Urine Drug Testing - What Do the Results Mean and What Do I Tell the Patient? Andrea Trescot, MD, FIPP

Urine Drug Testing - What Do the Results Mean and What Do I Tell the Patient? Andrea Trescot, MD, FIPP

Disclosure Andrea Trescot, MD, FIPP Pain and Headache Center Eagle River, AK President, Alaska Society of Interventional Pain Physicians Medical Director: Pinnacle Lab Services Urine toxicology and genetic testing

Objectives In this lecture, we will discuss: Why do we test? Who do we test? When do we test? How do we test? What are the ethical issues involving testing? What do I ask the patient? What do I tell the patient?

Actual Patient Current Medication List DURAGESIC 100 mg q3d days, 10, Ref: 0 METHADONE 10 mg 1 tid days, 90, Ref: 0 OXYCONTIN 20 mg 1 bid 30 days, 50, Ref: 0 OXYCODONE 5 mg 2-4 tabs qid days, 196, Ref: 0 OXYCODONE/APAP 10/325 1-2 tabs qid prn, 240, Ref: 0 LORCET 10/500 1 prn, 60 Ref: 0 ALPRAZOLAM 5 mg 1 bid days, 60, Ref: 0 KLONOPIN 0.5 mg 1 tid days, 90, Ref: 0 CARISOPRODOL 350 mg 1-2 tabs tid days, 180, Ref: 0 AMBIEN 10 mg ½-1 hs prn, 30, Ref: 0 BACLOFEN 10 mg 1 tid days, 90, Ref: 0 LIDODERM 5% 700 mg 1-3 pat days, 60 Ref: 0 DICYCLOMINE 20 mg 1 qid prn, 30, Ref: 0 POTASSIUM 20 meq 2 qd days, 60, Ref: 0 AXERT 12.5 mg days, 12, Ref: 4 FLONASE 2 puffs qhs days, 1, Ref: 5 UDT: Positive for Cocaine and Marijuana Negative for ALL Controlled Substances listed above Courtesy of: Dr. Manchikanti

Urine Drug Testing in Clinical Practice Why do we test? To evaluate patients To support assessment & diagnosis To monitor adherence To identify use of undisclosed substances To be a patient advocate To uncover diversion Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Urine Drug Testing To confirm the medicines prescribed are present Depends on timing and absorbsion To identify the presence of medicines not prescribed Need to understand the metabolism of these medicines Toxicology confirmation No different than following HbA1C for diabetes, LFTs and cholesterol levels for statins, or blood pressure for anti-hypertensives

Federally Regulated Urine Drug Testing Most established use of urine testing Federal Five marijuana (THC) cocaine (benzoylecgonine) opiates phencyclidine (PCP) amphetamine/methamphetamine Mandated cutoff concentrations too high to be of value in clinical practice Requirements of federally regulated testing not always applicable to clinical practice Shults TF. Medical Review Officer Handbook. 8th ed. 2002. Strategies [monograph]. 2004. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing

Typical Detection Times for Urine Testing of Common Drugs of Abuse Drug Detection Test in Urine Cutoff Level (ng/ml) Morphine 1 to 3 days (2 wks) 300 Methadone 2 to 4 days ( 2 wks) 300 Hydrocodone 2 to 4 days ( 2 wks) 50,000 Oxycodone 2 to 4 days ( 2 wks) 100 Benzodiazepines Up to 30 days 300 Barbiturates (short-acting) 2 to 4 days 300 Barbiturates (long-acting) Up to 30 days 300 Marijuana (chronic use) Up to 30 days 50 Cocaine (benzoylecgonine-cocaine metabolite) 1 to 3 days 300 Amphetamine or methamphetamine 2 to 4 days 1000 Note that detection times can vary considerably, depending upon acute versus chronic use, the particular drug used within a class, individual characteristics of the patient, and the method used to test for a substance.

