Drugs For Epilepsy

Treatment Guidelines
from The Medical Letter

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Volume 11 (Issue 126) February 2013
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Tables
1. Drugs of Choice
2. Some Antiepileptic Drugs
Page 9
Pages 10-11
Drugs for Epilepsy

Treatment of epilepsy should begin with a single
drug, increasing the dosage gradually until seizures
are controlled or adverse effects become unacceptable. If seizures persist, expert clinicians generally
prescribe at least one and sometimes a second alternative drug as monotherapy before considering use of
two drugs at the same time. When used for the appropriate seizure type, antiepileptic drugs are roughly
equivalent in efficacy. The choice of drug is usually
based on factors such as ease of use, adverse effects,
interactions with other drugs, presence of comorbid
conditions and cost.1
Controlled trials are difficult to conduct in patients
with epilepsy; use of a placebo would be unethical,
and patients whose seizures are controlled by one
medication are understandably reluctant to be randomized to another. Newer antiepileptic drugs (AEDs) are
usually initially approved by the FDA only as adjunctive therapy for partial seizures, but many may also be
effective for other types of seizures and as monotherapy, and are commonly used for these additional indications without FDA approval.
CARBAMAZEPINE Carbamazepine (Tegretol,
and generics) is an older AED with a broad indication
for use as an anticonvulsant. It is particularly effective
for treatment of partial and secondarily generalized
tonic-clonic seizures, but may make absence or
myoclonic seizures worse. Carbamazepine induces its
own metabolism; serum concentrations often fall after
a few weeks of treatment. Storing carbamazepine
tablets (both brand and generic) in humid conditions
can cause concretion of the tablets, resulting in poor
bioavailability and therapeutic failure.
Other Uses Carbamazepine is also used for bipolar
disorder and for treatment of pain due to trigeminal
neuralgia.
Table 1. Drugs of Choice1

Partial, Including Secondarily Generalized Seizures
Drugs of Choice:
Lamotrigine
Carbamazepine
Levetiracetam
Oxcarbazepine
Some Alternatives:
Topiramate
Valproate
Gabapentin
Zonisamide
Phenytoin
Pregabalin
Lacosamide
Ezogabine
Primary Generalized Tonic-Clonic Seizures

Drugs of Choice:
Valproate
Lamotrigine
Levetiracetam
Some Alternatives:
Topiramate
Zonisamide
Phenytoin
Absence Seizures
Drugs of Choice:
Ethosuximide
Valproate
Alternatives:
Lamotrigine
Clonazepam
Zonisamide
Levetiracetam
Atypical Absence, Myoclonic, Atonic Seizures

Drugs of Choice:
Valproate
Lamotrigine
Levetiracetam
Alternatives:
Topiramate
Zonisamide
Clonazepam
Felbamate
Clobazam
Rufinamide
1.Some of the drugs listed here have not been approved for such use
by the FDA. Approved indications are included in the text.
Adverse Effects Carbamazepine can cause drowsiness, blurred vision, diplopia, headache, dizziness,
ataxia, nausea and vomiting. Its cognitive effects can
interfere with learning. Use of an extended-release
formulation has been associated with fewer CNS
adverse effects.
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Drugs for Epilepsy

Table 2. Some Antiepileptic Drugs
Usual Adult
Daily Dosage1
Cost2
Drug
Oral Formulations
Carbamazepine generic
Tegretol (Novartis)
extended release generic
200 mg tabs; 100 mg chewable

tabs; 100 mg/5 mL susp
100, 200 mg ER caps and tabs;
300 mg ER caps, 400 mg ER tabs
100, 200, 400 mg ER tabs
100, 200, 300 mg ER caps
800-1600 mg
in 2 or 3 doses3
800-1600 mg in
2 doses3
Clobazam Onfi (Lundbeck)
5, 10, 20 mg tabs
20-40 mg in 1 or 2 doses
375.00
Clonazepam generic
0.5, 1, 2 mg tabs; 0.125, 0.25,

0.5, 1, 2 mg disintegrating tabs
0.5, 1, 2 mg tabs
1.5-8 mg in 2 or 3 doses
3.82
Ethosuximide generic
Zarontin (Pfizer)
250 mg caps; 250 mg/5 mL syrup
750-1250 mg in 2 doses
85.96
154.68
Ezogabine Potiga (GSK/Valeant)
50, 200, 300, 400 mg tabs
594.00
Felbamate generic
Felbatol (Meda)
400, 600 mg tabs;

600 mg/5 mL susp
2400-3600 mg in 3 or 4 doses
518.87
704.38
Gabapentin generic
100, 300, 400 mg caps; 100,

300, 400, 600, 800 mg tabs;
250 mg/5 mL soln
100, 300, 400 mg caps;
600, 800 mg tabs;
250 mg/5 mL soln
1800-3600 mg in 3 doses
Lacosamide Vimpat (UCB)
50, 100, 150, 200 mg tabs;

10 mg/mL soln
439.61
Lamotrigine generic
2, 5, 25, 50, 100, 150, 200, 250 mg

tabs; 2, 5, 25 mg chewable tabs
25, 100, 150, 200 mg tabs;
2, 5, 25 mg chewable tabs; 25, 50,
100, 200 mg disintegrating tabs
25, 50, 100, 200, 250, 300 mg ER tabs
7.29
Tegretol XR
Carbatrol (Shire)
Klonopin (Genentech)
Neurontin (Pfizer)
Lamictal (GSK)
extended-release generic
Lamictal XR
$ 6.87
136.80
93.38
139.20
212.74
154.96
55.58
376.99
197.52
200-600 mg once daily
N.A.4
381.18
30.24
313.13
114.28
283.87
Levetiracetam generic
Keppra (UCB)
extended release generic
Keppra XR
250, 500, 750, 1000 mg tabs;

100 mg/mL soln
500, 750 mg ER tabs
1000-3000 mg in 2 doses
Oxcarbazepine generic
Trileptal (Novartis)
extended-release
Oxtellar XR (Supernus)
150, 300, 600 mg tabs;

