Abstract
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.
References
Oaks JL, Gilbert M, Virani MZ, et al. Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 2004; 427(6975): 630–3
Ruhoy IS, Daughton CG. Beyond the medicine cabinet: an analysis of where and why medications accumulate. Environ Int 2008; 34(8): 1157–69
Daughton CG. Groundwater recharge and chemical contaminants: challenges in communicating the connections and collisions of two disparate worlds. Ground Wat Monitor Remediation 2004; 24(2): 127–38
Bosworth HB, Oddone EZ, Weinberger M, editors. Patient treatment adherence: concepts, interventions, and measurement. Hillsdale (NJ): Lawrence Erlbaum Associates, 2005
O’Donohue WT, Levensky ER, editors. Promoting treatment adherence: a practical handbook for health care providers. New York: Sage Publications, Inc., 2006
Teske J, Weiler JP, Larsch K, et al. Fatal outcome in a child after ingestion of a transdermal fentanyl patch. Int J Legal Med 2007; 121(2): 147–51
Flannagan LM, Butts JD, Anderson WH. Fentanyl patches left on dead bodies: potential source of drug for abusers. J Forensic Sci 1996; 41(2): 320–1
US Environment Protection Agency. Pharmaceuticals and personal care products (PPCPs): relevant literature [online]. Available from URL: http://www.epa.gov/ppcp/lit.html [Accessed 2007 Dec 29]
Kümmerer KE, editor. Pharmaceuticals in the environment: sources, fate, effects, and risk. 2nd ed. Berlin: Springer, 2004
Petrovic M, Barcelo D, editors. Analysis, fate, and removal of Pharmaceuticals in the water cycle. In: Barcelo E, editor. Wilson & Wilson’s comprehensive analytical chemistry series. Amsterdam: Elsevier, 2007
Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother 1995; 29(10): 969–71
Barnes AJ, Smith ML, Kacinko SL, et al. Excretion of metham-phetamine and amphetamine in human sweat following controlled oral methamphetamine administration. Clin Chem 2008; 54: 172–80
Høiby N, Pers C, Johansen HK, et al. Excretion of beta-lactam antibiotics in sweat: a neglected mechanism for development of antibiotic resistance? Antimicrob Agents Chemother 2000 Oct; 44(10): 2855–7
Cunningham VL, Buzby M, Hutchinson T, et al. Effects of human pharmaceuticals on aquatic life: next steps. Environ Sci Technol 2006; 40(11): 3456–62
Joss A, Zabczynski S, Gobel A, et al. Biological degradation of pharmaceuticals in municipal wastewater treatment: proposing a classification scheme. Water Res 2006 May; 40(8): 1686–96
Ruhoy IS, Daughton CG. Types and quantities of leftover drugs entering the environment via disposal to sewage: revealed by coroner records. Sci Total Environ 2007; 388(1–3): 137–48
Daughton CG. Environmental stewardship and drugs as pollutants. Lancet 2002; 360: 1035–6
National Small Flows Clearinghouse, National Environmental Services Center. West Virginia University: septic system information [online]. Available from URL: http://www.nesc.wvu.edu/NSFC/nsfc_septicnews.html [Accessed 2007 Dec 29]
Daughton CG. Pharmaceuticals as environmental pollutants: the ramifications for human exposure. In: Heggenhougen K, Quah S, editors. International encyclopedia of public health. San Deigo (CA): Academic Press, 2008: 66–102
US Senate. US Senate Committee on Environment and Public Works (Subcommittee on Transportation Safety, Infrastructure Security, and Water Quality), 15 April 2008, hearing on “pharmaceuticals in the nation’s water: assessing potential risks and actions to address the issue” [online]. Available from URL: http://www.epw.senate.gov/public/index.cfm?FuseAction=Hearings.Hearing&Hearing_ID=30641A14-802A-23AD-4B51-A10DD439793F [Accessed 2008 Sep 26]
US House of Representatives. US House of Representatives Committee on Transportation & Infrastructure (Subcommittee on Water Resources & Environment), 18 September 2008, hearing on “Emerging Contaminants in U.S. Waters” [online]. Available from URL: http://transportation.house.gov/hearings/hearingDetail.aspx?NewsID=742 [Accessed 2008 Sep 26]
Jones-Lepp TL, Stevens R. Pharmaceuticals and personal care products in biosolids/sewage sludge: the interface between analytical chemistry and regulation. Anal Bioanal Chem 2007; 387: 1173–83
Boxall ABA, Johnson P, Smith EJ, et al. Uptake of veterinary medicines from soils into plants. J Agric Food Chem 2006; 54(6): 2288–97
