Urine Drug Testing to Monitor Opioid Use In Managing Chronic Pain
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1 Faculty Disclosure Henry C. Nipper, PhD, DABCC Dr. Nipper has listed no financial interest/arrangement that would be considered a conflict of interest. Urine Drug Testing to Monitor Opioid Use In Managing Chronic Pain Henry C. Nipper, Ph.D., DABCC Professor of Pathology Creighton University School of Medicine March 9,
2 Who Gets Tested? For non-cancer pain patients on opioids, perform UDT: When starting a new patient in your practice When medications or dosages are changed When behavior or appearance is unusual (suspicious) When patient requests specific medications Randomly and/or periodically Opiates: Questions. Is my patient taking the drugs I have prescribed according to directions? 2
3 Opiates: Case 1 47 year-old male with history of chronic back pain Prescribed high dose Oxycontin Urine screen is negative for Opiate class Is the patient taking his Oxycontin? What else do you need to know? Case 1 Dose and Specimen Information Dosage: 20 mg/day for three weeks Last dose at 11 AM on Tuesday Specimen collected 8 AM on Wednesday Also taking gabapentin, ibuprofen, citalopram, omeprazole Half-life of Oxycontin: hrs. Detection window in urine: 1-3 days Does this information change your answer? What other question(s) do you have for the lab? 3
4 Some Facts About Urine Drug Screens Urine is outside the body not in equilibrium with the drugs in circulation. The level (concentration) of a drug or metabolite in urine depends on: The absolute amount of drug (metabolite) excreted. The state of hydration of the person in question. (Remember the drug result is keyed against or reported as ng/ml. A drug or metabolite that is present in the urine is not an indication of the effective concentration of the drug in the patient s body. Therefore a positive UDS cannot and should not be used to infer impairment from that drug. A positive UDS indicates that the drug was likely used in the past. All positive UDS screening results should be confirmed prior to definitive action being taken on the results. DAU Panel History Originally devised for workplace to determine who had used scheduled or illicit drugs. Replaced older, less specific and less sensitive tests Cutoffs for +/- were originally based on limit of detection of the test. Cutoffs are set by a quantitative calibrator, and may vary from lab to lab. Some antibodies used in common screens are highly analytically specific and some will respond to several drugs in the class. Most older panels used in hospitals and clinics are not optimized to follow pain clinic patients. 4
5 Drug Classes in Hospital and DAU Panels Typical Classes in Urine Panels: Amphetamines Opiates Benzodiazepines Cocaine Barbiturates Methadone Phencyclidine (PCP) Marijuana (THC) Oxycodone Hydrocodone Available from the CHI Labs: NIDA-5 (Or DS-8*) Cannabinoids Opiates Amphetamines PCP Cocaine (Alcohol*) (Barbiturate*) (Benzodiazepines*) Confirmation of + only on physician order as add-on. No reflex to confirmation or quantification. No separate tests for Oxycodone, Hydrocodone, Methadone or Fentanyl. Question 2: My patient is prescribed Tylenol #3 daily. Which of the following should be detected in urine? Codeine only Codeine and Morphine Heroin 6-Monoacetyl morphine 5
6 Question 3: The following are likely reasons for a negative urine opiate screen in a patient on opioid therapy: a) Patient used all of her supply of the drug and has not taken any for a few days. b) Patient is a fast metabolizer c) Drug screen does not detect that particular opioid d) Patient sold her opioids and has been using another drug for pain. e) Any of the above. Windows of Detection in Urine Drug Amphetamines Barbiturates Benzodiazepines Cocaine (as Benzoyl ecognine metabolite) Methadone (EDDP) Opiates (morphine, codeine) Oxycodone Phencyclidine Heroin Metabolite (6-AM) Ethanol THC (as THC-COOH metabolite) Drug Detection Window (Urine) 2-4 days 1-3 days (Phenobarbital ~ 2 weeks) Up to 2 weeks 2-3 days 2-4 days 2-3 days 1-3 days 3-8 days hrs < 24 hours 1 day to three months (or more) 6
7 Question 4: My patient is taking Oxycontin and is given a urine drug test. He claims to have eaten a poppy-seed coated bagel prior to the office visit. Which of the following might be seen in the urine? Oxycodone Morphine Codeine 6-MAM Oxymorphone Opiate Metabolism 7
