options for an upstream management of pharmaceuticals in the environment · 2012-11-28 · options...
TRANSCRIPT
Options for an upstream management of
pharmaceuticals in the environment
Benoit Roig, Olivier Thomas
EHESP Rennes, Sorbonne Paris Cité INSERM U1085-IRSET, LERES, France
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3rd International Conference on Sustainable Pharmacy - November 19–20, 2012, Osnabrück, Germany
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Introduction
Environment Human health
RISK ???
Pharmaceutical products are micropollutants of our
environment (waters)
Fish feminization
Vulture decline
…
Probably negligible ??
3
Introduction
Source: Roos et al. Science of the Total Environment, 2012
0,00000
0,00001
0,00010
0,00100
0,01000
0,10000
1,00000
10,00000
100,00000
1000,00000
RQ
High
Moderate
Weak
Insignificant
RISK QUOTIENT
RQ
Ethinylestradiol Atovaquone SertralineEstradiol Mycophenolate mofetil PropranololAcetylsalicylic acid Naproxen FelodipineKetoconazole Paracetamol AmitriptylineFluoxetine Dipyridamole ChlorprothixeneBromhexine Entacapone FulvestrantGalantamine Propofol LoratadineDuloxetine Warfarin AmlodipineFesoterodine Aripiprazole TestosteroneAlendronic acid Venlafaxine TerazosinCitalopram Carvedilol LevodopaFluvoxamine Bicalutamide ZuklopenthixolBenserazide Clopidogrel MetoprololZolpidem Tamoxifen ChlorhexidineMirtazapine Etoricoxib ParoxetineMefloquine Furosemide OrlistatRisedronic acid Donepezil DeferasiroxMontelukast Glyceryl trinitrate OlanzapineCelecoxib Quetiapine BisacodylValproic acid Rosuvastatin DiclofenacVarenicline Sodium picosulfate EbastineClobetasol Betamethasone Lamotrigine
RQ
Ethinylestradiol Atovaquone SertralineEstradiol Mycophenolate mofetil PropranololAcetylsalicylic acid Naproxen FelodipineKetoconazole Paracetamol AmitriptylineFluoxetine Dipyridamole ChlorprothixeneBromhexine Entacapone FulvestrantGalantamine Propofol LoratadineDuloxetine Warfarin AmlodipineFesoterodine Aripiprazole TestosteroneAlendronic acid Venlafaxine TerazosinCitalopram Carvedilol LevodopaFluvoxamine Bicalutamide ZuklopenthixolBenserazide Clopidogrel MetoprololZolpidem Tamoxifen ChlorhexidineMirtazapine Etoricoxib ParoxetineMefloquine Furosemide OrlistatRisedronic acid Donepezil DeferasiroxMontelukast Glyceryl trinitrate OlanzapineCelecoxib Quetiapine BisacodylValproic acid Rosuvastatin DiclofenacVarenicline Sodium picosulfate EbastineClobetasol Betamethasone Lamotrigine
RQ
Ethinylestradiol Atovaquone SertralineEstradiol Mycophenolate mofetil PropranololAcetylsalicylic acid Naproxen FelodipineKetoconazole Paracetamol AmitriptylineFluoxetine Dipyridamole ChlorprothixeneBromhexine Entacapone FulvestrantGalantamine Propofol LoratadineDuloxetine Warfarin AmlodipineFesoterodine Aripiprazole TestosteroneAlendronic acid Venlafaxine TerazosinCitalopram Carvedilol LevodopaFluvoxamine Bicalutamide ZuklopenthixolBenserazide Clopidogrel MetoprololZolpidem Tamoxifen ChlorhexidineMirtazapine Etoricoxib ParoxetineMefloquine Furosemide OrlistatRisedronic acid Donepezil DeferasiroxMontelukast Glyceryl trinitrate OlanzapineCelecoxib Quetiapine BisacodylValproic acid Rosuvastatin DiclofenacVarenicline Sodium picosulfate EbastineClobetasol Betamethasone Lamotrigine
RQ
Ethinylestradiol Atovaquone SertralineEstradiol Mycophenolate mofetil PropranololAcetylsalicylic acid Naproxen FelodipineKetoconazole Paracetamol AmitriptylineFluoxetine Dipyridamole ChlorprothixeneBromhexine Entacapone FulvestrantGalantamine Propofol LoratadineDuloxetine Warfarin AmlodipineFesoterodine Aripiprazole TestosteroneAlendronic acid Venlafaxine TerazosinCitalopram Carvedilol LevodopaFluvoxamine Bicalutamide ZuklopenthixolBenserazide Clopidogrel MetoprololZolpidem Tamoxifen ChlorhexidineMirtazapine Etoricoxib ParoxetineMefloquine Furosemide OrlistatRisedronic acid Donepezil DeferasiroxMontelukast Glyceryl trinitrate OlanzapineCelecoxib Quetiapine BisacodylValproic acid Rosuvastatin DiclofenacVarenicline Sodium picosulfate EbastineClobetasol Betamethasone Lamotrigine
RQ
Ethinylestradiol Atovaquone SertralineEstradiol Mycophenolate mofetil PropranololAcetylsalicylic acid Naproxen FelodipineKetoconazole Paracetamol AmitriptylineFluoxetine Dipyridamole ChlorprothixeneBromhexine Entacapone FulvestrantGalantamine Propofol LoratadineDuloxetine Warfarin AmlodipineFesoterodine Aripiprazole TestosteroneAlendronic acid Venlafaxine TerazosinCitalopram Carvedilol LevodopaFluvoxamine Bicalutamide ZuklopenthixolBenserazide Clopidogrel MetoprololZolpidem Tamoxifen ChlorhexidineMirtazapine Etoricoxib ParoxetineMefloquine Furosemide OrlistatRisedronic acid Donepezil DeferasiroxMontelukast Glyceryl trinitrate OlanzapineCelecoxib Quetiapine BisacodylValproic acid Rosuvastatin DiclofenacVarenicline Sodium picosulfate EbastineClobetasol Betamethasone Lamotrigine
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Mixture effect,
Chronic doses
Level of effect
…
Metabolites & transformation products,
Mode of exposure
Real contamination
…
SEVERAL UNCERTAINTIES
Exposure Effect
REDUCTION ACTIONS
Risk assessment
Regulatory
Industrial
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Reduction actions
