Drug Safety

, Volume 31, Issue 12, pp 1069–1082 | Cite as

The Afterlife of Drugs and the Role of PharmEcovigilance

Leading Article


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.


  1. 1.
    Oaks JL, Gilbert M, Virani MZ, et al. Diclofenac residues as the cause of vulture population decline in Pakistan. Nature 2004; 427(6975): 630–3PubMedCrossRefGoogle Scholar
  2. 2.
    Ruhoy IS, Daughton CG. Beyond the medicine cabinet: an analysis of where and why medications accumulate. Environ Int 2008; 34(8): 1157–69PubMedCrossRefGoogle Scholar
  3. 3.
    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): 127–38CrossRefGoogle Scholar
  4. 4.
    Bosworth HB, Oddone EZ, Weinberger M, editors. Patient treatment adherence: concepts, interventions, and measurement. Hillsdale (NJ): Lawrence Erlbaum Associates, 2005Google Scholar
  5. 5.
    O’Donohue WT, Levensky ER, editors. Promoting treatment adherence: a practical handbook for health care providers. New York: Sage Publications, Inc., 2006Google Scholar
  6. 6.
    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): 147–51PubMedCrossRefGoogle Scholar
  7. 7.
    Flannagan LM, Butts JD, Anderson WH. Fentanyl patches left on dead bodies: potential source of drug for abusers. J Forensic Sci 1996; 41(2): 320–1PubMedGoogle Scholar
  8. 8.
    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]
  9. 9.
    Kümmerer KE, editor. Pharmaceuticals in the environment: sources, fate, effects, and risk. 2nd ed. Berlin: Springer, 2004Google Scholar
  10. 10.
    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, 2007Google Scholar
  11. 11.
    Marquardt KA, Tharratt RS, Musallam NA. Fentanyl remaining in a transdermal system following three days of continuous use. Ann Pharmacother 1995; 29(10): 969–71PubMedGoogle Scholar
  12. 12.
    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: 172–80PubMedCrossRefGoogle Scholar
  13. 13.
    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): 2855–7PubMedCrossRefGoogle Scholar
  14. 14.
    Cunningham VL, Buzby M, Hutchinson T, et al. Effects of human pharmaceuticals on aquatic life: next steps. Environ Sci Technol 2006; 40(11): 3456–62PubMedCrossRefGoogle Scholar
  15. 15.
    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): 1686–96PubMedCrossRefGoogle Scholar
  16. 16.
    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): 137–48PubMedCrossRefGoogle Scholar
  17. 17.
    Daughton CG. Environmental stewardship and drugs as pollutants. Lancet 2002; 360: 1035–6PubMedCrossRefGoogle Scholar
  18. 18.
    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]
  19. 19.
    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: 66–102CrossRefGoogle Scholar
  20. 20.
    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]
  21. 21.
    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]
  22. 22.
    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: 1173–83PubMedCrossRefGoogle Scholar
  23. 23.
    Boxall ABA, Johnson P, Smith EJ, et al. Uptake of veterinary medicines from soils into plants. J Agric Food Chem 2006; 54(6): 2288–97PubMedCrossRefGoogle Scholar
  24. 24.
    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 pressGoogle Scholar
  25. 25.
    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]
  26. 26.
    Glassmeyer ST, Hinchey EK, Boehme SE, et al. Disposal practices for unwanted residential medications in the United States. Environ Intern. In pressGoogle Scholar
  27. 27.
    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]
  28. 28.
    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): 757–74PubMedCrossRefGoogle Scholar
  29. 29.
    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): 775–85PubMedCrossRefGoogle Scholar
  30. 30.
    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): 899–907CrossRefGoogle Scholar
  31. 31.
    Khetan SK, Collins TJ. Human Pharmaceuticals in the aquatic environment: a challenge to green chemistry. Chem Rev 2007; 107(6): 2319–64PubMedCrossRefGoogle Scholar
  32. 32.
    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 pressGoogle Scholar
  33. 33.
    Enick OV, Moore MM. Assessing the assessments: pharmaceuticals in the environment. Environ Impact Assess Rev 2007; 27(8): 707–29CrossRefGoogle Scholar
  34. 34.
    Aronson JK, editor. Meyler’s side effects of drugs: the international encyclopedia of adverse drug reactions and interactions. 15th rev. ed. Amsterdam: Elsevier Science, 2006Google Scholar
  35. 35.
