01/01/ years INCONSISTENT RESULTS - REPORTED MEDICATION NOT DETECTED (NEITHER PARENT DRUG NOR METABOLITE) REPORTED PRESCRIPTION

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1 Drug Adherence Assessment Report CleanAssure TM (DRIED BLOOD SPOT): Detection Range see NOTES. Prescribed Medications: ASPIRIN, BACLOFEN (LIORESAL, GABLOFEN), WARFARIN (COUMADIN), QUETIAPINE (SEROQUEL), OMEPRAZOLE (PRILOSEC, ZEGERID), TOLTERODINE (DETROL), FUROSEMIDE (LASIX), VITAMIN B1 (Thiamine), METOPROLOL (LOPRESSOR), FLUTICASONE (FLONASE), VITAMIN D2 (Ergocalciferol), CYCLOBENZAPRINE (FLEXERIL), PAROXETINE (PAXIL, PEXEVA) CONSISTENT RESULTS - REPORTED MEDICATION DETECTED (PARENT DRUG AND/OR METABOLITE) REPORTED PRESCRIPTION FLAG ANTICIPATED POSITIVE(S) TEST OUTCOME DETECTION WINDOW WARFARIN (COUMADIN) Warfarin Positive Plasma Half-Life: hours QUETIAPINE (SEROQUEL) Quetiapine Negative Plasma Half-Life: 6-7 hours QUETIAPINE (SEROQUEL) Norquetiapine Positive Plasma Half-Life: 7-12 hours FUROSEMIDE (LASIX) Furosemide Positive Plasma Half-Life: 4-10 hours METOPROLOL (LOPRESSOR) Metoprolol Positive Plasma Half-Life: 3-4 hours METOPROLOL (LOPRESSOR) Alpha-hydroxymetoprolol Positive Plasma Half-Life: 3-4 hours PAROXETINE (PAXIL, PEXEVA) Paroxetine Positive Plasma Half-Life: 21 hours INCONSISTENT RESULTS - REPORTED MEDICATION NOT DETECTED (NEITHER PARENT DRUG NOR METABOLITE) REPORTED PRESCRIPTION FLAG ANTICIPATED POSITIVE(S) TEST OUTCOME DETECTION WINDOW BACLOFEN (LIORESAL, GABLOFEN) Baclofen Negative Plasma Half-Life: 3-4 hrs CYCLOBENZAPRINE (FLEXERIL) Cyclobenzaprine Negative Plasma Half-Life: 8-37 hours OMEPRAZOLE (PRILOSEC, ZEGERID) Omeprazole Negative Plasma Half-Life: 1 hour OMEPRAZOLE (PRILOSEC, ZEGERID) Omeprazole Acid Negative Plasma Half-Life: 1 hour INCONSISTENT RESULTS - ANALYTE DETECTED BUT NO CORESPONDING PRESCRIPTION REPORTED REPORTED PRESCRIPTION FLAG ILLICIT MEASURED RESULT CUTOFF TEST OUTCOME DETECTION WINDOW Ranitidine No Positive Plasma Half-Life: 2-3 hours Acetaminophen No Positive Plasma Half-Life: 2-3 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 ASPIRIN, FLUTICASONE (FLONASE), TOLTERODINE (DETROL), VITAMIN B1 (Thiamine), VITAMIN D2 (Ergocalciferol) Page: 1 of 15

2 ADDITIONAL DETECTED ANALYTES ACETAMINOPHEN (TYLENOL, MAPAP), CAFFEINE (CAFCIT, ALERT), RANITIDINE (ZANTAC) Drug-Drug Interactions PAROXETINE (PAXIL, PEXEVA) & WARFARIN (COUMADIN) Concurrent use of selected anticoagulants and SSRIs or SNRIs may increase the risk for bleeding. WARFARIN (COUMADIN) & ASPIRIN SERIOUS SERIOUS The concurrent use of anticoagulants and salicylates leads to blockade of two distinct coagulation pathways and may increase the risk for bleeding. ACETAMINOPHEN (TYLENOL, MAPAP) & WARFARIN (COUMADIN) MODERATE Concurrent use of routine acetaminophen, especially at dosages greater than 2 grams/day, and coumarin anticoagulants may result in elevated anticoagulant effects. CYCLOBENZAPRINE (FLEXERIL) & PAROXETINE (PAXIL, PEXEVA) MODERATE Concurrent administration of fluoxetine or paroxetine with selected cyclic agents which are metabolized by CYP2D6 or CYP2C19 may result in an increase in serum levels, toxicities(e.g. risk for seizures, severe anticholinergic effect), and/or clinical effects of the tricyclic agent or trazodone.clomipramine, desipramine, imipramine, nortriptyline, and trimipramine are classified by CredibleMeds(3) as possible QT prolonging agents. Increased serum levels of these tricyclic agents may increase the risk for torsades de pointes.concurrent administration of fluoxetine or paroxetine with clomipramine and perhaps with imipramine, cyclobenzaprine or high dose amitriptyline, may increase the risk for serotonin syndrome.cyclic agents included in this monograph are amitriptyline (strengths <= 40 mg), amoxapine, clomipramine (strengths <= 25 mg), cyclobenzaprine (structurally similar to amitriptyline), doxepin (strengths <= 25 mg), imipramine (strengths <= 10 mg), melitracen, nortriptyline (strengths <= 30 mg), protriptyline, trazodone (strengths <= 75 mg), and trimipramine (strengths <= 25 mg). METOPROLOL (LOPRESSOR) & PAROXETINE (PAXIL, PEXEVA) Concurrent use of CYP2D6 inhibitors may result in elevated levels of and toxicity from metoprolol.(1,2) PAROXETINE (PAXIL, PEXEVA) & ASPIRIN MODERATE MODERATE Concurrent use of a selective serotonin reuptake inhibitor(1-7,13) or a serotonin-norepinephrine reuptake inhibitor(8-10) and a NSAID may result in bleeding. Page: 2 of 15

