interactions
LacosamideVimpatFocal-onset200-400 mg/d; bid13 hNot established

Dizziness

Ataxia

Diplopia

Vertigo

Gastrointestinal irritation

Cardiac conduction (PR interval prolongation)

Level decreased by enzyme-inducing drugsb
LamotrigineLamictalc

Focal-onset

Tonic-clonic

Atypical absence

Myoclonic

Lennox-Gastaut syndrome

150-500 mg/d; bid (immediate release), daily (extended release) (lower daily dose for regimens with valproic acid; higher daily dose for regimens with an enzyme inducer)

25 h

14 h (with enzyme-inducers), 59 h (with valproic acid)

2.5-20 µg/mL

Dizziness

Diplopia

Sedation

Ataxia

Headache

Skin rash

Stevens-Johnson syndrome

Level decreased by enzyme-inducing drugsb and oral contraceptives

Level increased by valproic acid

LevetiracetamKeppracFocal-onset1000-3000 mg/d; bid (immediate release), daily (extended release)6-8 h5-45 µg/mL

Sedation

Fatigue

Incoordination

Mood changes

Anemia

Leukopenia

No known significant interactions
OxcarbazepinecTrileptal

Focal-onset

Tonic-clonic

900-2400 mg/d (30-45 mg/kg, child); bid10-17 h (for active metabolite)10-35 µg/mL

Fatigue

Ataxia

Dizziness

Diplopia

Vertigo

Headache

See carbamazepine

Level decreased by enzyme-inducing drugsb

May increase phenytoin

PhenobarbitalLuminal

Tonic-clonic

Focal-onset

60-180 mg/d; qd-tid90 h10-40 µg/mL

Sedation

Ataxia

Confusion

Dizziness

Decreased libido

Depression

Skin rashLevel increased by valproic acid, phenytoin
Phenytoin (diphenylhydantoin)Dilantin

Tonic-clonic

Focal-onset

300-400 mg/d (3-6 mg/kg, adult; 4-8 mg/kg, child); qd-tid24 h (wide variation, dose-dependent)10-20 µg/mL

Dizziness

Diplopia

Ataxia

Incoordination

Confusion

Gingival hyperplasia

Lymphadenopathy

Hirsutism

Osteomalacia

Facial coarsening

Skin rash

Level increased by isoniazid, sulfonamides, fluoxetine

Level decreased by enzyme-inducing drugsb

Altered folate metabolism

PrimidoneMysoline

Tonic-clonic

Focal-onset

750-1000 mg/d; bid-tid

Primidone, 8-15 h

Phenobarbital, 90 h

Primidone, 4-12 µg/mL

Phenobarbital, 10-40 µg/mL

Same as phenobarbital

Level increased by valproic acid

Level decreased by phenytoin (increased conversion to phenobarbital)

RufinamideBanzelLennox-Gastaut syndrome3200 mg/d (45 mg/kg, child); bid6-10 hNot established

Sedation

Fatigue

Dizziness

Ataxia

Headache

Diplopia

Gastrointestinal irritation

Leukopenia

Cardiac conduction (QT interval shortening)

Level decreased by enzyme-inducing drugsb

Level increased by valproic acid

May increase phenytoin

TiagabineGabitrilFocal-onset32-56 mg/d; bid-qid (as adjunct to enzyme-inducing antiepileptic drug regimen)2-5 h (with enzyme inducer), 7-9 h (without enzyme inducer)Not established

Confusion

Sedation

Depression

Dizziness

Speech or language problems

Paresthesias

Psychosis

Gastrointestinal irritationLevel decreased by enzyme-inducing drugsb
TopiramateTopamax

Focal-onset

Tonic-clonic

Lennox-Gastaut syndrome

200-400 mg/d; bid (immediate release), daily (extended release)20 h (immediate release), 30 h (extended release)2-20 µg/mL

Psychomotor slowing

Sedation

Speech or language problems

Fatigue

Paresthesias

Renal stones (avoid use with other carbonic anhydrase inhibitors)

Glaucoma

Weight loss

Hypohidrosis

Level decreased by enzyme-inducing drugsb
Valproic acid (valproate sodium, divalproex sodium)

Depakene

Depakotec

Tonic-clonic

Absence

Atypical absence

Myoclonic

Focal-onset

Atonic

750-2000 mg/d (20-60 mg/kg); bid-qid (immediate and delayed release), daily (extended release)15 h50-125 µg/mL

Ataxia

Sedation

Tremor

Hepatotoxicity

Thrombocytopenia

Gastrointestinal irritation

Weight gain

Transient alopecia

Hyperammonemia

Level decreased by enzyme-inducing drugsb
ZonisamideZonegran

Focal-onset

Tonic-clonic

200-400 mg/d; qd-bid50-68 h10-40 µg/mL

Sedation

Dizziness

Confusion

Headache

Psychosis

Anorexia

Renal stones

Hypohidrosis

Level decreased by enzyme-inducing drugsb

aExamples only; please refer to other sources for comprehensive listings of all potential drug-drug interactions.

bPhenytoin, carbamazepine, phenobarbital.

cExtended-release product available.