May cause CNS depression. Hepatic failure resulting in fatalities occurred (higher risk in children <2 years of age, organic brain disease, mental retardation with severe seizure disorders, congenital metabolic disorders, and patients on multiple anticonvulsants). Hepatotoxicity usually reported. Should only be used as monotherapy in children <2 years of age and patients at high risk for hepatotoxicity. Hyperammonemia and/or encephalopathy, sometimes fatal, may be present with normal transaminase levels. Contraindicated in urea cycle disorder. Hypothermia reported with valproic acid therapy (may or may not be associated with hyperammonemia; may also occur with concomitant topiramate therapy). Potentially serious, sometimes fatal multiorgan hypersensitivity reactions rarely reported in adults and children. Cases of life-threatening pancreatitis, occurring at start of therapy or following years of use, reported in adults and children. Increased risk of suicidality (higher in epilepsy). May cause severe thrombocytopenia (may be dose-related), inhibition of platelet aggregation, and bleeding. Tremors may indicate overdosage. Contraindicated with severe impairment. Concomitant use with carbapenem antibiotics may reduce valproic acid levels to subtherapeutic levels. Concomitant use with clonazepam may induce absence status. Concomitant use with topiramate associated with hyperammonemia and hypothermia with or without encephalopathy. Use with caution in elderly patients (may be more sensitive to sedating effects). May cause teratogenic effects such as neural tube defects (e.g. spina bifida). In vitro studies suggested valproic acid stimulates replication of HIV and CMV viruses under experimental conditions (clinical consequence unknown). Therapy should be withdrawn gradually to minimize potential of increased seizure frequency.