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Excessive amounts of valproic acid can result in sleepiness, tremor, stupor, respiratory depression, coma, metabolic acidosis, and death.

In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/l during controlled therapy, but may reach 150–1500 mg/l following acute poisoning.

Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves.

It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (including carbamazepine, lamotrigine, phenytoin and phenobarbitone) and itself.

A 2009 study found that the 3-year-old children of pregnant women taking valproate had an IQ nine points lower than that of a well-matched control group.