Medication Disposal as a S Source for Drugs as f D Environmental - - PowerPoint PPT Presentation

Medication Disposal as a S f D Source for Drugs as Environmental Contaminants

Ilene S. Ruhoy, MD U.S. EPA Student Volunteer ORD NERL L V ORD, NERL, Las Vegas

Office of Research and Development National Exposure Research Laboratory, Las Vegas, NV

June, 2007

U.S. EPA Office of Research and Development Seminar presented for: presented for: U.S. EPA Office of Water Office of Science and Technology Emerging Contaminants Team at: at: U.S. EPA Ariel Rios South NETI Training Room 6226 W hi t DC Washington, DC 20 June 2007

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citation: Ruhoy IS “Medication Disposal as a Source for Drugs as Environmental Contaminants,” U.S. EPA Office of Research and Development Seminar, presented for U.S. EPA Office of Water, Office of Science and Technology, Emerging Contaminants Team, 20 June 2007, Washington, DC.

Affiliations: Ilene S. Ruhoy, MD

• EPA Student Volunteer at ORD’s National Exposure Research

Laboratory (NERL), Environmental Sciences Division, Las Vegas; mentored by Dr Christian Daughton Vegas; mentored by Dr. Christian Daughton

• UNLV Doctoral student, Department of Environmental Studies,

Greenspun College of Urban Affairs (Chaired by Prof. David Hassenzahl; committee members: Christian Daughton PhD EPA; Hassenzahl; committee members: Christian Daughton, PhD, EPA; Christopher Williamson, PhD, ONDCP; Shawn Gerstenberger, PhD, UNLV School of Public Health; Chad Cross, PhD, UNLV S h l f P bli H lth) School of Public Health)

• As an MD, serve on faculty at Touro University School of

Osteopathic Medicine (Henderson, NV) as Assistant Professor of

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Clinical and Basic Sciences

EPA Notice

Although this work was reviewed by EPA and approved for publication it may not and approved for publication, it may not necessarily reflect official Agency policy.

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Outline

• Overview of issues surrounding drug disposal
• Key, unresolved questions

Key, unresolved questions

• Overview of research on drug disposal at NERL-Las Vegas.

(Summary of Proposed APM under Water Quality MYP)

• Future Plans
• To obtain feedback from Program Offices and Regions in
• rder to make research responsive to Agency needs
• rder to make research responsive to Agency needs.

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Drug Disposal

• Pharmaceutical Waste
• Take-back events and programs

Take back events and programs

• Controlled Substances Act (CSA)
• Stakeholders & Beneficiaries:

Stakeholders & Beneficiaries: EPA, DEA, ONDCP, FDA, USFWS, state and local governments, municipal water districts, pharmacy & pharmaceutical industries, healthcare industry, insurance industry

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Environmental Impact of Disposal

• Pharmaceuticals owe their origins in the environment to

their worldwide, universal, frequent, and highly dispersed but cumulative usage by multitudes of individuals but cumulative usage by multitudes of individuals

• Occurrence of pharmaceuticals in the environment mirrors

the intimate, inseparable, and immediate connection p between the actions and activities of individuals and their environment di l i l li d b h i h

• Proper disposal is greatly complicated by the inherent,

fundamental conflict between the need to protect public safety and the need to minimize aquatic (and terrestrial)

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exposure

Major Unknown

• What fractions of drug residues occurring in the

ambient environment result from discarding leftover drugs? –No studies exist that provide objective data from well- defined populations to support any type of conclusion defined populations to support any type of conclusion.

• To gauge the significance of leftover drugs as potential

pollutants, data are needed on the types, quantities, and p , yp , q , frequencies with which drugs accumulate as household waste.

