Divalproex sodium administration

Oral products Bedtime administration may minimize effects of CNS depression. Gl irritation may be minimized by taking with food or by slowly increasing the dose. Delayed-release divalproex sodium may reduce the incidence of irritative Gl effects. Swallow the extended-release tablets whole do not crush or chew. Swallow the valproic acid capsules without chewing to avoid local irritation of the mouth and throat. 

Absorption - /a pro c acid is rapidly and almost completely absorbed from the Gl tract. Absorption of the drug is delayed but not decreased by administration with meals administration of the drug with milk products does not affect the rate or degree of absorption. The bioavailability of valproate from divalproex sodium delayed-release tablets and capsules containing coated particles has been shown to be equivalent to that of valproic acid capsules. 

The sodium salt of valproate is marketed in Europe as a tablet and is quite hygroscopic. In Central and South America, the magnesium salt is available, which is considerably less hygroscopic. The free acid of valproate was first marketed in the USA in a capsule containing corn oil the sodium salt is also available in syrup, primarily for pediatric use. An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by many patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. Various extended-release preparations are available not all are bioequivalent and may require dosage adjustment. 

An enteric-coated tablet of divalproex sodium is also marketed in the USA. This improved product, a 1 1 coordination compound of valproic acid and sodium valproate, is as bioavailable as the capsule but is absorbed much more slowly and is preferred by most patients. Peak concentrations following administration of the enteric-coated tablets are seen in 3-4 hours. 

A. Ahmad, E. D. Boudinot, and W. E. Barr, R. C. Reed, and W. R. Garnett, The use of Monte Carlo simulations to study the effect of poor compliance on the steady state concentrations of valproic acid following administration of enteric-coated and extended release divalproex sodium formulations. Biopharm Drug Disp 26 417 25 (2005). 

Grannemati GR, SchneckDW, Cavanaugh JH, Witt GF. Pharmacokinetic interactions and side effects resulting from concomitant administration of lithium and divalproex sodium. J Clin P chiatry (199( 57,204-6. 

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