{
 "query": "valproate",
 "ingredient": "valproate",
 "slug": "valproate",
 "rxcui": "40254",
 "brands": [],
 "names": [
  "valproate",
  "valproic acid",
  "divalproex sodium",
  "valproate sodium"
 ],
 "classes": [],
 "alternatives": [],
 "label": {
  "route_mode": "ORAL",
  "route_counts": {
   "ORAL": 142,
   "INTRAVENOUS": 5
  },
  "boxed_warning": "WARNING: LIFE THREATENING ADVERSE REACTIONS Hepatotoxicity General Population: Hepatic failure resulting in fatalities has occurred in patients receiving valproate and its derivatives. These incidents usually have occurred during the first six months of treatment. Serious or fatal hepatotoxicity may be preceded by non-specific symptoms such as malaise, weakness, lethargy, facial edema, anorexia, and vomiting. In patients with epilepsy, a loss of seizure control may also occur. Patients should be monitored closely for appearance of these symptoms. Serum liver tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months [see Warnings and Precautions ( 5.1 )] . Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease. When Depakote ER is used in this patient group, it should be used with extreme caution and as a sole agent. The benefits of therapy should be weighed against the risks...",
  "indications_and_usage": "Depakote ER is indicated for: Acute treatment of manic or mixed episodes associated with bipolar disorder, with or without psychotic features ( 1.1 ) 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 ( 1.2 ) Prophylaxis of migraine headaches ( 1.3 ) 1.1 Mania Depakote ER is a valproate and is indicated for the treatment of acute manic or mixed episodes associated with bipolar disorder, with or without psychotic features. A manic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood. Typical symptoms of mania include pressure of speech, motor hyperactivity, reduced need for sleep, flight of ideas, grandiosity, poor judgment, aggressiveness, and possible hostility. A mixed episode is characterized by the criteria for a manic episode in conjunction with those for a major depressive episode (depressed mood, loss of interest or pleasure in nearly all activities). The efficacy of Depakote ER is based in part on studies of Depakote (divalproex sodium delayed release tablets) in this indication, and was c...",
  "contraindications": "Depakote ER is contraindicated in patients: \u2022 with hepatic disease or significant hepatic dysfunction [see Warnings and Precautions ( 5.1 ) ]. \u2022 known to have mitochondrial disorders caused by mutations in mitochondrial DNA polymerase \u03b3 (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 ) ] . \u2022 with known hypersensitivity to divalproex sodium, sodium valproate, or valproic acid. Reactions have included multiorgan hypersensitivity, serious dermatologic reactions, and angioedema [see Warnings and Precautions ( 5.12 , 5.13 , 5.14 ) ]. \u2022 with known urea cycle disorders [see Warnings and Precautions ( 5.6 ) ]. \u2022 being treated for prophylaxis of migraine headaches: who are pregnant or in women of childbearing potential who are not using effective contraception [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.1 ) ] . Hepatic disease or significant hepatic dysfunction ( 4 , 5.1 ) Known mitochondrial disorders caused by mutations in mitochondrial DNA polymerase \u03b3 (POLG) ( 4 , 5.1 ) Suspected POLG-related disorder in children under two years...",
  "warnings_and_cautions": "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: Depakote ER should ordinarily be discontinued ( 5.5 ) Suicidal behavior or ideation: Antiepileptic drugs, including Depakote ER, 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 hypers...",
  "warnings": "",
  "adverse_reactions": "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 and Neurodevelopmental Disorders 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 ) ] Serious Dermatologic Reactions [see Warnings and Precautions ( 5.13 ) ] Angioedema [see Warnings and Precautions ( 5.14 ) ] Somnolence in the Elderly [see Warnings and Precautions ( 5.16 ) ] 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_abuse_and_dependence": "",
  "controlled_substance": "",
  "recent_major_changes": "Contraindications ( 4 ) 5/2025 Warnings and Precautions ( 5.2 , 5.3 ) 3/2026 Warnings and Precautions ( 5.13 , 5.14 ) 5/2025",
