Valpros Pedia Overdosage

There have been reports of accidental and deliberate valproate overdosage. Signs and symptoms of overdosage include somnolence, heart block, or deep coma.
At plasma concentrations of up to 5 or 6 times the maximum therapeutic levels, any symptoms other than nausea, vomiting and dizziness are unlikely to be observed. Signs of an acute massive overdose (with plasma concentrations 10 to 20 times the maximum therapeutic levels) usually include central nervous system (CNS) depression or coma with muscular hypotonia, hyporeflexia, miosis, impaired respiratory function, metabolic acidosis, hypotension, and circulatory collapse/shock. Symptoms of overdose, however, may be variable, and seizures have been reported in the presence of very high plasma levels. There have also been cases of intracranial hypertension related to cerebral edema. Deaths have been reported rarely; favorable outcomes are usual and patients have recovered from valproate levels as high as 2.12 mg/mL.
During an overdose, the presence of sodium content in the valproate formulations may lead to hypernatremia.
Since the fraction of the drug that is unbound to protein is high during overdose situations, hemodialysis or tandem hemodialysis with hemoperfusion may result in significant removal of drug and have been used successfully. Gastric lavage may still be useful up to 10 to 12 hours following ingestion. However, as valproic acid is absorbed very rapidly, the benefit of gastric lavage or emesis will vary with the time since ingestion of valproate. For valproate administered orally, activated charcoal may reduce the absorption of the drug when given one to two hours after ingestion.
Management of overdose should consist of general supportive therapy. Airway and breathing should be established, and circulatory status should be evaluated. Assisted mechanical ventilation may be required in cases of respiratory depression. Particular attention should be given for the prevention of hypovolemia and the maintenance of adequate urinary output. Hepatic and pancreatic function should be monitored. Provided that adequate supportive treatment is given, full recovery usually occurs.
Intravenous naloxone has been reported to successfully reverse the CNS depressant effects of valproate overdosage, sometimes in association with orally administered activated charcoal. However, naloxone should be used with caution since theoretically, it could reverse the anticonvulsant effects of valproate.