Effective methotrexate elimination using high-flux haemodialysis

Background: Methotrexate is a chemotherapeutic agent used to treat cancer (breast, gastric, bladder, lymphoma and sarcoma) as well as psoriasis and rheumatoid arthritis. In overdose, toxic effects can be severe, symptoms can include vomiting, diarrhoea, mucositis, haemorrhagic enteritis, renal failure, hepatotoxicity and bone marrow suppression leading to leucopenia, thrombocytopenia and anaemia. Standard treatment is symptomatic and supportive together with folinic acid or glucarpidase therapy but response can be variable. Enhanced elimination of the drug by haemodialysis is generally considered to be ineffective. We report a case in which serum methotrexate concentrations were effectively and rapidly reduced using high-flux haemodialysis. Case report: A 23-year old female patient on treatment with high dose methotrexate for lymphoma was admitted with renal failure. Her serum methotrexate concentration was 81.9 µmol/L upon presentation. She was started on folinic acid therapy and also haemodialysis using an FX 100 high-flux dialyser. Following a 6-hour dialysis session, a break of 2 hours and a further 6-hour session, the methotrexate concentration fell to 11.2 µmol/L. The following day this had rebounded to 24 µmol/L, following a further 2 sessions of dialysis this was reduced to 2.7µmol/L. Six-hourly sessions of dialysis/day for the following 3 days reduced circulating methotrexate concentrations to 0.2 µmol/L. Each morning there was evidence of a rebound in concentrations. Conclusion: Methotrexate toxicity can be severe and deaths have occurred. In this case high-flux dialysis rapidly decreased circulating concentrations. The use of this means of elimination should be considered in cases of life-threatening toxicity not responding to conventional treatment.