A wastewater-based evaluation of the effectiveness of codeine control measures in Australia

Abstract

Background and aim: From 1 February 2018, codeine was rescheduled from an over-the-counter (OTC) to a prescription-only medicine in Australia. We used wastewater-based epidemiology to measure changes in population codeine consumption before and after rescheduling.

Methods: We analysed 3703 wastewater samples from 48 wastewater treatment plants, taken between August 2016 and August 2019. Our samples represented 10.6 million people, 45% of the Australian population in state capitals and regional areas in each state or territory. Codeine concentrations were determined by liquid chromatography-tandem mass spectrometry and converted to per-capita consumption estimates using the site daily wastewater volume, catchment populations and codeine excretion kinetics.

Results: Average per-capita consumption of codeine decreased by 37% nationally immediately after the rescheduling in February 2018 [95% confidence interval (CI) = 35.3-39.4%] and substantially in all states between 24 and 51% (95% CI = 22.4-27.0% and 41.8-59.4%). The decrease was sustained at the lower level to August 2019. Locations with least pharmacy access decreased by 51% (95% CI = 41.7-61.7%), a greater decrease than 37% observed for those with greater pharmacy access (95% CI = 35.1-39.4%). Regional areas decreased by a smaller margin to cities (32 versus 38%, 95% CI = 30.2-34.1% versus 34.9-40.4%, respectively) from a base per-capita usage approximately 40% higher than cities.

Conclusion: Wastewater analysis shows that codeine consumption in Australia decreased by approximately 37% following its rescheduling as a prescription-only medicine in 2018. Wastewater-based epidemiology can be used to evaluate changes in population pharmaceutical consumption in responses to changes in drug scheduling.

Keywords: Drug use evaluation; policy change; prescription opioid; regulation change; rescheduling; wastewater analysis.

FIGURE 1

National‐level changes in codeine consumption before and after codeine rescheduling in February 2018, by wastewater analysis: (a) box‐plot showing all codeine data before and after (all samples from all sites individually) and (b) national population‐weighted average trend [± standard error of the mean (SEM)] of all locations, by month. A suggested oral morphine equivalent dose of codeine is 20 mg codeine for every 1 mg morphine [18]

FIGURE 2

Codeine consumption estimates by state and territory before and after it was rescheduled: (a) box‐plot showing before and after for each jurisdiction and (b) the population‐weighted average consumption estimate trends [± standard error of the mean (SEM)] before and after rescheduling. A suggested oral equivalent dose of codeine is 20 mg codeine for every 1 mg morphine [18]

FIGURE 3

Interrupted time–series analysis. The estimated marginal means and the corresponding 95% confidence band of the estimated codeine temporal trend by States/Territories, over time. The rescheduling month is indicated by the vertical dotted line