From the Guidelines
Depakote (valproic acid) requires baseline and periodic monitoring of liver function tests (LFTs) due to the risk of elevated LFTs and potential liver damage, as recommended in the practice parameter for the assessment and treatment of children and adolescents with bipolar disorder 1. When initiating Depakote therapy, baseline liver function tests, complete blood cell counts, and pregnancy tests are recommended 1.
- Key considerations for monitoring include:
- Obtaining baseline LFTs before starting Depakote
- Follow-up testing at 2-4 weeks, 3 months, 6 months, and then periodically thereafter
- Monitoring serum drug levels, plus hepatic and hematological indices, every 3-6 months
- The approach to managing elevated LFTs in patients on Depakote depends on the degree of elevation, with mild elevations typically requiring continued monitoring, moderate elevations potentially necessitating dose reduction and increased monitoring, and severe elevations or those accompanied by symptoms necessitating immediate discontinuation of the medication.
- It is crucial to advise patients and families about presenting symptoms of potential adverse effects, as periodic monitoring does not ensure that abnormalities will be readily identified 1.
- The risk of liver injury is highest in the first 6 months of treatment and in specific patient populations, such as children under 2 years, patients on multiple anticonvulsants, and those with metabolic disorders.
From the FDA Drug Label
Liver function tests should be performed prior to therapy and at frequent intervals thereafter, especially during the first six months However, healthcare providers should not rely totally on serum biochemistry since these tests may not be abnormal in all instances, but should also consider the results of careful interim medical history and physical examination. The drug should be discontinued immediately in the presence of significant hepatic dysfunction, suspected or apparent.
Elevated Liver Function Tests (LFTs) are a concern with Depakote (valproate) use.
- Monitoring of LFTs is recommended prior to therapy and at frequent intervals, especially during the first six months.
- Discontinuation of the drug should be considered if significant hepatic dysfunction is suspected or apparent. 2
From the Research
Depakote and Elevated Liver Function Tests (LFTs)
- Depakote, also known as valproic acid, has been associated with reversible or irreversible hepatotoxicity, as well as an increased risk of non-alcoholic fatty liver disease (NAFLD) with long-term therapy 3.
- Biochemical abnormalities of liver function in patients receiving valproate are not progressive and often relate to the intake of other drugs, rather than valproate alone 4.
- The formation of valproic acid reactive metabolites, inhibition of fatty acid β-oxidation, excessive oxidative stress, and genetic variants of certain enzymes have been reported to be associated with valproic acid-induced hepatotoxicity 3.
- Elevated liver function tests (LFTs) have been observed in patients taking valproate, particularly those with hepatitis C infection, and may be partially related to chronic hepatitis infection 5.
- Valproate-induced hyperammonemic encephalopathy has been reported in patients with normal liver functions, suggesting a possible synergistic interaction with other medications such as topiramate 6.
- Continuous therapy with valproate has been linked to an increased risk of nonalcoholic fatty liver disease, with characteristics of fatty liver disease present in 61% of valproate-treated patients compared to 23% receiving carbamazepine therapy 7.