Lower-dose prescribing: minimizing "side effects" of pharmaceuticals on society and the environment.

The prescribed use of pharmaceuticals can result in unintended, unwelcomed, and potentially adverse consequences for the environment and for those not initially targeted for treatment. Medication usage frequently results in the collateral introduction to the environment (via excretion and bathing) of active pharmaceutical ingredients (APIs), bioactive metabolites, and reversible conjugates. Imprudent prescribing and non-compliant patient behavior drive the accumulation of unused medications, which pose major public health risks from diversion as well as risks for the environment from unsound disposal, such as flushing to sewers. The prescriber has the unique wherewithal to reduce each of these risks by modifying various aspects of the practice of prescribing. By incorporating consideration of the potential for adverse environmental impacts into the practice of prescribing, patient care also could possibly be improved and public health better protected. Although excretion of an API is governed by its characteristic pharmacokinetics, this variable can be somewhat controlled by the prescriber in selecting APIs possessing environment-friendly excretion profiles and in selecting the lowest effective dose. This paper presents the first critical examination of the multi-faceted role of drug dose in reducing the ambient levels of APIs in the environment and in reducing the incidence of drug wastage, which ultimately necessitates disposal of leftovers. Historically, drug dose has been actively excluded from consideration in risk mitigation strategies for reducing ambient API levels in the environment. Personalized adjustment of drug dose also holds the potential for enhancing therapeutic outcomes while simultaneously reducing the incidence of adverse drug events and in lowering patient healthcare costs. Optimizing drug dose is a major factor in improving the sustainability of health care. The prescriber needs to be cognizant that the "patient" encompasses the environment and other "bystanders," and that prescribed treatments can have unanticipated, collateral impacts that reach far beyond the healthcare setting.

The afterlife of drugs and the role of pharmEcovigilance.

The prescribing and usage of medications (for both humans and domestic animals) have ramifications extending far beyond the traditional objectives of conventional medical care. The healthcare industry has an environmental footprint that includes the active pharmaceutical ingredients (APIs) from medications, residues of which can establish themselves as environmental pollutants. This occurs by a variety of routes, but primarily from excretion, bathing and disposal. Many parallels exist between healthcare and the protection and remediation of the environment, spanning the stages from symptomology and diagnosis to treatment. The critical role played by pharmacovigilance in healthcare has a counterpart with the ecological environment. The term ecopharmacovigilance has been used with respect to the unforeseen consequences APIs can have once they enter the environment. We propose that conventional pharmacovigilance could be expanded to encompass environmental concerns--a concept we term pharmEcovigilance--as a way to unify the parallel but interconnected needs for protecting both human and ecological health.To convey the scope of a pharmEcovigilance programme, we provide an overview of the occurrence of APIs as environmental pollutants, their ramifications for human health and the environment and some of the ways in which their impact could be reduced or minimized. The major areas discussed include: (i) the routes by which APIs become contaminants in the environment; (ii) the hazards of leftover drugs as a result of stockpiling and from disposal to sewage, which can also eventually contribute to the contamination of drinking water; (iii) why drugs accumulate unused; and (iv) the benefits for humans and the environment that could accrue from reducing the accumulation of leftover drugs and the subsequent introduction of APIs into the environment. A broad spectrum of actions could be taken by prescribers (including veterinarians) and the healthcare industry at large (including manufacturers and insurers) to reduce the release or introduction of APIs to the environment. Most significantly, however, a major reason to consider implementing a pharmEcovigilance programme--beyond reducing the environmental footprint of healthcare--is the previously unforeseen collateral benefit in making further progress in optimizing the delivery, effectiveness, outcomes and cost of healthcare, as well as improving safety for humans, pets and wildlife. For this reason, the relationships that healthcare professionals and patients have with medications might also include consideration of pharmEcovigilance. Like any profession that deals with chemicals, perhaps a major challenge to be faced is how to ensure the sustainability (and minimize the life cycle exposure hazards) of a chemical-based, chemical-centric society in the most cost-effective and safest manner. Given that the medical community is a major source of numerous 'exotic' chemical pollutants in the environment (with thousands of chemically distinct APIs in current use), albeit at very low levels, an imperative could be created for designing and implementing approaches for reducing and controlling this source of pollution. With reduced wastage of medications, in part driven by appropriate or rational prescribing and dispensing, the ecological footprint of medicine could be greatly reduced, with concomitant improvements in many aspects of healthcare.

Beyond the medicine cabinet: an analysis of where and why medications accumulate.

Active pharmaceutical ingredients (APIs) from medications can enter the environment as trace contaminants, at individual concentrations generally below a part per billion (microg/L). APIs enter the environment primarily via the discharge of raw and treated sewage. Residues of unmetabolized APIs from parenteral and enteral drugs are excreted in feces and urine, and topically applied medications are washed from skin during bathing. These trace residues may pose risks for aquatic life and cause concern with regard to subsequent human exposure. APIs also enter the environment from the disposal of unwanted medications directly to sewers and trash. The relative significance of this route compared with excretion and bathing is poorly understood and has been subject to much speculation. Two major aspects of uncertainty exist: the percentage of any particular API in the environment originating from disposal is unknown, and disposal undoubtedly occurs from a variety of dispersed sources. Sources of disposal, along with the types and quantities of APIs resulting from each source, are important to understand so that effective pollution prevention approaches can be designed and implemented. Accumulation of leftover, unwanted drugs poses three major concerns: (i) APIs disposed to sewage or trash compose a diverse source of potential chemical stressors in the environment. (ii) Accumulated drugs represent increased potential for drug diversion, with its attendant risks of unintentional poisonings and abuse. (iii) Leftover drugs represent wasted healthcare resources and lost opportunities for medical treatment. This paper has four major purposes: (1) Define the processes, actions, and behaviors that control and drive the consumption, accumulation, and need for disposal of pharmaceuticals. (2) Provide an overview of the diverse locations where drugs are used and accumulate. (3) Present a summary of the first cataloging of APIs disposed by a defined subpopulation. (4) Identify opportunities for pollution prevention and source reduction.

Types and quantities of leftover drugs entering the environment via disposal to sewage--revealed by coroner records.

Pharmaceuticals designed for humans and animals often remain unused for a variety of reasons, ranging from expiration to a patient's non-compliance. These leftover, accumulated drugs represent sub-optimal delivery of health care and the potential for environmentally unsound disposal, which can pose exposure risks for humans and wildlife. A major unknown with respect to drugs as pollutants is what fractions of drug residues occurring in the ambient environment result from discarding leftover drugs. To gauge the significance of leftover drugs as potential pollutants, data are needed on the types, quantities, and frequencies with which drugs accumulate. Absence of this data has prevented assessments of the significance of drug accumulation and disposal as a contributing source of drug residues in the environment. One particular source of drug accumulation is those drugs that become "orphaned" by the death of a consumer. A new approach to acquiring the data needed to assess the magnitude and extent of drug disposal as a source of environmental pollution is presented by using the inventories of drugs maintained by coroner offices. The data from one metropolitan coroner's office demonstrates proof of concept. Coroner data on leftover drugs are useful for measuring the types and amounts of drugs accumulated by consumers. This inventory also provides an accurate measure of the individual active ingredients actually disposed into sewage by coroners. The types of questions these data can address are presented, and the possible uses of these data for deriving estimates of source contributions from the population at large are discussed. The approach is proposed for nationwide implementation (and automation) to better understand the significance of consumer disposal of medications.