From the Guidelines
Repatha (evolocumab) is generally considered safe for the liver and is unlikely to cause liver impairment, as evidenced by the FOURIER trial, which showed no significant differences in rates of liver function test abnormalities between the evolocumab and placebo groups 1. The mechanism of action of Repatha, which involves blocking the PCSK9 protein to allow the liver to remove more LDL cholesterol from the blood, does not directly affect liver enzyme production, reducing the risk of liver damage. Key points to consider:
- Clinical trials, including the FOURIER trial, have not shown a significant risk of liver damage with Repatha use 1.
- Routine liver function monitoring is not typically required specifically for Repatha therapy, unless the patient has pre-existing liver disease 1.
- Some patients with severe liver impairment may need dose adjustments, but this is uncommon.
- If symptoms like unusual fatigue, pain in the upper right abdomen, dark urine, or yellowing of the skin or eyes occur while taking Repatha, patients should contact their healthcare provider promptly, although these side effects are rare with this medication. The FOURIER trial, which evaluated the efficacy and safety of evolocumab in patients with clinically evident cardiovascular disease, found that the rates of serious adverse events, including liver-related events, were comparable between the evolocumab and placebo groups 1. Additionally, the trial found that evolocumab reduced the risk of major adverse cardiovascular events, including myocardial infarction, stroke, and cardiovascular death, without increasing the risk of liver damage 1. Overall, the available evidence suggests that Repatha is safe for the liver and can be used to reduce the risk of cardiovascular events in patients with high cardiovascular risk.
From the FDA Drug Label
Following a single 140 mg subcutaneous dose of evolocumab in patients with mild or moderate hepatic impairment, a 20-30% lower mean Cmax and 40-50% lower mean AUC were observed as compared to healthy patients [see Use in Specific Populations (8. 7)]. The chance of liver impairment with Repatha is possible, as the drug label indicates that patients with mild or moderate hepatic impairment had lower mean Cmax and AUC values compared to healthy patients.
- Key points:
- 20-30% lower mean Cmax in patients with mild or moderate hepatic impairment
- 40-50% lower mean AUC in patients with mild or moderate hepatic impairment
- These differences may indicate a potential impact of liver impairment on Repatha pharmacokinetics 2
From the Research
Liver Impairment with Repatha
- There is no direct evidence in the provided studies that suggests Repatha (evolocumab) causes liver impairment 3, 4, 5, 6, 7.
- Evolocumab works by inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), which is a circulating enzyme secreted by the liver, but the studies do not report any liver-related adverse effects 3, 4, 5, 6, 7.
- The liver's role in lipid metabolism is affected by evolocumab, as it enhances LDL receptor recycling, leading to more efficient clearance of LDL-C from the bloodstream, but this does not seem to cause liver impairment 5, 7.
- The safety and tolerance of evolocumab have been studied in several trials, and the results show that it is well-tolerated, with no significant liver-related side effects reported 3, 4, 6, 7.
- Further research is needed to fully understand the long-term effects of evolocumab and to determine the best timing and dose for each patient, but current evidence does not suggest a significant risk of liver impairment 7.