Summary

The combination of leflunomide and methotrexate significantly increases the risk of hepatotoxicity and bone marrow suppression. This interaction requires careful monitoring and is generally avoided due to the potential for serious liver damage and hematologic toxicity.

Introduction

Leflunomide is a disease-modifying antirheumatic drug (DMARD) that inhibits dihydroorotate dehydrogenase, used primarily for treating rheumatoid arthritis and psoriatic arthritis. Methotrexate is an antimetabolite and folate antagonist, also classified as a DMARD, widely used for rheumatoid arthritis, psoriasis, and certain cancers. Both medications are immunosuppressive agents that can affect liver function and bone marrow activity.

Mechanism of Interaction

The interaction between leflunomide and methotrexate involves additive hepatotoxic effects and potential pharmacokinetic interactions. Both drugs are metabolized by the liver and can cause hepatocellular damage through different mechanisms. Leflunomide's active metabolite A77 1726 has a long half-life and may interfere with methotrexate elimination. Additionally, both drugs can cause folate depletion, leading to increased risk of bone marrow suppression and gastrointestinal toxicity.

Risks and Symptoms

The primary risks include severe hepatotoxicity with potential for acute liver failure, increased bone marrow suppression leading to pancytopenia, enhanced gastrointestinal toxicity, and increased susceptibility to infections due to immunosuppression. The combination has been associated with fatal outcomes in some cases. Patients may experience elevated liver enzymes, decreased white blood cell counts, thrombocytopenia, and severe mucositis.

Management and Precautions

This combination is generally contraindicated and should be avoided. If concurrent use is absolutely necessary, intensive monitoring is required including weekly complete blood counts and liver function tests initially, then every 2-4 weeks. Patients should be closely monitored for signs of hepatotoxicity, bone marrow suppression, and infection. Folic acid supplementation may be considered. If toxicity develops, both medications should be discontinued immediately and cholestyramine washout may be needed for leflunomide elimination. Alternative DMARD combinations should be considered.

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.

Methotrexate interactions with food and lifestyle

Alcohol consumption should be avoided or strictly limited while taking methotrexate due to increased risk of liver toxicity and hepatotoxicity. Both methotrexate and alcohol can cause liver damage, and their combination significantly increases this risk. Patients should also maintain adequate hydration and avoid excessive sun exposure, as methotrexate can increase photosensitivity. Folic acid supplementation is commonly recommended to reduce certain side effects, though this should be discussed with a healthcare provider as timing and dosing are important.