Is perampanel associated with liver toxicity?

Perampanel and Liver Toxicity

Perampanel does not cause clinically significant liver toxicity based on the most recent and highest quality evidence. 1

Evidence on Perampanel's Hepatic Safety Profile

• Pooled data from three Phase III clinical studies demonstrated that perampanel (at doses of 2,4,8, and 12mg) had no clinically important effects on liver function tests, indicating perampanel has a low potential for drug-induced liver toxicity 1
• Mean hepatobiliary laboratory values remained within normal ranges at baseline and end of treatment for all perampanel groups and placebo in these studies 1
• The incidence of markedly abnormal liver function test results was very low for perampanel and similar to placebo 1
• Treatment-emergent adverse events related to hepatobiliary parameters occurred in only 0.4% of perampanel patients compared to 0% of placebo patients 1
• No dose-related trends in liver function abnormalities were observed with perampanel treatment 1
• No cases meeting Hy's Law criteria (indicating severe liver injury) were reported in the clinical trials 1

Potential Drug Interactions to Consider

• While perampanel itself has low hepatotoxic potential, there have been isolated case reports suggesting it might affect liver enzyme activity in some patients 2
• Two case reports described patients who experienced decreased levels of concomitant antiepileptic drugs (phenytoin, phenobarbital, rufinamide) after perampanel introduction, suggesting possible enzyme induction in some individuals 2
• This potential for drug interactions warrants monitoring of concomitant medication levels when adding perampanel to a treatment regimen 2

Monitoring Recommendations

• Although not specifically required for perampanel due to its low hepatotoxic potential, general good practice for antiepileptic drugs includes:
  • Obtaining baseline liver function tests before initiating treatment 3
  • Periodic monitoring of liver function during treatment, particularly in patients with pre-existing liver disease or those taking multiple hepatically metabolized medications 3
  • Being alert for symptoms of hepatotoxicity (fatigue, nausea, vomiting, right upper quadrant pain, jaundice) 3

Special Populations

• Perampanel may be a safer option for patients with liver disease compared to antiepileptic drugs with extensive hepatic metabolism (such as valproic acid, phenytoin, and felbamate) 3
• For patients with hepatic impairment, dose adjustments may be considered, although specific guidelines for perampanel in this population are limited 3

Adverse Effects of Perampanel (Non-Hepatic)

• The most common adverse effects of perampanel are dizziness, somnolence, fatigue, irritability, nausea, and falls 4
• Psychiatric adverse effects, including depression and aggression, have been reported more frequently in patients taking perampanel, particularly at higher doses 4
• Weight increase of greater than 7% was seen in 14.6% of perampanel-treated patients versus 7.1% of placebo-treated patients 4
• The majority of treatment-emergent adverse events were mild or moderate in intensity 4

In conclusion, based on comprehensive clinical trial data, perampanel demonstrates a favorable hepatic safety profile with no evidence of clinically significant liver toxicity in most patients. However, as with any antiepileptic medication, appropriate monitoring and awareness of potential drug interactions remain important aspects of clinical management.