  "information_for_patients": "Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Hepatotoxicity Warn patients and guardians that nausea, vomiting, abdominal pain, anorexia, diarrhea, asthenia, and/or jaundice can be symptoms of hepatotoxicity and, therefore, require further medical evaluation promptly [see Warnings and Precautions ( 5.1 ) ] . Pancreatitis Warn patients and guardians that abdominal pain, nausea, vomiting, and/or anorexia can be symptoms of pancreatitis and, therefore, require further medical evaluation promptly [see Warnings and Precautions ( 5.5 ) ] . Birth Defects , Decreased IQ , and Neurodevelopmental Disorders Inform pregnant women and women of childbearing potential (including girls beginning the onset of puberty) that use of valproate during pregnancy increases the risk of birth defects, decreased IQ, and neurodevelopmental disorders in children who were exposed in utero [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.1 ) ] . Advise women to use effective contraception while taking valproate. When appropriate, counsel these patients about alternative therapeutic options. This is particularly important when valproate use...",
  "spl_medguide": "MEDICATION GUIDE DEPAKOTE ER (dep-a-kOte) (divalproex sodium) Extended-Release Tablets, for oral use DEPAKOTE (dep-a-kOte) (divalproex sodium) Delayed-Release Tablets, for oral use DEPAKOTE Sprinkle Capsules (dep-a-kOte) (divalproex sodium delayed release capsules) for oral use What is the most important information I should know about DEPAKOTE? Do not stop Depakote without first talking to a healthcare provider. Stopping Depakote suddenly can cause serious problems. Stopping a seizure medicine suddenly in a patient who has epilepsy can cause seizures that will not stop (status epilepticus). Depakote can cause serious side effects, including: 1. Serious liver damage that can cause death, especially in children younger than 2 years old and patients with mitochondrial disorders. The risk of getting this serious liver damage is more likely to happen within the first 6 months of treatment. Call your healthcare provider right away if you get any of the following symptoms: feeling very weak, tired, or uncomfortable (malaise) swelling of your face not feeling hungry nausea or vomiting that does not go away diarrhea pain on the right side of your stomach (abdomen) dark urine yellowing of y...",
  "clinical_studies": "Figure 1 Figure 2 Figure 3 14.1 Mania The effectiveness of Depakote ER for the treatment of acute mania is based in part on studies establishing the effectiveness of Depakote (divalproex sodium delayed release tablets) for this indication. Depakote ER\u2019s effectiveness was confirmed in one randomized, double-blind, placebo-controlled, parallel group, 3-week, multicenter study. The study was designed to evaluate the safety and efficacy of Depakote ER in the treatment of bipolar I disorder, manic or mixed type, in adults. Adult male and female patients who had a current DSM-IV TR primary diagnosis of bipolar I disorder, manic or mixed type, and who were hospitalized for acute mania, were enrolled into this study. Depakote ER was initiated at a dose of 25 mg/kg/day given once daily, increased by 500 mg/day on Day 3, then adjusted to achieve plasma valproate concentrations in the range of 85-125 mcg/mL. Mean daily Depakote ER doses for observed cases were 2,362 mg (range: 500-4,000), 2,874 mg (range: 1,500-4,500), 2,993 mg (range: 1,500-4,500), 3,181 mg (range: 1,500-5,000), and 3,353 mg (range: 1,500-5,500) at Days 1, 5, 10, 15, and 21, respectively. Mean valproate concentrations were 9...",
  "brand_name": "Depakote ER",
  "manufacturer": "AbbVie Inc.",
  "application_number": "NDA021168",
  "pharm_class_epc": [],
  "route": [
   "ORAL"
  ],
  "effective_time": "20260331",
  "set_id": "0dc024ce-efc8-4690-7cb5-639c728fccac",
  "has_boxed_warning": true,
  "controlled": false,
  "mentions_rems": false
 },
 "faers": {
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  "serious": 80271,
  "death": 7679,
  "hospitalization": 37810,
  "primary_suspect": 91919,
  "top_reactions": [
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    9254
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   [
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   [
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    6664
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   [
    "Drug Interaction",
    6173
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   [
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    4201
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   [
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    3744
   ],
   [
    "Foetal Exposure During Pregnancy",
    3434
   ],
   [
    "Fatigue",
    3056
   ],
   [
    "Epilepsy",
    2729
   ],
   [
    "Fall",
    2713
   ],
   [
    "Nausea",
    2709
   ],
   [
    "Condition Aggravated",
    2671
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   [
    "Vomiting",
    2644
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    2572
