Leflunomide is an inhibitor of pyrimidine synthesis, specifically acting on dihydroorotate dehydrogenase. This action reduces production of fast proliferating cells; a particular preference for B lymphocytes has been seen.
- Alopecia
- Diarrhoea and mucosal ulceration (mucositis) and nausea / vomiting
- Hypertension
- Bone marrow suppression and serious infection
- Hepatotoxicity
- Rash, which can be Steven-Johnson syndrome or toxic epidermal necrolysis
Leflunomide is teratogenic in animal studies. Appropriate contraception should be used to avoid pregnancy during therapy. Male patients should also be warned to use effective contraception.
If serious adverse effects occur, a "washout" procedure is recommended.
Cholestyramine interacts with leflunomide to reduce its effect (clinically useful if "washout" needed).
Risk of toxicity increased if used with methotrexate.
Avoid use with live vaccines.
Patients should be aware that monitoring blood tests are needed. They should be counselled about contraception.
Significant enterohepatic circulation is seen, so pharmacological effect is prolonged after drug discontinuation. If necessary, cholestyramine can be used to reduce this effect ("washout" procedure). Elimination is hepatic rather than renal.
