Valproic Acid

Drug class
Antiepileptic

Therapeutic
actions

Mechanism of action
not understood:
antiepileptic activity
may be related to
the metabolism of
the inhibitory
neurotransmitter,
GABA; divalproex so
dium is a compound
containing equal

proportions
of valproic acid and
sodium valproate.

Indications
Sole and adjunctive
therapy in simple
(petit mal) and

complex absence
seizures
Depakote
ER: Treatment of
epilepsy in
children > 10 yr;
treatment of acute
manic or mixed
episodes associated
with bipolar disorder,

with or without
psychotic features
Adjunctive therapy
with multiple seizure
types, including
absence seizures
Depakote
ER: Treatment of
bipolar mania

Depakote, Depacote
ER: Prophylaxis of
migraine headaches
Divalproex, sodium
valproate
injection: Treatment
of complex partial
seizures as
monotherapy or with
other antiepileptics

Unlabeled uses:
Adjunct in symptom
management of
schizophrenia,
treatment of
aggressive outbursts
in children with
attention-deficit
hyperactivity

disorder, organic
brain syndrome

Contraindications
and cautions
Contraindicated with
hypersensitivity
to valproic acid,

hepatic disease or
significant hepatic
impairment.
Use cautiously with
children < 18 mo;
children < 2 yr,
especially with
multiple
antiepileptics,
congenital metabolic

disorders, severe
seizures
accompanied by
severe mental
retardation, organic
brain disorders
(higher risk of
developing
fatal hepatotoxicity);
pregnancy (fetal

neural tube defects;

do not discontinue to
prevent major
seizures;
discontinuing such
medication is likely
to precipitate
status epilepticus,
hypoxia and risk to

both mother and

fetus); lactation.

Adverse effects
CNS: Sedation, trem
or (may be doserelated), emotional
upset, depression,
psychosis,

aggression,
hyperactivity,
behavioral
deterioration,
weakness
Dermatologic: Tran
sient increases in
hair loss,
rash, petechiae

GI: Nausea,
vomiting,
indigestion, diarrhea,
abdominal cramps,
constipation,
anorexia with weight
loss, increased
appetite with weight
gain, lifethreatening pancre

atitis, hepatic
failure
GU: Irregular
menses, secondary
amenorrhea
Hematologic: Slight
elevations in AST,
ALT, LDH; increases
in serum bilirubin,
abnormal changes in

other LFTs, altered

bleeding time;
thrombocytopenia;
bruising; hematoma
formation; frank
hemorrhage;
relative lymphocytosi
s; hypofibrinogenemi
a; leukopenia, eosino

philia, anemia, bone

marrow suppression

Interactions
Drug-drug
Increased
serum phenobarbital,
primidone, ethosuxi

mide,
diazepam, zidovudin
e levels
Complex interactions
with phenytoin;
breakthrough
seizures have
occurred with the
combination

of valproic acid
and phenytoin
Increased serum
levels and toxicity
with salicylates, cime
tidine,
chlorpromazine,
erythromycin, felbam
ate

Decreased effects
with carbamazepine,
rifampin, lamotrigine
Decreased serum
levels with charcoal
Increased sedation
with alcohol, other
CNS depressants

Interventions

Give drug with food

if GI upset occurs;
substitution of the
enteric-coated
formulation also may
be of benefit; have
patient swallow SR
tablet whole; do not
cut, crush, or chew.

WARNING: Reduce
dosage, discontinue,
or substitute other
antiepileptics
gradually; abrupt
discontinuation of all
antiepileptics may
precipitate absence
seizures.

BLACK BOX
WARNING: Arrange
for frequent LFTs;
discontinue drug
immediately with
significant hepatic
impairment,
suspected or
apparent significant
hepatic impairment;

continue LFTs to
determine if hepatic
impairment
progresses in spite of
drug discontinuation.
WARNING: Arrange
for patient to have
platelet counts,
bleeding time
determination before

therapy, periodically
during therapy, and
prior to surgery.
Monitor patient
carefully for clotting
defects (bruising,
blood-tinged
toothbrush).
Discontinue if there
is evidence of

hemorrhage,
bruising, or disorder
ofhemostasis.
Monitor ammonia
levels, and
discontinue if there is
clinically significant
elevation in level.
Monitor serum levels
of valproic acid and

other antiepileptic
drugs given
concomitantly,
especially during the
first few weeks of
therapy. Adjust
dosage on the basis
of these data and
clinical response.

BLACK BOX
WARNING: Arrange
for counseling for
women of
childbearing age who
wish to become
pregnant; drug may
be teratogenic.
BLACK BOX
WARNING: Disconti

nue drug at any sign

of pancreatitis.
WARNING: Evaluate
for therapeutic
serum levels
usually 50100
mcg/mL.

