10/16/2017. Objectives. Drug Testing Interpretation in Addiction Care. Background. Which is Nonadherent?

Transcription

1 Objectives Drug Testing Interpretation in Addiction Care Brandi Puet, Pharm.D. Describe the difference between immunoassay and confirmatory testing. List explanations for unexpected negative or positive drug testing results. Demonstrate the ability to interpret urine drug testing results through case studies. Background Clinical Scientist and Fellowship Director at a healthcare toxicology laboratory Doctor of Pharmacy Auburn University Postgraduate Training PGY-1 Pharmacy Practice at VA Tennessee Valley Healthcare System (Nashville) PGY-2 Medication Use Safety at Hospital Corporation of America (Nashville) Which is Nonadherent? Patient A Patient B Patient C Rx: none Rx: Suboxone Rx:Methadone EtG: 36,800 ng/ml EtS: None detected Buprenorphine: 69,007 ng/ml Norbuprenorphine: 48 ng/ml Methadone: 209 ng/ml EDDP: <200 ng/ml 1

2 Purpose of Drug Testing Unexpected Negatives Testing Considerations Collection/Specimen Validity? Laboratory method used? Appropriate test ordered? Appropriate threshold? Appropriate markers tested? Drug Stability? Immunoassay Screening, Point-of-Care Testing (POCT) Ability to detect a compound depends on cross-reactivity Advantages: Rapid Less expensive Considerations: Results not confirmed Identifies classes of drugs Qualitative Concerns with false (-) and false (+) Confirmatory GC/MS, LC/MS/MS Identifies compound based on its unique molecular fingerprint Advantages: Identifies specific drug Rules out false positives Identifies drugs/metabolites missed by screen Quantitative Considerations: Testing takes time to complete More training/expertise needed Cost 2

3 Testing Considerations: Immunoassay Methadone Methadone:5-50% Clinical Considerations Disease states? Concomitant medications? Dose/dosing schedule? Route of administration? Specimen type? EDDP: 3-25% False (-) rates reported in literature: 4-60% Baselt, 11 th ed.; Manchikanti, et al. Pain Physician ; Kirsh, et al. J Opioid Manag ; Mikel, et al. Ther Drug Monit ; Pesce, et al. Pain Physician ;Snyder, et al. Pain Physician Urine ph Nutrition Time of last dose Age Weight Medical Conditions Diet Concomitant Medications Time of last void Frequency of use Unexpected Positives Genetics Drug formulation Environment Hydration Specimen Storage 3

4 Unexpected Positives Crossreactivity Immunoassay Drug ingested Unexpected metabolite Contamination Confirmatory Drug impurity Minor metabolite Unexpected Positives: Cross-reactivity Immunoassay False Positive Rates Amphetamines 14-53% Benzodiazepines % Cocaine 0-12% Marijuana % MDMA/Methamphetamine % Methadone 0-45% Opiates 4-34% Oxycodone 2-41% PCP 100% Manchikanti, et al. Pain Physician 2011; 14(2): ; Johnson Davis, et al. 2016; 40: ; Kirsh, et al. J Opioid Manage. 2015; 11(1): Unexpected Positives: Cross-reactivity Unexpected Positives: Cross-reactivity Immunoassay False Positives Amphetamines Amantadine Aripiprazole Brompheniramine Bupropion Chloroquine Chlorpromazine Ciprofloxacin Desipramine Doxepin Ephedrine Fluorescein Fluoxetine Ginkgo Labetalol MDPV Metformin Methylphenidate Metronidazole Ofloxacin Phentermine Phenylephrine Promethazine Propranolol Pseudoephedrine Ranitidine Selegiline Thioridazine Trazodone Trimethobenzamide Trimipramine Tyramine Immunoassay False Positives Benzodiazepines Buprenorphine Marijuana Chlorpromazine Efavirenz Fenoprofen Codeine Dihydrocodeine Aspirin Baby wash Efavirenz Flurbiprofen Indomethacin Ketoprofen Morphine Methadone Hemp products NSAIDs PPIs Oxaprozin Sertraline Tolmetin Tramadol Rifampin Tolmetin 4

5 Unexpected Positives: Cross-reactivity Unexpected Positives: Metabolism IA False Positive 3A4 2D6 Norcodeine Codeine Morphine Methadone Opiates Phencyclidine Chlorpromazine Clomipramine Diphenhydramine Dextromethorphan Diphenhydramine Doxylamine Naloxone Dextromethorphan Diphenhydramine Doxylamine Ibuprofen Imipramine Doxylamine Olanzapine Quetiapine Pentazocine Quinine Quinolones Ranitidine Ketamine Lamotrigine MDPV Meperidine Thioridazine Tapentadol Thioridazine Verapamil Rifampin Tolmetin Verapamil Tramadol Venlafaxine O-desmethylvenlafaxine Norhydrocodone Noroxycodone 3A4 3A4 (minor) Hydrocodone Dihydrocodeine Oxycodone 2D6 2D6 (minor) Hydromorphone Oxymorphone Unexpected Positives: Pharmaceutical Impurities Unexpected Positives: Pharmaceutical Impurities Prescription Drug Pharmaceutical Impurities Allowable Limit (%) Typical Observed (%) Codeine Morphine Hydrocodone Codeine Hydromorphone Morphine Hydrocodone Morphine Codeine Oxycodone Hydrocodone Oxymorphone Hydromorphone Oxycodone Haddox et al. Poster: American Academy of Pain Medicine; February 2010; San Antonio, TX. 5

