Urine Drug Screening. Dr. Patricia Mark November 24, 2012

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1 Urine Drug Screening Dr. Patricia Mark November 24, 2012

2 Basics Urine drug screening must always be discussed with patients ahead of time. It is part of the physician/ patient agreement which all patients on MMP sign All patients must be treated the same way, and always with respect UDS is not a means of punishing rather, it is a tool to help best management

3 Why? To ensure that prescribers can help and support MMP patients to begin recovery and achieve stability Provides objective evidence of compliance with the treatment plan Are patients taking medications as prescribed? Are patients using illicit substances? Adjust treatment plans if necessary to work towards best outcomes for patients on opioids for opioid addiction or chronic pain.

4 Why? UDS is only one of several ways in which physicians can assess patients stability Careful history taking Frequent reassessment Contact with pharmacist Collateral information

5 Value of self-reporting of noncompliance Can be significantly unreliable in patients suffering from addiction disorders If UDS is found to be discordant with history of medications: Review medical records Review PharmaNet Collateral information from significant others

6 How? Urine specimens produced at office visits before physician encounter Supervised collection: bags, jackets, hoodies all left outside bathroom. Patient given labelled specimen container Urine temperature tested immediately Specific gravity checked if indicated Witnessed collection: seldom done, as an invasion of patient privacy; may sometimes be necessary

7 How? Enzyme Immunoassay (EIA) Specific anti-drug antibody added to urine. If that drug is present, antibody binds to drug giving a measurable indicator reaction as positive MMP protocol uses methadone metabolite, opioid, cocaine, benzo and methamphetamine screens

8 How? Gas chromatography Mass spectroscopy GC separates and quantifies drug components. MS specifically identifies them. Gold standard of urine toxicology but expensive Each test is about $40

9 When? Collected at every clinic visit may not necessarily be tested Random samples collected at varying intervals every 3 or 4 months and tested Random UDS is preferable and more valuable and should be used for all patients with methadone carries

10 Which opioids show up in UDS? Metabolites of: Heroin Morphine Codeine shows as morphine which is a metabolite of codeine Reliably detected on regular EIA testing

Heroin Metabolizes to diacetyl morphine and then to 6-monoacetyl morphine (6-MAM) These metabolites easily detected in standard opioid EIA testing from the 300 mg/ml level for up to 2 days

11 Heroin Metabolizes to diacetyl morphine and then to 6-monoacetyl morphine (6-MAM) These metabolites easily detected in standard opioid EIA testing from the 300 mg/ml level for up to 2 days after a single IV or inhaled heroin dose 6-MAM metabolite is unique to heroin, exceptionally useful forensic tool. Detectable only up to 12 hours post-use, after which metabolizes to morphine

12 Morphine Presence of morphine in UDS can indicate use of heroin, morphine, codeine or poppy seeds Urine from heroin users typically contains substantial quantities of morphine and smaller quantities of codeine reflecting poppy fluid contents Dividing morphine levels by codeine levels yields a valuable ratio. Morphine: codeine ratio of more than 2:1 as determined by GCMS is corroborative evidence of heroin use

13 Codeine Nearly identical to morphine in structure Easily detected by opioid EIA testing Metabolizes to morphine thus placing patients at risk of being identified as abusing morphine Morphine: codeine ratio of less than 2:1 in codeine use Greater than 2:1 suggests morphine, heroin or poppy seed use

14 Drugs of interest to methadone prescribers: oxycodone Is a semi-synthetic opioid, shows up in only about 10% positive tests There is a specific EIA for oxycodone that is reliable Problems associated with oxycodone screening include false negatives for patients for whom oxycodone has been prescribed

15 Drugs of interest to methadone prescribers: oxycodone Rapid metabolizers on oxycodone may also show negative UDS as urine levels are too low GCMS may be necessary to confirm presence or absence of oxycodone

16 Other synthetic opioids: fentanyl Wholly synthetic and does not react with EIA morphine antibody. Needs either a specific EIA or GCMS to confirm presence or absence. Patients who are on fentanyl and show positive for opioids WHICH IS NOT POSSIBLE using standard tests are abusing other opioids which react with the standard EIA testing.

17 Methadone Is a wholly synthetic opioid which does not show up on standard testing. Needs a specific EIA for methadone metabolites which is virtually 100% sensitive. All UDS kits, whether point-of-care testing or in labs, use the specific EIA for methadone metabolites to eliminate possibility of adulteration with methadone.

