Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands

Daniel R Morales, Steve V Morant, Thomas M MacDonald (Lead / Corresponding author), Isla S Mackenzie, Alexander S F Doney, Lyn Mitchell, Marion Bennie, Chris Robertson, Jesper Hallas, Anton Pottegard, Martin Thomsen Ernst, Li Wei, Lizzie Nicholson, Carole Morris, Ron M C, Jetty A Overbeek, Elisabeth Smits, Robert W V

Research output: Contribution to journalArticle

Abstract

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 amore 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.

Original languageEnglish
Number of pages10
JournalPharmacoepidemiology and Drug Safety
Early online date3 Jan 2020
DOIs
Publication statusE-pub ahead of print - 3 Jan 2020

Fingerprint

Diclofenac
Scotland
Denmark
England
Netherlands
Pain
Non-Steroidal Anti-Inflammatory Agents
Prescriptions
European Union
Acetaminophen
Chronic Pain
Opioid Analgesics
Anti-Inflammatory Agents
Referral and Consultation
Observation

Cite this

Morales, Daniel R ; Morant, Steve V ; MacDonald, Thomas M ; Mackenzie, Isla S ; Doney, Alexander S F ; Mitchell, Lyn ; Bennie, Marion ; Robertson, Chris ; Hallas, Jesper ; Pottegard, Anton ; Ernst, Martin Thomsen ; Wei, Li ; Nicholson, Lizzie ; Morris, Carole ; M C, Ron ; Overbeek, Jetty A ; Smits, Elisabeth ; W V, Robert. / Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands. In: Pharmacoepidemiology and Drug Safety. 2020.
@article{2472132504f04aabb039b2d467808a3e,
title = "Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands",
abstract = "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 amore 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.",
author = "Morales, {Daniel R} and Morant, {Steve V} and MacDonald, {Thomas M} and Mackenzie, {Isla S} and Doney, {Alexander S F} and Lyn Mitchell and Marion Bennie and Chris Robertson and Jesper Hallas and Anton Pottegard and Ernst, {Martin Thomsen} and Li Wei and Lizzie Nicholson and Carole Morris and {M C}, Ron and Overbeek, {Jetty A} and Elisabeth Smits and {W V}, Robert",
note = "Funding information The study was funded by the European Medicines Agency (Procurement procedure EMA/2014/50/RE). The EMA approved the final study protocol and had no influence on the results or decision to publish {\circledC} 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.",
year = "2020",
month = "1",
day = "3",
doi = "10.1002/pds.4955",
language = "English",
journal = "Pharmacoepidemiology and Drug Safety",
issn = "1053-8569",
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Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands. / Morales, Daniel R; Morant, Steve V; MacDonald, Thomas M (Lead / Corresponding author); Mackenzie, Isla S; Doney, Alexander S F; Mitchell, Lyn; Bennie, Marion; Robertson, Chris; Hallas, Jesper; Pottegard, Anton; Ernst, Martin Thomsen; Wei, Li; Nicholson, Lizzie; Morris, Carole; M C, Ron; Overbeek, Jetty A; Smits, Elisabeth; W V, Robert.

In: Pharmacoepidemiology and Drug Safety, 03.01.2020.

Research output: Contribution to journalArticle

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 - M C, Ron

AU - Overbeek, Jetty A

AU - Smits, Elisabeth

AU - W V, Robert

N1 - Funding information The study was funded by the European Medicines Agency (Procurement procedure EMA/2014/50/RE). The EMA approved the final study protocol and had no influence on the results or decision to publish © 2020 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

PY - 2020/1/3

Y1 - 2020/1/3

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 amore 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 amore 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.

U2 - 10.1002/pds.4955

DO - 10.1002/pds.4955

M3 - Article

C2 - 31899936

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

ER -