From the Guidelines
A valproic acid level is ordered to monitor the concentration of this medication in a patient's bloodstream, primarily to ensure therapeutic effectiveness while avoiding toxicity. Valproic acid (also known as Depakote, Depakene, or divalproex sodium) is an anticonvulsant used to treat epilepsy, bipolar disorder, and migraines. The therapeutic range is typically 50-100 μg/mL for seizure control and 50-125 μg/mL for bipolar disorder management, as recommended in the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 1. Testing is essential when initiating therapy, adjusting dosages, assessing medication compliance, evaluating treatment failure, or investigating potential toxicity. Levels should be drawn as trough samples (just before the next scheduled dose) for the most accurate assessment. Regular monitoring is particularly important in patients with liver disease, pregnancy, the elderly, children, and those on multiple medications due to potential drug interactions, as highlighted in a study on the long-term management of children with simple febrile seizures 1. Signs of toxicity include drowsiness, confusion, tremor, and in severe cases, coma or liver failure. Valproic acid levels help clinicians optimize dosing to maintain seizure control or mood stabilization while minimizing adverse effects, as supported by a clinical policy on the evaluation and management of adult patients presenting to the emergency department with seizures 1.
Key Considerations
- The therapeutic range for valproic acid is crucial for effective treatment and minimizing toxicity.
- Regular monitoring of valproic acid levels is necessary, especially in high-risk patients.
- The medication has potential drawbacks, including rare but serious side effects such as fatal hepatotoxicity and pancreatitis, as noted in the study on febrile seizures 1.
- Clinicians should be aware of the potential for drug interactions and adjust treatment plans accordingly, as recommended in the practice parameter 1.
Monitoring and Adjustment
- Valproic acid levels should be monitored periodically, typically every 3-6 months, as part of routine care for patients on this medication.
- Dosage adjustments should be made based on the patient's response to treatment and valproic acid levels, with the goal of maintaining therapeutic levels while minimizing adverse effects.
- Patients and families should be educated on the signs of potential adverse effects and the importance of regular monitoring, as emphasized in the clinical policy 1.
From the FDA Drug Label
The frequency of adverse effects (particularly elevated liver enzymes and thrombocytopenia) may be dose-related... The probability of thrombocytopenia appeared to increase significantly at total valproate concentrations of ≥ 110 μg/mL (females) or ≥ 135 μg/mL (males). Interaction with Carbapenem Antibiotics... Serum valproic acid concentrations should be monitored frequently after initiating carbapenem therapy
A valproic acid (Depakene) level may be ordered on a patient to:
- Monitor for toxicity: as the probability of thrombocytopenia increases significantly at high valproate concentrations
- Adjust dosage: to ensure therapeutic levels are maintained, especially when interacting with other medications like carbapenem antibiotics
- Prevent loss of seizure control: by monitoring serum valproic acid concentrations frequently after initiating carbapenem therapy 2
From the Research
Reasons for Ordering Valproic Acid Levels
- To monitor the therapeutic range of valproic acid in patients, as the relationship between dose and plasma concentration is unpredictable 3
- To assess the risk of hepatotoxicity, which can occur even at therapeutic concentrations, especially when combined with other antiepileptic drugs like phenobarbital or carbamazepine 4
- To identify patients at risk of thrombocytopenia, which has been associated with free valproic acid concentrations above 14.67 mcg/mL 5
- To adjust drug dosages and minimize toxicity in different age and gender groups of patients, as plasma concentrations can vary significantly 3
- To determine the need for continued laboratory monitoring, as annual follow-up may not be necessary after 2 years of valproic acid treatment in uncomplicated cases 6
Clinical Considerations
- Valproic acid has a low therapeutic index and is highly plasma protein bound, making monitoring of unbound plasma concentrations important, especially in critically ill patients with hypoalbuminemia 7
- Total plasma concentrations may not accurately reflect the patient's therapeutic state, and unbound plasma concentrations should be quantified or predicted to optimize dosing 7
- Clinical signs of liver toxicity may be present even at therapeutic concentrations, and careful attention should be paid to individual patient factors, such as age and gender, when interpreting plasma concentration results 4, 3