Antiseizure medications · Neurology
Valproate (valproic acid, divalproex)
valproic acid · divalproex sodium · sodium valproate · Depakene® · Epival® · Depakote®(brand names vary by market)
Broad-spectrum, highly effective, and the most teratogenic drug in common use.
Also: capsule, oral liquid, injection, modified release
Mechanism
Multiple actions: sodium channel blockade, increased GABA availability, and T-type calcium channel effects. The breadth of mechanism matches the breadth of seizure types it covers.
Indications
- Generalised epilepsy including absence and myoclonic seizures
- Bipolar disorder
- Migraine prophylaxis
Formulations
Dosing concepts
Pregnancy
Associated with major congenital malformations in roughly a tenth of exposed pregnancies and with neurodevelopmental impairment in a larger fraction. It is not prescribed to anyone who could become pregnant without a documented pregnancy-prevention programme.
Hyperammonemia
It can raise ammonia and cause encephalopathy with a normal drug level and normal liver enzymes. A confused patient on valproate needs an ammonia, not just a level.
Concepts, not prescribing instructions. Practice numbers live in current references and local protocols.
Pharmacokinetics
- Bioavailability
- High
- Half-life
- 9 to 16 h
- Elimination
- hepatic: Glucuronidation and beta-oxidation; an enzyme INHIBITOR, unlike phenytoin and carbamazepine
- Protein binding
- ~90%, and saturable, which is why free levels rise disproportionately at higher totals
Adverse effects
- TeratogenicityseriousNeural tube defects, facial and cardiac malformations, and reduced IQ after in-utero exposure.
- Weight gaincommon
- Tremorcommon
- HepatotoxicityseriousHighest risk in young children and in mitochondrial disease.
- Pancreatitisserious
- Thrombocytopeniacommon
- Hyperammonemic encephalopathyserious
- Hair losscommon
Contraindications & precautions
Contraindications
- Pregnancy, for epilepsy unless no alternative exists, and absolutely for bipolar disorder and migraine
- Known mitochondrial disorders
- Significant hepatic impairment
- Urea cycle disorders
Precautions
- Anyone of childbearing potential
- Concurrent lamotrigine, whose level it raises sharply
- Liver disease
Interactions
No curated interaction entries yet for this agent.
Monitoring
Pregnancy prevention and annual review of the risk discussion
The single most important thing about this drug
Full blood count and liver enzymes
Thrombocytopenia and hepatotoxicity · Baseline and periodically
Ammonia if confused, regardless of the level
Encephalopathy occurs at therapeutic levels
Level, where adherence or toxicity is in question
Interpreted alongside albumin because binding is saturable
Counselling points
- If you could become pregnant, this medicine requires a specific discussion and reliable contraception every time it is reviewed.
- Report abdominal pain, vomiting, yellowing, or unusual bruising.
- Do not stop it suddenly.
- Tell us if you feel confused or unusually drowsy.
Clinical pearls
- Valproate encephalopathy from hyperammonemia occurs with a therapeutic level and normal transaminases. If you only check the level, you will miss it.
- Adding valproate to lamotrigine roughly doubles the lamotrigine level and is a well-documented route to Stevens-Johnson syndrome; the lamotrigine dose is halved in advance.
References & review
- Valproate product monograph (consult the current version for your market) (monograph)
- Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed. (reference-work)
Last reviewed 2026-08-16 · jurisdiction: global · drug information changes; verify against current references before practice use.