3703 Camino del Rio South 100-A San Diego, CA, Phone Fax CLIA# 05D years

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1 Drug Adherence Assessment Report CleanAssure TM (DRIED BLOOD SPOT): Detection Range see NOTES. Prescribed Medications: HYDROMORPHONE (DILAUDID, EXALGO), CYCLOBENZAPRINE (FLEXERIL), METHADONE (METHADOSE), MARIJUANA (THC) CONSISTENT RESULTS - REPORTED MEDICATION DETECTED (PARENT DRUG AND/OR METABOLITE) REPORTED PRESCRIPTION FLAG ANTICIPATED POSITIVE(S) TEST OUTCOME DETECTION WINDOW METHADONE (METHADOSE) Methadone Positive Plasma Half-Life: hours METHADONE (METHADOSE) EDDP Negative Plasma Half-Life: hours MARIJUANA (THC) THC (Marijuana metabolite) Positive Plasma Half-Life: 4-12 hours INCONSISTENT RESULTS - REPORTED MEDICATION NOT DETECTED (NEITHER PARENT DRUG NOR METABOLITE) REPORTED PRESCRIPTION FLAG ANTICIPATED POSITIVE(S) TEST OUTCOME DETECTION WINDOW HYDROMORPHONE (DILAUDID, EXALGO) Hydromorphone Negative Plasma Half-Life: hours CYCLOBENZAPRINE (FLEXERIL) Cyclobenzaprine Negative Plasma Half-Life: 8-37 hours INCONSISTENT RESULTS - ANALYTE DETECTED BUT NO CORESPONDING PRESCRIPTION REPORTED REPORTED PRESCRIPTION FLAG ILLICIT MEASURED RESULT CUTOFF TEST OUTCOME DETECTION WINDOW (-)-Cotinine No Positive Plasma Half-Life:10-27 hours Caffeine No Positive Plasma Half-Life: 5-6 hours SPECIMEN VALIDITY TESTING REPORTED PRESCRIPTION N/A TEST OUTCOME MEASURED RESULT REFERENCE RANGE N/A N/A N/A ADDITIONAL MEDICATIONS REPORTED BUT NOT TESTED FOR IN THIS REPORT None Page: 1 of 10

2 CAFFEINE (CAFCIT, ALERT), NICOTINE ADDITIONAL DETECTED ANALYTES Drug-Drug Interactions CYCLOBENZAPRINE (FLEXERIL) & HYDROMORPHONE (DILAUDID, EXALGO) MODERATE Concurrent use of opioids and other CNS depressants, such as muscle relaxants, may result in profound sedation, respiratory depression, coma, and/or death.(1) CYCLOBENZAPRINE (FLEXERIL) & METHADONE (METHADOSE) MODERATE Caution is recommended if methadone is used in combination with other drugs that can prolong the QT interval, particularly in the setting of chronic pain management or methadone maintenance for opioid dependency where high dosages may be employed. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If taking drugs that also cause CNS-depressant or orthostatic effects (e.g., sedating antihistamines, psychotropic drugs like tricyclic antidepressants, phenothiazines, and neuroleptics), patients should be made aware of the possibility of additive effects with methadone and counseled to avoid activities requiring mental alertness until they know how these agents affect them. (1) Krantz MJ, Mehler PS "Synthetic opioids and QT prolongation." Arch Intern Med 163 (2003): 1615; author reply 1615 SYMBOL LEGEND Highly elevated risk for indicated condition or adverse drug reaction. Medication can be prescribed with monitoring; alternative therapy may be needed. Moderately elevated risk for indicated condition or adverse drug reaction. Medication can be prescribed with monitoring; therapy ajustment may be needed. Typical risk for indicated condition or adverse drug reaction. Medication can be prescribed according to standard dosing guidelines. MODERATE Drug interactions of moderate severity. The clinician should assess the patient`s characteristics and take action as needed. SERIOUS Severe drug interaction or contraindicated drug combination which may produces serious consequences in most patients. This drug combination generally should not be dispensed or administered to the same patient. Action is required to reduce risk of severe adverse interaction. 1. CleanAssure NARCOTIC ANALGESICS / OPIATES Acetaminophen Negative ng/ml No Page: 2 of 10

