From the Guidelines
Leflunomide should not be continued in patients with impaired renal function without careful consideration and monitoring, as the risk of accumulation of the active metabolite and increased toxicity is high. The most recent and highest quality study, 1, recommends modifying drugs based on renal clearance in patients with renal insufficiency, indicating a strong recommendation with high evidence quality. This suggests that leflunomide, which undergoes both hepatic metabolism and renal excretion, may require dose adjustment or alternative treatment in patients with impaired renal function.
When considering the use of leflunomide in patients with renal impairment, it is essential to weigh the potential benefits against the risks of toxicity. While some studies, such as 1, suggest reducing the dose in severe renal impairment, the most recent guideline, 1, emphasizes the importance of modifying treatment based on renal clearance. Key considerations include:
- Monitoring renal function, complete blood counts, and liver enzymes regularly
- Watching for signs of toxicity, such as liver dysfunction, bone marrow suppression, or skin reactions
- Possibly implementing a cholestyramine washout procedure to rapidly eliminate the drug if needed
- Considering alternative treatments or dose adjustments to minimize the risk of accumulation and toxicity.
In patients with severe renal failure (creatinine clearance <30 mL/min), the use of leflunomide is not recommended due to limited data and potential accumulation of the active metabolite. However, if a patient with renal failure is already on leflunomide and experiencing worsening kidney function, a careful assessment of the risks and benefits should be made, and consideration should be given to alternative treatments or dose adjustments to minimize the risk of toxicity.
From the FDA Drug Label
In light of the fact that the kidney plays a role in drug elimination and without adequate studies of leflunomide use in subjects with renal insufficiency, caution should be used when leflunomide is administered to these patients. The free fraction of M1 was almost doubled, but the mechanism of this increase is not known Single dose studies in dialysis patients show a doubling of the free fraction of M1 in plasma. There is no clinical experience in the use of leflunomide in patients with renal impairment Caution should be used when administering this drug in this population.
It is not safe to continue Leflunomide in patients with impaired renal function without caution.
- Key Points:
- The kidney plays a role in drug elimination
- There is no clinical experience in the use of leflunomide in patients with renal impairment
- Caution should be used when administering this drug in this population
- The free fraction of M1 is almost doubled in patients with chronic renal insufficiency, but the mechanism of this increase is not known 2 2 2
From the Research
Safety of Leflunomide in Patients with Impaired Renal Function
- The use of leflunomide in patients with impaired renal function has been studied, and the results suggest that it can be used without dosage modification 3, 4.
- A study published in 2013 found that the dialytic removal of teriflunomide, the active metabolite of leflunomide, is negligible, and leflunomide can be used for RA patients on chronic dialysis without any dosage modification 4.
- Another study published in 2015 found that leflunomide and numerous biologics can be used without dosage modification in patients with renal insufficiency, although biologics with a molecular weight < 60 kDa should be reduced in patients with renal insufficiency 3.
- In contrast, other disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine, azathioprine, mycophenolate mofetil, and cyclophosphamide require dosage reduction in patients with moderate and severe renal insufficiency 3.
- The renal toxicity of leflunomide is relatively low compared to other DMARDs, and it is considered a safe option for patients with impaired renal function 5.
Key Findings
- Leflunomide can be used without dosage modification in patients with impaired renal function 3, 4.
- The dialytic removal of teriflunomide is negligible, making leflunomide a safe option for RA patients on chronic dialysis 4.
- Leflunomide has relatively low renal toxicity compared to other DMARDs 5.
- Other DMARDs may require dosage reduction or have higher renal toxicity, and should be used with caution in patients with impaired renal function 3, 5.