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Pharmaceutical Accumulation Pharmaceutical Accumulation

• Pharmaceuticals designed for both humans and animals
• ften accumulate beyond the time of their intended use
• Numerous factors play roles in the accumulation of drugs by

end-users C h l h f i l h i i –Consumers, health care professionals, physicians, patients, veterinarians, farmers, humanitarian relief workers –Factors include expiry, non-adherence, over-prescribing,

• r excessive purchase

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Coroner

Accumulation and Disposal of Pharmaceuticals

IS Ruhoy & CG Daughton U.S. EPA-Las Vegas 15 December 2006

Decedent In-Patient D ti Unusable Donations Clan Labs Abandoned

15 December 2006

Cruise Ship Pharmacies

Consumer

Out-Patient Clinics Nurses Offices Abusers (e.g., "pharming") Internet Donations Medicine Cabinet Controlled Substances Dentists

Physicians

Pharmacies Black Market

Manufacturers

Drug Sharing Take-Backs & Collection Events Reverse Distributors Controlled Susbtances

NOTE: This diagram

Physicians

In-practice Use Transporter Diversion Illegal Via Pets Physician Samples Hospice Hospitals Law Enforcement st buto s

NOTE: This diagram is for EPA internal use only. Do not distribute or cite ith t t f

Pharmaceutical Representatives

Distributors

Veterinarians CAFOs LTCFs Points of Accumulation

without consent from the authors.

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Vendors Zoos Agriculture (farners) First Aid Kits Ambulances Discard to sewerage Discard to trash/landfill Incineration Accumulation

Pharmaceutical Accumulation Pharmaceutical Accumulation

• Consumer Homes

– Both human and animal medicine

• Physician Offices
• First Responder Services
• First-Aid Kits
• Border Check Points

y – Samples and in-office procedure use

• Veterinarian Offices
• Dental Offices
• Customs (airline and freight)
• Confined Animal Feeding Operations

(CAFOs)

• Agriculture
• Dental Offices
• Hospitals
• Long-Term Care Facilities
• Donations
• Agriculture
• Aquaculture
• Zoos
• Clan Labs
• Schools (confiscation and health care offices)
• Cemeteries
• Cruise Ships

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Pharmaceutical Accumulation

l f i d

• Accumulate for varied reasons

–NON-COMPLIANCE/NON-ADHERENCE

• Reduced ability to treat
• Reduced ability to treat

–INEFFICIENCES IN DISTRIBUTION AND PRESCRIBING –CONSUMER OVER-PURCHASING

• Wal-Mart

–EXPIRED

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Pharmaceutical Prescriptions in the US - 2005

• Top Ten # of prescriptions written (X1000)

–Hydrocodone/APAP 101,639 –Lipitor 63,219 –Amoxicillin 52,104 –Lisinopril 47,829 Lisinopril 47,829 –HCTZ 42,757 –Atenolol 42,001 Zith 38 110 –Zithromax 38,110 –Furosemide 34,782 –Alprazolam 34,230

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–Toprol-XL 33,598

New Approach to Mining Data for Types and Quantities of Disposed Drugs † y g

• Medications collected and disposed of by coroner
• ffices are potentially a large source of drugs in the

p y g g environment

• But arguably even more important, inventories of

di i id i f i di h medications provide information regarding the categories and dosage amounts of medications disposed disposed

†from unpublished dissertation research of I. Ruhoy 2006.

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New Approach to Mining Data for Types and Quantities of Disposed Drugs †

• Understanding the categories and quantities of drugs

disposed can help assess potential impacts on both the Types and Quantities of Disposed Drugs disposed can help assess potential impacts on both the environment and human health

– environmental scientists to better target APIs (active pharmaceutical

ingredients) for monitoring purposes g ) g p p – assessment of risk to human health from chronic and/or acute exposures (e.g., imprudent consumption of leftover drugs) – health care practitioners to address inefficient prescribing practices and patient non compliance and patient non-compliance – policymakers (including those in the insurance industry) to begin to understand and confront the growing issue of wasted and discarded medications.

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– Ultimate Objective: No Leftover Drugs

†from unpublished dissertation research of I. Ruhoy 2006.