3 Buprenorphine Negative ng/ml No Butorphanol Negative ng/ml No Codeine Negative ng/ml No EDDP Negative ng/ml No Fentanyl Negative ng/ml No Hydrocodone Negative ng/ml No Hydromorphone Negative ng/ml No Inconsistent Result Ketamine Negative ng/ml No Levorphanol Negative ng/ml No Meperidine Negative ng/ml No Methadone Positive ng/ml No Morphine Negative ng/ml No N-Desmethyl-Tramadol Negative ng/ml No Norbuprenorphine Negative ng/ml No Norfentanyl Negative ng/ml No Norhydrocodone Negative ng/ml No Norketamine Negative ng/ml No Noroxycodone Negative ng/ml No Norpropoxyphene Negative ng/ml No O-Desmethyl-Tramadol Negative ng/ml No Oxycodone Negative ng/ml No Oxymorphone Negative ng/ml No Propoxyphene Negative ng/ml No Tapentadol Negative ng/ml No Tramadol Negative ng/ml No Page: 3 of 10

4 2. CleanAssure BENZODIAZEPINES 7-Aminoclonazepam Negative ng/ml No Alpha-hydroxyalprazolam Negative ng/ml No Alpha-Hydroxytriazolam Negative ng/ml No Alprazolam Negative ng/ml No Buspirone Negative ng/ml No Chlordiazepoxide Negative ng/ml No Clobazam Negative ng/ml No Clonazepam Negative ng/ml No Diazepam Negative ng/ml No Estazolam Negative ng/ml No Flunitrazepam Negative ng/ml No Lorazepam Negative ng/ml No N-Desmethyl-Flunitrazepam Negative ng/ml No Norchlordiazepoxide Negative ng/ml No Nordiazepam Negative ng/ml No Oxazepam Negative ng/ml No Prazepam Negative ng/ml No Temazepam Negative ng/ml No Triazolam Negative ng/ml No 3. CleanAssure ANTI-PSYCHOTICS 9-Hydroxyrisperidone Negative ng/ml No Aripiprazole Negative ng/ml No Chlorpromazine Negative ng/ml No Clozapine Negative ng/ml No Clozapine_N_oxide Negative ng/ml No Fluphenazine Negative ng/ml No Haloperidol Negative ng/ml No Olanzapine Negative ng/ml No Quetiapine Negative ng/ml No Risperidone Negative ng/ml No Thioridazine Negative ng/ml No Ziprasidone Negative ng/ml No Page: 4 of 10

5 4. CleanAssure ANTI-DEPRESSANTS / SSRI / SNRI / TCA Amitriptyline Negative ng/ml No Bupropion Negative ng/ml No Citalopram Negative ng/ml No Clomipramine Negative ng/ml No D-L-Kavain Negative ng/ml No Desipramine Negative ng/ml No Dihydrokavain Negative ng/ml No Doxepin Negative ng/ml No Duloxetine Negative ng/ml No Fluoxetine Negative ng/ml No Fluvoxamine Negative ng/ml No Imipramine Negative ng/ml No Mirtazapine Negative ng/ml No N-Desmethyl-Clomipramine Negative ng/ml No Nortriptyline Negative ng/ml No O-Desmethyl-Venlafaxine Negative ng/ml No Paroxetine Negative ng/ml No Sertraline Negative ng/ml No Trazodone Negative ng/ml No Venlafaxine Negative ng/ml No 5. CleanAssure DEPRESSANTS Alpha-Hydroxymidazolam Negative ng/ml No Desalkylflurazepam Negative ng/ml No Flurazepam Negative ng/ml No Midazolam Negative ng/ml No Zaleplon Negative ng/ml No Zolpidem Negative ng/ml No Zopiclone-N-Oxide Negative ng/ml No Page: 5 of 10

