PMID- 37164926
OWN - NLM
STAT- MEDLINE
DCOM- 20230512
LR  - 20240321
IS  - 1672-7347 (Print)
IS  - 1672-7347 (Linking)
VI  - 48
IP  - 3
DP  - 2023 Mar 28
TI  - Signal mining and analysis for central nervous system adverse events due to 
      taking oxycodone based on FAERS database.
PG  - 422-434
LID - 1672-7347(2023)03-0422-13 [pii]
LID - 10.11817/j.issn.1672-7347.2023.220304 [doi]
AB  - OBJECTIVES: Central nervous system adverse events (AEs) occur when oxycodone is 
      used in combination with benzodiazepines, antidepressants and anticonvulsants. 
      There have been no reports of central nervous system AEs with oxycodone alone or 
      in combination with oxycodone. Based on USA Food and Drug Administration Adverse 
      Event Reporting System (FAERS) data, this study aims to explore the risk signals 
      of central nervous system AEs with oxycodone alone or in combination with 
      benzodiazepines, antidepressants and anticonvulsants, and to provide a reference 
      for the safe and rational use of this drug. METHODS: Extracted AEs data from the 
      FAERS for oxycodone alone and in combination with benzodiazepines, 
      antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal 
      mining analysis of AEs was performed using the proportional imbalance method and 
      Bayesian method. Number of reports >/=3 and lower 95% CI limit of reporting odds 
      ratio (ROR)>1; number of reports >/=3, proportional reporting ratio (PRR)>/=2 and 
      chi(2)>/=4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical 
      Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined 
      as positive signals. RESULTS: A total of 5 793 reports of central nervous system 
      AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined 
      benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers 
      and physicians were the main reporting population. The age distribution of 
      oxycodone alone was mainly from 61 to 80 years old. The age distribution of 
      oxycodone in combination with related drugs was mainly from 46 to 60 years old. 
      The risk of AEs was greater in women than in men, and the United States was the 
      predominant reporting country. Oxycodone alone was strongly associated with 
      myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, chi(2)(77.49); IC=1.52, 
      IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; 
      PRR=4.66, chi(2)(1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental 
      disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, chi(2)(206.93); IC=1.56, 
      IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression 
      [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, chi(2)(971.62); IC=1.52, IC025(1.33), 
      EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly 
      associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, 
      chi(2)(64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor 
      [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, chi(2)(48.93); IC=1.63, IC025 (1.17); 
      EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly 
      associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, 
      chi(2)(43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence 
      [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, chi(2)(53.42); IC=2.75, IC025(1.52); 
      EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly 
      associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, 
      chi(2)(971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium 
      [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, chi(2)(69.49); IC=2.28, IC025 (1.51); 
      EBGM=4.86, EBGM05(3.44)]. CONCLUSIONS: Based on pharmacovigilance studies of the 
      FAERS database, clinical medication monitoring of oxycodone alone and in 
      combination with benzodiazepines, antidepressants, and anticonvulsants should be 
      strengthened to be alert to the occurrence of central nervous system-related AEs.
FAU - Wu, Xiangping
AU  - Wu X
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008. wuxiangping97@163.com.
AD  - School of Pharmacy, Dali University, Dali Yunnan, 671000. wuxiangping97@163.com.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008. 
      wuxiangping97@163.com.
FAU - Zhang, Lu
AU  - Zhang L
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008.
FAU - Huang, Hangxing
AU  - Huang H
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008.
AD  - School of Pharmacy, Dali University, Dali Yunnan, 671000.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008.
FAU - Huang, Ling
AU  - Huang L
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008.
FAU - Lu, Xikui
AU  - Lu X
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008.
AD  - School of Pharmacy, Dali University, Dali Yunnan, 671000.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008.
FAU - Wang, Zhenting
AU  - Wang Z
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008.
AD  - School of Pharmacy, Dali University, Dali Yunnan, 671000.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008.
FAU - Xiao, Jian
AU  - Xiao J
AD  - Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 
      410008. admanoas@163.com.
AD  - National Clinical Research Center for Geriatric Disorders, Xiangya Hospital; 
      Laboratory for Rational and Safe Use of Elderly, Changsha 410008. 
      admanoas@163.com.
LA  - eng
LA  - chi
GR  - 2021JJ31043/the Natural Science Foundation of Hunan Province/
GR  - kq2007039/the Changsha Natural Science Foundation/
GR  - XYYYJSTG-15/the National Clinical Research Center for Geriatric Disorders 
      Appropriate Technology Promotion Project/
GR  - WDZC20205500121/the Parallel and Distributed Processing for the Stable Support 
      Project of the National Defense Science and Technology Key Laboratory/
PT  - Journal Article
TT  - 基于FAERS数据库的羟考酮中枢神经系统不良事件信号挖掘及分析.
PL  - China
TA  - Zhong Nan Da Xue Xue Bao Yi Xue Ban
JT  - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. 
      Medical sciences
JID - 101230586
RN  - CD35PMG570 (Oxycodone)
RN  - 0 (Anticonvulsants)
RN  - 12794-10-4 (Benzodiazepines)
SB  - IM
MH  - Male
MH  - Humans
MH  - Female
MH  - United States/epidemiology
MH  - Middle Aged
MH  - Aged
MH  - Aged, 80 and over
MH  - Oxycodone/adverse effects
MH  - Bayes Theorem
MH  - Anticonvulsants
MH  - United States Food and Drug Administration
MH  - *Myoclonus
MH  - Adverse Drug Reaction Reporting Systems
MH  - Benzodiazepines/adverse effects
MH  - Central Nervous System
MH  - *Delirium
PMC - PMC10930086
OAB - OBJECTIVE: Central nervous system adverse events (AEs) occur when oxycodone is 
      used in combination with benzodiazepines, antidepressants and anticonvulsants. 
