options for an upstream management of pharmaceuticals in the environment · 2012-11-28 · options...

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 ??

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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


RQ


RQ


RQ


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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


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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


Prescription changes via awareness campaign

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Start of the

campaign


“THE ANTIBIOTICS ARE NOT AUTOMATIC” (France)


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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)


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 %


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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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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options for an upstream management of pharmaceuticals in the environment · 2012-11-28 · options...

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