8 Testing Technologies Methodology Abbreviation Screen/Confirm Shake-a-cup immunoassays (point of care) POC Screen Radioimmunoassay RIA Screen Enzyme-linked immunosorbent assay ELISA Screen Enzyme-multiplied immunoassay technique EMIT Screen Cloned enzyme donor immunoassay CEDIA Screen Fluorescence polarization immunoassay FPIA Screen High performance liquid chromatography uv detection HPLC-UV Screen +/- Gas chromatography mass spectrometry GC-MS Confirm Liquid chromatography tandem mass spectrometry LC-MS/MS (MS) Screen &/or Confirm Liquid chromatography time-of-flight mass spectrometry LC-TOF Screen &/or Confirm Liquid chromatography high resolution mass spectrometry LC-HRMS Screen &/or Confirm Question 5: Your patient uses Fentanyl patches. He tests negative for opioids on a routine drug screen. You observe that the patch is in place as prescribed. He claims to be faithfully following the instructions. The most appropriate action is: a. Re-collect another urine and send it for a repeat test. b. Replace the Fentanyl Rx with another opiate. c. Refer the patient to de-tox/re-hab or to law enforcement because you suspect he is selling the patches. d. Call the lab and request a comprehensive LS-TOF or LS-Tandem MS confirmation assay for ALL drugs. e. Call the lab and request a specific screening assay for Fentanyl. 8
9 Opiates: Question2 Is my patient taking other drugs (prescribed or not prescribed) instead of or in addition to the opiates prescribed? Opiates Case 2 38 year-old female on Vicodin (hydrocodone) for chronic pain. UDT screen for opiates positive. On confirmation, concentrations of hydromorphone AND hydrocodone are reported. Is the patient also taking Dilaudid (hydromorphone)? 9
10 Opiate Metabolism Redux Screening For Opiates: Not All Assays are =! Older assays have antibodies directed at morphine and codeine (The better to find heroin addicts in the Armed Forces in Nam.) If you are looking for assays to pick up oxycodone and hydrocodone, specific assays are best. In the next slide: Cross reactivity is listed as 100% for morphine. Other drugs responses are measured relative to morphine. 10
11 Opiate Screening Cross Reactivity: % Response What About Methadone? Not detected by conventional opiates UDS. Separate immunoassay used - but it is very specific for methadone and/or EDDP metabolite. If you use a NIDA-5 or DS-8 at CHI you will not get a test for methadone, so it may have to be specifically ordered just as oxycodone, hydrocodone and fentanyl. Sometimes patients will substitute methadone for oxycodone but you know that! When that happens, opiate should be negative, and methadone +! 11
12 Possible Strategies for Opiate Class Testing: 1. Immunoassay Screening for DAU with add/on Confirmation 2. Immunoassay Screening Panel with additional specific testing for Oxycodone and for Hydrocodone with add/on Confirmation of positive screens 3. 1 or 2 with reflex Confirmation of positive screens 4. Use of a specific Pain Panel which includes both methods and also quantification of the opiates found (if any) 5. Keep in mind that most hospital and local labs do not have Mass Spectrometers, so delay may be at least overnight to 2-3 days. 12
13 Unexpected Lab Result.Why? 13
14 An Overview Of Using LC TOF. In Conclusion: Physician, know thy laboratory and speak with them often. Seek to strategize about false positive screens and false negative screens those unexpected results. Remember that immunoassays vary from vendor to vendor, but none is perfect. In confirmations, also try to understand the meaning of a quantitative result. In looking for opiates, broaden your peripheral vision. 14
15 Thank You! References: With thanks to ARUP s website for the diagrams and videos, and Kara Lynch, PhD, DABCC for her online PowerPoint on the topic. Reisfield GM, et al. Family Physicians Proficiency in Urine Drug Test Interpretation. J Opioid Manag 2007; Nov-Dec;3(6):333-7 Melanson SEF, et al. Optimizing Urine Drug Testing for Monitoring Medication Compliance in Pain Management. Pain Medicine 2013; 14; Reisfield GM, et al. Rational Use and Interpretation of Urine Drug Testing in Chronic Opioid Therapy. Annals of Clinical & Laboratory Science 2007; 37(4)
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