Environmental
Medical
Social Producers Prescriptors/dispensers Patients
Receptor
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Introduction
Regulatory
Industrial
Environmental
Medical
SocialProducers Prescriptors/dispensers Patients
Receptor
USAGE
UPSTREAM OPTIONS
DOWNSTREAM OPTIONS
(end of pipe)
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Downstream Reduction Options
IMPROVEMENT IN
- Effluent separation
- Wastewater treatment
- Drinking water treatment
- Drinking monitoring
DRAWBACKS
- Production of treatment by products
(oxydized, chlorinated)
- Costs
Downstream Option Cost: Ex
Regulation of EE2 under the WFD.
European countries would be required by 2021 to limit EE2 in water bodies to
an annual average of no more than 0.035 ppt
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For a UK town of around 250,000 people:
€8 million to install
around €800,000 a year to operate.
For the 1,400 wastewater works in England and Wales
> €30 billion in total.
Adsorption on to granular activated carbon
Source: Owen and Jobling, Nature, 2012
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Source: F. Keil, START project
Upstream reduction Options Policy frameworks
Discussion opportunities Targeted information opportunities promote opinion-formation in physicians and
pharmacists on the topic of contamination of water bodies by active pharmaceutical
ingredients
Professional retraining The topic of contamination of water bodies by active pharmaceutical ingredients will
become an integral part of the retraining of physicians and pharmacists
Change in Prescription Practices
Environmental classification
An environmental classification for human pharmaceuticals allows physicians to
prescribe environmentally compatible active ingredient alternatives
Drug consumption Reduction of drug consumption by the possibility to increasingly prescribe non-
medicinal forms of therapy that generally promote health
Avoidance of Medicinal Product Wastes
Information on drug
consumption
Control of patient demand through creating cost and quantity transparency for
insurants in statutory health insurance
Package sizes Offer of variable package sizes, starter packs for chronic diseases and
dispensing of partial quantities (for example tablet blisters)
Disposal of Unused or Expired Medicinal Products
Disposal standard Creation of a consistent and compulsory disposal standard through pharmacies and
simplification of the take-back system for pharmacies
Education and labelling Sweeping information campaigns relating to proper disposal as well as disposal
instructions on medicinal product packaging and package leaflets
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Source: F. Keil, START project
Upstream reduction Options Policy frameworks
Discussion opportunities Targeted information opportunities promote opinion-formation in physicians and
pharmacists on the topic of contamination of water bodies by active pharmaceutical
ingredients
Professional retraining The topic of contamination of water bodies by active pharmaceutical ingredients will
become an integral part of the retraining of physicians and pharmacists
Change in Prescription Practices
Environmental classification
An environmental classification for human pharmaceuticals allows physicians to
prescribe environmentally compatible active ingredient alternatives
Drug consumption Reduction of drug consumption by the possibility to increasingly prescribe non-
medicinal forms of therapy that generally promote health
Avoidance of Medicinal Product Wastes
Information on drug
consumption
Control of patient demand through creating cost and quantity transparency for
insurants in statutory health insurance
Package sizes Offer of variable package sizes, starter packs for chronic diseases and
dispensing of partial quantities (for example tablet blisters)
Disposal of Unused or Expired Medicinal Products
Disposal standard Creation of a consistent and compulsory disposal standard through pharmacies and
simplification of the take-back system for pharmacies
Education and labelling Sweeping information campaigns relating to proper disposal as well as disposal
instructions on medicinal product packaging and package leaflets
Consumption limitation
• Voluntary and public health spirit
– Amount of pharmaceuticals
– Doses of Active Ingredients
• Financial incentives
– Health insurance
– Reimbursement
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Consumption limitation
• Amount of pharmaceuticals
- Medical doctor Prescription
- Based on patient request
- Prudent prescribing / personalized medicine
- Off label
- …
- Patient Acquisition
- Internet forum (sharing misinformation)
- Automedication
- Advertising
- …
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Sources: Ruhoy and Daughton, Env. Intern., 2008
Voluntary and public health spirit
Consumption limitation options
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Sources: Daughton & Ruhoy, Expert Rev. Clin. Pharmacol. (2011)
Prescribing
Rational, evidence-based prescribing
Drug Utilization Review; concordance; focus on minimizing polypharmacy
