Valproic Acid

Valproic acid dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established.

• Valproic acid oral solution is indicated for: Monotherapy and adjunctive therapy of complex partial seizures; sole and adjunctive therapy of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 1.1 Epilepsy Valproic acid oral solution is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Valproic acid oral solution is indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures.ICD-10: G40.909

• Valproic acid should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 )] . Valproic acid is contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder [see Warnings and Precautions ( 5.1 )] .contraindicated

Valproic acid oral solution is intended for oral administration. ( 2.1 ) Simple and Complex Absence Seizures: Start at 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/week until seizure control or limiting side effects ( 2.1 ) Safety of doses above 60 mg/kg/day is not established ( 2.1 , 2.2 ) 2.1 Epilepsy Valproic acid oral solution is intended for oral administration. Patients should be informed to take valproic acid oral solution every day as prescribed. If a dose is missed it should be taken as soon as possible, unless it is almost time for the next dose. If a dose is skipped, the patient should not double the next dose. Valproic acid is indicated as monotherapy and adjunctive therapy in complex partial seizures in adults and pediatric patients down to the age of 10 years, and in simple and complex absence seizures. As the valproic acid dosage is titrated upward, concentrations of clonazepam, diazepam, ethosuximide, lamotrigine, tolbutamide, phenobarbital, carbamazepine, and/or phenytoin may be affected [see Drug Interactions ( 7.2 )] . Complex Partial Seizures For adults and children 10 years of age or older. Monotherapy (Initial Therapy) Valproic acid oral solution has not been systematically studied as initial therapy. Patients should initiate therapy at 10 to 15 mg/kg/day. The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response. Ordinarily, optimal clinical response is achieved at daily doses below 60 mg/kg/day.

Hepatotoxicity; evaluate high risk populations and monitor serum liver tests ( 5.1) Birth defects, decreased IQ, and neurodevelopmental disorders following in utero exposure; should not be used to treat women with epilepsy or bipolar disorder who are pregnant or who plan to become pregnant or to treat a woman of childbearing potential unless other medications have failed to provide adequate symptom control or are otherwise unacceptable. ( 5.2 , 5.3 , 5.4 ) Pancreatitis; valproic acid should ordinarily be discontinued ( 5.5 ) Suicidal behavior or ideation; Antiepileptic drugs, including valproic acid, increase the risk of suicidal thoughts or behavior ( 5.7 ) Bleeding and other hematopoietic disorders; monitor platelet counts and coagulation tests ( 5.8 ) Hyperammonemia and hyperammonemic encephalopathy; measure ammonia level if unexplained lethargy and vomiting or changes in mental status, and also with concomitant topiramate use; consider discontinuation of valproate therapy ( 5.6 , 5.9 , 5.10 ) Hypothermia; Hypothermia has been reported during valproate therapy with or without associated hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate ( 5.11 ) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reaction; discontinue valproic acid ( 5.12 ) Somnolence in the elderly can occur.

The following serious adverse reactions are described below and elsewhere in the labeling: Hepatic failure [see Warnings and Precautions ( 5.1 )] Birth defects [see Warnings and Precautions ( 5.2 )] Decreased IQ following in utero exposure [see Warnings and Precautions ( 5.3 )] Pancreatitis [see Warnings and Precautions ( 5.5 )] Hyperammonemic encephalopathy [see Warnings and Precautions ( 5.6 , 5.9 , 5.10 )] Suicidal behavior and ideation [see Warnings and Precautions ( 5.7 )] Bleeding and other hematopoietic disorders [see Warnings and Precautions ( 5.8 )] Hypothermia [see Warnings and Precautions ( 5.11 )] Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reactions [see Warnings and Precautions ( 5.12 ) Somnolence in the elderly [see Warnings and Precautions ( 5.14 )] Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. Most common adverse reactions (reported >5%) are abdominal pain, alopecia, amblyopia/blurred vision, amnesia, anorexia, asthenia, ataxia, bronchitis, constipation, depression, diarrhea, diplopia, dizziness, dyspepsia, dyspnea, ecchymosis, emotional lability, fever, flu syndrome, headache, increased appetite, infection, insomnia, nausea, nervousness, nystagmus, peripheral edema, pharyngitis, rhinitis, somnolence, thinking abnormal, thrombocytopenia, tinnitus, tremor, vomiting, weight gain, weight loss.

