Sales of over-the-counter products containing codeine in 31 countries, 2013-2019: a retrospective observational study

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>Introduction</jats:title><jats:p>Opioid prescribing trends have been investigated in many countries. However, the patterns of over-the-counter purchases of opioids without a prescription, such as codeine combinations, are mostly unknown.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>We aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over six years.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We conducted a retrospective observational study using electronic point-of-sale data from the human data science company, <jats:italic>IQVIA</jats:italic>, for countries that had such data, including Argentina, Belgium, Brazil, Bulgaria, Canada, Croatia, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Japan, Latvia, Lithuania, Mexico, The Netherlands, Poland, Portugal, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, Spain, Switzerland, Thailand, the UK, and the USA. We calculated annual mean sales (dosage units per 1000 of the population) and public expenditure (GBP, £ per 1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by <jats:italic>IQVIA</jats:italic>. We quantified changes over time and the types of products sold.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>31.5 billion dosage units (adjusted: 42.8 billion dosage units) of codeine, costing £2.55 billion (adjusted: £3.68 billion), were sold over-the-counter in 31 countries between April 2013 and March 2019. Total adjusted sales increased by 11% (3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (£263/1000 in 2013 to £451/1000 in 2019). Sales were not equally distributed; South Africa sold the most (36 mean dosage units/person), followed by Ireland (30 mean dosage units/person), France (20 mean dosage units/person), the UK (17.2 mean dosage units/person), and Latvia (16.8 mean dosage units/person). Types of products (n=569) and formulations (n=12) sold varied.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>In many parts of the world, substantial numbers of people may be purchasing and consuming codeine from over-the-counter products. Clinicians should ask patients about their use of over-the-counter products, and public health measures are required to improve the collection of sales data and the safety of such products.</jats:p></jats:sec><jats:sec><jats:title>Study protocol pre-registration</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://osf.io/ay4mc">https://osf.io/ay4mc</jats:ext-link></jats:p><jats:p>The pre-print version of this work is available on medRxiv:</jats:p><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://doi.org/10.1101/2021.04.21.21255888">https://doi.org/10.1101/2021.04.21.21255888</jats:ext-link></jats:p></jats:sec><jats:sec><jats:title>Key points</jats:title><jats:list list-type="bullet"><jats:list-item><jats:p>Codeine is one of the most accessible pain medicines available worldwide, yet data on its use as an over-the-counter drug has been limited.</jats:p></jats:list-item><jats:list-item><jats:p>We found that total sales and expenditure of over-the-counter products containing codeine increased from April 2013 to March 2019, but there was substantial variation in mean sales between countries and the coverage of data reported by <jats:italic>IQVIA</jats:italic>, with South Africa, France, Japan, the UK, and Poland accounting for 90% of all sales data.</jats:p></jats:list-item><jats:list-item><jats:p>In countries with access to over-the-counter codeine products, sales data should be collected, made available, and reviewed to inform regulatory decisions and public health measures to ensure safety.</jats:p></jats:list-item></jats:list></jats:sec>