Conflict of Interest Disclosure

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1 Patient Rx Drug Misuse and Abuse: Compliance Toxicology Monitoring in Clinical Practice Toxicology Staff Andrea Terrell, Ph.D., DABCC Chief Scientific Officer George Behonick, Ph.D., DABFT, Manager, FBU Majid Moridani, Ph.D., Toxicologist Kevin Shanks, MS, FTS-ABFT, Toxicologist Gina Cooper, Toxicologist Consultant Joan Woodside, Toxicologist Consultant Conflict of Interest Disclosure The speaker ( Dr. Behonick) and co-contributing parties of this presentation ( Dr. Terrell, Dr. Moridani, Kevin Shanks, Gina Cooper and Joan Woodside) have no conflict of interest disclosures to make. Objectives Become familiar with the current epidemiological trends in Rx drug misuse and abuse (especially the opiate/opioid class) Identify the basic elements of a risk mitigation strategy incorporating compliance monitoring (toxicology testing) in clinical practice Recognize the distinctive benefits and advantages of urine and blood analyses in a compliance monitoring strategy for clinical practice 1

2 AN EMERGING PROBLEM Rx. Opioid Abuse NSDUH 2002: 11 million Rx opioid abusers DAWN Mentions: Increase Rx Opioids Hydrocodone 117.8%, Oxycodone 346.9%, Methadone 205.6%, Morphine 113.5% Only MDMA mentions exceed (532%) 2

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6 MITIGATING THE RISK Recommendations Promising interventions and expert opinion from thought leaders throughout the field Intended to be implemented in a concerted and collaborative manner as integrated strategies by all relevant stakeholders Ongoing and future assessment is needed Impact on morbidity, mortality and addictive disease Impact on health care costs 6

7 Health Care Providers Conservatively prescribe opioid medications when alternative therapies fail to deliver adequate pain relief Conservative dosing regimens for opioids (lowest effective dose) Interventional pain alternatives when high daily dose opioids ( 120 morphine mg equivalents per day) fail to substantially improve pain relief and function Avoid long acting opioids (extended release forms of opioids, fentanyl, methadone) for acute pain Individual Patient Management Behavioral and addiction risk screening Articulated, signed patient-provider treatment agreements Utilization of PMP data bases to routinely assess prescription profiles of your patients (e.g., Doctor Shoppers ) Random Rx pill inventories and checks Individual Patient Management Compliance Toxicology Patient Monitoring -Urine - Blood 7

8 Urine General Considerations Long time, traditional specimen of choice for drug testing (e.g., work place, DOT, military) Primary specimen of choice for drug testing by most hospital laboratories Non-invasive specimen collection Urine - Attributes Identification of parent drug and metabolites Simplified reporting (CONSISTENT or INCONSISTENT) Excellent for detecting illicit substances (e.g. cocaine, methamphetamine) Extended detection time (days to weeks) Urine - Limitations No relationship between drug dose and drug concentration No inferences in terms of toxicity/impairment or functionality/lethality Subject to adulteration and other fraudulent manipulations ( pill scrapping, the Whizzinator ) 8

9 Interpretation of Results All results are confirmed using mass spectrometry 100% unequivocal identifications Identifications are 100% accurate; however, the origin of the drug may not always be obvious Examples: A positive morphine result could mean: 1. Morphine (pharmaceutical OR dietary) 2. Codeine 3. Heroin 9

10 Opiate Metabolism CODEINE MORPHINE HEROIN HYDROCODONE 6-MAM Is my patient drinking ETOH? Practical detection of ethanol in urine after drinking 2 to 3 hours after BAC becomes negative Assuming a peak BAC of 0.10%, then urine ethanol is detectable for ~ 8 to 10 hours Little effectiveness in compliance monitoring, especially when one drinks moderately and knows when he/she will be tested Ethyl Glucuronide (EtG) EtG is a minor metabolite of ethanol (0.5 to 1.5% of total elimination) EtG is detectable in urine ~ 1 hour after intake and remains detectable for hours after urine ethanol is no longer detectable EtG reportedly stable in urine at room temperature for up to 4 days Awareness for patients with UTI, or in- vitro formation in diabetics (E. coli + ethanol) and so called passive exposure 10