Pregnancy: Valproic acid can cause congenital malformations including neural tube defects, decreased IQ, and neurodevelopmental disorders ( 5.2 , 5.3 , 8.1 ) Pediatric: Children under the age of two years are at considerably higher risk of fatal hepatotoxicity ( 5.1 , 8.4 ) Geriatric: Reduce starting dose; increase dosage more slowly; monitor fluid and nutritional intake, and somnolence ( 5.14 , 8.5 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), including valproic acid oral solution, during pregnancy. Encourage women who are taking valproic acid 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, http://www.aedpregnancyregistry.org/. This must be done by the patient herself. Risk Summary For use in prophylaxis of migraine headaches, valproate is contraindicated in women who are pregnant and in women of childbearing potential who are not using effective contraception [see Contraindications ( 4 )] .

Metabolism

Absorption/Bioavailability Equivalent oral doses of divalproex sodium products and valproic acid capsules deliver equivalent quantities of valproate ion systemically. Although the rate of valproate ion absorption may vary with the formulation administered (liquid, solid, or sprinkle), conditions of use (e.g., fasting or postprandial) and the method of administration (e.g., whether the contents of the capsule are sprinkled on food or the capsule is taken intact), these differences should be of minor clinical importance under the steady state conditions achieved in chronic use in the treatment o…

Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however, patients have recovered from valproate levels as high as 2,120 mcg/mL. In overdose situations, the fraction of drug not bound to protein is high and hemodialysis or tandem hemodialysis plus hemoperfusion may result in significant removal of drug. The benefit of gastric lavage or emesis will vary with the time since ingestion. General supportive measures should be applied with particular attention to the maintenance of adequate urinary output. Naloxone has been reported to reverse the CNS depressant effects of valproate overdosage. Because naloxone could theoretically also reverse the antiepileptic effects of valproate, it should be used with caution in patients with epilepsy.

• Jul 1, 1986ANDAANDA070868Pharmobedient Cnsltg
• Oct 29, 1991ANDAANDA073229Catalent
• Aug 25, 1992ANDAANDA073178Ani Pharms
• Jun 29, 1993ANDAANDA073484Bionpharma
• Dec 15, 2000ANDAANDA075379Pharm Assoc
• Dec 22, 2000ANDAANDA075782Chartwell Rx
• May 28, 2010ANDAANDA090517Quagen

1. 1Drug Ineffective3,70012%
2. 2Drug Interaction3,49111%
3. 3Off Label Use2,1026.8%
4. 4Toxicity To Various Agents1,9686.4%
5. 5Seizure1,8886.1%
6. 6Completed Suicide1,2964.2%
7. 7Somnolence1,2644.1%
8. 8Depression1,2203.9%
9. 9Condition Aggravated1,0343.3%
10. 10Overdose9463.1%
11. 11Foetal Exposure During Pregnancy9032.9%
12. 12Pyrexia8792.8%
13. 13Product Use In Unapproved Indication8392.7%
14. 14Status Epilepticus7482.4%
15. 15Fatigue7062.3%

Recent PubMed references pinned to Valproic Acid as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Diosgenin ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.
  Metabolic brain disease · 2026 · Dehkhodaei S, Naghdibadi MR, Ahadi R, et al.
  PMID 42262415DOI 10.1007/s11011-026-01851-7
• Comparing the safety and efficacy of sodium valproate, levetiracetam, and phenytoin in attenuating the severity of agitation in patients with post-traumatic brain injury: An observational study.
  PloS one · 2026 · Singh S, Nayak R, Gangachannaiah S, et al.
  PMID 42234767DOI 10.1371/journal.pone.0350585
• Abnormal Enteric Nervous System Organization and Gastrointestinal Motility in Mice With Valproic Acid-Induced Neural Tube Defects.
  Neurogastroenterology and motility · 2026 · Barsh GR, Banducci K, Kaltschmidt JA, et al.
  PMID 42231590DOI 10.1111/nmo.70368
• Combinatorial drug repurposing of Valproic acid and Zebularine regulates Krüppel-like factor 4 and β-catenin expression in colon cancer cells.
  PloS one · 2026 · Kandhavelu J, Subramanian K, Moodley N, et al.
  PMID 42224286DOI 10.1371/journal.pone.0348215
• Impaired Neuregulin 1 Processing is Associated with Synaptic and Behavioral Abnormalities in a Prenatal Valproic Acid Model of Autism.
  International journal of biological sciences · 2026 · Kim YJ, Kim HB, Lim HM, et al.
  PMID 42212327DOI 10.7150/ijbs.133137
• Synergistic Cardiac Protection by Thymoquinone and Valproic Acid in Absence Epilepsy.
  Physiological research · 2026 · Cimen YA, Karakaya-Cimen FB, Demirci H, et al.
  PMID 42187503DOI 10.33549/physiolres.935733
• Quality improvement project improving awareness of family planning risks with valproate in male patients.
  The British journal of general practice : the journal of the Royal College of General Practitioners · 2026 · Shahul SF
  PMID 42134936DOI 10.3399/bjgp26X745605
• Determinants and Machine Learning Prediction of Subtherapeutic Sodium Valproate Concentrations in Epilepsy Management in Xinjiang, China.
  European journal of drug metabolism and pharmacokinetics · 2026 · Yang H, Lv X, Kadeer A, et al.
  PMID 42107022DOI 10.1007/s13318-026-00999-y

