From the Guidelines
Vezah, also known as lomitapide, may cause elevations in liver transaminases, including alanine transaminase (ALT) and alkaline phosphatase (ALP), as stated in its black box warnings 1.
Mechanism of Action and Side Effects
Lomitapide works by directly binding and inhibiting microsomal triglyceride transfer protein, which prevents the assembly of apoB-containing lipoproteins in enterocytes and hepatocytes, leading to reduced LDL-C. However, this mechanism can also lead to increases in hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases, which may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis 1.
Monitoring and Management
Given the potential for liver enzyme elevations, it is recommended to measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating lomitapide and to adjust the dose or discontinue the medication if ALT or AST levels become elevated to ≥3 times the upper limit of normal 1. The Risk Evaluation and Mitigation Strategy (REMS) program is also in place to monitor and manage the risk of hepatotoxicity associated with lomitapide 1.
Comparison with Other Evidence
While other studies discuss the management of suspected acute drug-induced liver injury during clinical trials in patients with nonalcoholic steatohepatitis 1 and provide guidelines for detection, assessment, and management of suspected drug-induced liver injury during clinical trials in oncology patients 1, the most relevant and recent evidence for lomitapide's potential to cause elevated ALP and ALT levels is found in the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1.
Key Points
- Lomitapide may cause elevations in liver transaminases, including ALT and ALP.
- Monitoring of liver function tests is recommended before initiating and during treatment with lomitapide.
- The REMS program is in place to manage the risk of hepatotoxicity associated with lomitapide.
- Individual responses to lomitapide may vary, and some patients may experience uncommon reactions, including elevated liver enzymes.
From the Research
Liver Enzyme Elevations
- Elevated alkaline phosphatase (ALP) and alanine transaminase (ALT) levels can be indicative of liver disease, with ALP elevations often associated with cholestasis and ALT elevations associated with hepatocellular injury 2, 3.
- Various conditions can cause abnormal liver enzymes, including mild and nonspecific to well-defined and life-threatening conditions 3.
- Extremely high levels of ALP can be seen in patients with sepsis, malignant obstruction, and AIDS, as well as other conditions such as bone involvement from malignancy or Paget's disease 4.
Specific Conditions Affecting ALP and ALT Levels
- Liver disease, such as alcohol-induced hepatitis, can cause elevated ALP levels, even in patients with hypophosphatasia, a rare inherited disorder characterized by low serum ALP 5.
- Biomarkers such as AST, ALT, ALP, GGT, and total bilirubin are commonly used to assess liver function, but efforts are being made to identify more precise biomarkers for liver disease 6.
Patterns of Enzyme Abnormalities
- The pattern of enzyme abnormalities can help distinguish between hepatocellular and cholestatic liver disease, with hepatocellular injury characterized by elevations in ALT and AST, and cholestasis associated with elevated ALP levels 2.
- In patients with concurrent hepatocellular and cholestatic disease, ALP and ALT levels can be beyond predicted values, making diagnosis more challenging 2.