Patient empowerment and patient–physician shared decision-making
Restricting insurance reimbursement for OTC drugs depending on national
regulation
Lifestyle modification (prescribing diet, nutrition, exercise, sleep hygiene)
Pharmacogenomics (improved selection of optimal API, dose, dosage form, and
dosing duration/regimen) API prescribed only to responders, avoiding
nonresponders
Improving dose effectiveness
Using pharmacokinetic profiles to select APIs that are extensively metabolized
(thereby reducing contributions from excretion) or to avoid nonresponders
Consumption limitation options
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Sources: Daughton & Ruhoy, Expert Rev. Clin. Pharmacol. (2011)
Dispensing
15-day limitation of initial prescriptions for certain drugs
Unit-dose dispensing
Eco-labeling (specifying proper disposal)
Pharmacist counseling
Off label limitation
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• Possibility to prescribe a drug for treatment regimens not specified in the
approved labeling or package insert
• Common medical practice even if the efficacy is not always proven
Ex: Canadian Study,
- the prevalence of off-label use was 11.0%;
- of the off-label prescriptions, 79.0% lacked strong scientific evidence.
- physicians with evidence-based orientation were less likely to prescribe
off-label
=> reduction of environmental API could result in the avoidance of these uses
in particular when off-label indications lack unambiguous evidence of
efficacy.
Source : Eguale, Arch Intern Med. 2012
Consumption limitation options
Prescription changes via awareness campaign
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Start of the
campaign
Consumption limitation options
“THE ANTIBIOTICS ARE NOT AUTOMATIC” (France)
Consumption limitation options
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• Doses of active ingredients
- lower doses prescription: “less can be more”
Acebutolol Estrogens Omeprazole
Atenolol Ibuprofen Pravastatin
Cimetidine Fluoxetine Propranolol
Diclofenac Furosemide Ranitidine
Doxepin Lovastatin Torsemide
Enalapril Metoprolol Trazodone
Effective doses are commonly one-half to one-quarter (and lower) of the
on-label low dose.
Sources: CMAJ, 2011; JoA, 2009
Voluntary and public health spirit
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Source : irdes
1 March 2006
End of reimbursement
Ex: Prescription rate of mucolytic and expectorant drugs before and after the end of
reimbursement in march 2006 (France)
Consumption limitation options
Financial incentives: Reimbursement changes
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Source : Pichetti et al., Health policy, 2011
Study suggest a report toward reimbursed medicines:
Antitussive + 12.9 %
Other broncodilatator + 4.4 %
Consumption limitation options
Financial incentives: Reimbursement changes
• Leftover drugs can be mitigated by modifying
– Drug usage
• Prescription, dispensing, automedication
• Non adherence and non compliance
Leftover management
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Leftover management
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Sources: Daughton & Ruhoy, Expert Rev. Clin. Pharmacol. (2011)
Non adherence/compliance
Wide array of devices and other technologies can sometimes improve compliance,
including design of packaging
Devices such as TDDS may increase compliance, but also lead to the disposal of
large quantities of residual API that remains in device
Educate patients that behaviors leading to leftover drugs are not in their self-interest
with regard to favorable therapeutic outcomes or because of risks to others
Drug Utilization Review; brown-bag reviews
Vouchers allow patient to decide not to accept free samples they do not want
Long-acting formulations that avoid confusion caused by more frequent dosing
regimens
Leftover management
• Leftover drugs can be mitigated by modifying
– Drug usage
• Prescription, dispensing, automedication
• Non adherence and non compliance
– Drug conditioning
• Is a decision of the national Health authorities
• Tendency is the reduction of the number of pills/box but:
• it’s still under debate (dispensing error)
• It can be also a problem of cost.
- In France, an experimentation (from 2005) of conditioning for 3 months
of treatment of 4 chronic diseases (including diabete, cholesterol) result in economy
of €105 millions in 2009
Leftover management
Leftover drugs can be mitigated by modifying
– Disposal
• Take back scheme/ financial incentives???
• Guidance
• Information
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Conclusion
• The reduction of Pharmaceutical products in the environment
by the way of upstream options is directly or indirectly linked
to the drug consumption.
• Stewardship involves much more than prudent disposal of
leftover drugs
• A major objective should be the design of
prescribing/dispensing practices that do not lead to the
accumulation of leftover drugs to begin with.
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THANK YOU FOR YOUR ATTENTION
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