INTRODUCTION
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.

OBJECTIVE
We aimed to assess national sales and expenditure trends of over-the-counter codeine-containing products purchased in countries with available data over 6 years.

METHODS
We conducted a retrospective observational study using electronic point-of-sale data from the human data science company, IQVIA, 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/1000 population) and public expenditure (£/1000 population) for each country between April 2013 and March 2019 and adjusted for data coverage reported by IQVIA. We quantified changes over time and the types of products sold.

RESULTS
In total, 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% (from 3911 dosage units/1000 population in 2013 to 4358 in 2019) and adjusted public expenditure increased by 72% (from £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.

CONCLUSION
In many parts of the world, substantial numbers of people may be purchasing and consuming codeine in 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. STUDY PROTOCOL PRE-REGISTRATION: https://osf.io/ay4mc . The pre-print version of this work is available on medRxiv: https://doi.org/10.1101/2021.04.21.21255888 .