Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system

Akiho Fukuda; Kohei Tahara; Yuuki Hane; Toshinobu Matsui; Sayaka Sasaoka; Haruna Hatahira; Yumi Motooka; Shiori Hasegawa; Misa Naganuma; Junko Abe; Satoshi Nakao; Hirofumi Takeuchi; Mitsuhiro Nakamura

doi:10.1371/journal.pone.0185654

Comparison of the adverse event profiles of conventional and liposomal formulations of doxorubicin using the FDA adverse event reporting system

PLoS One. 2017 Sep 27;12(9):e0185654. doi: 10.1371/journal.pone.0185654. eCollection 2017.

Authors

Affiliations

¹ Laboratory of Drug Informatics, Gifu Pharmaceutical University, Gifu-shi, Gifu, Japan.
² Laboratory of Pharmaceutical Engineering, Gifu Pharmaceutical University, Gifu University, Gifu-shi, Gifu, Japan.
³ Medical database Co., LTD, Shibuya-ku, Tokyo, Japan.

Abstract

Doxorubicin (DOX) is an anthracycline widely used for the treatment of solid and hematological tumors. The aim of this study was to assess the adverse event profiles of conventional DOX and liposomal DOX. This is the first study to evaluate the effect of a liposomal formulation of DOX using spontaneous reporting system (SRS) databases. The SRS used was the US Food and Drug Administration Adverse Event Reporting System (FAERS). This study relied on definitions of preferred terms provided by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ) database. We also calculated the reporting odds ratios (RORs) of suspected drugs (conventional DOX; PEGylated-liposome DOX; non-PEGylated-liposome DOX). The FAERS database contained 7,561,254 reports from January 2004 to December 2015. The number of reported AE cases for conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX was 5039, 3780, and 349, respectively. Conventional DOX and liposomal DOX have potential risks of causing myelosuppression, cardiotoxicity, alopecia, nausea, and vomiting, among other effects. The RORs (95% CI) from SMQ for haematopoietic leucopenia associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 12.75 (11.89-13.68), 6.43 (5.81-7.13), and 14.73 (11.42-18.99), respectively. Liposomal DOX formulations were associated with lower RORs with regard to myelosuppression, cardiotoxicity, and alopecia than the conventional DOX was. The RORs (95% CI) for palmar-plantar erythrodysesthesia (PPE) associated with conventional DOX, PEGylated-liposome DOX, and non-PEGylated-liposome DOX were 6.56 (4.74-9.07), 64.77 (56.84-73.80), and 28.76 (15.77-52.45), respectively. This study is the first to evaluate the relationship between DOX liposomal formulations and their adverse event profiles. The results indicate that careful observation for PPE is recommended with the use of liposomal DOX, especially PEGylated-liposome DOX formulations.

Publication types

Comparative Study

MeSH terms

Adverse Drug Reaction Reporting Systems*
Antibiotics, Antineoplastic / adverse effects*
Doxorubicin / adverse effects*
United States
United States Food and Drug Administration

Substances

Antibiotics, Antineoplastic
Doxorubicin

Grants and funding

This research was partially supported by JSPS KAKENHI Grant Number, 17K08452 to MN. JA was an employee of Medical Database Co., LTD during the time of the study and received a salary. The specific roles of these authors are articulated in the 'author contributions' section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for the study.