300 mg/5 mL susp
1200-2400 mg in 2 doses
105.37
417.56
150, 300, 600 mg ER tabs
1200-2400 mg once daily
454.80
1000-3000 mg
once daily
1. Most AEDs are started at a low dose and slowly titrated over a period of weeks. The usual dosage may vary depending on whether the drug is
prescribed as adjunctive therapy or monotherapy, or is used concomitantly with one or more interacting drugs. Dosage may also need to be
adjusted for renal or hepatic impairment.
2. Wholesale acquisition cost (WAC) for 30 days treatment at the lowest usual dosage. $ource Monthly (Selected from FDB MedKnowledge)
January 5, 2013. Reprinted with permission by FDB, Inc. All rights reserved. 2012. www.fdbhealth.com/policies/drug-pricing-policy/. Actual retail
prices may be higher.
3. Measurement of serum concentrations may be useful to guide therapy. Some usual therapeutic serum concentrations are: carbamazepine 4-12
mcg/mL, phenobarbital 10-40 mcg/mL, phenytoin 10-20 mcg/mL, valproate 50-100 mcg/mL. Some patients achieve complete seizure control at
lower concentrations, and occasional patients need higher concentrations.
Mild leukopenia and hyponatremia are fairly common. With high doses of the drug, thrombocytopenia
can occur, but it is usually reversible if the drug is
discontinued. Aplastic anemia, agranulocytosis, cardiac toxicity, aseptic meningitis, intractable diarrhea
and hepatitis are rare. Circulating concentrations of
thyroid hormones may be reduced even though TSH
remains normal. Abnormal color perception can
occur rarely.
10
Carbamazepine can cause rash, particularly with high

starting doses or rapid dose escalation. Severe reactions, such as Stevens-Johnson syndrome (SJS), are
rare. The risk of carbamazepine induced SJS is significantly higher in patients with the human leukocyte
antigen (HLA)-B*1502 allele, which occurs almost
exclusively in Asians.2,3 The FDA has recommended
that Asian patients, who have a ten-fold higher incidence of carbamazepine-induced SJS compared to
Treatment Guidelines from The Medical Letter Vol. 11 ( Issue 126) February 2013
Drugs for Epilepsy

Table 2. Some Antiepileptic Drugs (continued)
Drug
Oral Formulations
Usual Adult
Daily Dosage1
Perampanel Fycompa (Eisai)
2, 4, 6, 8, 10, 12 mg tabs
4-12 mg in 1 dose
Phenobarbital generic
15, 30, 60, 100 mg tabs;

20 mg/5 mL elixir
90-150 mg in 2 or 3
Phenytoin generic
30, 100, 200, 300 mg caps;

125 mg/5 mL susp; 50 mg
chewable tabs
300-400 mg
in 1-3 doses3,5
Dilantin (Pfizer)
Dilantin-125
Dilantin Infatabs
Pregabalin generic
30, 100 mg caps

125 mg/5 mL susp
50 mg chewable tabs
25, 50, 75, 100, 150, 200, 225,
300 mg caps
25, 50, 75, 100, 150, 200, 225,
300 mg caps; 20 mg/mL soln
Lyrica (Pfizer)
Cost2
N.A.4
doses3
$15.84
28.75
46.85
N.A.4
150-600 mg
in 2 or 3 doses
183.49
Primidone generic
Mysoline (Valeant)
50, 250 mg tabs
750-1250 mg in 3
or 4 doses
Rufinamide Banzel (Eisai)
200, 400 mg tabs; 40 mg/mL susp
3200 mg in 2 doses
2040.20
Tiagabine generic
Gabitril (Cephalon)
2, 4 mg tabs
2, 4, 12, 16 mg tabs
32-56 mg in
2-4 doses
1285.60
628.00
Topiramate generic
Topamax (Janssen)
Topamax Sprinkle
15, 25 mg caps; 25, 50 100, 200 mg tabs

25, 50, 100, 200 mg tabs
15, 25 mg caps
200-400 mg in
2 doses
16.28
512.75
860.36
250 mg caps; 250 mg/5 mL syrup
1000-3000 mg
in 2-3 doses3
44.40
367.90
245.88
38.99
Valproate
Valproic acid generic
Depakene (Abbott)
Stavzor (Noven)
Divalproex sodium generic
Depakote (Abbott)
Depakote Sprinkle
extended-release generic
Depakote ER
125, 250, 500 mg delayed-release caps

125, 250, 500 mg delayed-release tabs;
125 mg caps
125, 250, 500 mg delayed-release tabs
125 mg delayed-release caps
250, 500 mg ER tabs
1000-3000 mg in
2-3 doses3
1250-3500 mg once daily3
Vigabatran Sabril (Lundbeck)
500 mg tabs; 500 mg powder

for soln (50 mg/mL)
3 g in 2 doses
Zonisamide generic
Zonegran (Eisai)
25, 50, 100 mg caps
100-400 mg in 1 or 2 doses
34.90
663.63
237.74
250.27
62.51
264.84
8115.98
24.27
133.80
4. Cost not yet available.

5. Adjustments in maintenance dosage above 300 mg/day for adults should usually be made in 25- or 30-mg increments because metabolism
becomes saturated.
other ethnic groups, be tested for this allele before

starting the drug.
Drug Interactions Carbamazepine is a strong inducer of multiple hepatic enzymes; it can reduce serum
concentrations and possibly the effectiveness of many
other drugs, including other AEDs. Carbamazepine is
metabolized by CYP3A4; inducers or inhibitors of the
enzyme can decrease or increase carbamazepine concentrations.
CLOBAZAM Clobazam (Onfi) is a benzodiazepine FDA-approved only for use as adjunctive
treatment for seizures associated with the LennoxGastaut syndrome in patients 2 years old.4 It has been
widely used for years in Canada and other countries for
the treatment of many types of seizures.
Adverse Effects The most frequent adverse effects

of clobazam are somnolence, pyrexia, lethargy, drooling, and constipation. As with other benzodiazepines,
anterograde amnesia, ataxia, and withdrawal symptoms and seizures can occur if the drug is stopped
abruptly. Clobazam is classified as a schedule IV controlled substance; tolerance, dependence and abuse
have been reported.
Drug Interactions Clobazam inhibits CYP2D6;
drugs that are metabolized by CYP2D6, such as fluoxetine (Prozac, and generics), may require a reduction in dosage if taken concurrently. It is also a mild
inducer of CYP3A4. Clobazam is metabolized to its
active metabolite mainly by CYP3A4, which is further metabolized by CYP2C19. Concomitant use of
drugs that inhibit CYP2C19, such as fluconazole
11
Drugs for Epilepsy
(Diflucan, and generics) or omeprazole (Prilosec, and

