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September 10, 2024
As hospices operate with limited funds, minimizing drug costs is important. Therapeutic substitution, where one drug is replaced with a less expensive drug, is one tool to help with this. One substitution we’re occasionally asked about is using valproic acid (VPA) (Depakene) in place of divalproex sodium (Depakote). VPA costs about half as much as divalproex in most cases.1
VPA and its derivatives (Table 1) are effective treatments for seizures, bipolar disorder, and migraine prophylaxis.2-4 VPA, first marketed as Depakene, has been around since the 1970s.3,4 Divalproex sodium delayed release (DR) and extended release (ER) formulations were later developed with the intent of reducing the incidence of concentration dependent gastrointestinal (GI) side effects like dyspepsia, nausea, and vomiting.2,4 A literature review published in 2023 found that the forms are interchangeable without differences in efficacy.3-5
Table 1. Valproic Acid and Derivatives2
| Drug | Strength | Typical Dosing Frequency |
|---|---|---|
| Divalproex sodium ER tablet (Depakote ER) | 250mg | Once daily |
| 500mg | ||
| Divalproex sodium DR tablet (Depakote) | 125mg | 2 to 3 times daily |
| 250mg | ||
| 500mg | ||
| Divalproex sodium DR capsule (Depakote Sprinkles) | 125mg | |
| Valproic acid capsule (Depakene) | 250mg | 3 to 4 times daily |
| Valproic acid solution (sodium salt; Depakene) | 250mg/5ml |
VPA and divalproex DR are interchangeable on a 1:1 milligram (mg) per mg basis.2,4 Divalproex ER is less bioavailable, so when switching from ER to VPA, an 8-20% dose reduction is warranted. Recognize that VPA is dosed three to four times a day. So, when switching from divalproex DR 500mg twice a day, for example, you could substitute VPA 250mg four times a day.
The biggest potential downside to this substitution is that VPA tends to cause more GI side effects compared to divalproex.3-7 But, studies have demonstrated that substitution is well tolerated.3-7 If GI related side effects materialize after substituting VPA, it’s reasonable to consider switching back to divalproex.
Switching gears…you’ve undoubtedly seen valproate preparations being used in an attempt to manage behavioral and psychological symptoms of dementia (BPSD). However, a 2018 Cochrane Review concluded that these drugs can’t be recommended for dementia-related agitation and behaviors because they’re probably ineffective for this indication and are associated with adverse effects like dizziness (falls), sedation, insomnia, tremor, nausea, vomiting, diarrhea, infection, and thrombocytopenia.2,8 So if you see these drugs being used in dementia patients, deprescribe them via taper unless a valid indication exists.
Written by: OnePoint Patient Care Clinical Team
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