Can Levetiracetam (antiepileptic medication) cause liver toxicity?

Levetiracetam and Liver Toxicity

Levetiracetam rarely causes liver toxicity and is generally considered safe for patients with liver disease, making it one of the preferred antiepileptic drugs for patients with hepatic impairment. 1

Hepatic Safety Profile of Levetiracetam

• Levetiracetam is primarily eliminated by renal excretion (66% of dose excreted unchanged in urine) with minimal hepatic metabolism, which contributes to its favorable liver safety profile 2
• The FDA label for levetiracetam states: "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%)" 2
• In clinical practice guidelines, levetiracetam is listed as having "nausea, rash" as adverse effects, with no mention of liver toxicity as a significant concern 3

Rare Cases of Levetiracetam-Induced Liver Injury

• Despite its favorable hepatic profile, rare cases of drug-induced liver injury (DILI) associated with levetiracetam have been reported in the literature 4, 5
• A 2022 analysis of levetiracetam-induced liver injury found only 21 reported cases from 1999 to April 2021, confirming its rarity 5
• When liver injury does occur, the median time to onset is approximately 19 days (range 3-120 days) after starting levetiracetam 5
• Clinical presentations range from asymptomatic elevated liver enzymes (23.8% of cases) to symptomatic liver injury with fever, digestive symptoms, and skin rash (76.2% of cases) 5

Comparison with Other Antiepileptic Drugs

• Levetiracetam is considered safer for the liver compared to many other antiepileptic drugs, particularly valproic acid which is associated with fatal hepatotoxicity, especially in children under 2 years of age 6
• Clinical guidelines specifically note that valproic acid can cause "liver toxicity" as an adverse effect, while levetiracetam is not listed with this concern 3
• Newer antiepileptic drugs with minimal hepatic metabolism, including levetiracetam, are recommended as first-line therapy for patients with liver disease 1

Management Considerations

• For patients with epilepsy and concomitant liver disease, levetiracetam is considered "an attractive therapeutic option" 7
• In a study of patients with epilepsy and chronic liver disease treated with levetiracetam, none showed worsening of liver function based on blood chemistry, and some even showed improvement in liver enzyme values 7
• If liver injury is suspected with levetiracetam use, prompt discontinuation is recommended, with liver function typically returning to normal within a median of 9 days (range 2-270 days) 5

Monitoring Recommendations

• Routine liver function monitoring is not generally required for patients on levetiracetam without pre-existing liver disease 2
• For patients receiving long-term treatment with levetiracetam, especially those with risk factors for liver disease, periodic monitoring of liver function may be considered 5
• Clinicians should be aware of the potential for rare hepatotoxicity and monitor for symptoms such as jaundice, fatigue, abdominal pain, or unexplained illness in patients taking levetiracetam 8

In conclusion, while levetiracetam-induced liver injury is possible, it remains extremely rare due to the drug's minimal hepatic metabolism. This favorable hepatic safety profile makes levetiracetam one of the preferred antiepileptic medications for patients with underlying liver disease or those taking multiple medications.