generics), can increase serum concentrations of the
active metabolite.
CLONAZEPAM Clonazepam (Klonopin, and
generics) is a benzodiazepine approved to treat
Lennox-Gastaut syndrome, myoclonic and atonic
seizures. It is also used to treat absence seizures resistant to treatment with other antiepileptic drugs. It is
generally less effective for absence seizures than ethosuximide or valproate, and development of tolerance to
its effects is common.
Other Uses Clonazepam is also approved by the
FDA for treatment of panic disorder and is used to treat
other types of anxiety disorders.
Adverse effects Clonazepam can cause drowsiness,
ataxia and behavior disorders. Withdrawal symptoms
including seizures can occur after abrupt discontinuation.
Drug Interactions Clonazepam is partially metabolized by CYP3A4; inducers of this enzyme, such as
carbamazepine and phenytoin, may reduce serum concentrations of clonazepam and strong inhibitors, such
as clarithromycin (Biaxin, and generics), can increase
them.
impairment, blurred vision, asthenia and aphasia can

occur. Weight gain (1.2-2.7 kg), urinary retention,
sometimes requiring catheterization, psychotic symptoms and hallucinations have been reported. Like other
recently approved AEDs, it is a schedule V controlled
substance because of reports of euphoria.
Drug Interactions Carbamazepine and phenytoin
can decrease ezogabine serum concentrations; an
increase in the dosage of ezogabine may be needed.
Ezogabine decreases renal clearance of digoxin. QT
interval prolongation has been reported with ezogabine; monitoring is recommended in patients also
taking other drugs that can prolong the QT interval.
GABAPENTIN Gabapentin (Neurontin, and
generics) is FDA-approved for adjunctive treatment of
partial seizures with and without secondary generalization in adults and children age 3 years old and is
also effective, but not FDA-approved, as monotherapy
for these same types of seizures. Like carbamazepine,
gabapentin can exacerbate myoclonic seizures.
Other Uses Gabapentin is also FDA-approved for
treatment of neuropathic pain, and a prodrug,
gabapentin encarbil (Horizant), is approved for restless
legs syndrome.7
ETHOSUXIMIDE Ethosuximide (Zarontin, and

generics) is approved for treatment of absence seizures
and is usually well tolerated. Its elimination half-life is
about 60 hours in adults, but only about 30 hours in
children.5 It is not effective in generalized tonic-clonic
or partial seizures.
Adverse Effects Gabapentin can cause somnolence,

dizziness, ataxia, fatigue, nystagmus, blurred vision
and confusion. Edema, weight gain and movement disorders have been reported. Behavioral changes have
occurred in children, especially those with underlying
behavioral or developmental problems.
Adverse Effects Ethosuximide can cause nausea,

vomiting, lethargy, hiccups, headache and behavorial
changes. Psychotic behavior can occur. Hematologic
abnormalities, erythema multiforme, Stevens-Johnson
syndrome and systemic lupus erythematosus (SLE)
have been reported.
Drug Interactions Unlike some other AEDs,

gabapentin does not induce or inhibit hepatic microsomal enzymes.
Drug Interactions Ethosuximide is partially metabolized by CYP3A4; inducers of CYP3A4 may

decrease serum concentrations of the drug and strong
inhibitors can increase them.
LACOSAMIDE Oral lacosamide (Vimpat) is

FDA-approved as add-on therapy for adults with partial onset seizures.8 Lacosamide is also available in an
IV formulation for short-term use. The drug works by
slowly inactivating voltage dependent sodium channels.
EZOGABINE Ezogabine (Potiga) is FDAapproved for adjunctive treatment of partial onset

seizures in adults.6 It is available in Europe as retigabine (Trobalt). Ezogabine acts through potassium
channel activation.

of oral lacosamide are dizziness, headache, nausea,
vomiting, fatigue, ataxia, diplopia, somnolence and
tremor. Like other recently approved AEDs,
lacosamide has been designated as a schedule V controlled substance because of reports of euphoria.

of ezogabine are dizziness, somnolence and fatigue.
Confusion, tremor, abnormal coordination, memory
Drug Interactions Lacosamide is a substrate and

inhibitor of CYP2C19, but no clinically significant
drug interactions have been reported. A small, dose-
12
Drugs for Epilepsy
dependent increase in the PR interval has been reported during treatment with lacosamide; caution is
advised in patients with cardiac conduction problems
and in those taking other drugs that may prolong the
PR interval such as beta blockers or calcium channel
blockers.
adolescents 12 years old with myoclonic seizures. It

is commonly used as monotherapy for partial onset
and generalized seizures and may also be effective in
children with seizures of Lennox-Gastaut syndrome,
and in absence seizures.11,12 Levetiracetam is also
available in an IV formulation.
LAMOTRIGINE Lamotrigine (Lamictal, and

