Urine Drug Screen in Chronic Opiate Therapy

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Urine Drug Screen in Chronic Opiate Therapy

• Analia Castiglioni, MD
• General Internal Medicine Noon Conference
• February 5, 2008

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Objectives

• Review indications for urine drug testing in the
  setting of chronic opiate therapy
• Describe urine drug testing methodology and
  understand limitations of available tests
• Enhance knowledge for correct interpretation of
  drug screening results
• Develop a testing strategy

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Roadmap

• Background
• Case
• Testing methods
• Screening/Immunoassay
• Confirmatory/chromatography
• Interpretation of results
• Drug testing in clinical practice
• Why to test
• Whom to test
• When to test
• Develop a testing strategy

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Prescription drug abuse

• Epidemic numbers (2004)
• 15 million (94 increase in a decade)
• combined cocaine/hallucinoges/inhalants/heroin
• Oxycontin, Ritalin, Valium 4th most abused
• Following marijuana, alcohol and tobacco
• Concomitant Illicit drug use
• 34 on controlled substances
• 15 w/o controlled substances

National Center for Addiction and Substance Abuse
(CASA) report, 2005
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Chronic non-malignant pain (CNMP) management

• Opioids accepted approach for CNMP
• Data supports efficacy
• Long/short acting formulations
• Risks
• abuse and diversion
• Use of other illicit substances
• Random drug testing for adherence and presence of
  illicit drugs is common practice

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Case 1

• 54 yo AA male to re-establish PC
• Would like refill of chronic pain meds
• Admits recent heroin relapse, has appt in OSAC
• PMHx
• Chronic back pain
• Headaches
• Head trauma/sz disorder
• CKD, HTN
• Hep C
• Heroin abuse/relapse for 20 yrs
• SocHx on disability, lives with wife. Denies
  ETOH/tobacco

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Case 1

• Medications
• Methadone 40mg BID, 60mg qhs (420/mo)
• Tylenol 4 1 po QID prn (120/mo)
• Celexa, divalproex ER, dilantin, verapamil, HCTZ
• NKDA
• PE alert, slurred speech, multiple healed track
  marks on upper and lower extremities

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Case 1 Lab results

• UDS
• Barbiturate NEG
• Opiates POS
• Cocaine NEG
• Cannab NEG
• BZD POS

• Methadone (serum)
• 50ng/ml (cutt-off 50ng/ml)
• Opioid panel (urine)
• Oxycodone NEG
• Hydrocodone NEG
• Morphine 10000ng/ml
• Hydromorphone 240ng/ml
• Codeine 680ng/ml

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Drug screening in clinical practice

• Not real screening
• Only limited number of drugs
• Different tests needed depending clinical
  scenario
• Urine preferred biologic sample
• Parent drug or metabolite(s)
• Long window of detection (1-3 days)
• Non-invasive, low cost
• Drugs in serum have short ½ life (4-6 hours)

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Relative detection of drugs in various biologic
specimens
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Drug Testing methods Immunoassay

• Antibody mediated
• Qualitative, or -
• Fast, 1-multiple drugs
• POC or laboratory based
• Disadvantages
• Cross-reactivity
• Detection cut-offs vary

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Drug Testing methods Chromatography

• Gas (GC/MS) or liquid (HPLC)
• Lab-based, drug-specific
• Quantitative
• Applications
• Confirmation of screening
• Detection of other drugs not included in
  immunoassay

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Pros and Cons of Testing Methods
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Urine Drug Screen (UDS)

• Class-specific immunassay
• does not detect specific drugs
• or result
• High sensitivity (false are common)
• Vary per institution/lab and manufacturer
• Cross-reactivity, cutoffs, etc
• All results should be confirmed by more
  specific method (GC/MS)

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Urine Drug Screen (UDS)

• VA and UAB laboratories
• Barbiturates
• Opiates
• Marijuana
• 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

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Interpretation of UDS results

• Sensitivity vs Specificity
• Cross-reactivity
• High (amphetamines) vs low (cocaine)
• Limited for semi-synthetic/synthetic opioids
• Drug vs metabolite
• Drug metabolite concentrations

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Factors Affecting Drug Detection
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Sources of Opioid Analgesics
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UDS Interpretation Opiates

• Opiates
• Morphine
• Hydrocodone (lortab)
• Heroin
• Codeine
• Cross reactivity
• Poppy seeds
• Fluoroquinolones
• Amitriptyline

• Opiates
• True negative
• False negative
• Methadone
• Fentanyl
• Oxycodone

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Opiate Metabolism
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UDS Interpretation Opiates

• Synthetic opioids
• Most immunoassays wont reliable detect synthetic
  or semisynthetic opioids
• GC/MS can detect most
• Metabolites
• Minor amounts of metabolites, should not be
  interpreted as drug misuse (hydrocodone and
  hydromorphone)
• At no time should a metabolite be in excess of
  its parent

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UDS Interpretation

• Cocaine
• Deliberate use
• Amphetamine/Methamphetamine
• OTC products (Vicks), decongestants, diet
  products, selegiline
• d-l isomer distinction
• Benzodiazepines
• Variable cross-reactivity
• Clonazepam usually NOT detected

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UDS Interpretation Negative Results

• Usually a good thing!
• Except if adherence is an issue
• Negative drug level below detection threshold
• Diversion
• Bingeing
• Timing of sample
• Time of last use and quantity taken is helpful
• Order a more sensitive test if clinically
  indicated
• Sample validity (PH, temp, specific gravity, UCr)

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Back to case 1

• UDS
• Barbiturate NEG
• Opiates POS
• Cocaine NEG
• Cannab NEG
• BZD POS

• Methadone (serum)
• 50ng/ml (cutt-off 50ng/ml)
• Opioid panel (urine)
• Oxycodone NEG
• Hydrocodone NEG
• Morphine 10000ng/ml
• Hydromorphone 240ng/ml
• Codeine 680ng/ml

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Why test?

• Identify use of undisclosed substances
• Monitor adherence/uncover diversion
• Patient advocacy

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Whom to test?

• All pts on chronic opioid therapy!
• New pts already on narcotics
• Pts resistant to full evaluation
• Aberrant behavior
• Pseudo-addiction poor controlled pain
• Request a specific drug
• Pts in recovery

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When to test?

• Before starting a controlled substance
• Screening for substance abuse/misuse
• h/o abuse does not preclude use of narcotics
• Need well defined boundaries, close monitoring
• Pain contract/treatment agreement
• Initiation
• Randomly
• Changes in regimen
• Clearly understood and well defined boundaries

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Testing Strategy
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Key Points

• Urine is preferred biologic sample
• Adopt Universal approach
• Be familiar with your labs testing
  characteristics and communicate with them
• Order the right test depending on patient
• Use drug testing results in conjunction with
  other clinical information

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Cabo Polonio, Uruguay 2007