6 Heroin Positives Benzodiazepine Interpretation Benzodiazepine Interpretation Methamphetamine Interpretation No Yes Amphetamine (Adderall ) Methamphetamine (Desoxyn ) Dextroamphetamine (Dexedrine ) Benzphetamine Lisdexamfetamine (Vyvanse ) Selegiline (Eldepryl, EMSAM ) Phentermine (Adipex-P, Qsymia ) OTC Levmetamfetamine Vapoinhaler Pseudoephedrine (Sudafed ) Illicit Methamphetamine 6

7 Methamphetamine: Illegal in the Mirror D-methamphetamine: Stimulant, more commonly abused L-methamphetamine: Less stimulant, not as commonly abused D-Predominant Methamphetamine (Desoxyn ) % D (aka 0-5% L) C-II for treatment of ADHD, obesity Benzphetamine % D (aka 0-5% L) C-III for treatment of obesity, metabolizes to d-methamphetamine Illicit Methamphetamine (common) 0-100% D Image source: L-Predominant Selegiline (Eldepryl, EMSAM ) 0-5% D (aka % L) Rx for treatment of Parkinson disease or major depression Metabolizes to l-methamphetamine Levmetamfetamine (OTC vapoinhaler) 0-5% D (aka % L) OTC for congestion Illicit Methamphetamine (rare) 0-100% D D/L Isomer Interpretation 0% 5% 95% 100% 1. Selegiline 2. OTC Vapoinhaler 3. Illicit Meth (rare) D-Isomer Percentage 1. Illicit Meth 2. Selegiline or OTC vapoinhaler AND Methamphetamine Rx or Benzphetamine 1. Methamphetamine Rx 2. Benzphetamine 3. Illicit Meth 7

8 Unexpected Positives: Drug Present (Confirm) Unexpected Sources Amphetamine Dextroamphetamine (Dexedrine ) Lisdexamfetamine (Vyvanse ) Benzodiazepines Designer benzos Cocaine Coca tea Topical pharmaceutical cocaine (inpatient) Codeine Pharm impurity in morphine (up to 0.5%) Schedule V cough suppressants Poppy seeds (morphine more predominant) Heroin (morphine more predominant) Unexpected Positives: Drug Present (Confirm) Unexpected Sources Cotinine Nicotine replacement products Ethyl Glucuronide/ Ethyl Sulfate Post-collection fermentation (diabetes) Alcohol-containing medications Autobrewery syndrome (very rare) Electronic cigarette use Excessive hand sanitizer use Ingestion of baker s yeast with sugar Ingestion of large amounts of grape juice Ingestion of large amounts of nonalcoholic beer/wine Fentanyl Counterfeit pills sold on street (such as oxycodone) Contaminant of heroin products Audience Participation Unexpected Positives: Drug Present (Confirm) Unexpected Sources Hydrocodone Minor metabolite of codeine Pharmaceutical impurity in oxycodone (up to 1%) Prescription cough suppressants (e.g. Tussionex ) Hydromorphone Minor metabolite of morphine Metabolite of hydrocodone Marijuana Dronabinol (Marinol ) Hemp Cannibidiol products Morphine Metabolite of codeine Poppy seeds Heroin 8

9 Marijuana Period of Detection Carboxy-THC Serial Excretion Ratios 1.5 x 0.5 x Schwilke study Goodwin, et al. J Anal Toxicol. 2008; 32(8): Schwilke, et al. Addiction. 2011; 106(3): Case Studies Case Study #1 No Metabolites (Rx: Diazepam, Fentanyl, Oxycodone) Urine Oral Fluid 9

10 Case Study #2: Reuse? Case Study #2: Reuse? Date of Collection Carboxy- THC (ng/ml) Cr (mg/dl) CTHC/Cr x 100 (ng/mg Cr) Ratio 10/4/ /2/17 <20 77 N/A N/A 9/28/ /27/ /22/ /20/ N/A Case Study #3: Illicit or Not? (Rx: Methadone) Case Study #4: Illicit or Not? (Rx: Oxycodone PRN) 10

11 Case Study #5: How Many Drugs Ingested? (Rx: Buprenorphine, Alprazolam) Case Study #6: Consistent Results? (Rx: Alprazolam, Methadone) Case Study #7: Drugs Ingested? (Rx: Oxycodone) Case Study #8: Consistent Results? (Rx: Amphetamine, Gabapentin, Suboxone) Drug/Metabolite Concentration (ng/ml) Codeine 256 Norcodeine 118 Morphine 61,100 Hydromorphone 636 Oxycodone 430 Oxymorphone 1,350 Noroxycodone 231 Drug/Metabolite Buprenorphine Norbuprenorphine Naloxone Amphetamine Gabapentin Concentration 179 ng/ml 359 ng/ml 222 ng/ml 46,800 ng/ml 198 mcg/ml 11

12 Which is Nonadherent? Patient A Patient B Patient C Rx: none Rx: Suboxone Rx:Methadone EtG: 36,800 ng/ml EtS: None detected Buprenorphine: 69,007 ng/ml Norbuprenorphine: 48 ng/ml Methadone: 209 ng/ml EDDP: <200 ng/ml Urine ph Nutrition Time of last dose Age Weight Medical Conditions Diet Concomitant Medications Time of last void Frequency of use Genetics Drug formulation Environment Hydration Specimen Storage Questions? Brandi Puet, Pharm.D. brandi.puet@aegislabs.com