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 sod

ium 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 dose-

related), 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, life-

threatening pancr

eatitis, 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 f

ormation; 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 50–100

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 enteric-

coated 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/tramadol 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/clarithromycin/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 ↔ risperidoneApplies 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 ↔ risperidoneApplies to:acetaminophen/propoxyphene 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 ↔ risperidoneApplies 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 ↔ biperidenApplies 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 ↔ biperidenApplies 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 ↔ biperidenApplies 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 ↔ buprenorphineApplies 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 ↔ celecoxibApplies 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.