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*, 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, M. C. Ron, Jetty A. Overbeek, Elisabeth Smits, W. V. Robert

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftPharmacoepidemiology and Drug Safety
ISSN1053-8569
DOI
StatusE-pub ahead of print - 3. jan. 2020

Fingeraftryk

Diclofenac
Scotland
Denmark
England
Netherlands
Prescriptions
European Union
Acetaminophen
Chronic Pain
Referral and Consultation
Observation

Citer dette

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 ; Ron, M. C. ; Overbeek, Jetty A. ; Smits, Elisabeth ; Robert, W. V. / Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands. I: Pharmacoepidemiology and Drug Safety. 2020.
@article{4323bc3d35c44a79ad3a1f795cd923a3,
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.",
keywords = "diclofenac, impact, pharmacoepidemiology, pharmacovigilance, prescribing, regulation",
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 Ron, {M. C.} and Overbeek, {Jetty A.} and Elisabeth Smits and Robert, {W. V.}",
year = "2020",
month = "1",
day = "3",
doi = "10.1002/pds.4955",
language = "English",
journal = "Pharmacoepidemiology and Drug Safety",
issn = "1053-8569",
publisher = "JohnWiley & Sons Ltd.",

}

Morales, DR, Morant, SV, MacDonald, TM, Mackenzie, IS, Doney, ASF, Mitchell, L, Bennie, M, Robertson, C, Hallas, J, Pottegard, A, Ernst, MT, Wei, L, Nicholson, L, Morris, C, Ron, MC, Overbeek, JA, Smits, E & Robert, WV 2020, 'Impact of EMA regulatory label changes on systemic diclofenac initiation, discontinuation, and switching to other pain medicines in Scotland, England, Denmark, and The Netherlands', Pharmacoepidemiology and Drug Safety. https://doi.org/10.1002/pds.4955

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.; 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; Ron, M. C.; Overbeek, Jetty A.; Smits, Elisabeth; Robert, W. V.

I: Pharmacoepidemiology and Drug Safety, 03.01.2020.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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 - Ron, M. C.

AU - Overbeek, Jetty A.

AU - Smits, Elisabeth

AU - Robert, W. V.

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.

KW - diclofenac

KW - impact

KW - pharmacoepidemiology

KW - pharmacovigilance

KW - prescribing

KW - regulation

U2 - 10.1002/pds.4955

DO - 10.1002/pds.4955

M3 - Journal article

C2 - 31899936

AN - SCOPUS:85078041121

JO - Pharmacoepidemiology and Drug Safety

JF - Pharmacoepidemiology and Drug Safety

SN - 1053-8569

ER -