Valproate

Most widely prescribed antiepileptic drug worldwide.

Used in treatment of epilepsy, acute mania, bipolar disease, impulse-control disorders, migraine headaches, and neuropathic pain.

Hemorrhage

Platelet dysfunction

Coagulopathy

Hyperammonemic encephalopathy

Seizures with subtherapeutic plasma concentration

Decreased factor VII levels, plt count and function, factor VIII, protein C, fibrinogen, factor XIII, increased lipoprotein (a) levels, acquired von Willenbrand disease.

Serum valproate levels of >140 μg/mL may be related to low plt levels.

Children with a trough level of >450 μmol/L or a daily dose of >40 mg/kg are more likely to develop thrombocytopenia.

Nausea, gastric irritation, diarrhea, hyperammonemia, thrombocytopenia.

Highly protein-bound (88–92%); may displace other protein-bound drugs and increase their plasma concentration (e.g., warfarin).