Daughton CG, Ruhoy IS. Accumulation and disposal of leftover medications: a key aspect of pharmEcovigilance. In: Rahman SZ, Gupta V, editors. An introduction to environmental pharmacology. Aligarh: Ibn Sina Academy. In press
Office of National Drug Control Policy Washington, DC. Proper disposal of prescription drugs: federal guidelines [online]. Available from URL: http://www.whitehousedrugpolicy.gov/drugfact/factsht/proper_disposal.html [Accessed 2007 Dec 29]
Glassmeyer ST, Hinchey EK, Boehme SE, et al. Disposal practices for unwanted residential medications in the United States. Environ Intern. In press
EU. Directive 2004/27/EC of the European Parliament and of the Council of 31 March 2004 amending Directive 2001/83/EC on the Community code relating to medicinal products for human use. OJEU 30.04.2004 P,L 136/37 [online]. Available from URL: http://efcg.cefic.org/isoFILES/publications/items/DOWNLOAD_73.pdf [Accessed 2008 Jun 4]
Daughton CG. Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health: I. Rationale for and avenues toward a green pharmacy. Environ Health Perspect 2003; 111(5): 757–74
Daughton CG. Cradle-to-cradle stewardship of drugs for minimizing their environmental disposition while promoting human health: II. Drug disposal, waste reduction, and future direction. Environ Health Perspect 2003; 111(5): 775–85
Kummerer K. Sustainable from the very beginning: rational design of molecules by life cycle engineering as an important approach for green pharmacy and green chemistry. Green Chem 2007; 9(8): 899–907
Khetan SK, Collins TJ. Human Pharmaceuticals in the aquatic environment: a challenge to green chemistry. Chem Rev 2007; 107(6): 2319–64
Daughton CG, Ruhoy IS. PharmEcovigilance: aligning pharma-covigilance with environmental protection. In: Rahman SZ, Gupta V, editors. An introduction to environmental pharmacology. Aligarh: Ibn Sina Academy. In press
Enick OV, Moore MM. Assessing the assessments: pharmaceuticals in the environment. Environ Impact Assess Rev 2007; 27(8): 707–29
Aronson JK, editor. Meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions. 15th rev. ed. Amsterdam: Elsevier Science, 2006
WHO. WHO policy perspectives on medicines, no. 09, October 2004: pharmacovigilance: ensuring the safe use of medicines [online]. Available from URL: http://www.who.int/medicinedocs/collect/medicinedocs/pdf/s6164e/s6164e.pdf [Accessed 2008 Apr 18]
Dunlop D. Pharmacovigilance in the framework of recording and control of drugs in the United Kingdom [in French]. Therapie 1974 Nov–Dec; 29(6): 799–804
Efthymiou ML. Bibliography in pharmacovigilance [in French]. Eur J Toxicol Environ Hyg 1975 Sep–Oct; 8(5): 319–20
Evreux JC, Lagier G. The efficacy of pharmacovigilance: principles and proposals [in French]. Therapie 1976 Sep–Oct; 31(5): 581–6
Lagier G, Efthymiou ML, Lechat P, et al. Pharmacovigilance in the hospital: first results [in French]. Therapie 1974 Nov–Dec; 29(6): 805–10
Hurwitz N, Wade OL. Intensive hospital monitoring of adverse reactions to drugs. BMJ 1969; 1(5643): 531–6
Moore N, Paux G, Begaud B, et al. Adverse drug reaction monitoring: doing it the French way. Lancet 1985; 326(8463): 1056–8
van Grootheest K. The dawn of pharmacovigilance: an historical perspective. Int J Pharm Med 2003; 17(5–6): 195–200
US FDA. FDA’s sentinel initiative, 22 May 2008 [online]. Available from URL: http://www.fda.gov/oc/initiatives/advance/sentinel/ [Accessed 2008 Jun 4]
Rahman SZ, Khan RA. Environmental pharmacology: a new discipline. Indian J Pharmacol 2006 Aug; 38(4): 229–30
Kummerer K, Velo G. Ecopharmacology: a new topic of importance in pharmacovigilance. Drug Saf 2006; 29(5): 371–3
Keck G. Teaching environmental toxicology for veterinary students and veterinarians: some new trends. J Vet Pharmacol Therap 2006; 29 Suppl. 1: 15–6
Rahman SZ, Khan RA, Gupta V, et al. Pharmacoenviron-mentology: a component of pharmacovigilance. Environ Health 2007; 6: 20
Daughton CG, Ternes TA. Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 1999; 107 Suppl. 6: 907–38
Ankley GT, Brooks BW, Huggett DB, et al. Repeating history: Pharmaceuticals in the environment. Environ Sci Technol 2007; 41(24): 8211–7
Kidd KA, Blanchfield PJ, Mills KH, et al. Collapse of a fish population after exposure to a synthetic estrogen. Proc Natl Acad Sci U S A 2007; 104(21): 8897–901
