Prescribing Trends of Codeine-containing Medications and Other Opioids in Primary Care After A Regulatory Decision: An Interrupted Time Series Analysis

  • Niccolò Lombardi
  • Alfredo Vannacci
  • Alessandra Bettiol
  • Ettore Marconi
  • Serena Pecchioli
  • Alberto Magni
  • Claudio Cricelli
  • Francesco LapiEmail author
Original Research Article


Background and Objectives

In 2014, the Italian Medicines Agency (AIFA) amended the summary of product characteristics of codeine-containing medications limiting their use for maximum three days. This study attempted to clarify the impact of AIFA intervention on prescribing trends and appropriateness of use of codeine-containing medications and other opioids.


Using the Health Search Database, a quasi-experimental interrupted time series analysis was conducted to evaluate changes in prescribing trends and appropriateness of use of codeine-containing medications and opioids between 2013 and 2015.


Prescribing trends of codeine-containing medications significantly decreased (on average, − 352 days of treatment per month of observation), while long-acting opioids (LAOs) had an overall increase. Trends of inappropriate prescriptions significantly increased for two LAOs (i.e. tapentadol, naloxone-oxycodone), both before and after AIFA intervention.


The use of paracetamol-codeine combination was effectively decreased in Italy because of AIFA intervention. Instead, prescriptions of tapentadol and oxycodone-naloxone stably increased over the study period irrespective of regulatory intervention. Given that the choice of the most appropriate opioid therapy is not straightforward, especially in elderly and/or comorbid patients, general practitioners should consider carefully alternative therapies on the bases of regulatory interventions.


Compliance with Ethical Standards


This work was supported by the Italian College of General Practitioners and Primary Care, who played no role in the study design, execution, analysis or interpretation of data, writing of the paper, or decision to submit the paper for publication.

Conflicts of interest

Francesco Lapi provided consultancies in protocol preparation for epidemiological studies and data analyses for IBSA and Angelini. Claudio Cricelli provided clinical consultancies for IBSA, Angelini, Grunenthal, Alfa Wasserman, Pfizer, Prostrakan, Molteni, Dompè and Teva. Alberto Magni provided clinical consultancies for Bayer, Angelini, Doc and AlfaSigma. Niccolò Lombardi, Alfredo Vannacci, Alessandra Bettiol, Ettore Marconi, Serena Pecchioli, have no conflict of interest to disclose.

Ethical approval

With regard to the classification and implementation of observational drug-related research, as issued by the Italian National Drug Agency (an entity belonging to the Italian Ministry of Health), the present study does not require approval by an Ethics Committee in Italy (Italian Drug Agency note dated 3 August 2007).

Supplementary material

40261_2019_767_MOESM1_ESM.pdf (338 kb)
Supplementary material 1 (PDF 338 kb)


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and ToxicologyUniversity of FlorenceFlorenceItaly
  2. 2.Health Search, Italian College of General Practitioners and Primary CareFlorenceItaly
  3. 3.Italian College of General Practitioners and Primary CareFlorenceItaly

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