Is rosuvastatin safe for use in patients with liver cirrhosis?

From the Guidelines

Rosuvastatin can be safely used in patients with compensated liver cirrhosis, but should be used with caution and close monitoring in those with decompensated cirrhosis. According to the 2023 standards of care in diabetes, statin therapy, including rosuvastatin, is safe in adults with type 2 diabetes and compensated cirrhosis from nonalcoholic fatty liver disease, and should be initiated or continued for cardiovascular risk reduction as clinically indicated 1.

When using rosuvastatin in cirrhosis patients, it is essential to consider the following key points:

• Start at a low dose (5-10 mg daily)
• Monitor liver enzymes before starting and periodically during treatment
• Avoid in decompensated cirrhosis or acute liver failure
• Be aware of potential drug interactions, especially with medications metabolized by CYP3A4

The benefits of statin therapy in reducing cardiovascular risk should be weighed against the potential for liver toxicity, as rosuvastatin is primarily metabolized by the liver, and impaired liver function can lead to increased drug concentrations. If liver enzymes increase significantly (>3 times upper limit of normal) or symptoms of liver dysfunction occur, discontinue rosuvastatin and consult a hepatologist for further management. Rosuvastatin may have additional benefits in cirrhosis patients, including potential anti-inflammatory and anti-fibrotic effects, but these benefits must be balanced against the risk of hepatotoxicity 1.

From the FDA Drug Label

Rosuvastatin is contraindicated in patients with acute liver failure or decompensated cirrhosis. Chronic alcohol liver disease is known to increase rosuvastatin exposure. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury [see Contraindications (4), Warning and Precautions (5. 3)and Clinical Pharmacology (12.3)].

Rosuvastatin is not safe for use in patients with decompensated cirrhosis. However, the label does not explicitly address the safety of rosuvastatin in patients with compensated cirrhosis. Therefore, no conclusion can be drawn for patients with liver cirrhosis in general. 2

From the Research

Safety of Rosuvastatin in Patients with Liver Cirrhosis

• The safety of statins, including rosuvastatin, in patients with liver cirrhosis has been evaluated in several studies 3, 4, 5.
• According to a review published in 2018, statins are effective in the treatment of dyslipidemia in patients with liver disease and have pleiotropic properties that are independent of their effect on cholesterol levels 3.
• The study suggests that compensated cirrhosis is not a contraindication for statin use, but decompensated cirrhosis requires caution and low doses with frequent monitoring of creatinine phosphokinase levels 3.
• Another study published in 2021 found that the addition of statins to standard treatment in patients with cirrhosis is safe and effective, but the quality of evidence is low due to the observational nature of most studies 4.
• The study recommends further randomized controlled trials to evaluate the use of statins in patients with cirrhosis and to determine the optimal dose and type of statin to use 4.
• A review published in 2009 found that statins are generally well tolerated in patients with chronic liver disease, including NAFLD, primary biliary cirrhosis, and hepatitis C virus, as well as in patients with stable/compensated cirrhosis 5.
• However, decompensated cirrhosis and acute liver failure are considered contraindications for lipid-lowering therapy due to the grave prognosis of these patients 5.

Pharmacokinetic and Pharmacodynamic Considerations

• A study published in 2020 discussed the pharmacokinetic and pharmacodynamic considerations of medication use in patients with cirrhosis, including the altered pharmacology of medicines in this population 6.
• The study found that the influence of cirrhosis on pharmacokinetics depends on several drug and patient characteristics, and that patients with cirrhosis have an increased susceptibility to some toxicological effects of medicines, such as renal impairment and hematological toxicity 6.
• Another study published in 2013 provided a practical guide for prescribing medications in patients with cirrhosis, including recommendations for dosing and monitoring 7.
• The study found that most medications have not been adequately studied in cirrhosis, and that specific prescribing information is often lacking, but that lower doses are generally recommended based on pharmacokinetic changes 7.