Summary

The combination of leflunomide and rosuvastatin may increase the risk of hepatotoxicity due to their individual liver effects. Both medications can cause elevated liver enzymes, and concurrent use requires careful monitoring of hepatic function.

Introduction

Leflunomide is a disease-modifying antirheumatic drug (DMARD) primarily used to treat rheumatoid arthritis and psoriatic arthritis by inhibiting pyrimidine synthesis and reducing inflammatory cell proliferation. Rosuvastatin is a HMG-CoA reductase inhibitor (statin) used to lower cholesterol levels and reduce cardiovascular risk by blocking cholesterol synthesis in the liver.

Mechanism of Interaction

The interaction between leflunomide and rosuvastatin is primarily additive rather than pharmacokinetic. Leflunomide's active metabolite, teriflunomide, can cause hepatotoxicity through mitochondrial dysfunction and oxidative stress. Rosuvastatin, while having a lower hepatotoxicity profile compared to other statins, can still cause liver enzyme elevations. When used together, the hepatotoxic potential of both drugs may be additive, increasing the overall risk of liver injury.

Risks and Symptoms

The primary risk of combining leflunomide and rosuvastatin is increased hepatotoxicity, manifesting as elevated liver transaminases (ALT/AST). Patients may experience symptoms such as fatigue, abdominal pain, nausea, or jaundice in severe cases. The risk is particularly elevated in patients with pre-existing liver disease, alcohol use, or those taking other hepatotoxic medications. Severe hepatotoxicity, though rare, can lead to acute liver failure requiring immediate medical intervention.

Management and Precautions

Close monitoring of liver function tests (LFTs) is essential when using leflunomide and rosuvastatin concurrently. Baseline liver enzymes should be obtained before initiating therapy, followed by monitoring at 4-6 weeks, then every 8-12 weeks during treatment. Discontinue both medications if ALT/AST levels exceed 3 times the upper limit of normal. Consider alternative cholesterol management strategies such as ezetimibe or bile acid sequestrants if statin therapy must be discontinued. Patients should be counseled to report symptoms of liver dysfunction immediately and avoid alcohol consumption.

Leflunomide interactions with food and lifestyle

Alcohol consumption should be avoided or limited while taking leflunomide due to increased risk of liver toxicity. Both leflunomide and alcohol can cause liver damage, and their combination may significantly increase this risk. Patients should discuss alcohol use with their healthcare provider and follow recommendations for liver function monitoring. Additionally, live vaccines should be avoided during leflunomide treatment due to the drug's immunosuppressive effects, which may reduce vaccine effectiveness and increase infection risk.

Rosuvastatin interactions with food and lifestyle

Grapefruit and grapefruit juice should be avoided or consumed with caution while taking rosuvastatin, as they can increase blood levels of the medication and potentially increase the risk of side effects. Excessive alcohol consumption should be limited as it may increase the risk of liver problems when combined with rosuvastatin. Patients should maintain consistent dietary habits and inform their healthcare provider about any significant changes in diet or lifestyle.