From the FDA Drug Label
Hepatic Abnormalities There were no meaningful changes in mean liver function tests (LFT) in controlled trials in adult or pediatric patients; lesser LFT abnormalities were similar in drug and placebo treated patients in controlled trials (1.4%). Although most laboratory tests are not systematically altered with levetiracetam treatment, there have been relatively infrequent abnormalities seen in hematologic parameters and liver function tests. The major metabolic pathway of levetiracetam (24% of dose) is an enzymatic hydrolysis of the acetamide group. It is not liver cytochrome P450 dependent Levetiracetam and its major metabolite, at concentrations well above Cmax levels achieved within the therapeutic dose range, are neither inhibitors of, nor high affinity substrates for, human liver cytochrome P450 isoforms, epoxide hydrolase or UDP glucuronidation enzymes.
Levetiracetam does not significantly affect liver function tests. The majority of the data indicates that levetiracetam does not cause significant changes in liver function tests, with some studies showing no meaningful changes in mean liver function tests in controlled trials in adult or pediatric patients. However, rare cases of abnormal liver function tests, hepatic failure, and hepatitis have been reported in postmarketing experience 1.
From the Research
Levetiracetam generally does not significantly affect liver function tests, but rare cases of liver enzyme elevations have been reported, and patients with pre-existing liver disease should still be monitored appropriately. This antiepileptic medication is primarily eliminated unchanged through the kidneys rather than being extensively metabolized by the liver, making it a good choice for patients with liver disease or those taking other medications that might affect liver function 2. While some studies have reported asymptomatic elevation of liver enzymes due to levetiracetam, these occurrences are uncommon and typically mild 3. Unlike many other antiepileptic drugs such as carbamazepine, phenytoin, or valproate, levetiracetam does not require routine liver function monitoring as part of standard care. However, patients with pre-existing liver disease should still be monitored appropriately, and any unusual symptoms like jaundice, dark urine, or right upper quadrant pain should prompt medical evaluation. The minimal hepatic metabolism of levetiracetam explains its favorable liver safety profile and makes it a preferred option for patients with hepatic impairment or those at risk for drug-induced liver injury 4, 5.
Some key points to consider when prescribing levetiracetam include:
- The medication is primarily eliminated through the kidneys, making it a good choice for patients with liver disease 4
- Rare cases of liver enzyme elevations have been reported, but these are typically mild and asymptomatic 2, 3
- Patients with pre-existing liver disease should still be monitored appropriately, and any unusual symptoms should prompt medical evaluation 5, 6
- Levetiracetam does not require routine liver function monitoring as part of standard care, but monitoring may be necessary for patients with pre-existing liver disease or those at risk for drug-induced liver injury 4, 2
Overall, levetiracetam is a safe and effective option for patients with epilepsy, including those with liver disease, but monitoring and caution are still necessary to minimize the risk of adverse effects.