USE OF METHOTREXATE IN OLDER PATIENTS - A RISK-BENEFIT ASSESSMENT

Methotrexate is eliminated almost entirely by the kidneys. The risk of methotrexate toxicity is therefore increased in patients with poor re nal function, most likely as a result of drug accumulation. Declining renal function with age may thus be an important predictor of toxicity to methotrexate. Up to 60% of all patients who receive methotrexate f or rheumatoid arthritis (RA) discontinue taking it because of adverse effects, most of which occur during the first year of therapy. Gastroi ntestinal complications are the most common adverse effects of methotr exate, but hepatotoxicity, haematological toxicity, pulmonary toxicity , lymphoproliferative disorders and exacerbation of rheumatic nodules have all been reported, Decreased renal function as a result of diseas e and/or aging appears to be an important determinant of hepatic, lymp hoproli ferative and haematological toxicity, Concomitant use of low d oses of folic acid has been recommended as an approach to limiting tox icity. Interactions between methotrexate and several nonsteroidal anti -inflammatory drugs have been reported, but they may not be clinically significant. However, caution is advised in the use of such combinati ons in patients with reduced renal function. More serious toxicities ( e.g. pancytopenia) may result when other inhibitors of folate utilisat ion [e.g. cotrimoxazole (trimethoprim-sulfamethoxazole)] or inhibitors of renal tubular secretion (e.g. probenecid) are combined with methot rexate. Before starting low dose methotrexate therapy in patients with RA, a full blood count, liver function tests, renal function tests an d chest radiography should be performed. Blood counts and liver functi on tests should be repeated at regular intervals. Therapeutic drug mon itoring of methotrexate has also been suggested as a means of limiting toxicity. Patients with RA usually respond very favourably to low dos e methotrexate therapy, and the probability of patients continuing the ir treatment beyond 5 years is greater than for other slow-acting anti rheumatic drugs. Thus, given its sustained clinical utility and relati vely predictable toxicity profile, low dose methotrexate is a useful a ddition to the therapy of RA.