What is the conversion from intravenous (IV) valproate to oral (PO) valproate?

From the Guidelines

When converting valproate from intravenous (IV) to oral (PO) administration, a direct conversion can be considered, but the provided evidence does not specify the exact conversion ratio for valproate 1. However, based on general medical knowledge, valproate has excellent oral bioavailability, which supports a 1:1 conversion ratio. For example, if a patient is receiving 500 mg of IV valproate every 8 hours, they should likely receive 500 mg of oral valproate every 8 hours, but this should be confirmed with the most recent and highest quality evidence available. Some key points to consider when making this transition include:

• Using the same total daily dose and frequency of administration to maintain therapeutic serum levels
• Monitoring serum valproate levels after conversion to ensure they remain within the therapeutic range (typically 50-100 μg/mL for most indications)
• Considering a brief period of overlapping therapy in critically ill patients or those with absorption concerns
• Being aware of the different oral formulations, such as divalproex sodium (Depakote) or valproic acid (Depakene), with divalproex often being better tolerated due to less gastrointestinal side effects. It's essential to prioritize maintaining consistent blood levels to ensure continued efficacy in conditions like epilepsy, bipolar disorder, or migraine prophylaxis, as valproate's mechanism of action involves enhancing GABA neurotransmission and blocking sodium channels 1.

From the Research

Conversion from Intravenous (IV) Valproate to Oral (PO) Valproate

• The conversion from IV valproate to oral valproate can be guided by the pharmacokinetics of valproate, which exhibits nonlinear protein binding and has a narrow therapeutic range (50-100mg/l) 2.
• For uninduced children and adults, 7.5 and 3.5mg/kg q6h IV valproate sodium can maintain therapeutic plasma VPA concentrations, and oral maintenance regimens of delayed-release divalproex sodium can be initiated within 2h of a loading dose 2.
• Plasma VPA concentrations can be sustained in the therapeutic range using once-daily maintenance regimens of extended-release divalproex sodium tablets if initiated concurrently with IV loading dose in the uninduced population 2.
• A two-fold higher IV and oral maintenance regimen dose may be required in induced patients 2.
• There is no direct evidence in the provided studies to support a specific conversion ratio from IV to oral valproate, but the studies suggest that oral valproate dosing can be adjusted based on the patient's response and plasma VPA concentrations 2, 3.

Key Considerations

• The pharmacokinetics of valproate are dependent on age, induction status, and formulation, so titration and dosing vary between individuals 2.
• The conversion from IV to oral valproate should be guided by the patient's clinical response and plasma VPA concentrations 2, 3.
• The use of extended-release or delayed-release formulations may affect the conversion from IV to oral valproate 2, 3.

Additional Information

• The safety of rapid IV loading of valproate has been evaluated, and it was found to be well-tolerated at infusion rates up to 10 mg/kg/min and doses of up to 30 mg/kg 4.
• The efficacy of IV valproate in the treatment of chronic migraine has been evaluated, and it was found to be a safe and well-tolerated intervention 5.