Upload
others
View
0
Download
0
Embed Size (px)
Citation preview
Interpretation Of Urine
Drug Testing Results For
Pain Management
Alec Saitman, PhD, DABCC (CC, TC)
Director of Special Chemistry and Toxicology
Providence Regional Laboratories
The Intent Of The Session
Provide an introductory overview of structured drug
interpretation
Didactic lecture
Discuss typical and atypical case examples
And how to interpret them
Panel member discussion in real time
Requirements Before Any
Drug Interpretation
Technical knowledge of drug screening methodologies
If applicable
Screening cutoffs
Known interferences
Technical knowledge of confirmation methodologies
What parent drugs and metabolites are tested
Whether drugs are hydrolyzed or not prior to testing
Requirements Before Any
Drug Interpretation
All chromatographic data is:
Thoroughly reviewed by trained staff
Free of any chromatographic interferents
An updated medication list is available
Knowledge of prescribed medications
Parent drugs contained within them
At what dose
At what frequency
Requirements Before Any
Drug Interpretation
Ability to interpret use of illicit/non-prescribed drugs
Heroin
Methamphetamine/Amphetamine
Cocaine
Barbiturates
THC
PCP
Kratom
Pain management populations at high risk for illicit drug abuse
Drug testing for illicit use is typical
Requirements Before Any
Drug Interpretation
Thorough understanding of metabolism patterns of
drugs tested
Drug
Drug
Metabolite
Metabolite
Structured Method For Proper
Drug Testing Interpretation
Step 1
Identify all expected results
Using medication list
Knowledge of parent drugs and metabolites tested
Example: Mr. Smith prescribed methadone only
Possible expected results are
Methadone and EDDP (metabolite)
Methadone EDDP
Structured Method For Proper
Drug Testing Interpretation
Step 2
Identify all observed results
Using final confirmation data for particular drug collection
Example: Mr. Smith is positive for
Methadone
EDDP
Oxycodone
Noroxycodone
Oxymorphone
Structured Method For Proper
Drug Testing Interpretation
Step 3
Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Example: “Mr. Smith is not compliant with medications
prescribed.”
Structured Method For Proper
Drug Testing Interpretation
Step 4
Provide explanation/interpretation of decision
Explain any and all discrepancies observed for this testing
Note all parent drugs and metabolites which should have existed but
do not
Note all parent drugs and metabolites which should not have existed
but do
Be concise
Recommend using templates to maintain consistency
Structured Method For Proper
Drug Testing Interpretation
Example: “Mr. Smith was found to be positive for methadone and
its metabolite EDDP indicating the use of a drug containing
methadone. Mr. Smith was also found to be positive for oxycodone
along with its metabolites noroxycodone and oxymorphone. This
pattern indicates the use of a drug containing oxycodone.
Although the presence of methadone and EDDP is expected, the
presence of oxycodone and its metabolites is inconsistent with
the medications prescribed”
Many Times, Unexpected Drug
Results Exist That Can
Complicate Interpretation
What are these circumstances?
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
Pharmaceutical Impurities
May Be Present
Commercial Active
Pharmaceutical
Ingredient (API)
Process
Impurities
Allowable
Limit (%)
Typical
Observed (%)
Morphine Codeine 0.5 0.01-0.05
Codeine Morphine 0.15 0.01-0.1
Hydrocodone Codeine 0.15 0-0.1
HydromorphoneMorphine
Hydrocodone
0.15
0.1
0-0.025
0-0.025
Oxycodone Hydrocodone 1 0.02-0.12
OxymorphoneHydrocodone
Oxycodone
0.15
0.5
0.03-0.1
0.05-0.4
Pharmaceutical Impurities
May Be Present
Very common when main drug is found in high
concentrations (>5,000 ng/mL)
Allowable pharmaceutical limits can guide interpreters
as to whether there is an impurity or co-use
Pharmaceutical Impurities
May Be Present
Example: Sample contained 7,983 ng/mL Oxycodone
But also contained 23 ng/mL Hydrocodone
0.29% < 1.0 % allowable impurity limit
Likely pharmaceutical impurity and not co-use
Pharmaceutical Impurities
May Be Present
Example: Sample contained 8,247 ng/mL Oxycodone
But also contained 169 ng/mL hydrocodone
2.0 % >1.0% allowable impurity limit
Likely co-use and not pharmaceutical impurity
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
Up to 80% of drugs are metabolized by CYP enzymes
Drug
Drug
Metabolite
Metabolite
CYPCYP
CYP
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
CYP2C19
8%
CYP1A2
11%
CYP2C8/9
16%CYP2D6
19%
CYP3A4/5
36%
CYP2E1
4%
CYP2B6
3% CYP2A6
3%
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
Germline Variants
Slow Metabolizers
Intermediate Metabolizers
Rapid Metabolizers (Normal Metabolizers)
Ultra-rapid Metabolizers
Inhibitors and Inducers
Co-use of pharmaceutical drugs
Consumption of Food-Based Biologicals
Ex. Grapefruit Juice can inhibit CYP3A4 metabolism
Drug Metabolite
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
CYP2D6CYP3A4
Hydrocodone
1,549 ng/mL
Norhydrocodone
1,939 ng/mL
Hydromorphone
34 ng/mL
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
CYP2D6CYP3A4
Hydrocodone
1,549 ng/mL
Norhydrocodone
1,939 ng/mL
Hydromorphone
<10 ng/mL
Impact On CYP450 Deficiencies
And Co-Use Of Drug Inhibitors.
