From the Guidelines
The recommended monitoring protocol for leflunomide toxicity includes baseline laboratory tests followed by regular monitoring throughout treatment, with CBC and LFTs checked within the first 1-2 months of usage and every 3-4 months thereafter, as conditionally recommended by the 2021 American College of Rheumatology guideline 1. This monitoring protocol is essential to minimize the risk of leflunomide toxicity, particularly hepatotoxicity and bone marrow suppression.
- Key aspects of the monitoring protocol include:
- Baseline laboratory tests, including complete blood count (CBC) and liver function tests (LFTs)
- Regular monitoring of CBC and LFTs throughout treatment
- Particular attention to liver enzymes, with treatment interruption if ALT rises to >3 times the upper limit of normal, as per the package insert 1
- Consideration of cholestyramine or activated charcoal to accelerate leflunomide elimination if severe toxicity occurs or a woman wishes to become pregnant 1 The 2021 American College of Rheumatology guideline provides the most recent and highest-quality evidence for leflunomide toxicity monitoring, and its recommendations should be prioritized in clinical practice 1.
From the FDA Drug Label
Patients taking leflunomide should have platelet, white blood cell count and hemoglobin or hematocrit monitored at baseline and monthly for six months following initiation of therapy and every 6 to 8 weeks thereafter. If used with concomitant methotrexate and/or other potential immunosuppressive agents, chronic monitoring should be monthly At minimum, ALT (SGPT) must be performed at baseline and monitored initially at monthly intervals during the first six months then, if stable, every 6 to 8 weeks thereafter. In addition, if leflunomide and methotrexate are given concomitantly, ACR guidelines for monitoring methotrexate liver toxicity must be followed with ALT, AST, and serum albumin testing monthly
The recommended monitoring protocol for leflunomide toxicity includes:
- Hematologic monitoring: platelet, white blood cell count, and hemoglobin or hematocrit at baseline, monthly for six months, and every 6 to 8 weeks thereafter
- Liver enzyme monitoring: ALT (SGPT) at baseline, monthly for six months, and every 6 to 8 weeks thereafter, with additional monitoring of AST and serum albumin if concomitantly used with methotrexate
- Increased monitoring frequency if used with concomitant methotrexate and/or other potential immunosuppressive agents 2 2
From the Research
Leflunomide Toxicity Monitoring
- The recommended monitoring protocol for leflunomide toxicity includes regular liver function tests, as hepatotoxicity is a potential side effect of the drug 3.
- Studies have shown that grade 2 or 3 elevations in liver function blood tests can occur in approximately 8.9% of patients taking leflunomide, with most cases occurring within the first 6 months of therapy 3.
- Monitoring of liver functions is crucial, as hepatotoxicity can be a significant concern in patients taking leflunomide, especially those with a history of hepatic disease or concomitant use of potential hepatotoxic co-medication 3, 4.
- In addition to liver function tests, patients should be monitored for other potential side effects of leflunomide, including diarrhea, alopecia, and rash 5, 6.
- If an adverse event occurs, treatment may need to be stopped or the dose reduced, and patients should be informed about the likelihood of side effects and involved in their disease management 6.
Management of Leflunomide Toxicity
- In cases of severe toxicity, a cholestyramine washout may be used to expedite the removal of the drug, as leflunomide has a prolonged half-life due to enterohepatic recirculation 4.
- For minor adverse events, reducing the leflunomide dose or using symptomatic treatment may be considered, and patients should be adequately supported and involved in their disease management 6.
- The safety profile of leflunomide has been well documented in clinical trials and postmarketing surveillance, and most adverse events are considered manageable with proper monitoring and patient management 6.