6 6. CleanAssure ANTI-CONVULSANTS Dihydro-10- Hydroxycarbamazepine Negative ng/ml No Carbamazepine Negative ng/ml No Gabapentin Negative ng/ml No Lamotrigine Negative ng/ml No Levetiracetam Negative ng/ml No Oxcarbazepine Negative ng/ml No Pregabalin Negative ng/ml No Tiagabine Negative ng/ml No Zonisamide Negative ng/ml No 7. CleanAssure MUSCLE RELAXANTS Baclofen Negative ng/ml No Carisoprodol Negative ng/ml No Cyclobenzaprine Negative ng/ml No Inconsistent Result Meprobamate Negative ng/ml No 8. CleanAssure STIMULANTS / ADHD Amphetamine Negative ng/ml No Caffeine Positive ng/ml No Inconsistent Result Ephedrine Negative ng/ml No Lisdexamfetamine Negative ng/ml No Methylphenidate Negative ng/ml No Ritalinic Acid Negative ng/ml No 9. CleanAssure DECONGESTANTS Dextromethorphan Negative ng/ml No Pseudoephedrine Negative ng/ml No 10. CleanAssure APPETITE STIMULANTS Marinol Negative ng/ml No Phentermine Negative ng/ml No 11. CleanAssure ANTIDOTES Naloxone Negative ng/ml No Naltrexone Negative ng/ml No Page: 6 of 10

7 12. CleanAssure ILLICITS 5-MeO-DMT Negative ng/ml Yes 6-MAM (heroin metabolite) Negative ng/ml Yes 7-HydroxyMitragynine (Kratom) Negative ng/ml Yes AB-FUBINACA Negative ng/ml Yes Acetyl-Fentanyl Negative ng/ml Yes Alpha-PVP Negative ng/ml Yes AM2201 (Spice Cannabinoid) Negative ng/ml Yes Benzoylecgonine Negative ng/ml Yes Carfentanil Negative ng/ml Yes Cocaine Negative ng/ml Yes Didesmethyl-U Negative ng/ml Yes DMT Negative ng/ml Yes FDU-PB-22 Negative ng/ml Yes HU-210 (Spice Cannabinoid) Negative ng/ml Yes JWH-019 (Spice Cannabinoid) Negative ng/ml Yes JWH Hydroxybutyl (Spice Cannabinoid) Negative ng/ml Yes JWH-081 (Spice Cannabinoid) Negative ng/ml Yes JWH-122 (Spice Cannabinoid) Negative ng/ml Yes JWH-18-5-pentanoic acid (Spice Cannabinoid) JWH-18-5-pentanyl (Spice Cannabinoid) JWH-250-5OH-pentanyl (Spice Cannabinoid) Negative ng/ml Yes Negative ng/ml Yes Negative ng/ml Yes MDA Negative ng/ml Yes MDEA Negative ng/ml Yes MDMA Negative ng/ml Yes MDPV Negative ng/ml Yes Methamphetamine Negative ng/ml Yes Methylone Negative ng/ml Yes Mitragynine (Kratom) Negative ng/ml Yes MMB-CHMICA Negative ng/ml Yes N-Desmethyl-U Negative ng/ml Yes PCP Negative ng/ml Yes THC (Marijuana metabolite) Positive ng/ml Yes Page: 7 of 10

8 13. CleanAssure BARBITURATES Amobarbital Negative ng/ml No Butabarbital Negative ng/ml No Butalbital Negative ng/ml No Pentobarbital Negative ng/ml No Phenobarbital Negative ng/ml No Secobarbital Negative ng/ml No 14. CleanAssure DIRECT BIOMARKERS (-)-Cotinine Positive ng/ml No Inconsistent Result Ethyl Glucuronide (Ethanol) Negative ng/ml No Ethyl Sulfate (Ethanol) Negative ng/ml No Page: 8 of 10