The 10 most recently updated of 442 ClinicalTrials.gov registrations naming Valproic Acid as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine
  Recruiting · Phase 3 · Interventional · 424 enrolled · Bristol-Myers Squibb
  NCT07140913updated 2026-06-10
• A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
  Recruiting · Phase 3 · Interventional · 450 enrolled · Bristol-Myers Squibb
  NCT06929273updated 2026-06-02
• Bevacizumab and Temsirolimus Alone or in Combination With Valproic Acid or Cetuximab in Treating Patients With Advanced or Metastatic Malignancy or Other Benign Disease
  Terminated · Phase 1 · Interventional · 154 enrolled · M.D. Anderson Cancer Center
  NCT01552434updated 2026-05-15
• Rubinstein-Taybi Syndrome: Functional Imaging and Therapeutic Trial
  Completed · Phase 2 · Interventional · 41 enrolled · University Hospital, Bordeaux
  NCT01619644updated 2026-05-14
• Combining Sodium Valproate With Standard-of-care EGFR (Epidermal Growth Factor Receptor) Monoclonal Antibody Treatment in Patients With Metastatic Colorectal Cancer
  Active not recruiting · Phase 2 · Interventional · 38 enrolled · Australasian Gastro-Intestinal Trials Group
  NCT05694936updated 2026-05-08
• The Combination of Pharmacotherapy and Cognitive Behavioral Psychotherapy Under the Recovery Perspective.
  Active not recruiting · Phase 1 · Interventional · 107 enrolled · Rakitzi, Stavroula
  NCT06993662updated 2026-05-07
• Ketogenic Diet for New-Onset Absence Epilepsy
  Recruiting · Phase 3 · Interventional · 40 enrolled · Johns Hopkins University
  NCT04274179updated 2026-05-07
• Efficacy and Safety Trial of Sodium Valproate, in Paediatric and Adult Patients With Wolfram Syndrome
  Completed · Phase 2 · Interventional · 63 enrolled · University of Birmingham
  NCT03717909updated 2026-05-05
• Fast Acute Sedation at Intensive Care vs. High-dose i.v. Anti-seizure Medication for Treatment of Non-convulsive Status Epilepticus (FAST-trial)
  Recruiting · Phase 3 · Interventional · 140 enrolled · University of Southern Denmark
  NCT05263674updated 2026-05-04
• Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
  Active not recruiting · Phase 4 · Interventional · 84 enrolled · Dr. Stavroula Rakitzi
  NCT07047651updated 2026-05-01

CPIC-curated drug–gene pairs for Valproic Acid. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• ABL2CPIC B (provisional)
• ASLCPIC B (provisional)
• ASS1CPIC B (provisional)
• CPS1CPIC B (provisional)
• NAGSCPIC B (provisional)
• OTCCPIC B (provisional)FDA label: Actionable PGx
• POLGCPIC A/B (provisional)ClinPGx 3FDA label: Testing Required

Frequently asked questions

How does Valproic Acid work?

Valproic acid dissociates to the valproate ion in the gastrointestinal tract. The mechanisms by which valproate exerts its therapeutic effects have not been established.

What is Valproic Acid used for?

According to FDA labeling, Valproic Acid carries indications including: Valproic acid oral solution is indicated for: Monotherapy and adjunctive therapy of complex partial seizures; sole and adjunctive therapy of simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 1.1 Epilepsy Valproic acid oral solution is indicated as monotherapy and adjunctive therapy in the treatment of patients with complex partial seizures that occur either in isolation or in association with other types of seizures. Valproic acid oral solution is indicated for use as sole and adjunctive therapy in the treatment of simple and complex absence seizures, and adjunctively in patients with multiple seizure types which include absence seizures.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Valproic Acid?

Valproic Acid is classified as Fatty acid derivatives, Anti-epileptic Agent, Mood Stabilizer, GABA A Receptor Interactions, GABA B Receptor Interactions, Decreased Central Nervous System Disorganized Electrical Activity, Increased GABA Activity.

What are the contraindications for Valproic Acid?

Valproic Acid labeling lists contraindications including: Valproic acid should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 )] . Valproic acid is contraindicated in patients known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase γ (POLG; e.g., Alpers-Huttenlocher Syndrome) and children under two years of age who are suspected of having a POLG-related disorder [see Warnings and Precautions ( 5.1 )] .. Always consult the full prescribing information and a clinician.