Daughton CG. Pharmaceuticals in the environment: overarching issues and overview. In: Daughton CG, Jones-Lepp T, editors. Pharmaceuticals and personal care products in the environment: scientific and regulatory issues. Symposium series 791 [online]. Washington, DC: American Chemical Society, 2001: 2–38. Available from URL: http://www.epa.gov/nerlesd1/bios/daughton/book-summary.htm [Accessed 2008 Feb 13]
Grandjean P, Bellinger D, Bergman A, et al. The Faroes Statement: human health effects of developmental exposure to chemicals in our environment. Basic Clin Pharmacol Toxicol 2007; 102: 73–5
Collier AC. Pharmaceutical contaminants in potable water: concerns for pregnant women and children. EcoHealth J 2007; 4(2): 164–71
Kuehn BM. Traces of drugs found in drinking water: health effects unknown, safer disposal urged. JAMA 2008; 299(17): 2011–3
Pollock M, Bazaldua OV, Dobbie AE. Appropriate prescribing of medications: an eight-step approach. Am Fam Physician 2007; 75(2): 231–6
Crigger N. Improving nurse practitioner practice through rational prescribing. J Nurse Pract 2008; 4(2): 120–5
The Cochrane Collaboration. The Cochrane library [online]. Available from URL: http://www.cochrane.org/reviews/clibintro.htm [Accessed 2008 Feb 13]
US FDA. Good reprint practices for the distribution of medical journal articles and medical or scientific reference publications on unapproved new uses of approved drugs and approved or cleared medical devices [online]. Available from URL: http://oversight.house.gov/documents/20071130103225.pdf [Accessed 2008 Feb 14]
Stockholm City Council. Environmentally classified pharmaceuticals: January 2008 edition [online]. Available from URL: http://www.janusinfo.se/imcms/servlet/GetDoc?.meta_id=10205;viawww.janusinfo.se/environment [Accessed 2008 Apr 20]
Sherman R, Hickner J. Academic physicians use placebos in clinical practice and believe in the mind-body connection. J Gen Intern Med 2008; 23(1): 7–10
US FDA. Food and Drug Administration Amendments Act of 2007. H.R. 3580 [online]. Available from URL: http://www.fda.gov/oc/initiatives/advance/fdaaa.htmMaw [Accessed 2007 Dec 29]
National Conference of State Legislatures. 2008 prescription drug state legislation [online]. Available from URL: http://www.ncsl.org/programs/health/drugbill08.htm [Accessed 2008 Apr 20]
New York State. Title 27 Drug Management and Disposal. A00840: an Act to amend the environmental conservation law, in relation to the management and disposal of drugs [online]. Available from URL: http://assembly.state.ny.us/leg/?.bn=A00840&sh=t [Accessed 2008 Apr 20]
McKee G. Keeping drugs out of the toilet: the need for federal action to allow consumer drug donation. Quinnipiac Health Law J 2006; 10(1): 45–76
Doerr-MacEwen N, Haight M. Expert stakeholders’ views on the management of human Pharmaceuticals in the environment. Environ Manage 2006; 38(5): 853–66
CFR. Title 21: food and drugs, chapter I: Food and Drug Administration, Department of Health and Human Services, Subchapter C — drugs: general, part 203 — prescription drug marketing, subpart D: samples, § 203.39 donation of drug samples to charitable institutions [online]. Available from URL: http://ecfr.gpoaccess.gov/cgi/t/text/text-idx7.c=ecfr&sid=ec1033dbd03546f7dc73a2d35c683a6c&rgn=div8&view=text&node=21:4.0.1.1.4.4.1.10w&idno=21 [Accessed 2008 Apr 20]
WHO. Guidelines for the safe disposal of unwanted pharmaceuticals in and after emergencies: interagency guidelines, WHO/ EDM/PAR/99.2, 1999, 31pp [online]. Available from URL: http://www.who.int/water_sanitation_health/medicalwaste/unwantpharm.pdf [Accessed 2008 Jun 4]
Acknowledgements
ISR thanks David Hassenzahl, University of Nevada, Las Vegas, NV, USA for continued guidance, and the US EPA for granting an appointment as a US EPA Student Volunteer. US EPA Notice: The US EPA through its Office of Research and Development funded and managed the research described here. It has been subjected to the Agency’s administrative review and approved for publication as an EPA document. The authors have no conflicts of interest that are directly relevant to the content of this review.
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Daughton, C.G., Ruhoy, I.S. The Afterlife of Drugs and the Role of PharmEcovigilance. Drug-Safety 31, 1069–1082 (2008). https://doi.org/10.2165/0002018-200831120-00004
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DOI: https://doi.org/10.2165/0002018-200831120-00004