Valproic Acid Clinical Pearls

Valproic acid is most commonly used for the management of seizures, bipolar disorder, and migraines. In my practice, I do see it occasionally used to help manage dementia-related aggressive behaviors. There are a lot of valproic acid clinical pearls that you need to remember, and I’m going to highlight some of the most important ones that I’ve seen in practice.

Boxed Warnings

The use of valproic acid should not be taken lightly. I can’t help but equate the risk of a medication to the number of boxed warnings it carries. Valproic acid carries FOUR boxed warnings. Liver toxicity, fetal risks, and pancreatitis are all warnings. Additionally, patients with mitochondrial disease (DNA mutations of the POLG gene) may be at increased risk for liver toxicity. (These adverse effects could definitely show up on your board exams!)

Drug Levels – Valproic Acid

Maintaining a steady drug concentration is critical for the management of seizures. Therefore, monitoring levels is very important when epilepsy is the target indication. Drug levels are also critical and well-defined for bipolar disorders. Target concentrations for seizure disorder typically falls between 50 to 100 mcg/mL and 50 to 125 mcg/mL in bipolar disorder. In migraine management, drug levels tend to be less important unless toxicity is suspected.

Adverse Effects

Valproic acid has a ton of unique adverse effects. In general, if a patient is experiencing a unique adverse effect and they are taking valproic acid, it is a strong consideration for me as the potential culprit until proven otherwise. Removing and reducing this medication can obviously be difficult in the situation where the patient is taking the drug for seizures. One unique adverse effect I have encountered in practice is elevated ammonia – here’s a case study that demonstrates this risk.

Some of those unique and common adverse effects include:

  • GI upset
  • Hair loss (curbside consult)
  • Hepatotoxicity
  • Hematologic alterations (thrombocytopenia)
  • Sedation
  • Elevated ammonia levels
  • Pancreatitis
  • Weight loss or gain

Pharmacokinetics – Valproic Acid Clinical Pearls

Protein binding is a potential concern. Remember that patients who have lower albumin levels (i.e. malnourished, elderly, etc.) may have a greater free fraction of drug available for pharmacological action. Essentially this can lead to an increase in the effects of the drug.

Dose formulations are important are the bioequivalence ratio is not perfectly one-to-one. It is critical to pay attention as this can lead to errors. We do not want our seizure patients getting a different dosage form that may not provide the same bioavailability as another valproic acid product. Patient monitoring and drug levels are important for patients who are going to change dosage forms for one reason or another. Syrups, sprinkles, IV products, and capsules all exist.

What other valproic acid clinical pearls have you seen in your practice?

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Written By Eric Christianson

July 20, 2022

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