generics) is FDA-approved for adjunctive therapy in
patients 2 years old with partial seizures, primary
generalized tonic-clonic seizures or generalized
seizures of Lennox-Gastaut syndrome. It is also
approved as monotherapy as a substitute for carbamazepine, phenytoin, phenobarbital, primidone or valproate in patients 16 years old with partial seizures.
Adverse Effects Dizziness, somnolence and weakness occur commonly. Behavioral changes such as
agitation, hostility and irritability, hallucinations and
psychosis have also occurred, especially in patients
with underlying psychiatric diagnoses. Serious dermatological reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, and coordination difficulties have been reported. Mild decreases in
hematocrit and white blood cell count, which do not
require discontinuation of the drug, occur rarely.
Levetiracetam appears to have a low incidence of
adverse cognitive effects.
In elderly patients with newly diagnosed partial or generalized seizures, lamotrigine has been as effective as
carbamazepine and better tolerated.9 Some reports
suggest lamotrigine can make myoclonus worse, particularly in severe myoclonic epilepsy of infancy.
Lamotrigine may be less effective than ethosuximide
or valproic acid for absence seizures in children, but
some clinicians use it as first-line treatment because of
its tolerability.10
Other Uses Lamotrigine can improve depression in
some patients with epilepsy and is FDA-approved for
maintenance treatment of bipolar disorder.
Adverse Effects The most common adverse effects
of lamotrigine have been dizziness, ataxia, somnolence, headache, diplopia, nausea, vomiting, rash,
insomnia and incoordination. Acute hepatitis has been
reported. Life-threatening rashes including StevensJohnson syndrome have occurred rarely, usually during the first 2 months of use. The risk may be increased
by high starting doses, rapid increases in dosage or coadministration with valproate. The manufacturer recommends discontinuing lamotrigine at the first sign of
rash. Lamotrigine causes fewer adverse cognitive
effects than carbamazepine or topiramate. Cases of
aseptic meningitis have been reported in pediatric and
adult patients taking lamotrigine.
Drug Interactions Lamotrigine does not induce or
inhibit CYP450 enzymes. Enzyme-inducing drugs,
such as carbamazepine, reduce lamotrigine concentrations. Valproate increases lamotrigine concentrations
more than 2-fold.
LEVETIRACETAM Oral levetiracetam (Keppra,
and generics) is FDA-approved as adjunctive therapy
for adults and children 1 month old with partial
seizures, adults and children 6 years old with primary generalized tonic-clonic seizures, and adults and
Drug Interactions Levetiracetam is not an inhibitor

or substrate of CYP450 enzymes. No clinically significant drug-drug interactions have been reported.
OXCARBAZEPINE Oxcarbazepine (Trileptal,
and generics) is chemically similar to carbamazepine
but causes less induction of hepatic enzymes and
unlike carbamazepine, oxcarbazepine does not induce
its own metabolism. It is approved by the FDA for
treatment of partial seizures as monotherapy or
adjunctive therapy in adults and children 4 years old,
and as adjunctive therapy in children 2 years old.
Like carbamazepine, oxcarbazepine is also effective in
secondarily generalized seizures, but may make
myoclonic and absence seizures worse. Oxcarbazepine
has been as effective as phenytoin, carbamazepine or
valproate in treatment of partial seizures, and may be
better tolerated. Most of its clinical effect is due to the
10-monohydroxy metabolite (MHD), which has a halflife of 8-10 hours.
Other Uses Oxcarbazepine is used off-label for
treatment of bipolar disorder.
Adverse Effects Common adverse effects of oxcarbazepine are somnolence, dizziness, diplopia, ataxia,
nausea and vomiting. Taking the extended-release formulation with food increases peak concentrations of
the drug and the likelihood of adverse effects. StevensJohnson syndrome and toxic epidermal necrolysis
have occurred, and multi-organ hypersensitivity reactions have been reported. Cross-reactivity with carbamazepine hypersensitivity occurs in 20-30% of
patients. Hyponatremia is more common with oxcarbazepine than with carbamazepine.
13
Drugs for Epilepsy
Drug Interactions Oxcarbazepine induces

CYP3A4/5 and inhibits CYP2C19. It can increase
phenytoin levels by up to 40%. Levels of the active
metabolite are reduced in the presence of enzymeinducing drugs such as phenobarbital or phenytoin.
PERAMPANEL Perampanel (Fycompa) was
recently approved by the FDA as adjunctive treatment
for partial-onset seizures in patients 12 years old,13-15
but has not yet been marketed in the US. It acts as an
antagonist at the AMPA glutamate receptor.
of perampanel are dizziness and drowsiness. Weight
gain, mood change, ataxia, dysarthria, diplopia, vertigo, nausea and fatigue have also been reported. Serious
psychiatric and behavioral reactions, including irritability, aggression, anger and anxiety, can occur.
Drug Interactions Perampanel is partially metabolized by CYP3A. Inhibitors of the enzyme may
increase serum concentrations of perampanel and
inducers may decrease them.
PHENYTOIN Phenytoin (Dilantin, and generics)
is as effective as carbamazepine for treatment of partial and secondarily generalized tonic-clonic seizures,
but is no longer considered a drug of first choice
because of its complicated pharmacokinetics, adverse
effect profile and frequent drug-drug interactions.
Different formulations of phenytoin may not be bioequivalent, especially at higher doses. Fosphenytoin
(Cerebyx, and generics) is a water-soluble prodrug of
phenytoin available for IV and IM use.
Adverse Effects Nystagmus may occur with therapeutic serum concentrations of phenytoin and is
usually present at higher concentrations. Drowsiness,
ataxia and diplopia are more likely to occur at total
serum concentrations >20 mcg/mL, but can also occur
at lower levels, particularly in patients with low
serum albumin levels and in the elderly. Phenytoin
may interfere with cognitive function related to
learning. Cerebellar atrophy has been reported with
long-term use and after acute intoxication. Gingival
hyperplasia, coarsening of facial features and hirsutism can also occur.
A morbilliform or scarlatiniform rash may occur, usually in the first four weeks of treatment, sometimes
with hepatitis, fever and lymphadenopathy; rarely it
progresses to exfoliative dermatitis or StevensJohnson syndrome. Asian patients who test positive for
HLA-B*1502 may have an increased risk of serious
skin reactions with phenytoin or fosphenytoin. Patients
who develop hypersensitivity reactions to phenytoin
14
are often susceptible to similar reactions with carbamazepine and phenobarbital.