Urine Drug Testing in Clinical Practice Who do we test? New patients already on controlled substances Any patient for whom you are considering prescribing controlled substances Patients who are resistant to full evaluation Patients who display aberrant behavior Patients in recovery Patients who request a specific drug(s) Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

All of my patients take their medication as prescribed BMC Health Services: 32% of patients in primary care practice committed opioid misuse. Negative for prescribed opioid Positive for controlled substances not prescribed Multiple prescribers (doctor shopping) Diversion of opioids Prescription forgery Cocaine and/or amphetamines in urine (40%) Timothy J. Ives, etal. BMC Health Services Research 2006

Urine Drug Testing in Clinical Practice When do we test? Considering controlled substances treatment Making major treatment changes Support decision to refer Treatment agreements Any aberrant drug-related behavior Third-party reports about aberrant drug-related behaviors (family, friends, insurers, law enforcement, etc) Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Urine Drug Testing in Clinical Practice How do we test? Hair Blood Alcohol blood levels Saliva No point of service, no metabolites Urine Easy, less invasive Point of service is available Metabolite analysis is available

Urine Drug Testing - UDS vs UDT Urine drug screening (UDS) Point of service (POS) or point of care (POC) Immunoassay Rapid, inexpensive Table top analyzer Chromotographic Laboratory Qualitative (positive or negative), no metabolites Multiple drug interactions

Qualitative Testing

Initial Drug Test Methods EIA: Enzyme Immunoassay KIMS: Kinetic Interaction Microparticulates in Solution CEDIA: Cloned Enzyme Donor Immunoassay FPIA : Fluorescence Polarization Immunoassay RIA: Radioimmunoassay ELISA: Microplate Enzyme-Linked Immunosorbent TLC: Thin-Layer Chromatography Baxter 2003

Urine Drug Testing - UDS vs UDT Urine drug toxicology (UDT) Quantitative evaluation Gas chromatography (GC), or mass spectrophotometry (MS) Metabolites Very accurate

Quantitative Testing/Toxicology No lower limit allows for reporting of results below a standard cut off Trough levels Evaluated metabolites and potential drugdrug interactions Can correlate with patient symptoms Identifies pill scraping Very expensive

POC vs GC/LC/MS Urine toxicology takes time, and POC is instant

UDT Performance Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques, and utility. Pain Physician 2008;11:S155-180

Interpretation of Urine Testing Results Patient has taken drug Positive result True positive Patient has not taken drug False positive Negative result False negative True negative Wolff K, et al. Addiction. 1999;94:1279-1298. Haddox 2005

Pitfalls of Urine Drug Screening Detection of a particular drug by a drug-class specific immunoassay depends on The structural similarity of that drug or its metabolites to the reference drug The urine concentration of that drug The ability of the assay to detect semisynthetic/synthetic opioids differs among the various assays

Opiate Screens Most semisynthetic & synthetic opioids not reliably detected by commonly used screens Natural (from opium) codeine morphine thebaine Semisynthetic (opium-derived) hydrocodone oxycodone hydromorphone oxymorphone buprenorphine Synthetic (man-made) meperidine fentanyl sufentanil propoxyphene methadone Shults TF. Medical Review Officer Handbook. 8th ed. 2002.

Interpretation of Urine Drug Testing Results Requires that you know How specimen is collected What is prescribed Metabolism of drugs Alternative medical explanations Scams Laws, regulations, & guidelines

Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid analgesia. Pharmgenomics Pers Med. 2012;5:73-87.

Codeine Codeine is metabolized by CYP2D6 to its active metabolite - Morphine

Morphine Morphine is metabolized by UGT2B7 to M6G (analgesic) and M3G (hyperalgic)

Hydrocodone CYP2D6 CYP3A4

Oxycodone Oxycodone is metabolized by CYP2D6 to its active metabolite - oxycodone

Oxycodone Oxycodone is metabolized by CYP3A4 to its inactive metabolite - noroxymorphone

Tramadol Tramadol is metabolized by CYP2D6 to its active metabolite O- desmethyltramadol

Fentanyl Fentanyl is metabolized by CYP3A4 to its inactive metabolite - norfentanyl

1901 Any recent cough medication?

Heroin Heroin 6-MAM

Methadone is metabolized by CYP3A4 to the inactive EDDP. Secondary metabolism by 2B6, 2D6

Diazepam

THC -- Marijuana

THC Testing Marinol (A synthetic THC) is prescribed for nausea and weight gain- tests positive Casamet ( a synthetic cannabinoid) is marketed in Canada, tests NEGATIVE Sativex (also Canada) contains THC will test positive. CBD (now available OTC) may or may not contain THC depends on the source (marijuana vs hemp)

Poppy Seeds Causing Morphine?

