Valproic Acid

Reviewed on 6/27/2022

What Is Valproic Acid and How Does It Work?

Valproic Acid is a prescription medication used to treat the symptoms of Complex Partial Seizures, Simple and Complex Absence Seizures, Migraine, and Bipolar Mania.

What Are Side Effects Associated with Using Valproic Acid?

Common side effects of Valproic Acid include:

  • nausea, 
  • vomiting, 
  • stomach pain, 
  • diarrhea, 
  • dizziness, 
  • drowsiness, 
  • weakness, 
  • headache, 
  • tremors
  • problems with walking or coordination, 
  • blurred vision, 
  • double vision
  • hair loss, 
  • changes in appetite, and 
  • weight gain

Serious side effects of Valproic Acid include:

  • hives, 
  • difficulty breathing, 
  • swelling of the face, lips, tongue, or throat, 
  • skin rash
  • fever, 
  • swollen glands, 
  • muscle aches, 
  • severe weakness, 
  • unusual bruising, 
  • yellowing of the skin or eyes (jaundice), 
  • loss of appetite, 
  • upper stomach pain (that may spread to the back), 
  • ongoing nausea or vomiting, 
  • dark urine, 
  • mood or behavior changes, 
  • depression, 
  • anxiety, 
  • panic attacks
  • trouble sleeping, 
  • impulsive behavior, 
  • irritableness, 
  • agitation, 
  • hostility, 
  • aggression, 
  • restlessness, 
  • hyperactivity (mental or physical), and
  • thoughts of self-harm or suicide

Rare side effects of Valproic Acid include:

  • none 

Seek medical care or call 911 at once if you have the following serious side effects:

  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; sudden dizziness, lightheartedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.


If you have had a seizure, it means you have epilepsy. See Answer

What Are Dosages of Valproic Acid?

Adult and Pediatric dosage

Capsule (Depakene)

  • 250 mg

Capsule/tablet, delayed-release (Stavzor)

  • 125 mg
  • 250 mg
  • 500 mg

Tablet, extended-release 

  • 250 mg
  • 500 mg

Capsule delayed release sprinkle

  • 125 mg

Syrup (Depakene)

  • 250 mg/5mL

Injectable solution (Depacon as valproate sodium)

  • 100 mg/mL

Complex Partial Seizure

Adult dosage

  • IV (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral medication as soon as possible)
  • Orally: 10-15 mg/kg/day orally initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Pediatric dosage

  • Children younger than 10 years of age: safety and efficacy not established
  • Children 10 years or older: IV (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral medication as soon as possible)
  • Children 10 years or older: Orally (Depakene or Stavzor): 10-15 mg/kg/day orally initially; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day

Simple & Complex Absence Seizures

Adult dosage

  • IV (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral medication as soon as possible)
  • Orally (Depakene, Stavzor): 15 mg/kg/day orally initially, divided every 6-12 hours; increase by 5-10 mg/kg/day at weekly intervals; may increase dose up to 60 mg/kg/day        

Pediatric dosage

  • Children younger than 10 years of age: safety and efficacy not established
  • Children 10 years or older: IV (valproate sodium): 10-15 mg/kg/day IV divided every 12 hours infused over 1 hour; maximum dose 60 mg/kg/day; do not exceed 14 days (switch to oral medication as soon as possible)
  • Children 10 years or older: Orally (Stavzor): 250 mg orally every 12 hours; adjust dose based on clinical response up to 1000 mg/day


Adult dosage

  • Stavzor: 250 mg orally every 12 hours; adjust dose based on clinical response, not to exceed 1000 mg/day
  • Depakote ER: 500 mg orally every day for 7 days; based on patient response, may increase and adjust the dose to 500-1000 mg/day

Bipolar Mania

Adult dosage

  • Stavzor: 750 mg/day orally in divided doses; adjust the dose as rapidly as possible to desired therapeutic effect; not to exceed 60 mg/kg/day
  • Depakote ER: 25 mg/kg/day orally daily; adjust the dose to desired clinical effect, as rapidly as possible; not to exceed 60 mg/kg/day

Dosage Considerations – Should be Given as Follows: 

  • See "Dosages."