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    2529
   ]
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  "by_year": {
   "2019": 8319,
   "2020": 8093,
   "2021": 9699,
   "2022": 8421,
   "2023": 6708,
   "2024": 6348,
   "2025": 6062,
   "2026": 2753
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  "by_year_primary": {
   "2019": 8299,
   "2020": 8054,
   "2021": 9540,
   "2022": 8180,
   "2023": 6455,
   "2024": 6184,
   "2025": 5860,
   "2026": 2623
  }
 },
 "faers_base": {
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  "serious_share": 0.5742697381596559,
  "death_share": 0.09102355155810585
 },
 "recalls": [
  {
   "class": "Class II",
   "date": "20260626",
   "reason": "Presence of Foreign Tablets/Capsules",
   "firm": "Bionpharma Inc.",
   "status": "Ongoing"
  },
  {
   "class": "Class II",
   "date": "20231226",
   "reason": "Failed dissolution specifications",
   "firm": "Amneal Pharmaceuticals of New York, LLC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20220727",
   "reason": "Failed dissolution specifications.",
   "firm": "Amneal Pharmaceuticals of New York, LLC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20220627",
   "reason": "Failed Dissolution Specifications: Failure occurred during routine stability testing of dissolution test.",
   "firm": "SUN PHARMACEUTICAL INDUSTRIES INC",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20190424",
   "reason": "cGMP deviations: Product was exposed above 50% relative humidity levels during packaging operations.",
   "firm": "MAJOR PHARMACEUTICALS",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20190131",
   "reason": "Failed Dissolution Specifications: Out of specification results observed for high dissolution.",
   "firm": "Dr. Reddy's Laboratories, Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20171219",
   "reason": "Cross Contamination With Other Products: metronidazole powder was found in one bottle of Divalproex Sodium.",
   "firm": "Unichem Pharmaceuticals Usa Inc",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20150522",
   "reason": "Failed Dissolution Specifications; exceeded specification at the 9 hour time point",
   "firm": "Dr. Reddy's Laboratories, Inc.",
   "status": "Terminated"
  },
  {
   "class": "Class II",
   "date": "20150522",
   "reason": "Failed Dissolution Specifications; exceeded specification at the 9 hour time point",
   "firm": "Dr. Reddy's Laboratories, Inc.",
   "status": "Terminated"
  }
 ],
 "recall_total": 9,
 "drugsfda": {
  "applications": 67,
  "nda": 10,
  "anda": 56,
  "first_approval": "19780228",
  "rems": false,
  "rems_last": "",
  "labeling_supplements": 212,
  "labeling_recent": 23,
  "sponsors": [
   "ABBOTT",
   "ABBVIE",
   "ABBVIE INC",
   "ACTAVIS LABS FL INC",
   "ADAPTIS",
   "AJANTA PHARMA LTD",
   "ALEMBIC",
   "AMNEAL PHARMS"
  ],
  "unapproved": false,
  "first_approval_fmt": "02/28/1978"
 },
 "trials": {
  "total": 445,
  "completed": 290,
  "terminated": 69,
  "with_results": 101,
  "industry": 168,
  "phase3": 86,
  "results_share": 0.3482758620689655,
  "terminated_share": 0.1550561797752809
 },
 "pubmed": {
  "rct": 261,
  "meta": 71,
  "recent_rct": 26,
  "cochrane": [
   {
    "pmid": "33475151",
    "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents",
    "year": "2021"
   },
   {
    "pmid": "31621892",
    "title": "Valproate for acute mania",
    "year": "2019"
   },
   {
    "pmid": "30734919",
    "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents",
    "year": "2019"
   },
   {
    "pmid": "30293233",
    "title": "Valproate preparations for agitation in dementia",
    "year": "2018"
   },
   {
    "pmid": "30091458",
    "title": "Sodium valproate versus phenytoin monotherapy for epilepsy: an individual participant data review",
    "year": "2018"
   },
   {
    "pmid": "28195639",
    "title": "Ethosuximide, sodium valproate or lamotrigine for absence seizures in children and adolescents",
    "year": "2017"
   },
   {
    "pmid": "27884042",
    "title": "Valproate for schizophrenia",
    "year": "2016"
   },
   {
    "pmid": "27123830",
    "title": "Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures: an individual participant data review",
    "year": "2016"
   },
   {
    "pmid": "24132760",
    "title": "Valproic acid, valproate and divalproex in the maintenance treatment of bipolar disorder",
    "year": "2013"
   },
   {
    "pmid": "23970302",
    "title": "Phenytoin versus valproate monotherapy for partial onset seizures and generalised onset tonic-clonic seizures",
    "year": "2013"
   },
   {
    "pmid": "23797677",
    "title": "Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults",