Teaching points

Take this drug

exactly as
prescribed. Do not
chew tablets or
capsules before
swallowing them.
Swallow them whole
to prevent local
irritation of mouth
and throat. Sprinkle

tablets may be
opened and sprinkled
on applesauce or
pudding.
Do not discontinue
this drug abruptly or
change dosage,
except on the advice
of your health care
provider.

Avoid alcohol and

sleep-inducing and
over-the-counter
drugs. These could
cause dangerous
effects.
Have frequent
checkups, including
blood tests, to
monitor your drug

response. Keep all

appointments for
checkups.
Use contraceptive
techniques at all
times. If you want to
become pregnant,
consult your health
care provider.

Wear a medical ID
tag to alert
emergency medical
personnel that you
have epilepsy and
are taking
antiepileptic
medication.
If you have diabetes,
this drug may

interfere with urine

tests for ketones.
You may experience
these side effects:
Drowsiness
(avoid driving or
performing other
tasks requiring
alertness; take at
bedtime); GI upset

(take with food or

milk, eat frequent
small meals; if
problem persists,
substitute entericcoated drug);
transient increase in
hair loss.
Report bruising, pink
stain on the

toothbrush,
yellowing of the skin
or eyes, pale feces,
rash, pregnancy;
abdominal pain with
nausea, vomiting,
anorexia.

clozapine
tramadol
Applies to:clozapine
and
acetaminophen/tramado
l
TraMADol may cause
seizures, and combining
it with other
medications that can

also cause seizures such

as cloZAPine may
increase that risk. The
interaction may be more
likely if you are elderly,
undergoing alcohol or
drug withdrawal, have a
history of seizures, or
have a condition
affecting the central

nervous system such as

a brain tumor or head
trauma. You should
avoid or limit the use of
alcohol while being
treated with these
medications. Also avoid
driving or operating
hazardous machinery
until you know how the

medications affect you.

Talk to your doctor if
you have any questions
or concerns. It is
important to tell your
doctor about all other
medications you use,
including vitamins and
herbs. Do not stop
using any medications

without first talking to

your doctor.
clarithromycin
clozapine
Applies
to:amoxicillin/clarithro
mycin/lansoprazole and
clozapine

Using cloZAPine
together with
clarithromycin may
increase the effects of
cloZAPine. Contact
your doctor if you
experience confusion,
fast heart rate,
drowsiness, drooling,
weak or shallow

breathing, feeling like

you might pass out, and
seizure (convulsions). If
your doctor does
prescribe these
medications together,
you may need a dose
adjustment or special
test to safely use both
medications. It is

important to tell your

doctor about all other
medications you use,
including vitamins and
herbs. Do not stop
using any medications
without first talking to
your doctor.

lorazepam
risperidone
Applies to:Ativan
(lorazepam) and
risperidone
Using LORazepam
together with
risperiDONE may
increase side effects
such as dizziness,

drowsiness, and
difficulty concentrating.
Some people may also
experience some
impairment in thinking
and judgment. You
should avoid or limit
the use of alcohol while
being treated with these
medications. Avoid

driving or operating
hazardous machinery
until you know how the
medications affect you.
It is important to tell
your doctor about all
other medications you
use, including vitamins
and herbs. Do not stop
using any medications

without first talking to

your doctor.
propoxyphene
risperidone
Applies
to:acetaminophen/propo
xyphene and
risperidone

Using propoxyphene
together with
risperiDONE may
increase side effects
such as dizziness,
drowsiness, confusion,
difficulty concentrating,
and other nervous
system or mental
effects. Some people,

especially the elderly,

may also experience
impairment in thinking,
judgment, and
coordination. You
should take
propoxyphene exactly
as prescribed by your
doctor. Do not take
larger doses or use the

drug more frequently

than prescribed. Misuse
of propoxyphene can
lead to serious side
effects including death,
and the risk may be
increased if you have a
history of emotional
disturbances, suicidal
thoughts, or alcohol and

drug abuse. You should

avoid or limit the use of
alcohol while being
treated with
propoxyphene and/or
risperiDONE. Avoid
driving or operating
hazardous machinery
until you know how the
medications affect you,

and do not exceed the

dosage or frequency of
use prescribed by your
doctor. It is important to
tell your doctor about
all other medications
you use, including
vitamins and herbs. Do
not stop using any
medications without

first talking to your

doctor.
amlodipine
risperidone
Applies to:amlodipine
and risperidone
RisperiDONE and
amLODIPine may have
additive effects in

lowering your blood

pressure. You may
experience headache,
dizziness,
lightheadedness,
fainting, and/or changes
in pulse or heart rate.
These side effects are
most likely to be seen at
the beginning of

treatment, following a
dose increase, or when
treatment is restarted
after an interruption.
Let your doctor know if
you develop these
symptoms and they do
not go away after a few
days or they become
troublesome. Avoid

driving or operating
hazardous machinery
until you know how the
medications affect you,
and use caution when
getting up from a sitting
or lying position. It is
important to tell your
doctor about all other
medications you use,

including vitamins and

herbs. Do not stop
using any medications
without first talking to
your doctor.

