Can I increase the dose of valproic acid (VA) from 125mg twice a day?

Valproic Acid Dosage Adjustment

Yes, the valproic acid dose can be increased from 125mg twice daily, but should be done gradually with careful monitoring for side effects and therapeutic levels.

Current FDA-Approved Dosing Guidelines

The FDA-approved dosing for valproic acid in epilepsy provides clear guidance for dose adjustments 1:

• Initial therapy typically starts at 10-15 mg/kg/day
• Dosage can be increased by 5-10 mg/kg/week to achieve optimal clinical response
• Optimal clinical response is usually achieved at doses below 60 mg/kg/day
• Therapeutic plasma concentration range is 50-100 mcg/mL
• No recommendation for safety above 60 mg/kg/day

Recommended Dose Titration Approach

1. Calculate current dose: 125mg twice daily = 250mg/day total
2. Titration schedule: Increase by 5-10 mg/kg/week (or approximately 125mg increments)
3. Monitoring requirements:
   • Measure plasma levels to ensure they remain within therapeutic range (50-100 mcg/mL)
   • Watch for thrombocytopenia risk, which increases significantly at trough concentrations above 110 mcg/mL in females and 135 mcg/mL in males 1

Important Safety Considerations

Hepatic Function

• Valproic acid can cause hepatotoxicity ranging from reversible dysfunction to irreversible failure 2
• Monitor liver function tests (SGOT, SGPT) regularly during dose increases
• If liver enzymes become elevated, dose reduction of approximately 10 mg/kg/day may normalize values 3

Neurological Side Effects

• Be alert for Parkinsonism, a rare but documented adverse effect, especially in patients over 55 years 4
• Symptoms typically improve within weeks after dose reduction or discontinuation

Other Monitoring Parameters

• Watch for thrombocytopenia, particularly at higher plasma concentrations
• Monitor for hyperammonemia, which can occur even at therapeutic doses 2

Practical Implementation

1. Initial increase: Add 125mg to make dosing 125mg in morning and 250mg at night (total 375mg/day)
2. Wait 1-2 weeks to assess tolerability
3. Further increase: If tolerated, increase to 250mg twice daily (total 500mg/day)
4. Check plasma levels after reaching 500mg/day to ensure within therapeutic range
5. Continue gradual increases as needed, not exceeding 60 mg/kg/day

When to Hold Dose Increases

• If plasma levels exceed 100 mcg/mL
• If liver function tests become abnormal
• If patient develops significant side effects (thrombocytopenia, tremor, sedation)
• If therapeutic benefit is achieved at lower doses

Remember that the goal is to find the lowest effective dose that provides clinical benefit while minimizing adverse effects.