What Other Drugs Interact with Valproic Acid?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them.  Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Valproic Acid has severe interactions with no other drugs. 
  • Valproic Acid has serious interactions with at least 17 other drugs.
  • Valproic Acid has moderate interactions with at least 57 other drugs.
  • Valproic Acid has minor interactions with at least 50 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use.  Keep a list of all your medications with you, and share this information with your doctor and pharmacist.  Check with your health care professional or doctor for additional medical advice, or if you have health questions, or concerns.


What Is Epilepsy? Symptoms, Causes, and Treatments See Slideshow

What Are Warnings and Precautions for Valproic Acid?



  • Hepatic failure resulting in fatalities has occurred
  • Children younger than 2 years are at increased risk for fatal hepatotoxicity, particularly patients on multiple anticonvulsants, as well as those with congenital metabolic disorders, severe seizure disorders accompanied by mental retardation, or organic brain disease
  • Increased risk of valproate-induced acute liver failure and resultant deaths in patients with hereditary neurometabolic syndromes caused by DNA mutations of the mitochondrial DNA polymerase-gamma (POLG) gene (e.g., Alpers Huttenlocher Syndrome)
  • If used in children with these conditions, it should be administered with extreme caution as a sole agent
  • Hepatotoxicity usually occurs during the first 6 months of treatment and may be preceded by malaise, weakness, lethargy, facial edema, anorexia, and vomiting


  • Do not use in women of childbearing age unless the drug is essential to the management of the medical condition; all non-pregnant women of childbearing potential should use effective birth control if taking valproate products (see Contraindications and Pregnancy sections)
  • May cause neural tube defects
  • Children exposed in utero have an increased risk for lower cognitive test scores compared with those exposed in utero to other anti-seizure medications
  • Alternative medications that have a lower risk for adverse birth outcomes should be considered
  • Patients should not stop taking valproate without talking to a healthcare professional


  • Cases of life-threatening pancreatitis have been reported in children and adults
  • Some cases have been described as hemorrhagic with a rapid progression from initial symptoms to death
  • This medication contains valproic acid. Do not take Depakene, Stavzor, or Depacon if you are allergic to valproic acid or any ingredients contained in this drug.

This medication contains valproic_acid. Do not take Xarelto if you are allergic to valproic_acid or any ingredients contained in this drug.

Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.


  • Hypersensitivity
  • Liver disease, significant hepatic impairment
  • Urea cycle disorder
  • Mitochondrial disorders caused by mutations in mitochondrial DNA polymerase-gamma (POLG; eg, Alpers-Huttenlocher Syndrome) and children older than 2 years of age who are suspected of having a POLG-related disorder
  • Migraine headache prevention in women who are pregnant or plan to become pregnant

Effects of drug abuse

  • None

Short-Term Effects

  • See "What Are Side Effects Associated with Using Valproic Acid?"

Long-Term Effects

See "What Are Side Effects Associated with Using Valproic Acid?"