potassium chloride
biperiden

Applies to:K +
Potassium (potassium
chloride) and biperiden
The following
interaction applies only
if you are taking
potassium in a solid
formulation (i.E., tablet
or capsule swallowed
whole): Talk to your

doctor before using

potassium oral tablets
or capsules together
with biperiden.
Depending on the dose
of biperiden and your
overall physical health,
combining these
medications may
increase the irritant

effects of potassium on
your stomach and upper
intestine. This can
rarely result in ulcers,
bleeding, and other
gastrointestinal injury.
Contact your doctor
immediately if you
develop severe
abdominal pain,

bloating, sudden
dizziness or
lightheadedness,
nausea, vomiting
(especially with blood),
loss of appetite, and/or
black, tarry stools
during treatment with
these medications.
Alternatively, a liquid

formulation of
potassium may be
considered when used
in combination with
biperiden. It is
important to tell your
doctor about all other
medications you use,
including vitamins and
herbs. Do not stop

using any medications

without first talking to
your doctor.

azatadine
biperiden
Applies to:azatadine
and biperiden

Using azatadine
together with biperiden
may increase side
effects such as
drowsiness, blurred
vision, dry mouth, heat
intolerance, flushing,
decreased sweating,
difficulty urinating,
abdominal cramping,

constipation, rapid heart

beats, confusion, and
memory problems. Side
effects may be more
likely to occur in the
elderly or those with a
debilitating condition.
You should avoid or
limit the use of alcohol
while being treated with

these medications. Also

avoid activities
requiring mental
alertness such as
driving or operating
hazardous machinery
until you know how the
medications affect you.
It is important to tell
your doctor about all

other medications you

use, including vitamins
and herbs. Do not stop
using any medications
without first talking to
your doctor.
codeine
biperiden

Applies to:codeine and

biperiden
Using codeine together
with biperiden can
increase nervous system
side effects such as
dizziness, drowsiness,
and difficulty
concentrating. Some
people may also

experience impairment
in thinking and
judgment. You should
avoid or limit the use of
alcohol while being
treated with these
medications. Do not use
more than the dosages
prescribed by your
doctor, and avoid

activities requiring
mental alertness such as
driving or operating
hazardous machinery
until you know how the
medication affects you.
It is important to tell
your doctor about all
other medications you
use, including vitamins

and herbs. Do not stop

using any medication
without first talking to
your doctor.

valproic acid buprenorphine

Applies to:valproic acid and buprenorphine

Using buprenorphine together with other medications that cause central nervous system
depression such as valproic acid can lead to serious side effects such as respiratory distress,
coma, or even death. You may need a dose adjustment or more frequent monitoring by your
doctor to safely use both medications. Do not drink alcohol or self-medicate with these
medications without your doctor's approval, and do not exceed the doses or frequency and
duration of use prescribed by your doctor. Also, you should avoid driving or operating hazardous
machinery until you know how these medications affect you. Talk to your doctor or pharmacist if
you have any questions or concerns. It is important to tell your doctor about all other medications
you use, including vitamins and herbs. Do not stop using any medications without first talking to
your doctor.

valproic acid celecoxib

Applies to:valproic acid and celecoxib

Using valproic acid together with celecoxib can increase the effects of celecoxib. This can cause
abdominal pain, tarry stools, nausea, vomiting, lethargy or drowsiness. If you take both
medications together, tell your doctor if you have any of these symptoms. You may need a dose
adjustment if you take both medications. It is important to tell your doctor about all other
medications you use, including vitamins and herbs. Do not stop using any medications without
first talking to your doctor.

valproic acid celecoxib

Applies to:valproic acid and celecoxib

Using valproic acid together with celecoxib can increase the effects of celecoxib. This can cause
abdominal pain, tarry stools, nausea, vomiting, lethargy or drowsiness. If you take both
medications together, tell your doctor if you have any of these symptoms. You may need a dose
adjustment if you take both medications. It is important to tell your doctor about all other
medications you use, including vitamins and herbs. Do not stop using any medications without
first talking to your doctor.