Less common adverse effects include megaloblastic
anemia, a lupus-like syndrome, peripheral neuropathy,
nephritis, and hepatitis leading rarely to fatal hepatic
necrosis. Osteopenia can occur with long-term use.
Serum folic acid, thyroxine and vitamin K concentrations may decrease with long-term therapy.
Fosphenytoin is less likely to cause soft tissue injury
than older IV formulations, but at rapid infusion rates it
can cause transient paresthesias and pruritus.
Drug Interactions Phenytoin is metabolized by
CYP2C9 and 2C19; inducers and inhibitors of these
enzymes may affect its serum concentrations. Like carbamazepine, phenytoin is a strong enzyme inducer; it
can reduce serum concentrations and possibly the
effectiveness of many other drugs, including other
AEDs. It may initially cause an increase in warfarin
response followed by a reduction in its anticoagulant
effect.
PREGABALIN Pregabalin (Lyrica, and generics)
is FDA-approved for adjunctive treatment of partial
seizures in adults.16 Its mechanism of action is similar
to that of gabapentin, suggesting it will not be useful in
the treatment of myoclonic seizures.
Other Uses Pregabalin is also FDA-approved for
treatment of neuropathic pain and fibromyalgia;17 it is
approved in Europe for treatment of generalized anxiety disorder.
Adverse Effects Pregabalin causes somnolence,
dizziness, ataxia, weight gain, dry mouth, blurred
vision, peripheral edema and confusion. Newly developed myoclonus has been reported in patients with
epilepsy taking pregabalin. Pregabalin, like many new
antiepileptic drugs, is a schedule V controlled substance due to reports of euphoria.
Drug Interactions Like gabapentin, pregabalin has
no significant drug-drug interactions.
RUFINAMIDE Rufinamide (Banzel) is FDAapproved for adjunctive treatment of Lennox-Gastaut
syndrome in patients 4 years old.18 It appears to be
particularly effective for treatment of atonic seizures.19
There is also evidence that adjunctive treatment with
rufinamide reduces the frequency of partial seizures,
but it is not FDA-approved for such use.20
Adverse Effects The most frequent adverse effects of
rufinamide are somnolence and vomiting. Headache,
dizziness, fatigue, nausea, diplopia and tremor have
Drugs for Epilepsy
been reported. Rufinamide can shorten the QT interval

in some patients; it should not be prescribed to patients
with short QT syndrome or to those taking other drugs
known to shorten the QT interval (such as digoxin and
magnesium).
Drug Interactions Rufinamide is a mild inducer of
CYP3A4. It has been shown to reduce ethinyl estradiol, norethindrone and triazolam concentrations, and
could have a similar effect on other drugs metabolized
by CYP3A4.
TOPIRAMATE Topiramate (Topamax, and generics) is approved for partial and primary generalized
tonic-clonic seizures as monotherapy or adjunctive
therapy in adults and children 2 years old. It is also
approved as adjunctive therapy for children 2 years
old with Lennox-Gastaut syndrome and is effective in
atonic seizures in children.
Other Uses Topiramate is also FDA-approved for
migraine prophylaxis and for chronic weight management as part of a fixed-dose combination with phentermine (Qsymia).21,22
of topiramate are drowsiness, dizziness, headache and
ataxia. Nervousness, confusion, paresthesias, weight
loss and diplopia can occur. Psychomotor slowing,
word-finding difficulty, impaired concentration, and
interference with memory are common, particularly
with rapid dose escalation and higher maintenance
doses, and may require dosage reduction or stopping
the drug. Acute myopia associated with secondary
angle closure glaucoma, which is infrequent but
severe, typically occurs within one month of starting
treatment. Liver failure, oligohidrosis, hyperthermia
and heat stroke have been reported. Renal stones have
occurred due to metabolic acidosis caused by inhibition of carbonic anhydrase.
adjunctive therapy for complex partial seizures and

absence seizures and as adjunctive therapy for multiple
seizure types that involve absence. Because it is effective and usually well tolerated, valproate is widely
used for myoclonic and atonic seizures and is considered the drug of choice for primary generalized tonicclonic seizures. It is highly effective in treating photosensitive epilepsy and juvenile myoclonic epilepsy.
Valproate is less effective than carbamazepine in controlling complex partial seizures, but equally effective
in controlling secondarily generalized seizures. A
once-daily extended-release formulation (Depakote
ER) is as effective as Depakote. It is not bioequivalent
to older formulations, so when switching from valproate capsules or delayed-release tablets to Depakote
ER, the daily dosage should be increased by 8-20%.
Valproate is also available in an IV formulation
(Depacon).
Other Uses Valproate is FDA-approved for migraine
prophylaxis and bipolar disorder.
Adverse Effects Drowsiness due to valproate is usually mild and transient, and adverse cognitive effects
are generally minimal. Nausea and vomiting can be
minimized by using the enteric-coated formulation
(Depakote), by taking the drug with food, and by slow
titration to an optimal dose. Weight gain is common.
Use of valproate has been associated with polycystic
ovary syndrome, hyperinsulinemia, lipid abnormalities, hirsutism and menstrual disturbances in women,
and with increased serum androgen concentrations in
men. Dose-related tremor, transient hair thinning and
loss, decreased platelet function, and thrombocytopenia can also occur.
Drug Interactions Topiramate is a mild inducer of

CYP3A and an inhibitor of CYP2C19. It can increase
serum lithium levels, particularly at high doses.
Carbamazepine and phenytoin decrease topiramate
concentrations. Concomitant use of valproic acid and
topiramate has been associated with hyperammonemia
and hypothermia. Use of topiramate with other carbonic anhydrase inhibitors such as zonisamide or
acetazolamide could increase the severity of metabolic
acidosis.
Serious adverse effects of the drug are uncommon, but

fatal liver failure has occurred, particularly in children
<2 years old taking valproate in combination with
other AEDs and in patients with developmental delay
and metabolic disorders; liver failure has also been
reported in older children and adults taking valproate
alone. Valproate can interfere with conversion of
ammonia to urea. It can cause lethargy associated with
increased blood ammonia concentrations and fatal
hyperammonemic encephalopathy has occurred in
patients with genetic defects in urea metabolism; the
drug is contraindicated in these patients. Life-threatening pancreatitis, interstitial nephritis, reversible parkinsonism and edema requiring diuretics for control have
occurred rarely.
VALPROATE Valproic acid (Depakene, and

generics) and divalproex sodium (Depakote, and
generics) dissociate to valproate in the GI tract.
Valproate is approved by the FDA as monotherapy or
Drug Interactions Valproate has fewer drug interactions than carbamazepine or phenytoin. Enzyme inducing AEDs increase valproate clearance. Carbapenem
antibiotics, such as imipenem, also significantly
15
Drugs for Epilepsy
reduce valproate concentrations. Valproate is a weak

enzyme inhibitor; it can increase serum concentrations
of some other AEDs, including carbamazepine, phenytoin, phenobarbital, ethosuximide, lamotrigine and
rufinamide, and tricyclic antidepressants.
agranulocytosis have also been reported. Slow titration

and dosing with meals may decrease the incidence of
adverse effects. Zonisamide is a mild carbonic anhydrase inhibitor and can cause metabolic acidosis, which
increases the risk of symptomatic renal stones.
VIGABATRIN Vigabatrin (Sabril) is FDAapproved as monotherapy for infantile spasms and as

add-on therapy for complex partial seizures refractory
to several other AEDs.23 In the US, it is available only
through a restricted distribution program called
SHARE (Support, Help, and Resources for Epilepsy)
due to concerns about retinal toxicity and permanent
visual field loss. This program requires that prescribers
and pharmacists register, and that patients undergo
monitoring for visual field loss.
Drug Interactions Zonisamide is metabolized by

