Leflunomide
Leflunomide is a drug similar to methotrexate used for treatment of rheumatoid arthritis.
Leflunomide is a disease-modifying antirheumatic drug (DMARDs), which is FDA approved to treat individuals with rheumatoid arthritis. It is a non-biological novel isoxazole derivative that has demonstrated anti-inflammatory and immunomodulatory characteristics. Leflunomide maintains function in rheumatoid arthritis by delaying articular cartilage and bone disintegration and limiting irreversible joint damage. The medication is also useful in preventing synovitis and managing systemic symptoms of the disease. Leflunomide is also indicated for the treatment of psoriatic arthritis and would be a reliable and beneficial option for individuals with the disease. Despite the efficacy of improving swollen and tender joints, there is no FDA approval for the treatment of psoriatic arthritis due to minimal impact on the improvement of skin psoriasis. Being a potent dihydro-orotate dehydrogenase inhibitor, leflunomide has been clinically assessed for cancer treatment but failed to secure FDA approval. The indication for its use as a treatment of cancer comes from the inhibition of dihydro-orotate dehydrogenase, which arrests the S-phase in the cell cycle and can slow the rapid proliferation of cancer cells.[3]
Effect on the immune system
Adverse effects
If pregnant or desiring pregnancy and on LEF, use drug elimination protocol with cholestyramine. Drug elimination procedure: Due to slow elimination and variations in clearance, it may take up to 2 years to reach low levels of leflunomide metabolite (eg, teriflunomide) serum concentrations. An accelerated drug elimination procedure using cholestyramine or activated charcoal is recommended when a more rapid elimination is needed. Initiate accelerated elimination procedures in patients when a severe adverse reaction occurs (eg, severe dermatologic reaction, suspected liver injury, bone marrow suppression, serious infection, interstitial lung disease, peripheral neuropathy, suspected hypersensitivity) or if pregnancy occurs during treatment. Refer to the manufacturer's labeling for detailed accelerated elimination procedure. Verify plasma teriflunomide concentrations are <0.02 mg/L by tests at least 14 days apart. If concentrations are >0.02 mg/L, repeat the accelerated elimination procedure. Use of accelerated drug elimination may potentially result in return of disease activity if the patient has been responding to leflunomide treatment. [1]
Accelerated elimination of the drug (eg, to prevent fetal risk during pregnancy due to potential drug exposure) can be achieved through the administration of cholestyramine (8 g orally three times daily for 11 days); this is effective because the drug's persistence depends upon enterohepatic circulation of the active metabolite. This approach can be used if LEF is inappropriately taken during pregnancy, if the patient inadvertently becomes pregnant while taking LEF, or if a women of child-bearing age wishes to become pregnant and if levels persist from prior treatment. Serum concentrations <0.02 mg/L should be verified by two separate tests performed at least 14 days apart. If serum concentrations are >0.02 mg/L, additional cholestyramine treatment can be employed. As an alternative to cholestyramine, the Canadian labeling recommends that activated charcoal may be used to enhance drug elimination. [2]
