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

Abstract

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 10⁹/L [reference range[RR]:150-400 x 10⁹/L]) and an alanine aminotransferase 820 U/L [RR:10-35 U/L]. Methotrexate was undetectable [<0.04 µmol/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 10⁹/L, neutrophils, 0.0 x 10⁹/L [RR:2-8 x 10⁹/L] and white cell count, 0.6 x 10⁹/L [RR:4-11 x 10⁹/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.

Keywords:

• Methotrexate
• toxicity
• folinic acid
• pancytopenia
• neutropenia
• case report

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

GKI is funded by an National Health and Medical Research Council Senior Research Fellowship ID1154503.