Valproate

Valproate sodium exists as the valproate ion in the blood. The mechanisms by which valproate exerts its therapeutic effects have not been established.

• Valproate sodium injection is indicated as an intravenous alternative in patients in whom oral administration of valproate products is temporarily not feasible in the following conditions: • Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 1.1 Epilepsy Valproate sodium injection is indicated as an intravenous alternative in patients for whom oral administration of valproate products is temporarily not feasible in the following conditions: Valproate sodium injection 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. Valproate sodium injection is also indicated for use as sole and adjunctive therapy in the treatment of patients with simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.ICD-10: G40.909

• • Valproate sodium injection should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 )] . • Valproate sodium injection 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

Valproate sodium injection is intended for intravenous use only. • Epilepsy o Complex Partial Seizures in Adults and Children 10 years of age or older: Initial dose is 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/day to achieve optimal clinical response. Maximum recommended dose is 60 mg/kg/day ( 2.1 ). o Simple and Complex Absence Seizures: Initial dose is 10 to 15 mg/kg/day, increasing at 1 week intervals by 5 to 10 mg/kg/day to achieve optimal clinical response. Maximum recommended dose is 60 mg/kg/day ( 2.1 ). 2.1 Epilepsy Valproate sodium injection is for intravenous use only. Use of valproate sodium injection for periods of more than 14 days has not been studied. Patients should be switched to oral valproate products as soon as it is clinically feasible. Valproate sodium injection should be administered as a 60 minute infusion (but not more than 20 mg/min) with the same frequency as the oral products, although plasma concentration monitoring and dosage adjustments may be necessary. In one clinical safety study, approximately 90 patients with epilepsy and with no measurable plasma levels of valproate were given single infusions of valproate sodium injection (up to 15 mg/kg and mean dose of 1,184 mg) over 5 to 10 minutes (1.5 to 3 mg/kg/min). Patients generally tolerated the more rapid infusions well [see Adverse Reactions ( 6.1 )] . This study was not designed to assess the effectiveness of these regimens. For pharmacokinetics with rapid infusions, see Clinical Pharmacology ( 12.3 ).

• 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; valproate sodium should ordinarily be discontinued ( 5.5 ) • Bleeding and other hematopoietic disorders; monitor platelet counts and coagulation tests ( 5.7 ) • 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 , 5.8 , 5.9 ) • Hypothermia; Hypothermia has been reported during valproate therapy with or without associated hyperammonemia. This adverse reaction can also occur in patients using concomitant topiramate ( 5.10 ) • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reaction; discontinue valproate sodium ( 5.11 ) • Somnolence in the elderly can occur. Valproate sodium dosage should be increased slowly and with regular monitoring for fluid and nutritional intake ( 5.13 ) 5.1 Hepatotoxicity General Information on Hepatotoxicity Hepatic failure resulting in fatalities has occurred in patients receiving valproate.

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 , 5.8 , 5.9 )] • Bleeding and other hematopoietic disorders [see Warnings and Precautions ( 5.7 )] • Hypothermia [see Warnings and Precautions ( 5.10 )] • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan hypersensitivity reactions [see Warnings and Precautions ( 5.11 )] • Somnolence in the elderly [see Warnings and Precautions ( 5.13 )] 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. The adverse reactions that can result from valproate sodium use include all of those associated with oral forms of valproate. The following describes experience specifically with valproate sodium. Valproate sodium has been generally well tolerated in clinical trials involving 111 healthy adult male volunteers and 352 patients with epilepsy, given at doses of 125 to 6,000 mg (total daily dose). A total of 2% of patients discontinued treatment with valproate sodium due to adverse reactions.

• Pregnancy: Valproate sodium 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 ( 5.13 , 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 Valproate sodium, during pregnancy. Encourage women who are taking Valproate sodium 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

Bioavailability Equivalent doses of intravenous (IV) valproate and oral valproate products are expected to result in equivalent C max , C min , and total systemic exposure to the valproate ion when the IV valproate is administered as a 60 minute infusion. However, the rate of valproate ion absorption may vary with the formulation used.

Overdosage with valproate may result in somnolence, heart block, deep coma, and hypernatremia. Fatalities have been reported; however patients have recovered from valproate serum concentrations 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. 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.

• Nov 14, 2002ANDAANDA076295Sagent
• Jun 26, 2003ANDAANDA076539Fresenius Kabi Usa
• Feb 17, 2010ANDAANDA078523Hikma Farmaceutica

1. 1Drug Ineffective1,4277.1%
2. 2Drug Interaction1,2306.1%
3. 3Off Label Use1,1255.6%
4. 4Foetal Exposure During Pregnancy1,0435.2%
5. 5Somnolence9774.9%
6. 6Epilepsy8324.1%
7. 7Seizure7773.9%
8. 8Toxicity To Various Agents7703.8%
9. 9Pyrexia7503.7%
10. 10Vomiting6173.1%
11. 11Convulsion6123.0%
12. 12Neutropenia5362.7%
13. 13Diarrhoea5242.6%
14. 14Condition Aggravated5172.6%
15. 15Weight Increased5102.5%

Recent PubMed references pinned to Valproate 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 Valproate 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

Frequently asked questions

How does Valproate work?

Valproate sodium exists as the valproate ion in the blood. The mechanisms by which valproate exerts its therapeutic effects have not been established.

What is Valproate used for?

According to FDA labeling, Valproate carries indications including: Valproate sodium injection is indicated as an intravenous alternative in patients in whom oral administration of valproate products is temporarily not feasible in the following conditions: • Monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures; adjunctive therapy in patients with multiple seizure types that include absence seizures ( 1 ) 1.1 Epilepsy Valproate sodium injection is indicated as an intravenous alternative in patients for whom oral administration of valproate products is temporarily not feasible in the following conditions: Valproate sodium injection 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. Valproate sodium injection is also indicated for use as sole and adjunctive therapy in the treatment of patients with simple and complex absence seizures, and adjunctively in patients with multiple seizure types that include absence seizures.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Valproate?

Valproate is classified as Increased GABA Activity.

What are the brand names for Valproate?

Valproate is marketed under brand names including Depakote.

What are the contraindications for Valproate?

Valproate labeling lists contraindications including: • Valproate sodium injection should not be administered to patients with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 )] . • Valproate sodium injection 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.