What is the equivalent IV dose of valproate sodium (Depakote) when converting from oral Depakote?

Converting Oral Depakote to IV Valproate Sodium

When converting from oral Depakote to IV valproate sodium, use a 1:1 dose conversion ratio with a loading dose of 15-20 mg/kg administered at a rate of 6-10 mg/kg/minute for rapid therapeutic effect.

Conversion Principles

The conversion from oral Depakote (divalproex sodium) to IV valproate sodium follows these key principles:

• Dose Equivalence: IV valproate sodium is administered at the same total daily dose as oral Depakote (1:1 conversion)
• Loading Dose Strategy: For patients requiring rapid therapeutic levels
  • 15-20 mg/kg loading dose for most patients 1
  • Up to 30 mg/kg may be used in status epilepticus 1
  • Can be administered undiluted at rates up to 10 mg/kg/min 2

Administration Protocol

Loading Dose (for patients not currently on valproate):

• Dose: 15-20 mg/kg IV 3
• Rate: 6-10 mg/kg/min 2
• Expected Levels: Achieves therapeutic levels within 1 hour
  • Children: ~65 mg/L total and ~7.5 mg/L free concentration
  • Adults: ~80 mg/L total and ~11 mg/L free concentration 3

Maintenance Dosing:

• Timing: Begin 6 hours after loading dose 3
• Uninduced Patients:
  • Children: 7.5 mg/kg IV every 6 hours
  • Adults: 3.5 mg/kg IV every 6 hours 3
• Enzyme-Induced Patients:
  • May require twice the maintenance dose 3

Safety Considerations

IV valproate has several advantages over other IV antiepileptics:

• Cardiovascular Safety: No significant changes in heart rate or blood pressure even with rapid infusion 2
• Local Tolerance: Transient local irritation may occur but resolves within minutes without phlebitis 2
• Compared to Phenytoin: Similar efficacy but fewer hemodynamic side effects
  • In status epilepticus, valproate (88%) and phenytoin (84%) showed similar efficacy
  • 12% of phenytoin patients developed hypotension versus none with valproate 1

Special Situations

Status Epilepticus:

• Higher loading doses (30 mg/kg) may be used 1
• Infusion rate of 6 mg/kg/hour has shown 88% seizure control within 1 hour 1
• Efficacy rates range from 63-88% across multiple studies 1

Converting Back to Oral:

• When switching back to oral Depakote, begin oral dosing within 2 hours of the last IV dose if using delayed-release formulation
• Extended-release formulation can be initiated concurrently with the final IV dose 3

Common Pitfalls to Avoid

1. Underdosing: Inadequate loading doses may result in subtherapeutic levels
2. Ignoring enzyme induction: Patients on enzyme-inducing medications require higher maintenance doses
3. Delayed oral conversion: When converting back to oral therapy, delayed-release formulations should be started within 2 hours of the last IV dose to maintain therapeutic levels
4. Monitoring failure: Despite the safety profile, monitoring for adverse effects remains important, particularly with higher doses

IV valproate is well-tolerated even at rapid infusion rates and provides a safe alternative to phenytoin, especially in hemodynamically unstable patients.