  • The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations exceed 110 mcg/mL in females and 135 mcg/mL in males; because of reports of cytopenias, inhibition of secondary phase of platelet aggregation, and abnormal coagulation parameters (eg, low fibrinogen, coagulation factor deficiencies, acquired von Willebrand’s disease)
  • Measurements of complete blood counts and coagulation tests are recommended before initiating therapy and at periodic intervals; recommended that patients receiving drugs be monitored for blood counts and coagulation parameters prior to planned surgery and during pregnancy; evidence of hemorrhage, bruising, or a disorder of hemostasis/coagulation is an indication for reduction of dosage or withdrawal of therapy
  • Medication residue in the stool was reported; some patients have had anatomic (including ileostomy or colostomy) or functional gastrointestinal disorders with shortened GI transit times; in some reports, medication residues have occurred in the context of diarrhea; recommended that plasma valproate levels be checked in patients who experience medication residue in the stool, and patient's clinical condition monitored; If clinically indicated, may consider alternative treatment
  • Bleeding and other hematopoietic disorders may occur; monitor platelet counts and coagulation tests
  • Hepatotoxic (age older than 2 years, higher risk of fatal hepatotoxicity); evaluate high-risk populations and monitor serum liver tests; risk factors include organic brain disease, mental retardation with severe seizure disorders, congenital metabolic disorders, and patients on multiple anticonvulsants; discontinue immediately with signs/symptoms of significant or suspected impairment
  • POLG mutations; see Contraindications and Black Box Warnings
  • Discontinue if hyperammonemia occurs; check ammonia level if emesis occurs or if the patient displays lethargy or abnormal behavior; evaluate the patient for urea cycle disorder (see Contraindications) or hepatotoxicity (see Black Box Warnings)
  • Pancreatitis, including fatalities, reported (see Black Box Warnings)
  • Porphyria may occur
  • May produce false-positive urine ketone test and alter TFTs
  • May cause CNS depression, which may impair physical or mental to perform tasks requiring mental alertness
  • Birth defects and decreased IQ following in utero exposure compared with 3 other common AEDs (carbamazepine, lamotrigine, phenytoin); only use to treat pregnant women with epilepsy if other medications are unacceptable; should not be administered to a woman of childbearing potential unless essential; reversible and irreversible cerebellar atrophy reported; monitor motor and cognitive function routinely
  • Drug reaction with eosinophilia and systemic symptoms (DRESS)/multiorgan hypersensitivity reaction reported; discontinue therapy; monitor for possible disparate manifestations associated with lymphatic, renal, hepatic, and/or hematologic organ systems; therapy should be discontinued and not be resumed if an alternative etiology for signs or symptoms cannot be established
  • Not recommended for post-traumatic seizure prophylaxis in patients with acute head trauma (may increase mortality
  • Hypothermia is reported during valproate therapy with or without associated hyperammonemia; this adverse reaction can also occur in patients using concomitant topiramate
  • Somnolence in the elderly can occur; valproic acid dosage should be increased slowly and with regular monitoring for fluid and nutritional intake
  • Irreversible and reversible brain atrophy reported; routinely monitor motor and cognitive function to assess for signs and symptoms of brain atrophy
  • Serious, sometimes fatal drug reaction with eosinophilia and systemic symptoms (DRESS) reported; monitor for symptoms; may require discontinuation and conversion to alternate therapy
  • Suicidal thoughts and behavior may occur; monitor patients for changes in behavior that might indicate suicidal thoughts or depression

Pregnancy and Lactation

  • A pregnancy exposure registry monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), during pregnancy; encourage women on therapy during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling toll-free 1-888-233-2334 or visiting the website,; must be done by the patient herself
  • Although available studies have methodological limitations, the weight of evidence supports a causal association between valproate exposure in utero and subsequent adverse effects on neurodevelopment, including increases in autism spectrum disorders and attention-deficit/hyperactivity disorder (ADHD); because studies were observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder and ADHD cannot be considered definitive
  • Contraindicated for use in prophylaxis of migraine headaches in women who are pregnant and in women of childbearing potential who are not using effective contraception; for epilepsy or bipolar disorder, the drug should not be used to treat women who are pregnant or who plan to become pregnant unless other medications have failed to provide adequate symptom control or are otherwise unacceptable
  • Women with epilepsy who become pregnant while taking valproate should not discontinue therapy abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life; discontinuation of the drug may be considered prior to and during pregnancy in individual cases if seizure disorder severity and frequency do not pose a serious threat to patient
  • Maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects including spina bifida, but also malformations involving other body systems (e.g., craniofacial defects including oral clefts, cardiovascular malformations, hypospadias, limb malformations)
  • Risk is dose-dependent; a threshold dose below which no risk exists cannot be established; valproate polytherapy with other AEDs has been associated with increased frequency of congenital malformations compared with AED monotherapy; risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy
  • There have been reports of hypoglycemia in neonates and fatal cases of hepatic failure in infants following maternal use of valproate during pregnancy
  • Pregnant women taking valproate may develop hepatic failure or clotting abnormalities including thrombocytopenia, hypofibrinogenemia, and/or a decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death
  • Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population; not known whether the risk of neural tube defects or decreased IQ in offspring of women receiving valproate is reduced by folic acid supplementation; dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for patients using valproate
  • There have been reports of male infertility coincident with valproate therapy; in animal studies, oral administration at clinically relevant doses resulted in adverse reproductive effects in males
  • Lactation
    • The drug is excreted in human milk; data in the published literature describe the presence of valproate in human milk; there are no data to assess the effects of the drug on milk production or excretion
    • Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from drugs or from the underlying maternal condition
    • Monitor breastfed infant for signs of liver damage including jaundice and unusual bruising or bleeding; there have been reports of hepatic failure and clotting abnormalities in offspring of women who used valproate during pregnancy

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