      There have been no reports of central nervous system AEs with oxycodone alone or 
      in combination with oxycodone. Based on USA Food and Drug Administration Adverse 
      Event Reporting System (FAERS) data, this study aims to explore the risk signals 
      of central nervous system AEs with oxycodone alone or in combination with 
      benzodiazepines, antidepressants and anticonvulsants, and to provide a reference 
      for the safe and rational use of this drug. METHODS: Extracted AEs data from the 
      FAERS for oxycodone alone and in combination with benzodiazepines, 
      antidepressants, and anticonvulsants from Q1 2004 to Q2 2021. The risk signal 
      mining analysis of AEs was performed using the proportional imbalance method and 
      Bayesian method. Number of reports >/=3 and lower 95% CI limit of reporting odds 
      ratio (ROR)>1; number of reports >/=3, proportional reporting ratio (PRR)>/=2 and 
      chi(2)>/=4; lower information components (IC) lower 95% CI limit (IC025)>0; empirical 
      Bayes geometric mean (EBGM) lower 95% CI limit (EBGM05)>2, and N>0 were defined 
      as positive signals. RESULTS: A total of 5 793 reports of central nervous system 
      AEs with oxycodone alone were tapped, and 366, 622, and 740 reports of combined 
      benzodiazepines, antidepressants, and anticonvulsants, respectively. Consumers 
      and physicians were the main reporting population. The age distribution of 
      oxycodone alone was mainly from 61 to 80 years old. The age distribution of 
      oxycodone in combination with related drugs was mainly from 46 to 60 years old. 
      The risk of AEs was greater in women than in men, and the United States was the 
      predominant reporting country. Oxycodone alone was strongly associated with 
      myoclonus [ROR=2.92, 95% CI 2.28 to 3.76); PRR=2.92, chi(2)(77.49); IC=1.52, 
      IC025(0.65); EBGM=2.89, EBGM05(2.33)], delirium [ROR=4.69, 95% CI 4.24 to 5.21; 
      PRR=4.66, chi(2)(1 052.64); IC=2.17, IC025(1.81); EBGM=4.50, EBGM05 (4.13)], mental 
      disorder [ROR=2.95, 95% CI 2.53 to 3.44; PRR=2.94, chi(2)(206.93); IC=1.56, 
      IC025(0.96); EBGM=2.95, EBGM05(2.58)], and acute central respiratory depression 
      [ROR=2.87, 95% CI 2.68 to 3.08); PRR=2.82, chi(2)(971.62); IC=1.52, IC025(1.33), 
      EBGM=2.87, EBGM05 (2.76)]. Combination of benzodiazepines was most strongly 
      associated with mental disorder [ROR=10.08, 95% CI 9.38 to 10.78; PRR=9.90, 
      chi(2)(64.06); IC=3.33, IC025 (1.65); EBGM=10.08, EBGM05(5.61)], and tremor 
      [ROR=3.09, 95% CI 2.76 to 3.42); PRR=3.08, chi(2)(48.93); IC=1.63, IC025 (1.17); 
      EBGM=3.09, EBGM05(2.34)]. Combination of antidepressants was most strongly 
      associated with delirium [ROR=13.23, 95% CI 12.23 to 14.23; PRR=12.87, 
      chi(2)(43.86); IC=3.69, IC025(1.36); EBGM=12.23, EBGM05 (5.32)] and somnolence 
      [ROR=6.74, 95% CI 6.15 to 7.33); PRR=6.73, chi(2)(53.42); IC=2.75, IC025(1.52); 
      EBGM=6.73, EBGM05(4.10)]. Combination of anticonvulsants was most strongly 
      associated with myoclonus [ROR=17.89, 95% CI 17.46 to 18.32; PRR=17.72, 
      chi(2)(971.39); IC=4.16, IC025(2.70); EBGM=17.89, EBGM05(12.46)] and delirium 
      [ROR=4.86, 95% CI 4.45 to 5.27); PRR=4.82, chi(2)(69.49); IC=2.28, IC025 (1.51); 
      EBGM=4.86, EBGM05(3.44)]. CONCLUSION: Based on pharmacovigilance studies of the 
      FAERS database, clinical medication monitoring of oxycodone alone and in 
      combination with benzodiazepines, antidepressants, and anticonvulsants should be 
      strengthened to be alert to the occurrence of central nervous system-related AEs.
OABL- eng
OTO - NOTNLM
OT  - Food and Drug Administration Adverse Event Reporting System
OT  - adverse events
OT  - oxycodone
OT  - signal mining
COIS- 作者声称无任何利益冲突。
EDAT- 2023/05/11 00:41
MHDA- 2023/05/12 07:06
PMCR- 2023/03/28
CRDT- 2023/05/10 22:33
PHST- 2023/05/12 07:06 [medline]
PHST- 2023/05/11 00:41 [pubmed]
PHST- 2023/05/10 22:33 [entrez]
PHST- 2023/03/28 00:00 [pmc-release]
AID - 1672-7347(2023)03-0422-13 [pii]
AID - 10.11817/j.issn.1672-7347.2023.220304 [doi]
PST - ppublish
SO  - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Mar 28;48(3):422-434. doi: 
      10.11817/j.issn.1672-7347.2023.220304.