11 Rx meds: Oxycodone Self reported meds: Desoxyn, Marinol, and MSIR Ask to see prescriptions from other providers 1. Oxycontin 2. Oxycodone 3. Roxicodone 11

12 This is a very popular trick in clinics that rely solely on instant devices This trick is very popular in clinics that use only instant devices Blood General Considerations Gold standard specimen in toxicology for assessing toxicity, therapeutic efficacy, side effect profiles, impairment and functionality Detects parent and metabolite forms of a drug Adulteration or fraudulent manipulation of a specimen is impossible Alternative specimen choice for various clinical situations (e.g., dialysis patients, anuric patients, shy bladder ) 12

13 Dosing Correlations From Blood Toxicology For regimens of daily, multiple doses (not PRN or as needed) Pharmacokinetic parameters such as Vd, F, Dose, Kab, and Kel can be used to better understand the disposition of any drug in the patient These parameters can be combined with the patient s body weight to estimate the expected steady-state (SS) blood concentration for a drug based on the dose Blood vs. Urine Toxicology: Multiple Dose Urine concentrations will increase with increasing dose, but this relationship is not linear Blood concentrations will remain steady after 5-6 half lives Concentration URINE STEADY STATE CONCENTRATION BLOOD Day 1 Day 2 Day 3 Day 4 Multiple Dose Pharmacokinetics STEADY STATE Concentration Single or infrequent dosing prior to a drug test will mean that the blood concentration will not have reached steady state Time 13

14 Blood - Limitations Invasive and unique requirements (e.g., trained phlebotomist, equipment) Limited window of detection (hours) compared to urine Not the most optimal specimen for detecting illicit use Detection Windows Substance Retention Time: Blood Retention Time: Urine Amphetamines 1 5 days 1 5 days Barbiturates 1 30 days Short acting: 1 3 days Intermediate acting: 1 5 days Long acting: up to 30 days Benzodiazepines 1 6days 1 10 days Buprenorphine 1 10 days 1 10 days Cannabinoids (marijuana) Occasional user: 1 3 days Frequent user: 1 14 days Occasional user: 1 4 days Frequent user: 1 30 days Cocaine 8 hours 1 4 days Ethanol (alcohol) Ethyl glucuronide Eliminate 1 drink per hour N/A 1 24 hours 1 3 days Fentanyl 1 48 hours 1 3 days Methadone 1 10 days 1 10 days (ph dependent) Opiates 1 24 hours 1 4 days Phencyclidine (PCP) 1 7 days 1 7 days Propoxyphene 1 5 days 1 5 days Note: Retention times are approximate values that depend upon the nature of the drug, individual metabolism, dosage, and dosage forms. Lethal above 3 ng/ml 14

15 55 year old female Case Study 1 - Blood Prescribed medications: Hydrocodone Patient s blood was drawn during a routine office visit for the purpose of documenting steady state hydrocodone concentrations Expected to be above therapeutic due to the daily dose Case Study 49 year old female Case Study 2 - Blood Prescribed medications: Fentanyl, Morphine, Diazepam Patient s blood was taken as part of a routine office visit during which the patient reported good pain control 15

16 Case Study 3 - Blood 28 year old male Prescribed medications: Oxycodone (ER formulation): 560 mg (7 x 80mg tabs) BID Patient s blood was drawn during a routine office visit to evaluate steady state oxycodone concentrations Patient reported good pain control 16

17 Blood & Urine Toxicology When collected together, blood AND urine provide the most information possible and aid in identifying: Pill scraping Patients taking infrequent doses Patients dosing shortly before visit Patients over-medicating Patients exhibiting atypical metabolic patterns (fast/slow metabolizers) Summary Health care providers will continually be challenged by patient misuse and abuse of Rx medications Strategies to mitigate risk should be multiple and integrated; objective assessment of a patient s drug use can be accomplished via compliance toxicology monitoring (preferably a niche full service lab) Urine and blood are two specimen matrices employed in compliance monitoring protocols. Each specimen type yields unique information and provides different perspective into a patient s drug use (e.g., Rx compliance, illicit, non-prescribed self-medicating) Thank You George S. Behonick, Ph.D., DABFT gbehonick@aitlabs.com