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Leflunomide is a disease-modifying antirheumatic drug approved for therapy of rheumatoid arthritis and used off-label to reduce viral nephritis in renal transplant. It is a prodrug: rapid and complete metabolism converts leflunomide to its active metabolite, teriflunomide (also called A77 1726), which acts by inhibiting pyrimidine synthesis. Teriflunomide has a very long half-life, on average >2 weeks.
There is marked interindividual variability in leflunomide pharmacokinetics, thus therapeutic monitoring of serum teriflunomide concentrations may be helpful in optimizing therapy. Therapeutic targets remain only loosely defined and appear to vary depending on the purpose of therapy, but serum teriflunomide concentrations >40 mcg/mL have been associated with better clinical outcomes. Due to the long half-life, serum specimens for therapeutic monitoring may be drawn at any point in the dosing cycle, although trough (immediately before next schedule dose) sampling is preferred for consistency. Adverse reactions to leflunomide do not correlate well with serum drug concentration, but include diarrhea, hypertension, and liver toxicity.
Enhanced elimination of the drug may be required in patients who are or who wish to become pregnant, or who are experiencing toxicity; teriflunomide can persist up to 2 years after ceasing therapy unless elimination is accelerated. This can be accomplished through use of activated charcoal or a bile acid sequestrant such as cholestyramine, reducing the half-life of teriflunomide to approximately 1 day. Serum concentrations <0.020 mcg/mL (<20 ng/mL) on 2 independent tests at least 2 weeks apart are preferred for patients anticipating pregnancy to minimize the potential risk of teratogenesis associated with the drug.
Therapeutic monitoring of patients actively taking leflunomide
Assessment of elimination in patients requiring enhanced elimination of the drug
Therapy: clinical targets for serum teriflunomide (leflunomide metabolite) concentrations are still being determined, but levels >40 mcg/mL appear to correlate with better outcome.
Elimination: serum concentrations <0.020 mcg/mL (20 ng/mL) are preferred to minimize potential teratogenesis for patients considering pregnancy.
Leflunomide toxicity does not appear to correlate with teriflunomide concentrations, thus, this assay is unlikely to aid in evaluation of potential adverse drug reactions.
Therapeutic: >40 mcg/mL
Elimination: <0.020 mcg/mL
1. Cannon GW, Kremer JM: Leflunomide. Rheum Dis Clin North Am 2004;30(2):295-309
2. Chan V, Charles BG, Tett SE: Population pharmacokinetics and association between A77 1726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis. Br J Clin Pharmacol 2005;60(3):257-264
3. Teschner S, Gerke P, Geyer, et al: Leflunomide therapy for polyomavirus-induced allograft nephropathy: efficient BK virus elimination without increased risk of rejection. Transplant Proc 2009;41(6):2533-2538
4. Temprano KK, Bandlamudi R, Moore TL: Antirheumatic drugs in pregnancy and lactation. Semin Arthritis Rheum 2005;35(2):112-121