Environmental pollution from pharmaceuticals is increasing, drawing increasing attention from scientists and other communities. Addressing this challenge will require a coordinated global approach grounded in the One Health principle, which links the health of people, the environment, and all living organisms.

A review published in Drug Discovery Today examined how medicines affect the environment throughout their life cycle, from chemical synthesis and manufacturing to packaging, prescribing, and patient use. The analysis also highlighted the roles that physicians and patients can play in limiting pharmaceutical pollution.

Speaking with Univadis Italy, part of the Medscape Professional Network,Giovanna Paolone, PhD, coordinator of the Working Group on the Environmental Impact of Drugs at the Italian Society of Pharmacology and professor of pharmacology at the University of Verona in Verona, Italy, said, “A global health approach is necessary because we are facing a widespread and circular phenomenon: The more medicines we consume, the more enter the environment. These molecules affect animals and plants that absorb them and eventually return to humans, for example through the food chain,” Paolone said.

Excretion Risks

“It is well known that after consumption, medicines might not be fully metabolized in the body. Indeed, between 30% and 90% of the medicine ends up unaltered in the sink after excretion,” wrote researchers from the Basque Sustainable Pharmacy and Biotherapy Research Group at the School of Pharmacy of the University of the Basque Country in Vitoria-Gasteiz, Spain.

Continuous release of drugs and their metabolites into the environment is a key concern. Although the quantities may be small — described as “drops in a pool” — their constant release means that these substances remain present over time.

In addition, many current water treatment systems are not designed to remove pharmacologically active compounds. As a result, these substances enter water, soil, and air, where they can accumulate and interact. “Many molecules are designed to be persistent or to cross biological membranes, features that can increase their environmental impact,” Paolone said, referring to the “mixture effect.”

Most studies have assessed individual compounds. In real-world conditions, however, multiple substances are present at the same time and may interact as agonists or antagonists.

“Today we are beginning to understand which drugs are present in the environment and in what quantities, but experimental data on their biological effects remain limited,” Paolone said.

“Even extremely low concentrations, such as 10 µg/L, can induce significant effects in animal models, sometimes with differences between the sexes,” the expert added, citing studies conducted by her research group.

Packaging Burden

Environmental contamination is not limited to active pharmaceutical ingredients. Drug metabolites, excipients, and packaging materials also contribute to contamination.

Plastic packaging used in blister packs and containers is an environmental burden. Some drug delivery systems also rely on propellants that contribute to greenhouse gas emissions, which in turn contribute to global warming.

All stages of a drug’s life cycle must be addressed, starting with monitoring and data collection as a critical first step toward sustainable pharmacology. “At both national and international levels, several programs and initiatives are already underway,” Paolone said, citing efforts in Italy by the Water Research Institute of the National Research Council and the Italian National Institute of Health, both in Rome, Italy, which monitor a range of pollutants, including pharmaceuticals.

She added that Italy is aligning with European regulations and that national experts are contributing to the broader regulatory framework. This includes work on “watchlists,” which are lists of pharmaceuticals identified for monitoring based on their environmental impact.

Risk Assessments

At the regulatory level, an environmental risk assessment (ERA) has been made mandatory since 2006 for the authorization of new drugs in the European Union, according to the European Medicines Agency guidelines. The assessment evaluates persistence, bioaccumulation, and toxicity, as well as estimated exposure based on the dose and extent of use.

Although companies are committed to conducting this assessment, ERA findings currently do not influence the benefit-risk balance of human medicines and are not grounds for refusal of authorization, unlike in veterinary medicine. In addition, the assessment focused only on the active substance and did not consider the entire product, excluding components such as excipients.

As noted in the article, the ongoing reform of European pharmaceutical legislation is expected to strengthen environmental requirements, with potential implications for future drug approvals.

Training Needed

“Over the past three decades, the global carbon footprint attributed to the pharmaceutical sector has increased by 77%, mainly due to rising consumption.” This finding, reported by Lertxundi, Orive, and colleagues, highlights another key area for reducing the environmental impact of pharmaceuticals: more careful and informed use.

Education is one of the cornerstones to build this new approach to pharmacology. Courses dedicated to environmental sustainability should be offered to everyone involved across the entire drug life cycle, from pharmacologists and prescribers to chemists and professionals involved in manufacturing and packaging. More environmentally friendly choices should be considered when choosing the type of excipient, how many tablets to put in a blister pack, or which material to use in the final packaging.

“Although drugs are often lifesaving and have improved both quality of life and life expectancy, their use is often inappropriate, which has led to the development of programs promoting appropriate prescribing,” Paolone said. She added that tools enabling prescribers to select medications with lower environmental impact while maintaining efficacy and safety could provide valuable support.

However, she noted that such tools alone are not sufficient. Patients also need to use their medication more responsibly. “The population, from children to older adults, must be educated on the appropriate use and disposal of medications, taking environmental impact into account,” Paolone said, noting that Italy is among the European countries with the highest consumption of several drug classes, including anti-inflammatory agents.

This story was translated from Univadis Italy.