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, with a therapeutic range typically between 50-100 μg/mL 1. Testing is essential when initiating therapy, adjusting dosages, assessing compliance, evaluating treatment failure, or investigating potential toxicity. Levels should be drawn as trough samples (just before the next scheduled dose) for accurate interpretation. Monitoring is particularly important because valproic acid has a narrow therapeutic window, meaning the difference between effective and toxic doses is small. Additionally, valproic acid can interact with many other medications, potentially altering its concentration. Signs of toxicity include drowsiness, confusion, tremor, and in severe cases, liver damage or pancreatitis. Regular monitoring helps clinicians optimize dosing to maintain seizure control or mood stabilization while minimizing adverse effects.
Key Considerations
- The therapeutic range of valproic acid is typically between 50-100 μg/mL 1.
- Monitoring is crucial due to the narrow therapeutic window of valproic acid.
- Valproic acid can interact with many other medications, potentially altering its concentration.
- Signs of toxicity include drowsiness, confusion, tremor, and in severe cases, liver damage or pancreatitis.
Clinical Evidence
- A study published in the Journal of the American Academy of Child and Adolescent Psychiatry in 2007 recommends baseline liver function tests, complete blood cell counts, and pregnancy tests for patients taking valproate, as well as periodic monitoring of serum drug levels, hepatic and hematological indices 1.
- Another study published in Pediatrics in 2008 notes that valproic acid is effective in preventing recurrent simple febrile seizures, but highlights the potential drawbacks of therapy, including rare association with fatal hepatotoxicity and thrombocytopenia 1.
- A more recent study published in the Annals of Emergency Medicine in 2014 discusses the use of valproate in the treatment of status epilepticus, highlighting its efficacy and safety profile 1.
Recommendations
- Valproic acid levels should be monitored regularly to ensure therapeutic effectiveness and minimize adverse effects.
- Clinicians should be aware of the potential interactions between valproic acid and other medications, as well as the signs of toxicity.
- Patients should be advised to report any symptoms of potential adverse effects, and periodic monitoring should be performed to identify any abnormalities.
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 effectiveness of valproic acid in patients with epilepsy, as it is a broad-spectrum antiepileptic drug effective against all seizure types 3
- To minimize the risk of adverse effects, such as hepatotoxicity, which can be severe and potentially life-threatening, especially in high-risk groups like infants below 2 years of age receiving anticonvulsant polytherapy 3, 4
- To adjust the dosage of valproic acid, as the relationship between dose and plasma concentration is unpredictable, and regular measurement of plasma concentration is necessary to ensure therapeutic levels are maintained 5
- To detect potential interactions with other medications, such as phenobarbital, carbamazepine, and benzodiazepines, which can affect valproic acid plasma concentrations and increase the risk of adverse effects 4, 6
- To identify patients who may be at risk of thrombocytopenia, hyperammonemia, or hepatotoxicity, as these adverse effects can occur even at therapeutic plasma concentrations of valproic acid 6
Patient Factors to Consider
- Age and gender, as plasma concentrations of valproic acid can vary significantly between different age and gender groups 5
- Presence of co-morbidities or concomitant medications, which can affect valproic acid plasma concentrations and increase the risk of adverse effects 7
- Duration of valproic acid treatment, as the risk of adverse effects may decrease over time, and annual laboratory follow-up may not be necessary after 2 years of treatment in uncomplicated cases 7