Summary

Rifampin significantly reduces leflunomide effectiveness by inducing hepatic enzymes that accelerate the metabolism of leflunomide's active metabolite. This interaction may lead to reduced therapeutic efficacy in treating rheumatoid arthritis and other autoimmune conditions.

Introduction

Leflunomide is a disease-modifying antirheumatic drug (DMARD) used primarily to treat rheumatoid arthritis and psoriatic arthritis by inhibiting pyrimidine synthesis and reducing inflammatory cell proliferation. Rifampin is a potent antibiotic belonging to the rifamycin class, commonly used to treat tuberculosis, atypical mycobacterial infections, and certain other bacterial infections. Both medications are metabolized through hepatic pathways, creating potential for significant drug interactions.

Mechanism of Interaction

Rifampin is a potent inducer of cytochrome P450 enzymes, particularly CYP3A4, and other drug-metabolizing enzymes. When co-administered with leflunomide, rifampin significantly increases the hepatic metabolism of teriflunomide (A77 1726), the active metabolite of leflunomide. This enhanced metabolism leads to reduced plasma concentrations of the active metabolite, potentially compromising the immunosuppressive and anti-inflammatory effects of leflunomide therapy.

Risks and Symptoms

The primary clinical risk of this interaction is reduced therapeutic efficacy of leflunomide, which may result in inadequate control of rheumatoid arthritis symptoms, increased disease activity, and potential progression of joint damage. Patients may experience increased joint pain, swelling, morning stiffness, and systemic inflammation. The reduced immunosuppressive effect may also compromise treatment outcomes in other autoimmune conditions for which leflunomide is prescribed.

Management and Precautions

Close monitoring of rheumatoid arthritis disease activity is essential when rifampin is co-administered with leflunomide. Healthcare providers should assess joint symptoms, inflammatory markers (ESR, CRP), and disease activity scores more frequently. Consider alternative antibiotics when possible, or if rifampin is necessary, leflunomide dose adjustments may be required under specialist supervision. Patients should be counseled to report any worsening of arthritis symptoms. Regular monitoring of liver function tests is also recommended due to the hepatotoxic potential of both medications.

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.

Rifampin interactions with food and lifestyle

Rifampin should be taken on an empty stomach, at least 1 hour before or 2 hours after meals, as food can significantly reduce its absorption and effectiveness. Alcohol consumption should be avoided or limited while taking rifampin, as both rifampin and alcohol can cause liver toxicity, and the combination may increase the risk of hepatotoxicity. Patients should be counseled to take rifampin consistently either with or without food (preferably without) to maintain consistent blood levels.