DRUG
(USUAL DOSE)
Carbamazepine
Adults: 600-1600 mg/day
Children: 20-40 mg/kg/day
EFFICACY FOR
COMPLEX PARTIAL
SEIZURES
Comparative efficacy:
1. Monotherapy- up to
80% effective
TIME
OF
ONSET
SIDE EFFECTS
CONVENIENCE
DRUG
INTERACTIONS
COST
(MONTH)
Conventional dosage
form: TID
• autoinduction
• induces metabolism
-warfarin
-other AEDs
-oral contraceptives
•  carbamazepine
-phenytoin
-barbiturates
•  carbamazepine
-cimetidine
-erythromycin
-isoniazid
-valproate
< $ 20
DOSEDEPENDENT
IDIOSYNCRATIC
nausea, headache,
dizziness, diplopia,
lethargy, leukopenia,
hyponatremia
rash, agranulocytosis,
aplastic anemia
(rare), hepatotoxicity
2-3 days
nausea, vomiting,
diarrhea,  appetite,
 weight, postural
tremor, (hepatitis),
thinning of hair,
drowsiness,
personality changes,
hyperammonemia
thrombocytopenia,
hepatotoxicity (esp.
children < 2 y.o.),
pancreatitis, bone
marrow depression
TID-QID
• inhibits metabolism
-barbiturates
-carbamazepineepoxide
•  valproate
-barbiturates
-carbamazepine
-phenytoin
•  free valproate
-salicylate
$20 (acid)
$>100
(divalproex)
5 days
(maximal
effects
take up to
30 days)
drowsiness, ataxia,
nystagmus,
sedation, dizziness,
diplopia,
 concentration,
folate/vitamin D
deficiency,
osteomalacia,
(hirsutism), (gingival
hypertrophy), coarse
facial features,
peripheral
neuropathy
rashes, bone marrow
depression,
hepatoxicity (rare),
lymphadenopathy
(rare)
Adults: DAILY-BID
Children: DAILY-TID
• induces metabolism
-quinidine
-dexamethasone
-oral contraceptives
-folic acid
-most AEDs
(valproate,
primidone,
carbamazepine)
-bishydrocoumarin
•  phenytoin
-disulfuram,
antimetabolites
-INH
-chloramphenicol
--cimetidine
-ethanol
•  phenytoin (free)
-ASA
< $20
8-16 days
sedation,  learning
ability, tiredness,
 attention,
depression
rash, bone marrow
depression,
hyperactivity in
children
Adult: DAILY-BID
Children: BID
• induces metabolism
-AEDs
-oral contraceptives
-quinidine
•  phenobarbital
-valproate
< $20
2-4 days
Slow release: BID
NEJM 1985;313:145-51
carbamazepine more
efficacious than
phenobarbital @ 1-3 yrs
follow-up
Valproate
15-60 mg/kg/day
NEJM 1992;327:765-71
carbamazepine more
efficacious than valproate
@ 12 months (in newly
diagnosed patients)
2. Polytherapy only gains
another 5-10% seizurefree
3. 10-15% of patients will
be refractory
Phenytoin
Adult: 200-500 mg/day
Children: 5-8 mg/kg/day
Phenobarbital
Adults: 1-4 mg/kg/day
Children: 4-5 mg/kg/day
DRUG
(USUAL DOSE)
Primidone
Adults: 500-1000 mg/day
Children: 10-20 mg/kg/day
Clonazepam
Adults:
1.5 - 10 mg/day (in
2-3 divided doses)
Initiate at
1.5 mg/day and
increase by 0.5 - 1.0
mg every 3 days.
Children: 0.01 - 0.03 mg/kg
daily in 2-3
divided doses,
increase to a
maximum of 0.2
mg/kg daily.
