By Ilene Ruhoy. This slidecast is part of the GreenPharmEdu.org program.

1. PharmEcovigilance GreenPharmEdu.org

2. PharmEcovigilance Conventional pharmacovigilance expanded beyond conventional focus on ADRs to encompass environmental concerns Unify the parallel but interconnected needs for protecting both human and ecological health Daughton CG and Ruhoy IS "The Afterlife of Drugs and the Role of PharmEcovigilance," Drug Safety, 2008, 31(12):1069-1082; doi: 10.2165/0002018-200831120-00004.

3. Actions to reduce APIs in the environment and protect human health & safety Unit dosing and trial scripts Low-quantity packaging of OTC medications Increased monitoring of patient Samples and donations Reduce incentives for excessive purchasing Personalized medicine (e.g., lower doses) Reduce polypharmacy Lower doses via non-racemic APIs Environmental assessments of newly designed drugs Prescribers to account for possible environmental impact Widespread implementation of sustainable take-back programs Improved record keeping of disposed pharmaceuticals by institutions

4. Stewardship Stewardship involves much more than prudent disposal of leftover drugs Actions taken to reduce PPCPs in the environment will have collateral benefits in also capturing chemicals we are currently not aware of and may lessen human morbidity and mortality

5. Variables in calculating relative environmental footprint of a disposed drug Total consumption Fraction disposed Fraction excreted unchanged urine & feces bathing: residues in sweat residues from dermally applied drugs Fraction excreted as conjugates

6. Unintended Consequences By avoiding the flushing of unwanted drugs into sewers could human morbidity and mortality perhaps be exacerbated? The ultimate objective might not be to determine the relative contributory role of disposal in the occurrence of PPCPs in the environment, but rather to design systems that result in eliminating the need for disposal in the first place

7. Data Gaps Comparatively slight coverage of extent and scope of PPCPs occurrence in finished or point-of-use drinking water and landfills The majority of APIs have never been targeted for environmental monitoring Monitoring tens to focus on a core set of roughly a hundred or so of the thousands of APIs (or the degrades) from commercial use Scant coverage also on: Occurrence of environmentally derived residues of PPCPs in tissues of aquatic organisms and plants Inventories of disposed medications and of the usage frequency of the methods of disposal Potential for human effects and immune responses

8. Models of Change European Union “Green” drugs – requires pharmaceutical companies to analyze environmental risks of new drugs (database available to physicians) KNAPPE Knowledge and Need Assessment on Pharmaceutical Products in Environmental Waters In Sweden, systems for classification of drug environmental risk and hazard have been used for 5 years START: Management strategies for pharmaceutical residues in drinking water - Pharmaceuticals for Human Use: Options of Action for Reducing the Contamination of Water Bodies

10. Proper disposal is greatly complicated by the conflict between the need to protect public safety (e.g., from drug diversion) and the need to minimize environmental exposure* DaughtonCG and Ruhoy IS. "Environmental Footprint of Pharmaceuticals: The Significance of Factors Beyond Direct Excretion to Sewers," Environmental Toxicology & Chemistry 2009, 28(12):2495-2521; doi:10.1897/08-382.1; available: http://www3.interscience.wiley.com/cgi-bin/fulltext/123234136/PDFSTART

11. 10 Major Unknown What fractions of drug residues occurring in the ambient environment result from discarding leftover drugs? No studies provided objective data from well-defined populations to support any type of conclusion Data are needed on the the types, quantities, and frequencies with which drugs accumulate and are disposed of as household waste

12. Drug Disposal: Major Unknowns ? Unknown: types, quantities, or frequencies by which APIs enter the environment via disposal. What percentage of any given API’s environmental loading is contributed by disposal: Disposal could be significant for certain APIs and insignificant for others. This means that conscientious control of disposal may not lead to any detectable change in the environmental occurrence of many (or most) APIs. ? !

13. Drug Disposal: Major Unknowns ? Significance of antibiotic residues in environment with respect to evolution of pathogen resistance Portion of human poisonings resulting from accidental ingestion and abuse of diverted drugs that are stored or disposed imprudently Prevention of diversion and human poisonings may be the more important driver for prudent disposal. ? !