소아 급성림프구성백혈병 환자에서 Trimethoprim-Sulfamethoxazole과 Methotrexate 병용 투여 시 약물 부작용 평가
Evaluation of Adverse Drug Reaction Caused by Concomitant Use of Trimethoprim-Sulfamethoxazole and Methotrexate in Pediatric Acute Lymphoblastic Leukemia Patients
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Background : As maintenance therapy for pediatric acute lymphoblastic leukemia (ALL), oral methotrexate (MTX) and mercaptopurine (6-MP) are administered to prevent relapses. In addition to these anticancer drugs, oral trimethoprim-sulfamethoxazole (TMP-SMX) is usually prescribed to reduce the risk of Pneumocystis jiroveci Pneumonia. However, concomitant use of MTX and TMP-SMX may result in an increase of toxicity of MTX. As a matter of fact, a new contraindication against the use of TMP-SMX with MTX has been announced by the Ministry of Health and Welfare in December 2020. The objective of this study was to evaluate adverse drug reactions associated with concomitant use of TMP-SMX and MTX in pediatric ALL. Methods : Sixty-five patients received a maintenance therapy between January 2016 and July 2021 at Seoul St. Mary’s Hospital. Patient’s medical records and histories from the beginning to the end of maintenance therapy were reviewed retrospectively. We analyzed each patient’s basic characteristics, incidence and severity of adverse drug reactions (myelotovicity, hepatotoxicity and nephrotoxicity), methotrexate (MTX) reduction or discontinuation according to adverse drug reactions and completion of maintenance therapy. Results : Incidence rates of chemotherapy cycles that have myelotoxicity, hepatotoxicity, and nephrotoxicity were 100%, 92.3%, and 63.1%, respectively. Majority (90.9%) of these adverse events fell into grade 1 or 2. All patients completed the maintenance therapy successfully. Conclusion : Despite recently announced contraindication against concomitant use of MTX and TMP-SMX, the maintenance therapy including both MTX and TMP-SMX for pediatric ALL patients might be safe when adverse drug reactions are carefully monitored.
Abstract
Background : As maintenance therapy for pediatric acute lymphoblastic leukemia (ALL), oral methotrexate (MTX) and mercaptopurine (6-MP) are administered to prevent relapses. In addition to these anticancer drugs, oral trimethoprim-sulfamethoxazole (TMP-SMX) is usually prescribed to reduce the risk of Pneumocystis jiroveci Pneumonia. However, concomitant use of MTX and TMP-SMX may result in an increase of toxicity of MTX. As a matter of fact, a new contraindication against the use of TMP-SMX with MTX has been announced by the Ministry of Health and Welfare in December 2020. The objective of this study was to evaluate adverse drug reactions associated with concomitant use of TMP-SMX and MTX in pediatric ALL. Methods : Sixty-five patients received a maintenance therapy between January 2016 and July 2021 at Seoul St. Mary’s Hospital. Patient’s medical records and histories from the beginning to the end of maintenance therapy were reviewed retrospectively. We analyzed each patient’s basic characteristics, incidence and severity of adverse drug reactions (myelotovicity, hepatotoxicity and nephrotoxicity), methotrexate (MTX) reduction or discontinuation according to adverse drug reactions and completion of maintenance therapy. Results : Incidence rates of chemotherapy cycles that have myelotoxicity, hepatotoxicity, and nephrotoxicity were 100%, 92.3%, and 63.1%, respectively. Majority (90.9%) of these adverse events fell into grade 1 or 2. All patients completed the maintenance therapy successfully. Conclusion : Despite recently announced contraindication against concomitant use of MTX and TMP-SMX, the maintenance therapy including both MTX and TMP-SMX for pediatric ALL patients might be safe when adverse drug reactions are carefully monitored.
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