Repeated daily dosing of weekly methotrexate therapy causing multiorgan toxicity: a case report

Methotrexate toxicity following intravenous (IV) methotrexate is well reported, but there is less information on accidental daily dosing of a prescribed weekly dose of oral methotrexate. A 70 year old female presented following accidentally taking 20 mg methotrexate for five days, with multiple oral ulcers, thrombocytopenia (platelets 80 x 10(9)/L [reference range[RR]:150-400 x 10(9)/L]) and an alanine aminotransferase 820 U/L [RR:10-35 U/L]. Methotrexate was undetectable [<0.04 <mu>mol/L]. She was treated with folinic acid, 15 mg orally and then 15 mg IV every six hours. She became progressively pancytopenic, with the lowest counts occurring days 3-6: Hb, 87 g/L, platelets, 22 x 10(9)/L, neutrophils, 0.0 x 10(9)/L [RR:2-8 x 10(9)/L] and white cell count, 0.6 x 10(9)/L [RR:4-11 x 10(9)/L]. She received 2 units of platelets, filgrastim 300 mcg daily for days 3-7 and IV ceftazidime/gentamicin for a fever. On day 6, her platelet and neutrophil counts began to recover, and her ALT was almost normal on discharge day 9. She had alopecia in the 3 months post-discharge. Our patient developed severe toxicity, consistent with complete absorption and cellular uptake of methotrexate, with slow cellular elimination. She was treated with folinic acid, granulocyte-colony stimulating factor and blood product transfusions.