Divalproex toxicity

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Divalproex sodium toxicity is manifested by drowsiness, weakness, incoordination, and confusion (Menkes, 1999) Treatment is supportive, requiring hospitalization. 

The program is straightforward in its call to start drugging children in the absence of any scientific basis In the absence of treatment data, treatment of childhood bipolar illness is modeled on that of adults. Even if the child shows no signs of psychosis, the most toxic adult drugs are recommended For non-psychotic children, in descending order, treatment should be tried with lithium, divalproex, atypical antipsychotic, combining any of these approaches, and other anticonvulsants plus atypical antipsychotics or conventional antipsychotic. ... 

Divalproex sodium extended-release (Depakote ER) is a once daily (QD) formulation for VPA that was developed to improve patient compliance and reduce side effects compared to the standard twice-daily (BID) delayed release (DR) formulation (Depakote tablets). However, there are concerns of potential subthera-peutic concentrations following delayed or missed doses or toxic concentrations with replacement doses for the ER and DR formulations. 

The most commonly observed side effects for valproate are gastrointestinal (anorexia, nausea, and Indigestion). These effects can be minimized by selecting divalproex sodium, which is enterically coated, and by Initiating therapy at a low dose. More Importantly, however, valproate is associated with the development of fatal hepatotoxicity, especially in children or when coadministered with other AEDs. Frequent monitoring of liver function tests is mandatory for determining the onset of toxicity. 

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