    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]
  36. 36.
    Dunlop D. Pharmacovigilance in the framework of recording and control of drugs in the United Kingdom [in French]. Therapie 1974 Nov–Dec; 29(6): 799–804PubMedGoogle Scholar
  37. 37.
    Efthymiou ML. Bibliography in pharmacovigilance [in French]. Eur J Toxicol Environ Hyg 1975 Sep–Oct; 8(5): 319–20PubMedGoogle Scholar
  38. 38.
    Evreux JC, Lagier G. The efficacy of pharmacovigilance: principles and proposals [in French]. Therapie 1976 Sep–Oct; 31(5): 581–6PubMedGoogle Scholar
  39. 39.
    Lagier G, Efthymiou ML, Lechat P, et al. Pharmacovigilance in the hospital: first results [in French]. Therapie 1974 Nov–Dec; 29(6): 805–10PubMedGoogle Scholar
  40. 40.
    Hurwitz N, Wade OL. Intensive hospital monitoring of adverse reactions to drugs. BMJ 1969; 1(5643): 531–6PubMedCrossRefGoogle Scholar
  41. 41.
    Moore N, Paux G, Begaud B, et al. Adverse drug reaction monitoring: doing it the French way. Lancet 1985; 326(8463): 1056–8CrossRefGoogle Scholar
  42. 42.
    van Grootheest K. The dawn of pharmacovigilance: an historical perspective. Int J Pharm Med 2003; 17(5–6): 195–200Google Scholar
  43. 43.
    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]
  44. 44.
    Rahman SZ, Khan RA. Environmental pharmacology: a new discipline. Indian J Pharmacol 2006 Aug; 38(4): 229–30CrossRefGoogle Scholar
  45. 45.
    Kummerer K, Velo G. Ecopharmacology: a new topic of importance in pharmacovigilance. Drug Saf 2006; 29(5): 371–3PubMedCrossRefGoogle Scholar
  46. 46.
    Keck G. Teaching environmental toxicology for veterinary students and veterinarians: some new trends. J Vet Pharmacol Therap 2006; 29 Suppl. 1: 15–6CrossRefGoogle Scholar
  47. 47.
    Rahman SZ, Khan RA, Gupta V, et al. Pharmacoenviron-mentology: a component of pharmacovigilance. Environ Health 2007; 6: 20PubMedCrossRefGoogle Scholar
  48. 48.
    Daughton CG, Ternes TA. Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect 1999; 107 Suppl. 6: 907–38PubMedCrossRefGoogle Scholar
  49. 49.
    Ankley GT, Brooks BW, Huggett DB, et al. Repeating history: Pharmaceuticals in the environment. Environ Sci Technol 2007; 41(24): 8211–7PubMedCrossRefGoogle Scholar
  50. 50.
    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): 8897–901PubMedCrossRefGoogle Scholar
  51. 51.
    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]CrossRefGoogle Scholar
  52. 52.
    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: 73–5Google Scholar
  53. 53.
    Collier AC. Pharmaceutical contaminants in potable water: concerns for pregnant women and children. EcoHealth J 2007; 4(2): 164–71CrossRefGoogle Scholar
  54. 54.
    Kuehn BM. Traces of drugs found in drinking water: health effects unknown, safer disposal urged. JAMA 2008; 299(17): 2011–3PubMedCrossRefGoogle Scholar
  55. 55.
    Pollock M, Bazaldua OV, Dobbie AE. Appropriate prescribing of medications: an eight-step approach. Am Fam Physician 2007; 75(2): 231–6PubMedGoogle Scholar
  56. 56.
    Crigger N. Improving nurse practitioner practice through rational prescribing. J Nurse Pract 2008; 4(2): 120–5CrossRefGoogle Scholar
  57. 57.
    The Cochrane Collaboration. The Cochrane library [online]. Available from URL: http://www.cochrane.org/reviews/clibintro.htm [Accessed 2008 Feb 13]
  58. 58.
    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]
  59. 59.
    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]
  60. 60.
    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): 7–10PubMedCrossRefGoogle Scholar
  61. 61.
    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]
  62. 62.
    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]
  63. 63.
    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]
  64. 64.
    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): 45–76Google Scholar
  65. 65.
    Doerr-MacEwen N, Haight M. Expert stakeholders’ views on the management of human Pharmaceuticals in the environment. Environ Manage 2006; 38(5): 853–66PubMedCrossRefGoogle Scholar
  66. 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: [Accessed 2008 Apr 20]
  67. 67.
    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]

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  1. 1.Environmental Chemistry Branch, National Exposure Research LaboratoryUS Environmental Protection AgencyLas VegasUSA
  2. 2.Basic and Clinical SciencesTouro University Nevada, College of Osteopathic MedicineHendersonUSA

Personalised recommendations