CYP2D6CYP3A4
* In my lab, 38% of patients with both hydrocodone and
norhydrocodone >500 ng/mL did not have a hydromorphone
>10 ng/mL.
HydrocodoneNorhydrocodone Hydromorphone
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
Diversion Tactics And What To
Look For
Diversion is not taking a prescribed drug when one
should be
Selling drugs
Hoarding drugs
Forgetting to take drugs
Masking diversion by adding drug directly to urine
Diversion Tactics And What To
Look For
Example 1
Oxycodone 2,934 ng/mL
Noroxycodone 3,145 ng/mL
Oxymorphone 157 ng/mL
Example 2
Oxycodone 6,800 ng/mL
Noroxycodone <10 ng/mL
Oxymorphone <10 ng/mL
How do we know this is not a error or inhibition in metabolism?
Diversion Tactics And What To
Look For
Example 1
Oxycodone 2,934 ng/mL
Noroxycodone 3,145 ng/mL
Oxymorphone 157 ng/mL
Example 2
Oxycodone 6,800 ng/mL
Noroxycodone <10 ng/mL
Oxymorphone <10 ng/mL
Look at past drug results. Did they have typical drug metabolism patterns?
Diversion Tactics And What To
Look For
Example 1
Buprenorphine 835 ng/mL
Norbuprenorphine 674 ng/mL
Naloxone <100 ng/mL
Is this diversion?
Example 2
Buprenorphine 2,835 ng/mL
Norbuprenorphine 16 ng/mL
Naloxone 3601 ng/mL
Is this diversion?
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
Detection Windows
Detection windows
“My patient claims they took XX tablets of XX drug XX days
ago but the sample is screened and/or confirmed
negative. Is that possible?”
“My patient claims they haven’t used XX drug of since XX
days ago but the sample is screened and/or confirmed
positive. Is that possible?”
Drug Metabolite(s)Detection Window
(Days)
HydrocodoneNorhydrocodone
Hydromorphone1-4
Hydromorphone N/A 1-4
CodeineMorphine
Hydrocodone1-4
Morphine Hydromophone 1-4
OxycodoneNoroxycodone
Oxymorphone1-4
Oxymorphone N/A 1-4
Buprenorphine Norbuprenorphine 1-6
Fentanyl Norfentanyl 1-4
Methadone EDDP 1-5
Detection Windows
Know your common detection windows for the drugs you
analyze
Know that detection windows have many variables
Use caution with providing strong-worded interpretation
on detection windows
Ex. “Based on the presence of the metabolite for
oxycodone, the patient has likely ingested a drug
containing oxycodone in the last 1-4 days”
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
False Negative Drug
Screening May Have Occurred
Many drug screening algorithms only reflex presumptive
positive results
False negative results common for particular
benzodiazepines prescribed
Clonazepam and sometimes Lorazepam
Why Do Some Screens Not
Pick Up Benzodiazepines?
Oxazepam Clonazepam 7-amino
clonazepam
Many screening
antibodies are
raised against
Why Do Some Screens Not
Pick Up Benzodiazepines?
Oxazepam Clonazepam 7-amino
clonazepam
This prescribed
benzodiazepine
extensively
metabolizes to
Why Do Some Screens Not
Pick Up Benzodiazepines?
Oxazepam Clonazepam 7-amino
clonazepam
This metabolite which is
structurally too dissimilar
to oxazepam to be
detected reliably
1. Pharmaceutical Impurities
2. Metabolism Abnormalities
3. Diversion Tactics
4. Drug Detection Windows
5. False Negative Drug Screening
6. False Positive Drug Screening
False Positive Drug Screening
May Have Occurred
“My patient screened positive for methamphetamine
but confirmed negative. What caused the false
positive?”
False Positive Drug Screening
May Have Occurred
“My patient screened positive for methamphetamine
but confirmed negative. What caused the false
positive?”
Serotonin Norepinephrine
Dopamine
Other Frequently Asked
Questions From Providers
Positive because of passive exposure
“My patient claims they were in an apartment where
others were using cocaine and that is why they are
confirmed positive at 7,305 ng/mL.”
“Is this possible?”