9 Historical Result Data Comments: Morphine is a commonly detected metabolite among patients taking Codeine. Hydromorphone is a commonly detected metabolite among patients taking Hydrocodone and Morphine. An active molecule of OPANA, Oxymorphone is a commonly detected metabolite among patients taking Oxycodone. OPANA (Oxymorphone) will not metabolize to Noroxycodone or Oxycodone. Oxazepam is a commonly detected metabolite among patients taking Diazepam, Nor-Diazepam or Temazepam. Temazepam and Nor- Diazepam are commonly detected metabolites among patients taking Diazepam. Alprazolam, Alpha-OH-Alprazolam, Clonazepam, and 7- amino-clonazepam are not detected in patients taking Diazepam, Nor-diazepam, Lorazepam, Oxazepam, and Temazepam. Meprobamate is a commonly detected metabolite among patients taking Carisoprodol and its presence is consistent with the use of Carisoprodol. An active (drug) or metabolite may be listed as a Negative Outcome, however, if either the active or any metabolite(s) are present (Positive), then the result is listed as Consistent for that reported prescribed medication. In dried blood spot specimens (CleanAssure TM DBS) parent drugs are often detected in higher concentrations than the metabolite. Sometimes only the metabolite may be detected in urine specimens and not the parent drug. In case of patients consuming HYDROCODONE-containing medications: Norhydrocodone is the major metabolite of Hydrocodone indicating presence of Hydrocodone in the urine. While Hydrocodone can also be metabolized to Hydromorphone, identification of just Hydromorphone by itself is not a confirmation of Hydrocodone being present, since recent studies suggest that urine specimens of patients taking Hydrocodone always show presence of Hydrocodone or Norhydrocodone in combination with Hydromorphone. FOR PATIENT RESULTS INDICATING JUST THE PRESENCE OF HYDROMORPHONE: THIS MAY BE DERIVED FROM MORPHINE- CONTAINING PRESCRIPTION DRUGS OR HYDROMORPHONE-ONLY PRESCRIPTIONS (FOR EXAMPLE, DILAUDID). Further reading: Valtier,S. and Bebarta,V.S. (2012) Excretion profile of hydrocodone, hydromorphone and norhydrocodone in urine following single dose administration of hydrocodone to healthy volunteers. J. Anal. Toxicol., 36, and Barakat,N.H., Atayee,R.S., Best,B.M. and Ma,J.D. (2014) Observations of Urinary Hydrocodone and Metabolite Distributions in Pain Patients. J. Anal. Toxicol., 38, ) Page: 9 of 10

10 REFERENCES for DRUG-DRUG-INTERACTIONS are available upon request. Notes: Specimen collected by CleanAssure TM : Dried Blood Spot Mitra TM Microsampling. This procedure is to determine the presence and concentration of prescription/non-prescription drugs from dried blood spots collected using Mitra TM Microsampling devices by finger pricks. This method and associated validation is intended for patient compliance testing only (i.e. determination of the presence or absence and concentrations of prescribed and illicit drugs in dried blood spots) and is not validated for therapeutic drug monitoring (TDM) of drug plasma levels. Detection ranges may be reduced (compound-specific) versus urine toxicology test results. Mitra TM Microsampling devices improve patient comfort and increase operational efficiencies. THC- Tetrahydrocannabinol - was observed. Reviewed By: 07/17/ :30 Date: Page: 10 of 10

3703 Camino del Rio South 100-A San Diego, CA, Phone Fax CLIA# 05D Director: David J.

3703 Camino del Rio South 100-A San Diego, CA, Phone Fax CLIA# 05D Director: David J. Drug Adherence Assessment Report Prescribed Medications: NO MEDICATION LIST PROVIDED CONSISTENT RESULTS - REPORTED MEDICATION DETECTED (PARENT DRUG AND/OR METABOLITE) REPORTED PRESCRIPTION FLAG ANTICIPATED