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Methotrexate is used in the treatment of a variety of conditions, such as rheumatoid arthritis and cancers (including leukaemias, non-Hodgkin’s lymphoma and head and neck cancer). Leflunomide (Arava) is used in the treatment of rheumatoid arthritis and psoriatic arthritis. Leflunomide is not authorised for use in conjunction with any other disease-modifying medicine, such as methotrexate.Reports of suspected adverse drug reactions (ADRs) are collected by the Medicines and Healthcare products Regulatory Agency (MHRA) and the Commission for Human Medicines (CHM) through the spontaneous reporting scheme, the Yellow Card Scheme.For the three year period up to 30 April 2007, the MHRA/CHM had received a total of 19 spontaneous reports of suspected ADRs with a fatal outcome in association with methotrexate when used in the treatment of rheumatoid arthritis. In the majority of the 19 reports the cause of death was attributed to lung disorders (such as pulmonary fibrosis and pneumonitis) and infections (septicaemia/septic shock). There were seven reports with a fatal outcome that were reported in association with leflunomide therapy. The cause of death in the seven reports was attributed to liver failure (one), lung disorder (two), heart attack (one), chest infection (one) and toxic epidermal necrolysis (two). The MHRA has not received any ADR reports with a fatal outcome associated with the combined use of methotrexate and leflunomide.It is important to note that the submission of a suspected ADR report does not necessarily mean that it was caused by the drug. Many factors have to be taken into account in assessing causal relationships including temporal association, the possible contribution of concomitant medications and the patient's underlying disease. Patients with rheumatoid arthritis are at increased risk of developing serious infections and lung disorders as part of the natural disease process even in the absence of drug treatment.The product information for methotrexate and leflunomide which is provided to doctors and patients has extensive information regarding the risk of developing serious lung disorders and infections. The product information also mentions the need for patients to have a full blood count and liver function tests before starting treatment and at regular intervals thereafter to detect potential adverse effects on the blood and liver. As with all medicines, the MHRA and CHM will continue to closely monitor the safe use of methotrexate and leflunomide. |