Pharmaceutical drugs:maintaining appropriate use while preventing diversion

Dr Malcolm Dobbin

Senior Medical AdviserMental Health, Drugs and Regions Division

Victorian Dept Health

benefitsRisks•Patient-centred

Clinical drug use decisions

Clinical drug use decisions

benefitsRisks•Patient-centred•population level

Heterogeneous population

Passik S D Mayo Clin Proc. 2009;84:593-601

Heterogeneous population

Passik S D Mayo Clin Proc. 2009;84:593-601

hidden population

At-risk cohorts

Mental health disorders– 20% of adult population

Substance use disorders – personal, family– 7% of adult population

Comorbidity prevalentAbusive childhood prevalent

Opioid base supply: Australia, 1991-2009

morphineoxycodone

methadone

codeine

pethidine

Opioid base supply: USA 1997-2006

Source: ARCOS Automated Reports and Consolidated Orders. DEA, US DoJ.

oxycodone

hydrocodone

morphine

methadone

codeine

(OxyContin(OxyContin®® ))

(Vicodin(Vicodin®® ))

pethidine

Consequences of increased supply

“…very strong correlation between therapeutic exposure to opioid analgesics…..and their abuse”

– Cicero TJ et al. Relationship between therapeutic use and abuse of opioid analgesics in rural, suburban and urban locations in the United States. Pharmacoepidemiol Drug Saf 2007;16(8):827-40.

“..suggest..non-medical use of opioids is predictable based on potency and extent of prescriptive use.”

– Dasgupta N et al. Association between non-medical and prescriptive usage of opioids. Drug Alc Dep 2006;82:135-42.

“…linear relationship between total opioid analgesic sales and drug poisoning mortality.”

– Paulozzi LJ, Ryan GW. Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Preve Med 2006;31(6):506-11..

Unintentional drug overdose deathsby major type of drug, U.S., 1999-2006

SOURCE: CDC/NCHS, National Vital Statistics System. Data Brief Number 22, Increase in Fatal Poisonings Involving Opioid Analgesics in the United States, 1999–2006

Unintentional drug overdose deathsby major type of drug, U.S., 1999-2006

SOURCE: CDC/NCHS, National Vital Statistics System. Data Brief Number 22, Increase in Fatal Poisonings Involving Opioid Analgesics in the United States, 1999–2006

Source

Dealer 69%Forged prescription 10%Stolen 24%Doctor 63%Friend/relative 68%ER 29%Internet 7%

Cicero TJ et al. Co-morbid pain and psychopathology in males and females admitted totreatment for opioid analgesic abuse. Pain 2008;139:127-35 .

BUT SEE: Inciardi JA et al. The “Black Box” of prescription drug diversion. J Addict Dis 2009;28:332-47.

Chain of supply: to Australia

Internet Internet PostPost importimportfreightfreight

importimportpersonalpersonal

Licit import

Illicit importIllicit import

Licit chain of supply:within Australia

Port

Warehouse Pharmacy,Hospital, ERFactory

Patient

Prescriber

Diversion

Warehouse

Diversion in transitDiversion in transit

Armed robberyArmed robberyPilferPilfer TheftTheft

False invoiceFalse invoice

Prescriber

Identity fraudIdentity fraud

False representation of disease False representation of disease ““doctor shoppingdoctor shopping””

Stolen prescription Stolen prescription stationery, forgery, stationery, forgery, alteration of scriptsalteration of scripts

Inappropriate prescribingInappropriate prescribing

SelfSelf--administrationadministration

Diversion

Intimidation, Intimidation, threatthreat

Across State Across State bordersborders

Pharmacy

Robbery, theft, ram raidRobbery, theft, ram raid

Intimidation, threat:Intimidation, threat:outside pharmacy,outside pharmacy,General threatGeneral threat

Forged prescriptionForged prescription

Diversion

False representation of disease False representation of disease ““pharmacy shoppingpharmacy shopping””

