Aim This study builds upon the environmental risk analysis presented in the 2022 National Report on Medicines Use in Italy by the Italian Medicines Agency and aims to assess the environmental risk posed by medicines in Italy and in its regions.

Methods The analysis selected 90 medicines based on three criteria: high utilization, low PNEC, and inclusion or candidacy for the European Watch List. For each medicine, the environmental risk was computed as the ratio between the Predicted Environmental Concentration (PEC) and the Predicted No Effect Concentration (PNEC). PEC was derived following the approach of the Swedish Association of Pharmaceutical Industries and Italian drug utilization data. The risk was classified high if the ratio was greater than 10, and moderate if greater than 1.

Results Overall, 13 medicines were identified as posing a high risk, including cardiovascular agents, antibiotics, analgesics, antidepressants, and antiparasitic agents. The high risk was driven by either a very low PNEC (e.g., estradiol and lacidipine), and high utilization (e.g., amoxicillin, ibuprofen, and diclofenac). Regional analysis showed higher risk due to high consumption for azithromycin and ofloxacin in Central and Southern Italy, and for levonorgestrel in Northern Italy.

Conclusion This study points to the need of prioritizing targeted sampling in surface waters for medicines estimated at high risk. To prevent and mitigate the risk, a more conscious clinical practice coupled with appropriate waste management are required.

What is already known about this subject

Medicines represent a growing concern as a source of contamination in water systems.

Traditional surface water samplings are resource-expensive and should be supported by estimation methods.

The Italian Medicines Agency’s National report on medicines use included, for the first time in its 2022 version, an assessment of the environmental impact.

What this study adds

90 medicines with either high utilization, low Predicted No-Effect Concentration, or present in the European Watch List were included.

13 medicines were at high environmental risk either because of their high toxicity to aquatic species or their high consumption in Italy.

Regional differences potentially reflect various social and prescribing habits.

The authors have declared no competing interest.

This study did not receive any funding.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

We utilized aggregated data on the consumption of medicines in Italy and its regions sourced from the OsMed database. This database is owned and maintained by the Italian Medicines Agency (AIFA) and is accessible upon request. Through our collaboration with AIFA, who are also co-authors of the article, we gained access to this data. Since the data provided is aggregated and does not contain any identifiable patient information, no ethical consent was required.

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data and scripts used in this analysis are available in the supplementary material.