Side effects divalproex

The enteric-coated tablet divalproex sodium causes fewer GI side effects. It is metabolized in the gut to valproic acid. When switching from Depakote to Depakote-ER, the dose should be increased by 14% to 20%. Depakote ER may be given once daily. 

Side effects of valproic acid and divalproex sodium include nausea (less common with divalproex sodium and gradual dosing titration), tremor,... 

Carbamazepine (CBZ) and divalproex sodium (DVP) are the most common anticonvulsant agents prescribed for adult BD (Bowden et ah, 1994) Post et ah, 1998b) and pediatric epileptic disorders (Trimble, 1990 Dunn et al., 1998). As a consequence of their documented efficacy in these populations, their use has been extended to pediatric behavioral and mood disorders (Biederman et ah, 1998). We review here their mechanisms of action, pharmacokinetics, side effects, and pediatric uses. The multiple cytochrome P450 (CYB)-mediated potential drug interactions of CBZ and DVP are not covered in detail in this chapter. For a comprehensive review of this subjects the reader is referred to a recent publication by Flockhart and Oesterheld (2000). 

Divalproex (Depakote) was found to reduce temper outbursts and emotional lability in 10 adolescents with conduct disorder (Donovan et al., 1997). Studies of carbamazepine have yielded conflicting results. Cueva et al. (1996) did not find carbamazepine to be more effective than placebo in treating children hospitalized for conduct disorder in a double-blind, placebo-controlled study. As in the case of lithium, side effects (rashes, leukopenia, nausea, drowsiness) can be an issue with carbamazepine, offsetting its use. 

Indigestion, heartburn, and nausea are common side effects of valproate therapy. Use of the divalproex sodium preparation will help mitigate these effects. Patients may also be encouraged to take their doses with food. The symptomatic use of histamine H2 blockers, such as famotidine, is sometimes warranted. In most cases, however, dyspepsia is transient and not severe. Pancreatitis is a rare occurrence in patients receiving relatively high doses of valproate. If vomiting and severe abdominal pain develop during valproate therapy, serum amylase levels should be determined immediately. 

Sodium valproate is useful in the control of most seizure types and has the shortest half-life of the commonly used anticonvulsants (4—15 hours) a slowly absorbed form of the drug, divalproex sodium, is sometimes preferred. Valproate is relatively free from cognitive and behavioural side effects, but alopecia and weight gain frequently occur. The most severe side effect is idiosyncratic hepatotoxicity and pancreatitis, particularly in younger patients. However, these side effects are more frequent in patients taking valproate as a co-medication with other anticonvulsants. 

Divalproex immediate release formulation reduces gastrointestinal side effects compared to generic valproate... 

Divalproex ER Improves gastrointestinal side effects and alopecia compared to immediate release divalproex or generic valproate... 

Levine J, Chengappa KN, ParepaUy H. Side effect profile of enteric-coated divalproex sodium versus valproic acid. J Clin Psychiatry 2000 61(9) 680-1. 

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. 

Predictors of a positive response with valproate include rapid cycling, mixed episodes, comorbid panic disorder, organic mental disorders (e.g., head trauma), and mental retardation. " Low-dose valproate (125 to 500 mg/day) has been reported to be effective in reducing mood cycling in bipolar II disorder and cyclothymia. Oral loading with divalproex sodium, 20 mg/kg per day, may produce a rapid reduction in manic and psychotic symptoms within 4 days without causing major side effects, although there may be a lag time to obtain full antimanic efficacy. Development of tolerance and loss of efficacy with valproate occurs in some patients after several years of treatment." ... 

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. 

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. 

Aukst-Margetid B, Margetic B. Stuttering as a side-effect of divalproex sodium. Psychiatry Clin Neurosci 2008 62(6) 748. 

Pierre-Louis SJ, Brannegan RT, Evans AT. Seizure control and side-effect profile after switching adult epileptic patients from standard to extended-release divalproex sodium. Clin Neurol Neurosurg 2009 111(5) 437-41. 

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