Altered prescriptionAltered prescription

PatientTheft from Theft from & within home& within home

Patient onPatient on--sellingselling

Intimidation, threat:Intimidation, threat:outside pharmacy,outside pharmacy,

General threatGeneral threat

Friends, family share, sellFriends, family share, sell

Diversion

Inject, snort tabletsInject, snort tablets

High risk - low value drugs: characteristics

Euphorigenic, sedatingIntoxicatingRapid onset of effect Low margin – therapeutic & toxic doseLow therapeutic advantageFormulation problem - high dose, gelcap

High risk - low value drugs:removed

chloral hydratebarbituratesmethaqualonetemazepam gelcaps (UK, Australia)flunitrazepam 2 mgdextromoramidepropoxyphene (UK, NZ)

High risk - low value drugs: current concerns

Compound analgesics – opioid + simple analgesic

midazolam oral tabletsquetiapine (antidepressant)alprazolam (e.g. Xanax®)propoxyphenepethidine (meperidine)

ToolboxProblem countermeasureHigh risk, low value drugs

• Registration process – assess diversion risk• Enhanced information systems to monitor drugs subject to diversion• Early identification of adverse trends•Agile and adaptable regulatory system• Review and remove• Reschedule to more restrictive

Clinically importantCommonly misused, divertedDependence-producing, intoxicating effectCriminal activity - to obtain & under-the-influenceContribute to severe morbidity, mortalityHeterogeneous, hidden sub-populations– Include non-injectors, not from drug subculture

High risk - high value drugs: characteristics

OpioidsBenzodiazepines & other sedativesAntipsychotic, antidepressant drugsPharmacotherapies (opioid dependence)Precursor drugsOther (e.g. anti-Parkinson’s drugs, appetite suppressants, stimulants)Performance-enhancing - veterinary & human

High risk - high value drugs: categories

Toolbox HRHV drugsProblem countermeasureRegulatory control

•Appropriate regulatory control•Prescription - quantities in words & figures•Pharmacist to know handwriting or contact prescriber•Special prescription pads•Oversight - problematic prescribing• National uniformity

Toolbox HRHV drugsProblem countermeasureInsufficient information about HRHV drug supply to individuals-> unsafe supply

•Coordinated medication management•Real time, for prescribers, pharmacists, at time of prescribing, dispensing• available to regulators – detect injudicious supply, diversion•Automated real-time analysis•Software to detect forged or altered scripts, drug-seeker, at-risk individuals•Privacy safeguards, audit trail of access•Encryption• Unique health-care identifiers• National – across State/Provinces•Include OTC high risk drugs

Coordinated medication mgmt “Prescription monitoring”

1st generation: inspecting pharmacies2nd generation: paper based scripts to central point3rd generation: electronic transmission4th generation: real time information for prescribers, pharmacists, regulators

Coordinated medication mgmt “Prescription monitoring”

3rd generation deficiencies– Historical, after-the-event– Limited capacity to identify individuals– Responsibility of operators to notify on

limited information – How? Criteria? Delay– Difficult access for professionals needing

immediate information for safe supply decisions

Coordinated medication mgmt “Prescription monitoring”2nd generation deficiencies– As for 3rd generation, PLUS– ‘chilling’ effect on appropriate prescribing.

NY triplicate prescription program 1989:– ~60% reduction in benzodiazepine scripts– Increased prescribing of older, more toxic

sedatives– Greater impact on non-problematic use

Wintraub et al. JAMA 1991;266:2392-7 plus others

Forged benzodiazepine scripts:1995

Total forged items 223. Bzds 115 (49%)

Forged benzodiazepine scripts:to May 2001

85% temazepam

Toolbox HRHV drugsProblem countermeasureForged, altered prescriptions

• Tamper-proof, dedicated prescriptions for HRHV drugs• Secure storage• Software programs to detect at time of supply• Electronic prescribing• Specify number of items on script• Words and figures• Cross out unmarked space

Tamper-resistant scripts

34

In 2007In 2007‐‐2008 Where Pain Relievers Were Obtained 2008 Where Pain Relievers Were Obtained for Most Recent Nonmedical Use: Ages 12+for Most Recent Nonmedical Use: Ages 12+

Note: Totals may not sum to 100% because of rounding or because suppressed estimates.

