TY - JOUR
T1 - Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands
AU - Morales, Daniel R
AU - Morant, Steve V
AU - MacDonald, Thomas M
AU - Mackenzie, Isla S
AU - Doney, Alexander S F
AU - Mitchell, Lyn
AU - Bennie, Marion
AU - Robertson, Chris
AU - Hallas, Jesper
AU - Pottegard, Anton
AU - Ernst, Martin Thomsen
AU - Wei, Li
AU - Nicholson, Lizzie
AU - Morris, Carole
AU - Herings, Ron M C
AU - Overbeek, Jetty A
AU - Smits, Elisabeth
AU - Flynn, Robert W V
N1 - © 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
PY - 2020/3
Y1 - 2020/3
N2 - PURPOSE: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland.METHODS: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression.RESULTS: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (-0.42%, 95% CI, -0.66% to -0.18%), England (-0.09%, 95% CI, -0.11% to -0.08%), and Scotland (-0.67%, 95% CI, -0.79% to -0.55%); and falling trends in diclofenac initiation in the Netherlands (-0.03%, 95% CI, -0.06% to -0.01% per quarter) and Scotland (-0.04%, 95% CI, -0.05% to -0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation.CONCLUSIONS: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching.
AB - PURPOSE: In June 2013 a European Medicines Agency referral procedure concluded that diclofenac was associated with an elevated risk of acute cardiovascular events and contraindications, warnings, and changes to the product information were implemented across the European Union. This study measured the impact of the regulatory action on the prescribing of systemic diclofenac in Denmark, The Netherlands, England, and Scotland.METHODS: Quarterly time series analyses measuring diclofenac prescription initiation, discontinuation and switching to other systemic nonsteroidal anti-inflammatory (NSAIDs), topical NSAIDs, paracetamol, opioids, and other chronic pain medication in those who discontinued diclofenac. Absolute effects were estimated using interrupted time series regression.RESULTS: Overall, diclofenac prescription initiations fell during the observation periods of all countries. Compared with Denmark where there appeared to be a more limited effect, the regulatory action was associated with significant immediate reductions in diclofenac initiation in The Netherlands (-0.42%, 95% CI, -0.66% to -0.18%), England (-0.09%, 95% CI, -0.11% to -0.08%), and Scotland (-0.67%, 95% CI, -0.79% to -0.55%); and falling trends in diclofenac initiation in the Netherlands (-0.03%, 95% CI, -0.06% to -0.01% per quarter) and Scotland (-0.04%, 95% CI, -0.05% to -0.02% per quarter). There was no significant impact on diclofenac discontinuation in any country. The regulatory action was associated with modest differences in switching to other pain medicines following diclofenac discontinuation.CONCLUSIONS: The regulatory action was associated with significant reductions in overall diclofenac initiation which varied by country and type of exposure. There was no impact on discontinuation and variable impact on switching.
KW - Analgesics/therapeutic use
KW - Analgesics, Non-Narcotic/therapeutic use
KW - Analgesics, Opioid/therapeutic use
KW - Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
KW - Chronic Pain/drug therapy
KW - Denmark
KW - Diclofenac/therapeutic use
KW - Drug Labeling
KW - England
KW - Humans
KW - Netherlands
KW - Practice Patterns, Physicians'/statistics & numerical data
KW - Scotland/epidemiology
U2 - https://doi.org/10.1002/pds.4955
DO - https://doi.org/10.1002/pds.4955
M3 - Article
C2 - 31899936
SN - 1053-8569
VL - 29
SP - 296
EP - 305
JO - Pharmacoepidemiology and drug safety
JF - Pharmacoepidemiology and drug safety
IS - 3
ER -