EFFICACY FOR
COMPLEX PARTIAL
SEIZURES
TIME
OF
ONSET
SIDE EFFECTS
CONVENIENCE
DRUG
INTERACTIONS
COST
(MONTH)
DOSEDEPENDENT
IDIOSYNCRATIC
2-3 days
(maximal
effects
take up to
2 wks)
sedation, ataxia, GI,
cognitive effects,
hyperactivity in
children, impotence,
folate deficiency,
vitamin D deficiency
bone marrow
depression
Adults: BID-TID
Children: TID-QID
• induces metabolism
-AEDs
-quinidine
-tricyclics
-corticosteroids
-chlorpromazine
-furosemide
•  primidone
-valproate
< $20
2-3 days
(maximal
effects in
2 weeks)
sedation, ataxia,
behavioural
problems in children,
bronchial
hypersecretions,
hypersalivation
bone marrow
depression (anemia,
leukopenia,
thrombocytopenia)
BID-TID
• Effect of
clonazepam on:
< $20
• levodopa 
• digoxin 
•  clonazepam by
phenytoin
DRUGS
(USUAL DOSE)
Vigabatrin
Adult: 2-4 g/day
Children (wt-specific):
(e.g. 35kg, 1.5-3 g/day)
Gabapentin
Adult: 900-2400 mg/day
Children (4-12): 15-20
mg/kg/day
Lamotrigine
Adult:
with valproate: 50-100 mg/day
with inducers: 200-500 mg/day
alone: 50-200 mg/day
Children:
with valproate: 1-5 mg/kg
with inducers: 5-15 mg/kg
alone: 2-8 mg/kg
Topiramate
Adult:*
200-400 mg/day
(2 divided doses)
Initiate at 50 mg qhs
and increase weekly
by 50 mg/day (in 2
divided doses) to
effect.
Children: approved for use in
children 2-16 years.
Dosage reduction required
in renal disease patients.
Fosphenytoin (Cerebyx - PD)
Adult :
LD: 10-20 Phenytoin
Equivalents (PE)/kg
IV (not to exceed
150mg PE/min)
MD: 4-6 mg
PE/kg/day
EFFICACY FOR
COMPLEX PARTIAL
SEIZURES
(BGH #10)
SIDE EFFECTS
CONVENIENCE
DRUG
INTERACTIONS
COST/MONTH
 50%  in seizure
frequency in 50% of
patients when used as
adjunct therapy
maximal
doses
achieved
in 1-2
wks
somnolence (12%), fatigue (9%), wt gain (5%),
headache (4%), ataxia (2%), (microvaculization
of white matter of brain of rats), long-term sideeffects, ophthalmalogical abnormalities (optic
atrophy, visual field constriction, etc.)
DAILY-BID
(FC-tablets)
• none
• ( phenytoin after
3-4 weeks?)
$113-226
Sabril®
- Marion Merrel
Dow
 50%  in seizure
frequency in 26% of
patients when used as
adjunct therapy
maximal
doses
achieved
in 1-2
wks
somnolence (5%), dizziness (20%), ataxia
(17%), fatigue (15%)
Three divided doses
daily (capsules)
• none
• dose-dependent
absorption
• antacids 
absorption by 25%
$65->194
Neurontin®
- Parke-Davis
 50%  in seizure
frequency in 18-69% when
used as adjunct therapy.
Lancet 1995 345:476-9
maximal
doses
achieved
in 2-4
wks
dizziness (15-40%), ataxia (36%), diplopia
(14%), nausea (29%)
rash (dose-related)
DAILY-BID
(scored tablet)
•  lamotrigine
-inducers
•  lamotrigine
-valproate
• carbamazepineepoxide  levels?
$22-176
Lamictal®
- Borroughs
Wellcome
50%  in seizure
frequency in 44-57% when
used as adjunct therapy.
Neurology 2001; 56(Suppl
3): A332
Topiramate comparable to
carbamazepine and
valproate in newly
diagnosed patients with
partial seizures
maximal
doses
achieved
in 2-4
weeks
somnolence (18%), dizziness (15 %),
ataxia (15 %), headache (17%)
paresthesia (15%), psychomotor slowing (6%),
speech-related problems, mood changes
(irritability, depression), rarely kidney stones
(1.5%), weight loss, acute myopia (decreased
visual acuity, ocular pain, redness) and
secondary angle closure glaucoma.
BID (available as 25,
100 and 200 mg
tablets)
• drugs which 
topiramate
concentrations
• phenytoin
• carbamazepine
• (valproic acid)
• effect of topiramate
on other drugs
• valproate 
• digoxin 
$120-190
Topamax®
- JanssenOrtho
Restricted to use as an
alternative to IV phenytoin
For status epilepticus
Converts
to
phenytoi
n
Identical to phenytoin except: increased
frequency of paresthesias and pruritis (not
usually at the infusion site).
Daily infusion
(ampoules)
Caution when
administered with
drugs highly bound to
albumin.
$17.64 per
amp
(100mg/2ml
amp)
Lamotrigine comparable to
carbamazepine in newly
diagnosed patients with
partial seizures
For short
term use
only
Children: safety has not been
established
Marijuana
TIME OF
ONSET
Category 2 of Marijuana
Medical Access
Regulations (July 30th,
2001)
Interacting drugs
identical to phenytoin