CYP3A4; drugs that induce or inhibit CYP3A4 could
affect serum concentrations of zonisamide. Zonisamide
does not inhibit the metabolism of drugs metabolized
by CYP450 enzymes. Use of zonisamde with other carbonic anhydrase inhibitors such as topiramate could
increase the risk of renal stone formation.
Adverse Effects The most serious adverse effect of

vigabatrin is concentric peripheral visual field deficit
(pVFD) which is potentially irreversible. Patients are
usually unaware of the visual field loss, particularly in its
initial mild phase. Evidence suggests that pVFD is rare
during the first 6 months of treatment; patients without a
good response to this therapy should be taken off the
drug within this time. Headache, fatigue, pain, balance
disorder, dizziness, somnolence, depression (including
suicidality), expressive language disorder, pruritus and
weight gain have also been reported.
Drug Interactions Vigabatrin is not significantly
metabolized. It can lower serum concentrations of
phenytoin by inducing CYP2C9, but it does not induce
other CYP450 enzymes.
ZONISAMIDE Zonisamide (Zonegran, and others) is FDA-approved for adjunctive treatment of partial seizures in adults with epilepsy. It appears to have
a broad spectrum of activity (infantile spasms,
myoclonic, generalized and atypical absence seizures),
and there is considerable experience worldwide with
its use in children, as monotherapy, and for other
seizure types.
Other Uses Zonisamide also appears to be effective
for migraine prophylaxis and for weight loss in obese
patients but is not approved by the FDA for these indications.24,25
Adverse Effects Adverse effects include somnolence, dizziness, confusion, anorexia, nausea, diarrhea,
weight loss, agitation, irritability and rash. Fatal
Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported. Oligohidrosis, hyperthermia
and heat stroke have occurred in children. Psychosis,
psychomotor slowing, word-finding difficulty and
impaired concentration can occur. Aplastic anemia and
16
OTHER DRUGS Felbamate (Felbatol) is

approved as monotherapy or adjunctive therapy of partial and secondarily generalized seizures, and for
adjunctive therapy of seizures associated with the
Lennox-Gastaut syndrome in patients who have failed
other drugs. There is an appreciable risk of aplastic anemia and hepatic failure, estimated at about 1:3000-5000
patients. Phenobarbital and primidone (Mysoline,
and others) are effective for partial and secondarily
generalized tonic-clonic seizures, but they have a higher incidence of sedation compared to other drugs.
Tiagabine (Gabitril) is approved only for adjunctive
treatment of partial seizures, and is associated with gastrointestinal and CNS adverse effects. Use in
nonepileptic patients (for bipolar disorder, anxiety and
neuropathic pain) has been associated with development of new-onset seizures and status epilepticus.26
Rectal administration of diazepam gel (Diastat
AcuDial) is approved for intermittent use in the treatment of increased seizure activity in patients taking
other antiepileptic drugs. When given rectally,
diazepam is rapidly and completely absorbed. Diastat
AcuDial is supplied as a prefilled syringe with either
10 mg (which can be used to deliver 5, 7.5 or 10 mg)
or 20 mg (which can be used to deliver 12.5, 15, 17.5
or 20 mg) for single-dose administration by the caregiver. At-home use of rectal diazepam in children may
help terminate seizure activity and reduce emergency
room visits.27
OTHER ISSUES Suicidality The FDA reported
in 2008 that a meta-analysis of data from placebo-controlled studies of 11 AEDs found an increased risk of
suicidal behavior and ideation in patients taking these
drugs: 0.43% of patients on AEDs (n=27,863) compared to 0.22% of those on placebo (n=16,029). The
overall incidence was extremely low, however, and its
clinical significance was questionable. The results of a
large cohort study among patients in the US suggest
that gabapentin, lamotrigine, oxcarbazepine and
tiagabine, compared with topiramate or carba-
Drugs for Epilepsy
mazepine, may increase the risk of suicidal acts.28

Another cohort study in the UK found that use of
AEDs in patients with epilepsy was not associated
with an increased risk of suicide-related events, but
patients with depression taking AEDs did have an
increased risk.29
Bone Density Prolonged use of antiepileptic drugs,
particularly those that result in enzyme induction
(phenytoin, carbamazepine, phenobarbital, primidone), may increase the risk of osteoporosis.
Valproate, which does not induce hepatic enzymes, has
also been associated with decreases in bone mineral
density.
AEDs and Oral Contraceptives Enzyme-inducing
AEDs such as carbamazepine, phenytoin, primidone,
and phenobarbital, and, to a lesser extent, felbamate,
topiramate, oxcarbazepine, rufinamide, clobazam and
perampanel, may decrease serum concentrations of
estrogens and/or progestins, possibly resulting in contraceptive failure.30 Use of vigabatrin has been associated with reduced ethinyl estradiol serum concentrations. Perampanel and lamotrigine have decreased levels of levonorgestrel. Levetiracetam and valproate do
not affect serum concentrations of oral contraceptives.
Oral contraceptives can reduce lamotrigine concentrations, which then transiently increase if the contraceptive includes a week of inactive tablets.
AEDs and Pregnancy AEDs should be used as
monotherapy at the lowest possible dose in pregnant women; the risk to offspring is generally considered to be less than the risk of seizures during
pregnancy.31
Most pregnant patients exposed to antiepileptic drugs
deliver normal infants, but fetal exposure to older
AEDs, particularly valproate and phenobarbital, can
cause congenital anomalies, including oral cleft and
cardiac, urinary tract and neural tube defects.32
Children exposed to valproate in utero have also been
reported to have lower IQs.33 Available data from pregnancy registries suggest that use of some newer AEDs
such as lamotrigine, levetiracetam, oxcarbazepine and
gabapentin is associated with low rates of major malformations.34 Topiramate appears to increase the risk
of oral cleft35 and has been associated with hypospadias in male infants.
Pregnancy itself tends to induce the metabolism of
AEDs, particularly lamotrigine; monitoring lamotrigine serum concentrations may improve seizure control.36 Use of an enzyme-inducing AED such as
phenytoin, phenobarbital, primidone or carbamazepine may cause hemorrhage in the newborn
infant due to vitamin K deficiency; vitamin K supplementation has been recommended for the mother in
the final month of pregnancy, but whether it reduces
the risk of hemorrhagic complications is unclear.
Newborns should receive vitamin K at delivery.37
Generic Substitution of Brand-Name Drugs
Generic versions of many antiepileptic drugs are now
available. In general, a generic drug offers a lower-cost
alternative that is roughly bioequivalent (pharmacokinetic parameters within 80-125%) to the brand-name
drug. A meta-analysis of randomized controlled trials
comparing use of brand-name and generic forms of
phenytoin, carbamazapine and valproate found no difference in seizure control.38 However, switching
between generic products could lead to significant differences in total and peak serum concentrations.39 If
possible, prescription refills should be from the same
manufacturer.
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
E Perucca and T Tomson. The pharmacological treatment of epilepsy in

