Sideeffect profile

Common adverse reactions with leflunomide include diarrhoea, nausea, reversible alopecia and rashes. Diarrhoea has been reported by >15% of patients in clinical trials. This side effect is of particular concern as it often causes patients to discontinue treatment. There is some evidence that omitting the loading dose reduces the frequency and severity of diarrhoea. Hypertension is sometimes seen and regular blood pressure monitoring is recommended. However, other concomitant therapies such as NSAIDs can also raise blood pressure so it can be difficult to identify the contribution of each agent. Occasionally, patients report weight loss with leflunomide treatment, although its relationship to therapy has not been proved. There is

Change in 0.10-Larsen score


12 months

24 months

■ Leflunomide

□ Sulfasalazine

Figure 4.5.

also a small increase in risk of infections, in common with other immuno-suppressive drugs. A small proportion of patients develop low white blood cell or platelet counts, and in these circumstances treatment should be stopped.

The main cause of concern with leflunomide is liver damage. Transient increases in liver enzymes are commonplace, and usually need no more than careful observation. If the levels rise to more than three times the normal level, treatment should be stopped. Only a minority of patients have developed either cirrhosis or liver failure whilst taking leflunomide, and the issue of causality is unclear. Careful consideration should be made before commencing leflunomide therapy in patients with prior liver disease or in those with significant levels of alcohol intake and there has also been concern about concomitant prescription of other hepatotoxic drugs, notably methotrexate. Patients receiving leflunomide should have their liver function monitored and blood counts assessed regularly for early detection of liver problems. These tests should be undertaken every two weeks for the first 6 months, although the frequency can reduce thereafter.

Leflunomide, like other DMARDs, can cause foetal damage and for this reason it should not be given to women at risk of pregnancy. Given the long half-life of the drug, it needs to be stopped for many months prior to conception, and some authorities recommend a two-year period of cessation. A washout procedure can be considered in patients having severe side effects or in men or women considering conception. This involves giving cholestyramine or activated powdered charcoal for one or two weeks.

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