1 The Other category includes the sources:  “Wrote Fake Prescription,” “Stole from Doctor’s Office/Clinic/Hospital/Pharmacy,” and “Some Other Way.”

Bought/Took  from Friend/Relative14.3%

Drug Dealer/Stranger4.3%

Bought on Internet0.4% Other 1

4.8%

Source Where Respondent Obtained

One Doctor18.0%

More than One Doctor2.4%

Free from Friend/Relative55.9%

Free from Friend/Relative6.2%

Bought/Took fromFriend/Relative5.4%

OneDoctor81.7%

Drug Dealer/Stranger1.6%Bought on

Internet0.1%

Source Where Friend/Relative Obtained

More than One Doctor3.4%

Source:  SAMHSA, 2008 National Survey on Drug Use and l h

Other 11.6%

Toolbox HRHV drugsProblem countermeasurePatient selection

Management of request

• Identify higher risk patients – MHD, SUD-personal or family history• Examination for evidence of SUD• Screening tools• Universal precautions• Inherited patients special precautions – confirm with previous prescriber directly• Borrowed protection• Scripted responses• Broken record, use “we”

Pharmacy robbery

OxyContin in timeOxyContin in time--delay safedelay safe

Ram raid

Toolbox HRHV drugsProblem countermeasureCrime to obtain: pharmacy, warehouse, transit, domestic robbery

• Requirement to keep in original pack• Indelibly marked or embossed blister packs• Hotline for law enforcement to track to whom dispensed, by whom prescribed and dispensed• ‘Pedigree’ chain records

Toolbox HRHV drugs

Problem countermeasureTheft, robbery • time-release safes, segmented

• Mandatory high quality CCTV• indelibly labelled blister packs

Blister pack

Toolbox HRHV drugsProblem countermeasureIdentity fraud • unique health-care identifiers

• ‘inherited’ patients: special precautions

Toolbox HRHV drugsProblem countermeasurePatient on-selling

• Requirement to keep in original indelibly marked or embossed pack• Coordinated medication management system to detect unusually high doses• Pill counts• Urine drug screen

Toolbox HRHV drugsProblem countermeasureTrafficking, brokering

• Requirement to keep in original indelibly marked or embossed pack • Supported by hotline for law enforcement• Penalty for unauthorised possession, or not in original pack• Coordinated medication management system to detect unusually high dose supply, potential on-selling•

Toolbox HRHV drugsProblem countermeasureSharing, domestic source, medicine cabinet

• Patient information – risks, safe storage• Limited quantity of supply• Return unused HRHV medicines• Safe storage

Toolbox HRHV drugsProblem countermeasurePoisoning risk

• Patient information – risks, safe use, storage• Labelling, package inserts, leaflets, advice – prescribers & pharmacists• Information about recognition of coma• Advice about use of other CNS depressants

Enhanced data systems

Population surveys: initiation & illicit use

AOD treatment

ED treatment Poisoning hospitalisations

Poisoning deaths Coroner etc.

Population survey - dependence, abuse (DSM-IV)

Poisons information systemsPrison, police custody, law enforcement

Forged prescriptions

School children surveysInjecting drug user surveys

Enhanced data systems

Provide real-time dataUnaggregated drug data– data aggregated (ICD-10), can’t identify

individual drugs, formulations, brands Automated analysisEarly identification of emerging trends, effects of controlsAgile, targeted & tailored response

Abuse-resistant formulations

Different targets for a heterogeneous cohorts of non-medical users:– IDU – incorporate antagonist– Different routes: nasal – irritant– Excessive oral intake – sorbitol or other

agent active in high dose only

DEMAND CONTROL

Prescriber/pharmacist education about optimal use of high risk high value drugsPatient information about safe use, risksReconfigure services to attract and retain individuals in treatmentReconfigure treatment regimes tailored to needs.Integrated multi-disciplinary care

Heath Ledger

OxycodoneAlprazolam

"died as the result of acute intoxication by the combined effects ofoxycodone, hydrocodone, diazepam, temazepam, alprazolam, and doxylamine,"