adults. Lancet Neurol 2011; 10:446.
WH Chung et al. Medical genetics: a marker for Stevens-Johnson syndrome. Nature 2004; 428:486.
P Chen et al. Carbamazepine-induced toxic effects and HLA-B*1502
screening in Taiwan. N Engl J Med 2011; 364:1126.
Clobazam (Onfi) for Lennox-Gastaut Syndrome. Med Lett Drugs Ther
2012; 54:18.
EP Vining. Ethosuximide in childhood absence epilepsy - older and better. N Engl J Med 2010; 362:843.
Ezogabine (Potiga) for epilepsy. Med Lett Drugs Ther 2012; 54:65.
Gabapentin encarbil (Horizant) for restless legs syndrome. Med Lett
Drugs Ther 2011; 53:70.
Lacosamide for epilepsy. Med Lett Drugs Ther 2009; 51:50.
AJ Rowan et al. New onset geriatric epilepsy: a randomized study of
gabapentin, lamotrigine, and carbamazepine. Neurology 2005;
64:1868.
TA Glauser et al. Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy. N Engl J Med 2010; 362:790.
EC De Los Reyes. Levetiracetam in the treatment of Lennox-Gastaut
syndrome. Pediatric Neurol 2004; 30:254.
J Cavitt and M Privitera. Levetiracetam induces a rapid and sustained
reduction of generalized spike-wave and clinical absence. Arch Neurol
2004; 61:1604.
GL Krauss et al. Randomized phase III study 306: adjunctive perampanel for refractory partial-onset seizures. Neurology 2012; 78:1408.
JA French et al. Adjunctive perampanel for refractory partial-onset
seizures: randomized phase III study 304. Neurology 2012; 79:589.
JA French et al. Evaluation of adjunctive perampanel in patients with
refractory partial-onset seizures: Results of randomized global phase III
study 305. Epilepsia 2012 Aug 20 (epub).
Pregabalin (Lyrica) for neuropathic pain and epilepsy. Med Lett Drugs
Ther 2005; 47:75.
Pregabalin (Lyrica) for fibromyalgia. Med Lett Drugs Ther 2007;
49:77.
Rufinamide (Banzel) for epilepsy. Med Lett Drugs Ther 2009; 51:18.
G Kluger et al. Adjunctive rufinamide in Lennox-Gastaut syndrome: a
long-term, open-label extension study. Acta Neurol Scand 2010; 122:202.
V Biton et al. A randomized, double-blind, placebo-controlled, parallelgroup study of rufinamide as adjunctive therapy for refractory partialonset seizures. Epilepsia 2011; 52:234.
Topiramate (Topamax) for prevention of migraine. Med Lett Drugs
Ther 2005; 47:9.
17
Drugs for Epilepsy

22. Two new drugs for weight loss. Med Lett Drugs Ther 2012; 54:69.
23. Vigabatrin (Sabril) for epilepsy. Med Lett Drugs Ther 2010; 52:14.
24. SE Mohammadianenejad et al. Zonisamide versus topiramate in
migraine prophylaxis: a double-blind randomized clinical trial. Clin
Neuropharmacol 2011; 34:174.
25. KM Gadde et al. Zonisamide for weight reduction in obese adults: a 1year randomized controlled trial. Arch Intern Med 2012; 172:1557.
26. CM Flowers et al. Seizure activity and off-label use of tiagabine. N
Engl J Med 2006; 354:773.
27. C ODell et al. Rectal diazepam gel in the home management of
seizures in children. Pediatr Neurol 2005; 33:166.
28. E Patorno et al. Anticonvulsant medications and the risk of suicide,
attempted suicide, or violent death. JAMA 2010; 303:1401.
29. A Arana et al. Suicide-related events in patients treated with antiepileptic drugs. N Engl J Med 2010; 363:542.
30. DS Reddy. Clinical pharmacokinetic interactions between antiepileptic
drugs and hormonal contraceptives. Expert Rev Clin Pharmacol 2010;
3:183.
31. CL Harden et al. Practice parameter update: management issues for
women with epilepsyfocus on pregnancy (an evidence-based review):
teratogenesis and perinatal outcomes: report of the Quality Standards
Subcommittee and Therapeutics and Technology Assessment
Subcommittee of the American Academy of Neurology and American
Epilepsy Society. Neurology 2009; 73:133.
32. J Jentink et al. Valproic acid monotherapy in pregnancy and major congenital malformations. N Engl J Med 2010; 362:2185.
33. KJ Meador et al. Effects of fetal antiepileptic drug exposure: outcomes
at age 4.5 years. Neurology 2012; 78:1207.
34. D Mlgaard-Nielsen and A Hviid. Newer-generation antiepileptic
drugs and the risk of major birth defects. JAMA 2011; 305:1996.
35. S Hernndez-Diaz et al. Comparative safety of antiepileptic drugs during pregnancy. Neurology 2012; 78:1692.
36. PB Pennell et al. Lamotrigine in pregnancy: clearance, therapeutic
drug monitoring, and seizure frequency. Neurology 2008; 70:2130.
37. CL Harden et al. Practice parameter update: management issues for
women with epilepsyfocus on pregnancy (an evidence-based review):
vitamin K, folic acid, blood levels, and breastfeeding: report of the
Quality Standards Subcommittee and Therapeutics and Technology
Assessment Subcommittee of the American Academy of Neurology
and American Epilepsy Society. Neurology 2009; 73:142.
38. AS Kesselheim et al. Seizure outcomes following the use of generic
versus brand-name antiepileptic drugs: a systematic review and metaanalysis. Drugs 2010; 70:605.
39. GL Krauss et al. Assessing bioequivalence of generic antiepilepsy
drugs. Ann Neurol 2011; 70:221.
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Issue 126 Questions

