Abstract

Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day–1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1-year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard-exposure users and 58 (0.12%) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95% CI 1.11, 2.70), and high-exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.

Original languageEnglish
Pages (from-to)2000-2009
Number of pages10
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

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Metoclopramide
Parkinsonian Disorders
Cohort Studies
Population
Health Insurance
Databases
Confidence Intervals

Keywords

  • cohort study
  • drug safety
  • drug-induced parkinsonism
  • metoclopramide
  • pharmacoepidemiology

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

@article{ae58d469847d469eab48fa87b372de84,
title = "High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism: a nationwide population-based cohort study",
abstract = "Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day–1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95{\%} confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1-year period, 122 of 218 931 (0.06{\%}) users of metoclopramide vs. 56 of 218 931 (0.03{\%}) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04{\%}) were from 168 566 standard-exposure users and 58 (0.12{\%}) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95{\%} CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95{\%} CI 1.11, 2.70), and high-exposure (aHR 3.15; 95{\%} CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95{\%} CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81{\%}) users and 55 of 58 (94.83{\%}) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19{\%}) users and 3 of 58 (5.17{\%}) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06{\%}), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.",
keywords = "cohort study, drug safety, drug-induced parkinsonism, metoclopramide, pharmacoepidemiology",
author = "Tsai, {Shin Chia} and Sheu, {Shiow Yunn} and Chien, {Li Nien} and Lee, {Hsin Chien} and Yuan, {Eunice Jia Shiow} and Yuan, {Rey Yue}",
year = "2018",
month = "9",
day = "1",
doi = "10.1111/bcp.13630",
language = "English",
volume = "84",
pages = "2000--2009",
journal = "British Journal of Clinical Pharmacology",
issn = "0306-5251",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - High exposure compared with standard exposure to metoclopramide associated with a higher risk of parkinsonism

T2 - a nationwide population-based cohort study

AU - Tsai, Shin Chia

AU - Sheu, Shiow Yunn

AU - Chien, Li Nien

AU - Lee, Hsin Chien

AU - Yuan, Eunice Jia Shiow

AU - Yuan, Rey Yue

PY - 2018/9/1

Y1 - 2018/9/1

N2 - Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day–1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1-year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard-exposure users and 58 (0.12%) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95% CI 1.11, 2.70), and high-exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.

AB - Aims: We conducted a cohort study utilizing a nationwide health insurance database to assess the European Medicines Agency's restrictions on using metoclopramide and its association with the risk of parkinsonism. Methods: New oral metoclopramide users aged ≥20 years, and age- and gender-matched non-users were recruited between 2001 and 2011. Users were divided into high-exposure (dose >30 mg day–1 and/or duration >5 days) and standard-exposure (dose ≤30 mg day–1 and duration ≤5 days) groups. The adjusted hazard ratio (aHR) with 95% confidence interval (CI) estimated the risk of parkinsonism. Results: During a 1-year period, 122 of 218 931 (0.06%) users of metoclopramide vs. 56 of 218 931 (0.03%) non-users developed parkinsonism (P < 0.001). Among the 122 cases of parkinsonism in users, 64 (0.04%) were from 168 566 standard-exposure users and 58 (0.12%) from 50 365 high-exposure users. Compared with non-users, the risk of parkinsonism was higher in users (aHR 2.16; 95% CI 1.54, 3.02), including standard-exposure (aHR 1.73; 95% CI 1.11, 2.70), and high-exposure (aHR 3.15; 95% CI 1.78, 5.57) users. High-exposure users had a higher risk of parkinsonism than standard-exposure users (aHR 1.83; 95% CI 1.28, 2.63). Within the high-exposure group, 45 233 of 50 365 (89.81%) users and 55 of 58 (94.83%) parkinsonism were from long-duration exposure; 5 132 of 50 365 (10.19%) users and 3 of 58 (5.17%) parkinsonism were from high-dose exposure and long-duration + high-dose exposure. Conclusions: The risk of parkinsonism in metoclopramide users, although extremely low (0.06%), is 2.16-fold greater than in non-users. High-exposure users have a 1.83-fold higher risk than standard-exposure users. As users in high-exposure group had a higher risk of parkinsonism than in standard-exposure group, and the majority of users and parkinsonism in high-exposure group were from long-duration exposure; thus, physician are advised to avoid prescribing metoclopramide for >5 days, even if the daily dose is ≤30 mg.

KW - cohort study

KW - drug safety

KW - drug-induced parkinsonism

KW - metoclopramide

KW - pharmacoepidemiology

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U2 - 10.1111/bcp.13630

DO - 10.1111/bcp.13630

M3 - Article

AN - SCOPUS:85051287093

VL - 84

SP - 2000

EP - 2009

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

SN - 0306-5251

IS - 9

ER -