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,"