From the FDA Drug Label
If satisfactory clinical response has not been achieved, plasma levels should be measured to determine whether or not they are in the usually accepted therapeutic range (50 to 100 μg/mL)
The patient's valproate level is 150 micromoles per liter, which is below the therapeutic range of 50 to 100 μg/mL when considering the unit difference (1 μg/mL = 7.08 micromoles/L, so 150 micromoles/L is approximately 21.2 μg/mL).
- The recommended adjustment would be to increase the dose of valproate.
- The dosage should be increased by 5 to 10 mg/kg/week to achieve optimal clinical response.
- Monitoring of plasma levels and clinical response is necessary to determine the optimal dose.
- The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions 1.
From the Research
For a patient with a subtherapeutic valproate level of 150 micromoles per liter, the recommended adjustment is to increase the daily dose by approximately 20-30%. The therapeutic range for valproate is typically 350-700 micromoles per liter, so at 150 micromoles per liter, the patient is significantly below the target range. After increasing the dose, a follow-up serum level should be checked in 5-7 days to ensure the new dose is achieving therapeutic concentrations. It's essential to increase the dose gradually to minimize side effects such as sedation, gastrointestinal disturbances, or tremor. If the patient is experiencing breakthrough seizures or symptoms due to the low level, more frequent monitoring may be warranted. The adjustment should consider the patient's current formulation (extended-release vs. immediate-release) and dosing schedule, maintaining the same formulation while adjusting the amount. Valproate has dose-dependent protein binding, so small increases in dose can sometimes lead to disproportionate increases in free (active) drug concentration, which explains why a modest 20-30% increase is often sufficient initially rather than a larger adjustment 2.
Some key points to consider when adjusting the valproate dose include:
- The patient's current dose is 500mg daily, and increasing this by 20-30% would result in a new dose of 600-650mg daily.
- The therapeutic range for valproate is typically 350-700 micromoles per liter, and the patient's current level is 150 micromoles per liter.
- Gradually increasing the dose can help minimize side effects and ensure the patient achieves a therapeutic level.
- Regular monitoring of serum levels and clinical response is crucial to determine the effectiveness of the dose adjustment and make any necessary further adjustments 3, 4.
It's also important to note that the clinical response to valproate can be augmented by increasing it to the maximum tolerated dose, and some patients may require higher doses to achieve optimal seizure control 3. However, the goal is to find the lowest effective dose that minimizes side effects while maintaining therapeutic efficacy.