Pharmacology · Antiseizure medicines
Valproic acid !
A broad-spectrum antiseizure and mood-stabilizing medicine. It is the most teratogenic of its class and can damage the liver and pancreas.
Updated 2026-11-01
Also called: Valproate, Sodium valproate, Divalproex sodium
Mechanism of action
Valproate slows the recovery of sodium channels from inactivation, reduces T-type calcium currents in thalamic neurons and raises GABA levels in the brain. It also inhibits histone deacetylases, which may relate to its effects on mood and on the fetus. This combination makes it effective against focal, generalized and absence seizures.
- Slows the recovery of sodium channels after each discharge
- Reduces T-type calcium currents in the thalamus
- Raises GABA levels in the brain
- Works against focal, generalized and absence seizures
Pharmacokinetics
- Absorption
- Well absorbed by mouth
- Distribution
- Highly bound to plasma proteins; other drugs can displace it
- Metabolism
- In the liver; it inhibits the metabolism of several other drugs
- Elimination
- Metabolites in the urine
Indications
- Focal seizures, absence seizures and mixed seizure types Epilepsy and seizures →
- Mania in bipolar disorder
- Migraine prevention (not during pregnancy) Migraine →
Adverse effects
Common
- Nausea, vomiting and abdominal pain
- Tremor and drowsiness
- Weight gain
- Hair loss
- Thrombocytopenia
Contraindications
- Liver disease or significant liver dysfunction
- Mitochondrial disorders from POLG mutations
- Urea cycle disorders
- Migraine prevention in pregnancy or without effective contraception
Key interactions
- Carbapenem antibiotics (meropenem, imipenem, ertapenem)
- Valproate levels fall sharply, with loss of seizure control
- Lamotrigine
- Lamotrigine levels and half-life rise, raising the risk of serious rash
- Topiramate
- Higher risk of hyperammonaemia and hypothermia
- Aspirin
- Displaces valproate from proteins and inhibits its metabolism
What is monitored
- Liver tests before treatment and often during the first six months
- Platelet count and coagulation
- Ammonia if there is lethargy, vomiting or a change in mental state
- Serum valproate level when needed
Administration and safety
- Given by mouth
- Capsules are swallowed whole, without chewing, to avoid irritating the mouth and throat
- Withdrawn gradually: stopping suddenly can trigger seizures
Nursing care
- Teach to report abdominal pain, vomiting or loss of appetite (pancreatitis) and jaundice, weakness or swelling of the face (liver)
- Watch for bruising or bleeding
- Watch for drowsiness, confusion or vomiting that may signal high ammonia
- For women who could become pregnant: confirm effective contraception and a pregnancy plan
Pregnancy and breastfeeding
Major teratogen: neural tube defects, other malformations and lower IQ; it is not used in pregnancy unless other medicines have failed or are unsuitable.
Test yourself
Think of the answer, then tap the question to see it.
What birth defects are most linked to valproate?
Neural tube defects such as spina bifida, other major malformations and lower IQ or neurodevelopmental disorders in exposed children.
Which group has the highest risk of fatal valproate liver failure?
Children under two years, especially on several antiseizure medicines or with metabolic disease such as POLG mitochondrial disorders.
Why is a carbapenem a problem in a patient on valproate?
Carbapenems lower valproate levels sharply and quickly, and seizures can return.
What happens to lamotrigine when valproate is added?
Valproate inhibits lamotrigine metabolism: levels and half-life rise, and the risk of serious rash increases.
Related drugs
Related conditions
← Back to the class: Antiseizure medicines
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Valproic Acid: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - VALPROIC ACID capsule, liquid filled (DailyMed (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 20 (McGraw Hill, 2023); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.