Documentation of Valproic Acid Measurement
Yes, document it as "valproic acid level" in the medical record, with the understanding that this represents total serum valproate concentration, typically targeting a therapeutic range of 50-100 μg/mL. 1, 2, 3
Standard Terminology and Measurement
- The term "valproic acid level" is the accepted clinical terminology, though it technically measures total serum valproate ion concentration after dissociation in the gastrointestinal tract 4
- The therapeutic range for epilepsy is commonly 50-100 μg/mL of total valproate, though some patients achieve control at lower or higher concentrations 1, 2, 4
- In refractory cases, some evidence supports levels up to 200 μg/mL, though this is not standard practice 3
Critical Documentation Pitfalls
Total valproate levels do not reliably reflect the bioactive (unbound) drug fraction, which is the pharmacologically active component. 4 This creates several important clinical scenarios:
- Protein binding is concentration-dependent: the free fraction increases from approximately 10% at 40 μg/mL to 18.5% at 130 μg/mL 4
- Higher free fractions occur in elderly patients, those with hyperlipidemia, hepatic disease, renal impairment, and hypoalbuminemia 4, 5
- Patients can develop valproic acid toxicity with total levels in the "therapeutic range" if they have conditions causing increased free drug fraction 5
When to Consider Free (Unbound) Level Measurement
Document and order free valproic acid levels specifically in these high-risk situations:
- Elderly patients 4
- Hypoalbuminemia 5
- Renal impairment 4, 5
- Hepatic disease 4
- Patients on drugs that displace valproate from protein binding (aspirin, phenytoin, carbamazepine, warfarin) 4
- Neurological symptoms (sluggishness, muscle weakness, gait disturbance, urinary dysfunction) despite "therapeutic" total levels 5
Documentation Best Practices
- Always document whether the level is total or free valproic acid 5
- Note clinical context: timing relative to dose, adherence verification, and presence of interacting medications 1, 2
- Document carbapenem use separately, as meropenem, imipenem, and ertapenem dramatically reduce valproic acid levels and can precipitate seizures 1, 2
- Record any symptoms of toxicity (tremor occurs in 20-40% of patients, encephalopathy, hyperammonemia) even when levels appear therapeutic 2, 6