UDS Cross Reactions Manchikanti L et al. Monitoring opioid adherence in chronic pain patients: tool, techniques, and utility. Pain Physician 2008;11:S155-180

Additional Methadone False Positives Verapamil (Calan ) Doxylamine (Unisom ) Cyamemazine (Tercian ) Alimemazine (Nedeltran ) Levomepromazine (Nozinan ) Thiordazine (Mellaril ) Olanzapine (Zyprexia ) Lancelin F et al. False positive results in the detection of methadone in urines of patients treated with psychotropic substances. Clinical Chem 2005;51:2176-2177

UDT PCP Cross Reaction Roche DAT Handbook 1.1

UDT THC Cross Reaction Roche DAT Handbook 1.1

Amphetamine

Medical Explanations for Positive Results: Amphetamine/Methamphetamine Prescription medication Adderall Cross-reaction with structurally similar prescription drugs for Parkinson s disease & OTC diet agents & decongestants dopamine, isoxsuprine, ephedrine, phenmetrazine, phentermine, fenfluramine, mephentermine Drugs metabolized to amphetamine/ methamphetamine Selegiline (for Parkinson s), benzphetamine, dimethylamphetamine, fenproporex Shults TF. Medical Review Officer Handbook. 8th ed. 2002.

Screen and Confirm

Urine Results Reported as None Detected May mean any of following Patient Does not use drug Has not recently used drug Excretes drug/metabolite faster than normal Peak and trough levels Urine testing used was not sufficiently sensitive to detect drug at concentration present Ask for no threshold testing (GCMS) Clerical error (wrong sample) In adherence testing, may raise concerns about misuse/diversion Wolff K, et al. Addiction. 1999;94:1279-98. Gourlay DL, et al. Urine Drug Testing in Clinical Practice: Dispelling the Myths & Designing Strategies [monograph]. 2004.

Common Errors of Interpretation Patient taking hydrocodone Urine screen for opiates is listed as morphine ; result reported as positive Patient accused of not adhering to treatment plan & discharged GC/MS confirms hydrocodone & hydromorphone Solution: understand POC testing Explaination: Some cups label opiates as morphine Added by Jordan Haddox 2005

Common Errors of Interpretation Patient taking oxycodone Urine screen for opiates reported as none detected GC/MS not performed Patient accused of not adhering to treatment plan & discharged Solution: order GC/MS GC/MS=gas chromatography/mass spectrometry Von Seggern RL, et al. Headache. 2004;44:44-7.

OXYCODONE The Federal Five screen does NOT include oxycodone Standard POCT immunoassay will NOT reliably detect oxycodone under the OPIATE group Specialized oxycodone immunooassay now available

Urine Toxicology - Metabolites

Urine Toxicology - Stopped Taking Meds

Methadone and Buprenorphine

Other Testable Drugs

Urine Drug Testing in Clinical Practice What are the ethical issues involved in urine drug testing?

Ethical Perspectives A false-negative or false-positive result can have a significant impact on a patient s access to pain management. Prescribing physicians should always be cognizant of the limitations that urine drug screens present. The results of these tests should not be used in isolation to diagnose addiction nor should they dictate management decisions without clinical context.

Ethical Perspectives The most common scenarios faced when interpreting urine drug test results are 1) the urine sample is positive for prescribed drugs and negative for all other prescribed or illicit drugs 2) the urine sample is positive for illicits or nonprescribed opioids 3) the urine sample is negative for the prescribed opioids 4) the urine is negative for the prescribed opioids and positive for ilicits

Ethical Perspectives The immense magnitude of the revenue streams associated with drug screens may potentially influence prescribing physicians to routinely incorporate screening into their practice. Diagnostic laboratories have benefited from the growth in urine screens with revenues purported to have surpassed $2 billion in 2013

Pain Physicians, and Testing Labs, Have Been at the Center of the Increase in Urine Testing Medicare data demonstrates that the total number of drug tests reimbursed at physicians offices increased from 101 tests performed in 2000 to over 3.2 million in 2009

Urine Testing Costs are Increasing and Threatening Access

Fraud Comes at a Steep Price

Random Testing vs Routine Testing No evidence to support either First visit, any unexpected problems, dose escalation, early refill request, periodic. Patients at higher risk for abuse might require more frequent screening. Screening consistently helps to normalize the routine nature of providing a specimen. It makes the request less awkward during an encounter that is complicated by subversion and otherwise warrants a UA.

How Often is Enough but Not Too Much? Some specialists recommend 3 random screens (POC) within the first 12 15 months of therapy and once annually afterwards Owen GT, Burton AW, Schade CM, Passik S. Urine drug testing: Current recommendations and best practices. Pain Physician 2012; 15:ES119-E133. However, that does not assess pill scraping and adulterated urines

Deception Techniques

How Often is Enough but Not Too Much? Consider intermittent toxicology Initial assessment When medications stop working With red flags Medical necessity How will this change your treatment?

