PMID- 37279701
OWN - NLM
STAT- MEDLINE
DCOM- 20231010
LR  - 20231010
IS  - 1423-0232 (Electronic)
IS  - 0030-2414 (Linking)
VI  - 101
IP  - 10
DP  - 2023
TI  - Adverse Event Profile of Azacitidine: Analysis by Route of Administration Using 
      Japanese Pharmacovigilance Database.
PG  - 664-674
LID - 10.1159/000531390 [doi]
AB  - INTRODUCTION: Azacitidine is a useful drug for myelodysplastic syndromes and 
      acute myeloid leukemia. In clinical trials, hematologic toxicity and infection 
      have been observed as adverse events (AEs) of this drug. However, information on 
      the time to onset of high risk AEs and subsequent outcomes, as well as 
      differences in the frequency of AEs due to the route of administration is 
      lacking. In this study, we investigated azacitidine-induced AEs comprehensively 
      using the Japanese Adverse Event Reporting Database (JADER) published by the 
      Pharmaceuticals and Medical Devices Agency, with disproportionate analysis of AE 
      incidence trends, time to onset, and subsequent outcomes. In addition, we 
      analyzed the differences in AEs by route of administration and the number of days 
      until the occurrence of AEs and generated hypotheses. METHODS: The study used 
      JADER data reported from April 2004 to June 2022. Risk estimation was conducted 
      using reported odds ratio. A signal was detected when the lower limit of the 95% 
      confidence interval of the calculated ROR was >/=1. RESULTS: A total of 34 signals 
      were detected as AEs due to azacitidine. Among them, 15 were hematologic 
      toxicities and 10 were infections, which demonstrated a particularly high rate of 
      death. Signals of AEs such as tumor lysis syndrome (TLS) and cardiac failure, 
      which have been described in case reports, were also detected, and the rate of 
      death after onset was high. In addition, more AEs generally occurred within the 
      first month of treatment. CONCLUSION: The results of this study suggest that more 
      attention should be paid to cardiac failure, hematologic toxicity, infection, and 
      TLS. Because many patients in clinical trials have discontinued treatment due to 
      serious AEs before the therapeutic effect became apparent, appropriate supportive 
      care, dose reduction, and drug withdrawal are important for the continuation of 
      treatment.
CI  - (c) 2023 S. Karger AG, Basel.
FAU - Yamaoka, Kenta
AU  - Yamaoka K
AD  - Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.
AD  - School of Pharmacy, Hyogo Medical University, Kobe, Japan.
FAU - Fujiwara, Masaki
AU  - Fujiwara M
AD  - Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.
AD  - School of Pharmacy, Hyogo Medical University, Kobe, Japan.
FAU - Uchida, Mayako
AU  - Uchida M
AD  - Department of Education and Research Center for Pharmacy Practice, Faculty of 
      Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, 
      Japan.
FAU - Uesawa, Yoshihiro
AU  - Uesawa Y
AD  - Department of Medical Molecular Informatics, Meiji Pharmaceutical University, 
      Tokyo, Japan.
FAU - Muroi, Nobuyuki
AU  - Muroi N
AD  - Department of Pharmacy, Kobe City Medical Center General Hospital, Kobe, Japan.
FAU - Shimizu, Tadashi
AU  - Shimizu T
AD  - School of Pharmacy, Hyogo Medical University, Kobe, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230606
PL  - Switzerland
TA  - Oncology
JT  - Oncology
JID - 0135054
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Humans
MH  - *Azacitidine/administration & dosage/adverse effects
MH  - *Drug-Related Side Effects and Adverse Reactions
MH  - East Asian People
MH  - Heart Failure/chemically induced
MH  - Pharmacovigilance
OTO - NOTNLM
OT  - Azacitidine
OT  - DNA methylation Inhibitors
OT  - Japanese Adverse Drug Event Report
OT  - Myelodysplastic syndromes
OT  - Pharmacovigilance
EDAT- 2023/06/07 01:07
MHDA- 2023/10/04 06:43
CRDT- 2023/06/06 18:23
PHST- 2023/02/09 00:00 [received]
PHST- 2023/05/17 00:00 [accepted]
PHST- 2023/10/04 06:43 [medline]
PHST- 2023/06/07 01:07 [pubmed]
PHST- 2023/06/06 18:23 [entrez]
AID - 000531390 [pii]
AID - 10.1159/000531390 [doi]
PST - ppublish
SO  - Oncology. 2023;101(10):664-674. doi: 10.1159/000531390. Epub 2023 Jun 6.