Valproic Acid Level

Valproic acid is an 8-carbon 2-chain fatty acid that is metabolized by the liver and processed at a variable rate based on the patient’s liver function and age, in addition to patient’s other routine medications with which valproic acid may interact. At therapeutic concentrations, valproic acid mediates prolonged recovery of voltage-activated Na+ channels, thereby inhibiting repetitive firing induced by depolarization of cortical and spinal cord neurons. Its action is similar to that of other common anticonvulsants, such as phenytoin and carbamazepine.

The therapeutic range for valproic acid is 50-100 mcg/mL. The toxic level is >100 mcg/mL. ^[1]

Valproic acid is a broad-spectrum antiseizure drug with a narrow therapeutic window. It is absorbed rapidly and completely after oral administration, with peak plasma concentrations observed in 1-4 hours. Within the therapeutic ranges listed above, most patients experience therapeutic drug effects without excessive side effects. Even within the recommended therapeutic range, however, results vary between individual patients and some may experience adverse effects at the low end of the spectrum. The range of effectiveness and adverse reactions seen with this drug require monitoring of serial drug levels to ensure optimized dosing for each individual patient. ^{[2, 3]}

Generally, the dosage is considered optimal if the valproic acid level is within the therapeutic range and the patient is receiving treatment benefits (eg, suppression of seizures or mood swings) without adverse effects. Valproic acid levels should be obtained on patients taking this medication regularly for medical treatment and should also be considered in addition to standard toxicology panels when ingestion or overdose of valproic acid is suspected.

See the list below:

• Specimen type: Whole blood; draw volume is 0.6 mL ^[2]

• Container: Green-top (lithium Heparin) tube; an alternative is the red-top (plain, no gel) tube

• Panels: Valproic acid levels are not traditionally included in standard toxicology panels; however, they should be considered on a case-specific basis when evaluating patients with known seizure disorder, patients presenting with altered mental status, and in patients suspected of drug ingestion/overdose

Description

Valproic acid is an 8-carbon 2-chain fatty acid that is metabolized by the liver and processed at a variable rate based on the patient’s liver function and age, in addition to patient’s other routine medications with which valproic acid may interact. At therapeutic concentrations, valproic acid mediates prolonged recovery of voltage-activated Na+ channels, thereby inhibiting repetitive firing induced by depolarization of cortical and spinal cord neurons. Its action is similar to that of other common anticonvulsants, such as phenytoin and carbamazepine. ^[3]

Valproic acid is used for the treatment and control of conditions such as the following: ^{[4, 5, 2, 3, 6]}

• Simple and complex partial seizures

• Absence seizures

• Generalized tonic-clonic seizures

• Myoclonic epilepsy

• Acute and maintenance therapy of bipolar disease

• Migraine prophylaxis

• Chronic pain syndromes

A valproic acid level measures the amount of valproic acid in the blood: either the total level or free level of the drug. Monitoring of serial valproic acid levels is required to maintain the drug within the narrow recommended therapeutic range. Subtherapeutic levels place the patient at risk of recurrence of the condition for which they are taking valproic acid, and supratherapeutic levels place the patient at risk of adverse and toxic side effects.

Indications

Dosages of valproic acid must be adjusted carefully based on valproic acid blood levels until a steady drug concentration is ensured within the therapeutic range. The drug dose needed to reach this steady state varies between patients and may change over time, requiring serial valproic acid levels to ensure ongoing appropriate drug dosing. A valproic acid level is generally obtained shortly after initiation of this medication and after dosage adjustments. After serial levels reveal values consistently in the therapeutic range, the valproic acid level may then be monitored at less frequent but regular intervals to ensure that it remains within this range. ^{[4, 5, 2, 3]}

Additional testing of levels may be required if a patient’s condition is not responding to the medication to determine whether the concentration is too low, to determine if the medication is ineffective, or to confirm the patient's compliance with the medication. A level should also be obtained if a patient develops side effects or complications secondary to valproic acid use. The most common side effects are gastrointestinal effects including anorexia, nausea, and vomiting; however, less frequent but more serious effects on the central nervous system are also reported including sedation, ataxia, and tremor.

Considerations

Patients using multiple medications, especially other anticonvulsants, may require more frequent evaluation of valproic acid levels due to potential drug interactions. Furthermore, most valproic acid is bound to protein in the blood; however, it is the unbound portion of the drug that is the active component. Therefore, a patient with a condition resulting in lower-than-normal amounts of protein in their blood may be at increased risk of having a supratherapeutic or excess amount of circulating valproic acid and therefore require monitoring of both total and free valproic acid levels. ^{[2, 3]}