Urine Drug Testing in Chronic Opiate Management: Tips for Primary Care Physicians

1. Urine Drug Testing in Chronic Opiate Management:Tips for Primary Care Physicians Analia Castiglioni, MD GIM Noon Conference February 2, 2010

3. Case UDS Barbiturates NEGATIVE Opiates POSTITIVE Marijuana NEGATIVE Cocaine NEGATIVE BZD NEGATIVE Urine Opiate Panel ++++morphine ++ codeine + hydrocodone + hydromorphone Methadone <50mg/L

4. Objectives Review utility of urine drug testing in chronic opiate management Describe different testing methods and limitations Enhance knowledge for correct interpretation of drug testing Develop a testing strategy

5. Roadmap Background Testing methods Screening Confirmatory Interpretation of results Drug testing in clinical practice Why test Whom to test When to test

6. Prescription drug abuse Epidemic numbers (2004) 15 million (94% increase in a decade) > combined cocaine/hallucinoges/inhalants/heroin 4th most abused < marijuana, alcohol and tobacco Oxycontin, Ritalin, Valium Concomitant illicit drug use 34% on controlled substances 15% w/o controlled substances Psychotropic drugs taken non-medicallyPsychotropic drugs taken non-medically

7. Chronic Non-Malignant Pain (CNMP) Majority managed by PCP Opiates accepted approach Data supports efficacy Long/short acting formulations Risks abuse and diversion Use of other illicit substances Random drug testing Screening/Monitor adherence 8% Family Physicians use it

8. Drug �screening� in clinical practice Not real �screening� Only limited number of drugs Drugs detected depend on setting/test used Urine preferred biologic sample Parent drug or metabolite(s) Longer detection time (1-3 days) Easy to collect, low cost Drugs in serum short � life (4-6 hours)

9. Detection of drugs in biologic specimens

11. Urine Drug Screen (UDS) Screening Antibody mediated: Qualitative (+ or -) Advantages Sensitive, inexpensive, rapid 1-many drugs Point of Care/Lab Disadvantages: Cross-reactivity Detection cut-offs vary �Presumptive results� until confirmed

12. Chromatography Confirmatory Test Gas (GC/MS) or liquid (HPLC) Quantitative, drug-specific Advantages: Accurate, sensitive, reliable Detect specific drugs Disadvantages Costly, insurance may not pay lab-based, time consuming

13. Urine Drug Screen (UDS) VA and UAB lab: Barbiturates Opiates Cannab (VA), Amph (UAB) Cocaine Benzodiazepines +Urine is saved 5d (UAB) and 60d (VA) Confirmatory test needed r/o false +, cross reactivity Determine specific drug detected in a class

14. Interpretation of UDS results Accurate interpretation requires Detailed history of med used (sched/prn) OTC/herbal products Time of last use Test Sensitivity vs Specificity Limited for semi-synthetic/synthetic opioids Cross-reactivity High (amphetamines) vs low (cocaine) Sensitivity: ability to detect a class of drug Specificity: ability to detect specific drug Sensitivity: ability to detect a class of drug Specificity: ability to detect specific drug

15. Going back to the case� UDS Barbiturates NEGATIVE Opiates POSTITIVE Marijuana NEGATIVE Cocaine NEGATIVE BZD NEGATIVE Urine Opiate Panel ++++morphine ++ codeine + hydrocodone + hydromorphone Methadone <50mg/L

16. UDS: Unexpected Positive Results What if you detect drugs you didn�t prescribe? Metabolite of a prescribed drug or OTC Pt may be using other drugs Prescribed (second provider) Illicit False Positive (cross-reactivity)

18. UDS: Unexpected Negative Results What if the Prescribed drug is absent? Check if drug is detected by UDS test Dose below detection cutoff (prn use) Pt not taking medication as prescribed Not at all, run out early Diversion, altered urine, wrong patient Medical condition (lactic ac, osm diuresis) False Negative BZD, synthetic opiates

19. Opiates

20. UDS Interpretation: Opiates Prescribed or illicit use Analgesic, antitussive, antidiarrheal Not all opiates are detected by UDS Sensitivity varies natural vs synthetic opioids False - (pt on opiates but test -) Cross reactivity False + (pt not on opiates but test +) Poppy Seeds, Rifampin, Fluoroquinolones

22. Opiate Metabolism Drug vs metabolite Drug > metabolite concentrations Different half-lives

23. Semi-synthetic/Synthetic Opiates Oxycodone Opiate screen negative at dose <100mg/d <10% excreted in urine Opiate panel Methadone Opiate screen negative Specific urine methadone level Average dose >40mg/24hr Verapamil metabolite can cause false+ Fentanyl Opiate screen negative Urine Fentanyl level Trazodone can cause false +

24. Poppy Seeds Screening cutoff for DHHS changed 1998 From 300ng/ml to 2000ng/ml 1 bagel 1.5mg Morphine and 0.1mg codeine Results + in some pts up to 24hrs Clinical UDS still use 300ng/ml Rifampin 12% cross-reactivity, up to 18-24hrs Quinolones Opiate Screen Cross Reactivity

25. UDS Interpretation: Opiates Opiate + True positive Morphine Hydrocodone Heroin Codeine False positive Poppy seeds Fluoroquinolones Amitriptyline Opiate � True negative False negative Methadone Fentanyl Oxycodone (<100mg/day)

27. UDS Interpretation + Cocaine Deliberate use Cross-reactivity minimal + Amphetamine/Methamphetamine High cross-reactivity OTC products (Vicks�), decongestants, diet products, selegiline Benzodiazepines Variable cross-reactivity Clonazepam usually NOT detected

28. Going back to the case� UDS Barbiturates NEGATIVE Opiates POSTITIVE Marijuana NEGATIVE Cocaine NEGATIVE BZD NEGATIVE Urine Opiate Panel ++++morphine ++ codeine + hydrocodone + hydromorphone Methadone <50mg/L

29. Why test? UDS developed to detect illicit drugs in criminal, workplace and military setting Chronic opiate treatment Aid management of prescription drugs Diagnose substance misuse/abuse/addiction Monitor adherence Guide treatment Advocate for patients

30. Whom to test? Universal approach All pts on chronic opiate regimen New pt already on narcotics Those that you �inherit� Aberrant behavior: �Pseudo-addiction� Pt resistant to full evaluation Request a specific drug Pts in recovery

31. When to test? Before starting controlled substances Clear, well defined boundaries Screening for substance abuse/misuse Difficult to treat pain in setting of underlying addiction Pain contract/treatment agreement Initiation Randomly (1-3/year) Changes in regimen h/o substance misuse does not preclude from appropriate treatment with ant medication when indicated, but deoes require rx plan with firmly defined boundaries Need to document well, indication of treatment and treatment goals.h/o substance misuse does not preclude from appropriate treatment with ant medication when indicated, but deoes require rx plan with firmly defined boundaries Need to document well, indication of treatment and treatment goals.

32. Key Points Urine is preferred biologic sample �Universal� approach Be familiar with tests you order Anticipate results Oxycodone typically not detected by UDS Specific tests needed methadone/fentanyl Use drug testing results in conjunction with other clinical information

33. References Urine Drug Screening: Practical Guide for Clinicians. KE Moeller et al. Mayo Clin. Proc. 2008;83(1)66-76 Urine Drug testing in clinical practice: Dispelling Myths and Designing Strategies. www.familydocs.org/files/UDTmonograph.pdf 2009 SGIM Workshop materials on chronic pain management. www.paineducation.vcu.org