    "year": "2013"
   },
   {
    "pmid": "23797674",
    "title": "Antiepileptics other than gabapentin, pregabalin, topiramate, and valproate for the prophylaxis of episodic migraine in adults",
    "year": "2013"
   }
  ]
 },
 "payments": {
  "year": "2024",
  "usd": 0.0,
  "records": 0,
  "by_name": [],
  "names_checked": [
   "valproate"
  ],
  "source": "bulk-index"
 },
 "partd": {
  "year": "2024",
  "claims": 5261475,
  "beneficiaries": 718509,
  "spend": 245977016.76,
  "by_brand": [
   {
    "brand": "Divalproex Sodium",
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    "is_generic": true
   },
   {
    "brand": "Divalproex Sodium ER",
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   },
   {
    "brand": "Valproic Acid",
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   {
    "brand": "Depakote",
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    "brand": "Depakote ER",
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   },
   {
    "brand": "Depakote Sprinkle",
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   }
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 "mdl": [],
 "dsc": [
  {
   "date": "20130506",
   "title": "Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ Scores in Exposed Children",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm350684.htm",
   "kind": "drug",
   "matched": "valproate"
  },
  {
   "date": "20110630",
   "title": "Valproate - Children born to mothers who took Valproate products while pregnant may have impaired cognitive development",
   "url": "https://www.fda.gov/Drugs/DrugSafety/ucm261543.htm",
   "kind": "drug",
   "matched": "valproate"
  }
 ],
 "settlements": [],
 "prescrire": null,
 "eml": {
  "listed": false,
  "status": "",
  "name": "",
  "matched": null,
  "stewardship": []
 },
 "exposure": {
  "years": [
   "2024",
   "2025",
   "2026"
  ],
  "reports_recent": 14667,
  "fills": 5261475,
  "per_million": 2787.6213419240803,
  "ratio": 1.0067432022224598,
  "median": 2768.949753790441
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 "scores": {
  "safety": {
   "score": 49,
   "letter": "F",
   "why": [
    "Carries an FDA boxed warning, the strongest warning the FDA issues (-30)",
    "FDA issued 2 Drug Safety Communication(s) naming this drug since 2010, most recently 2013 (-16)",
    "2,788 FDA reports naming it as the suspect drug per million Medicare fills, 1.0x the median drug on this site",
    "Death share in reports is near or below the FAERS average (0.9x)",
    "Off-label use is among the five most-reported items: widely used beyond its approved evidence (-5)"
   ],
   "weight": 0.35
  },
  "evidence": {
   "score": 60,
   "letter": "D",
   "why": [
    "261 randomized trials and 71 systematic reviews/meta-analyses indexed in PubMed",
    "12 independent Cochrane review(s) exist",
    "Only 35% of completed registered trials posted results (-15)",
    "'Drug ineffective' is the single most-reported item about this drug in FAERS (-5)"
   ],
   "weight": 0.25
  },
  "regulatory": {
   "score": 81,
   "letter": "B",
   "why": [
    "Recalls since 2016: 0 Class I, 7 Class II, 0 Class III across 56 generic makers (-6)",
    "23 label changes approved since 2021: the safety story is still moving (-8)",
    "Label lists recent major changes to warnings or indications (-5)"
   ],
   "weight": 0.15
  },
  "conflict": {
   "score": 100,
   "letter": "A",
   "why": [
    "Pharma paid doctors $0 tied to this drug last year: negligible",
    "Not named in any pending federal MDL"
   ],
   "weight": 0.15
  },
  "options": {
   "score": 70,
   "letter": "C",
   "why": [
    "Generic versions approved (56 applications)",
    "No same-class alternatives found: little leverage to switch (-30)"
   ],
   "weight": 0.1
  }
 },
 "total": 66,
 "grade": "C",
 "questions": [
  "In 2013 the FDA issued a safety communication about this drug (Valproate Anti-seizure Products Contraindicated for Migraine Prevention in Pregnant Women due to Decreased IQ ). Does that risk apply to me?",
  "This drug carries a boxed warning. Which specific risk does it cover, and does it apply to me?",
  "The most-reported problems in FDA's adverse event data are seizure, drug interaction. How would we recognize and handle those?",
  "Off-label use is among the most-reported items for this drug. Is my use on-label, and if not, what evidence supports it?",
  "What result are we expecting, by when, and what is the plan if it does not happen?",
  "If 100 people like me took this drug, how many would actually get better because of it, and how many would be harmed by it? (Doctors call these the number needed to treat and the number needed to harm.)"
 ]
}