New Approach to Mining Data for Types and Quantities of Disposed Drugs †

C h i hi h h d d di d l h h

• Coroner cases are those in which the decedent died alone or when there

were unusual circumstances regarding the death – Standard definition of coroner cases as used nationally – Population demographics from which coroner cases are derived do not differ from the general population

• Coroner inventory is the only ready source of accurate data that:

– Indicates what types of drugs accumulate – Indicates which drugs may result in disposal – Indicates what categories of drugs are actually disposed of (by the Indicates what categories of drugs are actually disposed of (by the coroner) – Encompasses all medication – OTC and prescription

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†from unpublished dissertation research of I. Ruhoy 2006.

DISPOSAL

New Data † Clark County Coroner

• Based on Clark County Coroner Cases for 13 month period (January

2005 – January 2006)

• Population: 3 million people
• 1,623 cases reviewed

– Approximately 325,000 pills/tablets/capsules disposed into sewage system

• Controlled substances/Non-controlled substances

– Greater than 102,000,000 mg (102 kg) of APIs disposed into the environment

• 92% flushed into sewage system
• 7% trash disposal
• 1% incinerated

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†from unpublished dissertation research of I. Ruhoy 2006.

DISPOSAL

• Benzodiazepines

– Alprazolam, diazepam, lorazepam

New Data † Clark County Coroner

p , p , p

• Hormonal Compounds

– Estrogens

• Cardiovascular

Verapamil furosemide propanolol warfarin simvastatin HCTZ – Verapamil, furosemide, propanolol, warfarin, simvastatin, HCTZ, spironolactone, torsemide

• Antibiotics

– Gentamicin, amoxicillin, clindamicin i

• Narcotics

– Hydrocodone, oxycodone, morphine, methadone

• Psychiatry

– Olanzipine, mirtazapine, bupropion, quetiapine, gabapentin, fluoxetine, Olanzipine, mirtazapine, bupropion, quetiapine, gabapentin, fluoxetine, depakote

• GI

– Omeprazole, pantoprazole

• Respiratory

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• Respiratory

– Theophylline

†from unpublished dissertation research of I. Ruhoy 2006.

Decedent Non-Compliance

N D

† Cl

k C t C

• Assessment of compliance of coroner cases demonstrated

non-compliance rate of 29% Categories of drugs most often found amongst those non

New Data † Clark County Coroner

• Categories of drugs most often found amongst those non-

compliant – Anti-hypertensive medication – Lipid-lowering medication Lipid lowering medication – Anti-depressant medication – Hormonal therapies Osteoporosis medication – Osteoporosis medication

†from unpublished dissertation research of I. Ruhoy 2006.

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Decedent Non-Compliance

New Data † Clark County Coroner

• 29% of decedents were non-compliant
• The causes of death, as reported by the medical examiner,

The causes of death, as reported by the medical examiner, were the result of a disease process the medications were intended to treat in 68% of the non-compliant decedents

†from unpublished dissertation research of I. Ruhoy 2006.

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Decedent Non-Compliance

New Data † Clark County Coroner

• The greater the number of medications prescribed, the

greater the chance of non-compliance

• Of the non-compliant decedents, average number of

medications = 8 per decedent

• Of the compliant decedents, average number of medications

Of the compliant decedents, average number of medications = 3 per decedent

†from unpublished dissertation research of I Ruhoy 2006 †from unpublished dissertation research of I. Ruhoy 2006.

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Pharmaceutical Accumulation Pharmaceutical Accumulation

• Represents lost opportunities for optimal delivery of health

care as well as the undesired potential for drug diversion and environmentally unsound disposal –Can pose acute and chronic poisoning risks for humans and wildlife alike and wildlife alike

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Pharmaceutical Accumulation Pharmaceutical Accumulation

• The fate of unused pharmaceuticals in our communities may

be varied –DISPOSAL

• Distributed by various routes to the natural environment

h h b ll where they become pollutants –MISUSE ABUSE –ABUSE –POISONING –CRIME

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C

DISPOSAL

New Data † Clark County Coroner

• Greater than 400 different APIs disposed

– From abacavair to zonisamide CA A A

• CARBAMAZEPINE

– 1,755 tablets equivalent to 307,300 mg of API – Most common dose prescribed is 200 mg – It would require between 51,000 and 154,000 oral doses of CBZ for excretion to contribute the equivalent (assuming an excretion rate ranging from 1 to 3%). – The Clark County sewage system has average sewage flows of 144.4x106 gal/day (MGD) Assuming a hypothetical uniform and consistent daily disposal to sewage a (MGD) Assuming a hypothetical, uniform and consistent daily disposal to sewage, a minimum concentration of 1.4 ppt CBZ could be expected in the influent, as well as possibly the effluent, from the disposal of CBZ by the CCCO alone. – Can be extroplated nationwide

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p

†from unpublished dissertation research of I. Ruhoy 2006.

