title: [Management recommendations in patients with methotrexate intoxication].
abstract: Intoxication due to insufficient renal clearance developed in 2 patients, a 54-year-old man and a 61-year-old woman, who were under treatment with methotrexate (MTX) for a primary cerebral lymphoma and a recurrence of large-cell B-cell-non-Hodgkin lymphoma, respectively. Both were treated with folinic acid rescue, thymidine, and alkalisation of the urine. MTX is a cytotoxic drug that is often used in oncology and rheumatology. Significant and even lethal toxicity can develop when the elimination ofMTX is delayed or when supportive care, such as folinic acid rescue, is inadequate. Delayed elimination can be caused by reduced renal function, by the 'third space' phenomenon such as in case of ascites, pleural fluid accumulation and oedema, and by drug-drug interactions leading to reduced renal function or a disturbance in the plasma protein binding ofMTX. Once toxicity has developed, the therapy must be directed at protection of the normal tissues, restoration of renal function and hence the renal elimination ofMTX, restoration of the alkalisation of the urine, and general supportive therapy.
authors.affiliation: Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis, afd. Medische Oncologie, Plesmanlaan 121, 1066 CX Amsterdam. j.schellens@nki.nl
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D002955:Leucovorin / Q000627:therapeutic use; D008223:Lymphoma / Q000188:drug therapy; D016393:Lymphoma, B-Cell / Q000188:drug therapy; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D051437:Renal Insufficiency / Q000139:chemically induced*; D013936:Thymidine / Q000627:therapeutic use; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D002955:Leucovorin; D013936:Thymidine; D008727:Methotrexate