1. Drawbacks of carbamazepine include:
a. multiple interactions with other drugs
b. may make myoclonic seizures worse
c. cognitive and other CNS effects
d. all of the above
Issue 126
2. An obese 45-year-old woman with frequent migraines needs a
drug to treat partial seizures. Which of the following drugs may be
effective for her seizure disorder and also be helpful in treating
her other conditions?
a. clobazam
b. gabapentin
c. perampanel
d. topiramate
Issue 126
3. Which one of the following drugs is not a good choice for an 8year-old girl with absence seizures?
a. carbamazepine
b. ethosuximide
c. lamotrigine
d. valproic acid
Issue 126
4. Gabapentin is used for:
a. partial seizures
b. neuropathic pain
c. restless legs syndrome
d. all of the above
Issue 126
5. Compared to carbamazepine in elderly patients with newly diagnosed seizures, lamotrigine has been:
a. less effective
b. better tolerated
c. more effective
d. less well tolerated
Issue 126
6. Levetiracetam:
a. does not have significant interactions with other drugs
b. has a low incidence of cognitive effects
c. is effective for generalized and partial seizures
d. all of the above
7. Phenytoin is no longer considered a drug of choice for partial

seizures due to:
a. its complicated pharmacokinetics and dosing
b. its adverse effect profile
c. frequent drug interactions
d. all of the above
Issue 126
8. Pregabalin:
a. is effective in treating myoclonic seizures
b. is used to treat fibromyalgia
c. interacts with many other drugs
d. none of the above
Issue 126
9. Caution is advised if rufinamide is taken with other drugs that:
a. increase serum serotonin levels
b. are sympathomimetic
c. affect hepatic transaminases
d. shorten the QT interval
Issue 126
10. Valproate is:
a. safe in pregnancy
b. not available generically
c. effective and usually well tolerated
d. none of the above
Issue 126
11. Many antiepileptic drugs can induce the metabolism of oral hormonal contraceptives, reducing their efficacy. Which of the following antiepileptic drugs would be the safest choice in a woman taking an oral contraceptive?
a. carbamazepine
b. levetiracetam
c. perampanel
d. topiramate
Issue 126
12. Most pregnant patients exposed to antiepileptic drugs during
pregnancy deliver normal infants, but major malformations can
occur. The highest risk appears to be with:
a. valproate and phenobarbital
b. carbamazepine and phenytoin
c. lamotrigine and carbamazepine
d. phenytoin and lamotrigine
Issue 126
ACPE UPN: 0379-0000-13-126-H01-P; Release: January 2013, Expire: January 2014

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Drugs For Epilepsy

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Treatment Guidelines

from The Medical Letter

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Drugs for Epilepsy..............................................................p 9

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Drugs for Epilepsy

Table 1. Drugs of Choice1

Primary Generalized Tonic-Clonic Seizures

Atypical Absence, Myoclonic, Atonic Seizures

Drugs for Epilepsy

200 mg tabs; 100 mg chewable

Clobazam Onfi (Lundbeck)

0.5, 1, 2 mg tabs; 0.125, 0.25,

250 mg caps; 250 mg/5 mL syrup

Ezogabine Potiga (GSK/Valeant)

50, 200, 300, 400 mg tabs

400, 600 mg tabs;

100, 300, 400 mg caps; 100,

Lacosamide Vimpat (UCB)

50, 100, 150, 200 mg tabs;

2, 5, 25, 50, 100, 150, 200, 250 mg

200-600 mg once daily

250, 500, 750, 1000 mg tabs;

150, 300, 600 mg tabs;

150, 300, 600 mg ER tabs

1200-2400 mg once daily

Carbamazepine can cause rash, particularly with high

Drugs for Epilepsy

Perampanel Fycompa (Eisai)

15, 30, 60, 100 mg tabs;

30, 100, 200, 300 mg caps;

30, 100 mg caps

50, 250 mg tabs

Rufinamide Banzel (Eisai)

200, 400 mg tabs; 40 mg/mL susp

15, 25 mg caps; 25, 50 100, 200 mg tabs

250 mg caps; 250 mg/5 mL syrup

125, 250, 500 mg delayed-release caps

1250-3500 mg once daily3

Vigabatran Sabril (Lundbeck)

500 mg tabs; 500 mg powder

25, 50, 100 mg caps

4. Cost not yet available.

other ethnic groups, be tested for this allele before

Adverse Effects The most frequent adverse effects

Drugs for Epilepsy

(Diflucan, and generics) or omeprazole (Prilosec, and

impairment, blurred vision, asthenia and aphasia can

ETHOSUXIMIDE Ethosuximide (Zarontin, and

Adverse Effects Gabapentin can cause somnolence,

Adverse Effects Ethosuximide can cause nausea,

Drug Interactions Unlike some other AEDs,

Drug Interactions Ethosuximide is partially metabolized by CYP3A4; inducers of CYP3A4 may

LACOSAMIDE Oral lacosamide (Vimpat) is

EZOGABINE Ezogabine (Potiga) is FDAapproved for adjunctive treatment of partial onset

Adverse Effects The most frequent adverse effects

Adverse Effects The most frequent adverse effects

Drug Interactions Lacosamide is a substrate and

Drugs for Epilepsy

adolescents 12 years old with myoclonic seizures. It

LAMOTRIGINE Lamotrigine (Lamictal, and