Does Wysonole cause transaminitis?

Wysonole and Transaminitis

Wysonole can cause transaminitis (elevated liver enzymes) and requires regular monitoring of liver function tests during treatment. 1

Mechanism and Risk

Wysonole (lomitapide) carries a black box warning regarding liver toxicity:

1. It may cause elevations in liver transaminases (ALT, AST)
2. It increases hepatic fat (hepatic steatosis) with or without concomitant increases in transaminases
3. Hepatic steatosis associated with lomitapide may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis 1

Due to these risks, lomitapide is only available through a Risk Evaluation and Mitigation Strategy (REMS) program.

Monitoring Requirements

• Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment
• During treatment, adjust dose if ALT or AST ≥3 times the upper limit of normal
• Discontinue medication for clinically significant liver toxicity 1

Contraindications

Lomitapide is contraindicated in patients with:

• Moderate/severe hepatic impairment
• Active liver disease
• Unexplained persistent abnormal liver function tests 1

Clinical Context

Transaminitis refers to elevated liver enzymes (ALT and AST) indicating inflammatory processes in the liver 2. While many medications can cause transaminitis, lomitapide carries a specific risk that requires careful monitoring.

Comparison with Other Medications

For context, other medications have varying rates of transaminitis:

• Tolvaptan: Approximately 5% of patients develop elevated transaminases (>3× upper limit of normal) compared to 1% with placebo 1
• Statins: 0.5% to 2.0% develop elevated hepatic transaminases, which are dose-dependent 3
• Lomitapide: Specific rate not provided in the evidence, but significant enough to warrant a black box warning and REMS program 1

Management Recommendations

If transaminase elevations occur during lomitapide treatment:

1. For ALT or AST ≥3 times the upper limit of normal: Adjust dose
2. For clinically significant liver toxicity: Discontinue medication
3. Monitor liver enzymes regularly throughout treatment 1

Practical Considerations

• The risk of hepatotoxicity must be weighed against the benefits of lomitapide in reducing LDL-C, total cholesterol, apoB, and non-HDL-C in patients with homozygous familial hypercholesterolemia
• Lomitapide should be used as an adjunct to a low-fat diet and other lipid-lowering treatments
• Patients should be informed about the risk of liver injury and the importance of regular monitoring 1

Lomitapide's effects on liver enzymes should be taken seriously, as hepatic steatosis can progress to more severe liver conditions if not properly monitored and managed.