What is the effect of Keppra (levetiracetam) on liver function?

Levetiracetam (Keppra) and Liver Function

Levetiracetam has minimal effects on liver function and is considered a safe choice for patients with hepatic impairment, making it one of the preferred antiepileptic drugs for patients with liver disease. 1, 2

Hepatic Safety Profile of Levetiracetam

Minimal Hepatic Metabolism

• Levetiracetam is primarily eliminated through renal excretion (66% of the dose is excreted unchanged in urine) 1
• Unlike many other antiepileptic drugs, levetiracetam does not undergo significant hepatic metabolism 1, 2
• It is not dependent on liver cytochrome P450 enzymes, which significantly reduces its potential for hepatotoxicity 1

Liver Function Tests

• According to the FDA drug label, there were no meaningful changes in mean liver function tests in controlled trials 1
• Minor liver function test abnormalities with levetiracetam were similar to those seen with placebo (1.4%) 1
• Only 1 adult epilepsy patient (0.07%) was discontinued from controlled trials due to liver function test abnormalities 1

Use in Hepatic Impairment

• In patients with mild to moderate hepatic impairment (Child-Pugh A and B), the pharmacokinetics of levetiracetam remain unchanged 1
• In severe hepatic impairment (Child-Pugh C), total body clearance decreases by 50%, but this is primarily due to decreased renal clearance rather than impaired hepatic metabolism 1
• No dose adjustment is needed for patients with hepatic impairment 1

Comparative Advantage in Liver Disease

• Levetiracetam is recommended as a first-line therapy for seizures in patients with liver disease due to its minimal hepatic metabolism 2
• Other antiepileptic drugs that undergo extensive hepatic metabolism (such as valproic acid, phenytoin, and felbamate) should be used as drugs of last resort in patients with liver disease 2
• In some cases, levetiracetam treatment has been associated with normalization or improvement of liver enzyme values in patients with chronic liver disease 3

Rare Reports of Hepatotoxicity

• While generally safe for the liver, there have been isolated case reports of asymptomatic elevation of liver enzymes attributed to levetiracetam 4
• In one case report, liver enzymes returned to normal after levetiracetam was discontinued 4
• A comparative study found that levetiracetam did not induce significant increases in liver enzymes compared to control groups 5

Clinical Implications

Monitoring Recommendations

• Routine liver function monitoring is not generally required for patients taking levetiracetam 1
• For patients with pre-existing liver disease, standard clinical monitoring is appropriate, but specific liver function test monitoring for levetiracetam is not mandated 1, 2

Special Populations

• In patients with both epilepsy and liver disease, levetiracetam represents an attractive therapeutic option 3, 2
• For status epilepticus in patients with liver disease, levetiracetam (available in intravenous form) is recommended as a good second-line therapy after benzodiazepines 2

Common Pitfalls and Caveats

• Do not assume all antiepileptic drugs have similar hepatic safety profiles - levetiracetam has distinct advantages over enzyme-inducing antiepileptic drugs
• While levetiracetam is generally liver-safe, individual cases of liver enzyme elevation can occur, so clinical vigilance is still warranted
• Remember that in patients with severe renal impairment, levetiracetam dosage should be reduced, as it is primarily eliminated through the kidneys 1

In summary, levetiracetam has minimal impact on liver function and does not require dose adjustment in hepatic impairment, making it one of the safest antiepileptic drug options for patients with compromised liver function.