DISPOSAL

New Data † Clark County Coroner y

• Greater than 600,000 mg of Beta-Blockers disposed

Greater than 600,000 mg of Beta Blockers disposed

• Greater than 1,200,000 mg of antimicrobials disposed
• Greater than 11,500,000 mg of analgesics disposed

–NSAIDs –Non-opioids –Opioids

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Coroner Inventory Record facsimile

• facsimile -

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Coroner Drug Inventories g Can Be Used To DETERMINE:

• Types and relative amounts of APIs disposed
• Types and relative amounts of APIs disposed
• Actual quantities of APIs disposed
• Fraction of APIs disposed by various routes (e.g., sewerage vs. trash)
• Minimum limits on amounts of individual APIs disposed
• Putative maximum limits on amounts of individual APIs disposed
• Predicted concentrations introduced to STPs
• Relative significance of disposal with respect to the overall

environmental occurrence of an individual API

• Those APIs for which disposal is insignificant with respect to their
• Those APIs for which disposal is insignificant with respect to their
• verall environmental occurrence
• Those APIs for which disposal might play a significant role in their
• erall en ironmental occ rrence

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• verall environmental occurrence
• Those medications for which patient compliance rates are low

Coroner Drug Inventories Can Be Used To GUIDE:

• Selection of APIs for targeted monitoring in

sewage streams and the environment in sewage streams and the environment in specific geographic locales R i i f API h b i

• Recognition of APIs that are being over-

prescribed

• Recognition of medications with poor

patient compliance

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Details of Research

• First in a series of manuscripts: “Types and Quantities of

Leftover Drugs Entering the Environment via Disposal to Sewerage – Revealed by Coroners’ Records” – authors: Ilene Ruhoy and Christian Daughton t th f ’ i t f i i – paper presents the use of coroner’s inventory for mining drug disposal data – submitted for publication in May 2007 p y

• currently in review

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Note re: Human Subjects Testing

• Important to understand that mining data from

coroner’s offices does NOT constitute human coroner s offices does NOT constitute human subject research because: (1) a human subject research participant MUST be a LIVING research participant MUST be a LIVING individual, and (2) furthermore, when data are mined, any linkage with the decedent is omitted. , y g

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Linkage of Research g with Agency Priorities

Proposed APM for Water Quality MYP under Contaminants p Q y

• f Emerging Concern (CECs)
• APG 3 – Conduct the research necessary to address those

t i t / l i d f l ti l ti contaminants/classes in need of evaluation or regulation.

• Proposed APM (FY10): A systematic methodology for

measuring leftover medications as a source of active measu ing leftove medications as a sou ce of active pharmaceutical ingredients (APIs) occurring as ambient environmental pollutants (Ruhoy and Daughton). P T d i h h d di l

• Purpose: To determine whether consumer drug disposal

leads to measurable portions of environmental residues of APIs that can justify the design and implementation of drug

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j y g p g take-back programs.

Future Plans Future Plans

• Nationwide database of coroner inventories
• Prioritize list of APIs to be selected for monitoring
• Human health risk assessment
• Assess risk abatement strategies
• Consumer education and awareness

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Comments/Questions?

• Your feedback is welcomed
• How might my dissertation research better

answer EPA questions, needs, or concerns q , , regarding drug disposal?

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Contact

• Ilene S. Ruhoy, MD

ruhoy ilene@epa gov ruhoy.ilene@epa.gov ilene.ruhoy@unlv.edu iruhoy@touro.edu iruhoy@touro.edu (702) 798-2621 (EPA-Las Vegas office) (702) 339-8370 (cellular)

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