My Meds Stopped Working

Drug-Drug Interactions

Diagnostic Dilemmas MSER 120mg TID Oxycodone 30mg q 4 hrs pain score 9/10 Morphine > 6400 Norhydrocodone 36 Hydromorphone 57 Oxycodone >6400 Noroxycodone >6400 Oxymorphone 148

Morphine With Hydromorphone

Drug Impurities

Urine Drug Testing in Clinical Practice What do we ask the patient? How well is the medication working? How long before you notice an an effect? How much relief do you get? % improvement How long does it last? This helps to create a dose/response curve

toxicity analgesia 6 8 12 18 24

Other Things to Ask What is going to be in your urine today? Establishes trust and allows for on-the-spot counseling Tell me about how you are taking the medication Tell me about times that you miss or don t take the medication Tell me about how you secure the medication and who has access to it.

Urine Drug Testing in Clinical Practice What do we tell the patient? If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids. If no metabolites, confront the patient (I offer a 30 second amnesty tell me the truth, and there will not be any consequences) If no active metabolites, consider changing medications

Diagnostic Dilemmas MSER 120mg TID Oxycodone 30mg q 4 hrs pain score 9/10 Morphine > 6400 Norhydrocodone 36 Hydromorphone 57 Oxycodone >6400 Noroxycodone >6400 Oxymorphone 148

Morphine >64000

Urine Drug Testing in Clinical Practice What do we tell the patient? If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids. If no metabolites, confront the patient (I offer a 30 second amnesty tell me the truth, and there will less consequences) If no active metabolites, consider changing medications

No Metabolites

What Do You Do Now? Discuss why they adulterated the urine. Consider the risk of continued opioid prescribing. Closer monitoring Consider buprenorphine Based on the therapeutic relationship, an alternative to immediate discharge may be referring the patient to an addiction specialist. A cry for help

Urine Drug Testing in Clinical Practice What do we tell the patient? If levels (and metabolites) are high, and yet patient denies relief, discuss opioid hyperalgia and begin wean of opioids. If no metabolites, confront the patient (I offer a 30 second amnesty tell me the truth, and there will be less consequences) If no or low active metabolites, consider changing medications

Diagnostic Dilemmas MSER 120mg TID Oxycodone 30mg q 4 hrs pain score 9/10 Morphine > 6400 Norhydrocodone 36 Hydromorphone 57 Oxycodone >6400 Noroxycodone >6400 Oxymorphone 148 Changed to oxymorphone

Alcohol Toxicology A Chance to Discuss

Acc VTA FCX AMYG VP ABN Raphé LC GLU GABA ENK OPIOID GABA GABA GABA DYN 5HT 5HT 5HT NE HIPP PAG RETIC To dorsal horn END DA GLU Opiates ICSS Amphetamine Cocaine Opiates Cannabinoids Phencyclidine Ketamine Opiates Ethanol Barbiturates Benzodiazepines Nicotine Cannabinoids OPIOID HYPOTHAL LAT-TEG BNST NE CRF OFT

I would suggest quantitative UDT

(or UDT)

Consider addiction referral/discharge

Continue opioids Nonopioid treatment Addictionology referral Discharge

Their Conclusion

Summary: Before You Order a UDT Ask patient Are you taking any prescribed, OTC, or herbal drugs? When was last dose? Quantity? Drug misuse/addiction history Let laboratory know what you are looking for Illicit substance Prescription drug misuse Presence of prescribed medication

Summary Give the patient the benefit of the doubt Minimize doubt through education and collaboration, but understand that drug testing remains an evolving field and there are several aspects (specific metabolites, metabolite concentrations, metabolite ratios, assay limitations, interferences) that are incompletely understood.

Summary (continued) False accusations of abuse or diversion are unacceptable and may impact the patients ability to receive appropriate present and future care. The diseases of abuse and addiction are chronic and often progressive, and are rarely (if ever) made on the basis of a urine drug test. Place drug testing data in the context of the total clinical picture.

Summary - Continued Finally, have an action plan. What will you do with the results? Depending on the situation, this may entail no special action; close observation; challenges to change behavior; tightening of treatment boundaries; consultation with an addiction medicine specialist; or referral to a drug treatment center. Reisfield G. Pitfalls in urine drug test interpretation. The Pain Practitioner 2009;19(3):16-24

Thank you! Andrea Trescot DrTrescot@gmail.com