Other Medication causing positive confirmed illicit drug
“My patient claims they took Tylenol 3 (from a friend) and
that is why they are positive for heroin metabolite at 348
ng/mL”
“Is this possible”
Moving Into Case Presentations
All further discussions are based off of real cases
Some data may have been altered for demonstration
purposes
Case Study 1Presented by: Alec Saitman PhD, DABCC (CC, TC)
Director of Toxicology and Special Chemistry
Providence Regional Laboratories, Portland, OR
Case Study 1-Background
Patient and History
35 y/o female
Persistent pain following a MVA 3 years prior
Current Medications
Percocet®
(oxycodone and acetaminophen 5/325 mg 2X daily)
Case Study 1-Results
Screened positive for oxycodone
By IA at 100 ng/mL oxycodone cut-off
Confirmed for
Oxycodone at 738 ng/mL
Noroxycodone at 984 ng/mL
Oxymorphone at 24 ng/mL
Case Study 1-Panel Discussion
Step 1: Identify all expected results
Step 2: Identify all observed results
Step 3: Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Step 4: Provide explanation/interpretation of decision
Case 1- Final Interpretation
Case Study 2Presented by: Deborah French Ph.D., DABCC (CC, TC), FAACC
Assistant Director of Chemistry and Director of Mass Spectrometry
at the University of California San Francisco Medical Center
Case Study 2-Background
Patient and History
71 y/o male
Depression
Hypertension
Persistent pain
Current Medications
Norco®
(hydrocodone and acetaminophen 5/325 mg 4 times daily)
Zestril®
(Lisinopril 5 mg daily)
Wellbutrin®
(bupropion 150 mg daily)
Case Study 2-Results
Screened positive for opiates
By IA at 300 ng/mL Opiates cut-off
Confirmed for
Hydrocodone at 76,254 ng/mL
Norhydrocodone at 84,528 ng/mL
Hydromorphone at 5,402 ng/mL
Oxycodone at 68 ng/mL
Noroxycodone at 76 ng/mL
Oxymorphone at < 10 ng/mL
Case Study 2-Panel Discussion
Step 1: Identify all expected results
Step 2: Identify all observed results
Step 3: Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Step 4: Provide explanation/interpretation of decision
Case 2- Final Interpretation
Case Study 3Presented by: Deborah French Ph.D., DABCC (CC, TC), FAACC
Assistant Director of Chemistry and Director of Mass Spectrometry
at the University of California San Francisco Medical Center
Case Study 3-Background
Patient and History
46 y/o female
Anxiety
Persistent pain
Current Medications
Norco®
(hydrocodone and acetaminophen 10/325 mg 4 times daily)
Xanax®
(Alprazolam 1 mg daily)
Case Study 3-Results Screened positive for opiates only
By IA at 300 ng/mL opiates cut-off
Confirmed for
Hydrocodone at 70,906 ng/mL
Norhydrocodone at <10 ng/mL
Hydromorphone at <10 ng/mL
Oxycodone at 206 ng/mL
Noroxycodone at <10 ng/mL
Oxymorphone at < 10 ng/mL
Directly analyzed for
Alprazolam at <10 ng/mL
a-hydroxy alprazolam at <10 ng/mL
Case Study 3-Panel Discussion
Step 1: Identify all expected results
Step 2: Identify all observed results
Step 3: Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Step 4: Provide explanation/interpretation of decision
Case 3- Final Interpretation
Case Study 4Presented by: Amadeo Pesce Ph.D. DABCC
Professor in the Department of Pathology and Laboratory Medicine, University of California, San Diego, School of Medicine
Laboratory Director Precision Diagnostics LLC, San Diego
Case Study 4-Background
Patient and History
55 y/o male
Depression
Persistent pain
Current Medications
Tylenol 3®
(Tylenol and acetaminophen 15/300 mg 4 times daily)
Prozac®
(Fluoxetine 40 mg daily)
Case Study 4-Results
Screened positive for opiates
By IA at 300 ng/mL opiates cut-off
Confirmed for
Codeine at 2,150 ng/mL
Morphine at <10 ng/mL
Hydrocodone <10 ng/mL
Norhydrocodone at 150 ng/mL
Hydromorphone at <10 ng/mL
Case Study 4-Panel Discussion
Step 1: Identify all expected results
Step 2: Identify all observed results
Step 3: Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Step 4: Provide explanation/interpretation of decision
Case 4- Final Interpretation
Case Study 5Presented by: Frederick G. Strathmann, PhD, MBA, DABCC (CC, TC)
Vice President of Quality Assurance, Director of New Technology and
Innovation, and Assistant Laboratory Director, NMS Labs, Horsham, PA
Case Study 5-Background
Patient and History
61 y/o male
Persistent pain
In addiction treatment
Current Medications
Suboxone®
(Buprenorphine and naloxone 4/1 mg daily)
Case Study 5-Results
Screened negative for all drug components
Confirmed for
Buprenorphine at 142 ng/mL
Norbuprenorphine at 186 ng/mL
Buprenorphine glucuronide at 368 ng/mL
Naloxone at <100 ng/mL
Oxycodone at <10 ng/mL
Noroxycodone at <10 ng/mL
Oxymorphone at <10 ng/mL
Noroxymorphone at 65 ng/mL
Previous collections revealed similar patterns
Case Study 5-Panel Discussion
Step 1: Identify all expected results
Step 2: Identify all observed results
Step 3: Identify whether the patient is
Compliant with medications prescribed
Not Compliant with medication prescribed.
Step 4: Provide explanation/interpretation of decision
Nornaloxone = Noroxymorphone!
noroxymorphone | nornaloxone
noroxycodone
oxymorphone
naloxone
oxycodone
Final Interpretation
Questions For The Panel?