Management recommendations in patients with methotrexate intoxication

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 of MTX 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 of MTX. Once toxicity has developed, the therapy must be directed at protection of the normal tissues, restoration of renal function and hence the renal elimination of MTX, restoration of the alkalisation of the urine, and general supportive therapy.