Drug utilization evaluation of high-dose methotrexate in a cancer center in north of Iran

Methotrexate (MTX) is commonly used in the hematology-oncology units and is frequently associated with adverse effects. High-dose methotrexate (HDMTX) is indicated in the treatment of acute lymphoblastic leukemia (ALL), osteosarcoma, systemic non-Hodgkin lymphoma and primary central nervous system (CNS) lymphoma. The side effect profile of MTX varies markedly according to dose. The aim of this study was to evaluate the uses and adverse effects of HDMTX in a cancer center in north of Iran.
This cross-sectional descriptive study carried out in Emam Sajjad Hospital, Ramsar, Iran from June 2016 to July 2017. Doses more than 500 mg/m2 of MTX was considered as a high-dose. Hydration status, evaluation of the renal and hepatic function, blood tests, urine pH, doses and frequencies of leucovorin administration, measurement of serum levels of MTX and side effects were evaluated. Recommendations of UpToDate 2017 were considered as standards of administration of HDMTX.
Forty-four courses of HDMTX were evaluated in this study. HDMTX were prescribed for lymphoma (30 cases), ALL (8 cases) and osteosarcoma (6 cases). In all patients, hydration was done with 1340.9±894 normal saline plus 25 ml sodium bicarbonate 8.4%, one to two hours before HDMTX. The solution used for dilution of MTX was 5% dextrose (1022.7±105.5 ml). Urine pH was not measured in any patient. The frequency of leucovorin administration was 5.64±3.03 times with doses of 17.6±1.7 mg/m2 every 6 hours. Serum levels of MTX were not measured in any patient. Blood urea nitrogen and creatinine measurement was carried out before administration of HDMTX in all patients. The most common adverse effects were nausea (64.4%), anxiety (44%) and headache (43.2%).
The appropriate aspects of HDMTX usage were good hydration, urine alkalinization with bicarbonate and administration of leucovorin in patients receiving HDMTX, whereas monitoring of serum levels of MTX and administration of bicarbonate based on urinary pH were not done in any of the patients.