From the FDA Drug Label
The maximum recommended dosage is 60 mg/kg/day. No recommendation regarding the safety of valproate for use at doses above 60 mg/kg/day can be made. The probability of thrombocytopenia increases significantly at total trough valproate plasma concentrations above 110 μg/mL in females and 135 μg/mL in males.
The maximum recommended dose of valproic acid is 60 mg/kg/day.
- The benefit of improved seizure control with higher doses should be weighed against the possibility of a greater incidence of adverse reactions.
- No dose above 60 mg/kg/day is recommended due to the increased risk of adverse effects, including thrombocytopenia 1.
From the Research
The maximum recommended dose of valproic acid (valproate) is 140 mg/kg, as determined by a recent Phase I dose-escalation trial 2. This dose is significantly higher than the previously established maximum tolerated dose of 60-75 mg/kg. The study found that the most common adverse events were hypoacusis, chills, and headache, but no drug-related abnormalities were seen in other safety measures, including laboratory tests, hemodynamic parameters, cardiac rhythm monitoring, and cognitive testing. Some key points to consider when prescribing valproic acid include:
- Starting with a lower dose of 10-15 mg/kg/day and gradually increasing to the effective dose while monitoring serum levels
- Individualizing dosing based on clinical response and tolerability
- Monitoring liver function, complete blood count, and platelets before starting treatment and periodically thereafter
- Administering the medication in divided doses (2-3 times daily) with extended-release formulations allowing for once-daily dosing in some cases It's essential to note that the maximum tolerated dose may vary depending on the individual patient and their specific condition, and dose adjustments may be necessary in patients with hepatic impairment, elderly patients, or those taking other medications that interact with valproic acid 3, 4. However, the study by 2 provides the most recent and highest quality evidence for the maximum recommended dose of valproic acid.