Jump to content

depakote diazepam interaction - significance?


[Wi...]

Recommended Posts

My son is on depakote for bipolar disorder.  I have read that depakote will interact with diazepam.  But I am having difficulty understanding the significance of this, or if adjustments need to be made in his taper if there are changes to his depakote.  HIs depakote is too high, and needs to be lowered.  I'm worried this will lower his diazepam level as well and may need to adjust taper for this??

 

Here is what I found:  (I don't really understand it - help needed!)

 

"During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N-desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.

 

 

His depakote level is currently too high.  So doc want to lower it.  Doc says he is unaware of interaction, even though the prescribing info says:

 

Diazepam

Valproate displaces diazepam from its plasma albumin binding sites and inhibits its metabolism. Co-administration of valproate (1500 mg daily) increased the free fraction of diazepam (10 mg) by 90% in healthy volunteers (n=6). Plasma clearance and volume of distribution for free diazepam were reduced by 25% and 20%, respectively, in the presence of valproate. The elimination half-life of diazepam remained unchanged upon addition of valproate.

 

Anyone know what this means in practical terms??

 

 

 

 

Link to comment
Share on other sites

×
×
  • Create New...