18 Hydromorphone Is a semi-synthetic opioid which may or may not show up on routine UDS with standard opioid EIA testing but more likely to show up if very high dosing Will require GCMS or specific EIA to confirm presence or absence

19 Buprenorphine Is a semi-synthetic morphine-based molecule which has been so altered that does not show up on standard opioid EIA testing Specific and highly reliable EIA tests available in labs and in point-of-care test kits

20 Other confounding variables Poppy seed from the opium poppy Papaver Somniferum contains small amounts of morphine and codeine Baked goods with poppy seeds are widely available Consumption of one poppy seed Danish streusel pastry can easily produce positive opioid EIA tests Positive UDS can last for 24 hours

21 Poppy seeds Morphine:codeine ratio in poppy seed ingestion is also 2:1 or greater, consistent with opium poppy fluid as the opiate source of heroin and poppy seeds Difficult to determine whether opioid-positive EIA is due to poppy seed or heroin use High levels of morphine more likely to be heroin but may be misleading Advise patients to avoid baked goods with poppy seeds

22 Fluoroquinolones Can also produce positive-opioid EIAs Is correlated to peak levels. In one study, urine collected at 6 8 hours after fluoroquinolone ingestion was 100% (false) positive for opioids Essentially unknown why fluoroquinolones have this effect If a true false positive, GCMS will demonstrate no opioid present

23 Benzodiazepines Always monitored by UDS, as are contraindicated for patients on the MMP EIA for benzos is based on the diazepam antibody Shows reliably positive test for diazepam and alprazolam Most diazepam EIAs do not detect clonazepam or lorazepam GCMS is needed to identify both these benzos

24 Urine detection time frame Methadone 4 5 days Opioids 2 3 days Cocaine/metabolites 2 4 days Benzodiazepines 1 42 days THC single use 2 3 days THC habitual use up to 12 weeks Methamphetamine 3 5 days Alcohol 6 24 hours

25 Other exceptions Z drugs zopiclone and zaleplon are not detected in spite of the fact that they metabolize down to benzos Chloral hydrate not detected seldom now prescribed except on occasions in hospital

26 Sertraline Patients on sertaline may produce intermittent false positive benzo EIA specimens Due to a metabolite of sertraline Chemical structure of sertraline and its metabolite bear a striking resemblance to diazepam which is the likely cause of false positive reactions GCMS needed, if necessary, to determine the presence of absence of specific benzos

27 UDS interpretation What shows in UDS is important What doesn t show in UDS is equally important: Methadone metabolites Benzos Synthetic and semi-synthetic opioids

28 Limitations of UDS Assesses the presence or absence of a particular drug and/or metabolite at a specific threshold of concentration at a specific time Unexpected result does not diagnose Abuse or addiction Physical dependence Diversion Does not provide accurate information on Time of last use Amount and frequency of use

29 Potential harms of UDS Incorrect interpretation of UDS could result in: Unwarranted discontinuation of opioids Damage to physician/patient relationship If very unexpected result, especially with POC testing, always get laboratory confirmation Potential for false reassurance Adulteration/cheating Alteration of behaviour in anticipation of UDS, hence need for random UDS

30 Consequences of dirty urine drug screens Always review results of UDS with patient UDS result one of many factors taken into account when making clinical decisions Review physician/patient agreement Review treatment plan Increase frequency of office visits Methadone dose if opioid-positive: is it appropriate? May have to discontinue carries in the face of instability Increase counselling and other support services

31 Conclusion Urine drug screening is an important part of the comprehensive care of patients who are on MMP or are receiving opioids for chronic pain and must be undertaken in a respectful, nonjudgmental manner Should be considered as an objective test within the greater biopsychosocial context Should always be interpreted in the context of broad based clinical care of the individual patient

32 Reference: Tenore PL. Advanced urine toxicology testing. Journal of Addictive Diseases Oct; 29(4): THANK YOU

Urine Drug Testing Methadone 101 Methadone for hospitalists

Urine Drug Testing Methadone 101 Methadone for hospitalists Dr. Patricia Mark MB, BCh LEARNING OBJECTIVES Clarify the purpose of urine drug testing Distinguish between UDT for detection of illicit drug