3 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 Positive ng/ml No Inconsistent Result Buprenorphine Negative ng/ml No Butorphanol Negative ng/ml No Codeine Negative ng/ml No Dihydrocodeine Negative ng/ml No EDDP Negative ng/ml No Fentanyl Negative ng/ml No Hydrocodone Negative ng/ml No Hydromorphone Negative ng/ml No Ketamine Negative ng/ml No Levorphanol Negative ng/ml No Meperidine Negative ng/ml No Methadone Negative ng/ml No Morphine Negative ng/ml No N-Desmethyl-Tramadol Negative ng/ml No Norbuprenorphine Negative ng/ml No NorCodeine 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 Page: 3 of 15

4 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 2. CleanAssure BENZODIAZEPINES 6-Hydroxybuspirone Negative ng/ml No 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 Page: 4 of 15

5 3. CleanAssure ANTI-PSYCHOTICS 9-Hydroxyrisperidone Negative ng/ml No Aripiprazole Negative ng/ml No Asenapine Negative ng/ml No Brexpiprazole Negative ng/ml No Chlorpromazine Negative ng/ml No Clozapine Negative ng/ml No Clozapine_N_oxide Negative ng/ml No Dehydro-Aripiprazole Negative ng/ml No Fluphenazine Negative ng/ml No Haloperidol Negative ng/ml No Iloperidone Negative ng/ml No Lurasidone Negative ng/ml No Norquetiapine Positive ng/ml No Olanzapine Negative ng/ml No Perphenazine Negative ng/ml No Quetiapine Negative ng/ml No Risperidone Negative ng/ml No Thioridazine Negative ng/ml No Thiothixene Negative ng/ml No Ziprasidone Negative ng/ml No Page: 5 of 15

6 4. CleanAssure ANTI-DEPRESSANTS / SSRI / SNRI / TCA Amitriptyline Negative ng/ml No Amoxapine 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 Desmethoxyyangonin Negative ng/ml No Dihydrokavain Negative ng/ml No Dihydromethysticin Negative ng/ml No Doxepin Negative ng/ml No Duloxetine Negative ng/ml No Fluoxetine Negative ng/ml No Fluvoxamine Negative ng/ml No Hydroxybupropion Negative ng/ml No Imipramine Negative ng/ml No Methysticin Negative ng/ml No Milnacipran Negative ng/ml No Mirtazapine Negative ng/ml No N-Desmethyl-Clomipramine Negative ng/ml No Nordoxepin Negative ng/ml No Norfluoxetine Negative ng/ml No Normirtazapine Negative ng/ml No Nortriptyline Negative ng/ml No O-Desmethyl-Venlafaxine Negative ng/ml No Paroxetine Positive ng/ml No Sertraline Negative ng/ml No Trazodone Negative ng/ml No Venlafaxine Negative ng/ml No Vilazodone Negative ng/ml No Vortioxetine Negative ng/ml No Yangonin Negative ng/ml No Page: 6 of 15

7 5. CleanAssure DEPRESSANTS Alpha-Hydroxymidazolam Negative ng/ml No Desalkylflurazepam Negative ng/ml No Eszopiclone 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 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 Licarbazepine Negative ng/ml No Oxcarbazepine Negative ng/ml No Phenytoin Negative ng/ml No Pregabalin Negative ng/ml No Primidone Negative ng/ml No Tiagabine Negative ng/ml No Topiramate Negative ng/ml No Valproic Acid Negative ng/ml No Zonisamide Negative ng/ml No 7. CleanAssure MUSCLE RELAXANTS Baclofen Negative ng/ml No Inconsistent Result Carisoprodol Negative ng/ml No Cyclobenzaprine Negative ng/ml No Inconsistent Result Meprobamate Negative ng/ml No Metaxalone Negative ng/ml No Methocarbamol Negative ng/ml No Page: 7 of 15

8 8. CleanAssure STIMULANTS / ADHD Amphetamine Negative ng/ml No Atomoxetine Negative ng/ml No Caffeine Positive ng/ml No Inconsistent Result Ephedrine Negative ng/ml No Guanfacine 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: 8 of 15

9 12. CleanAssure ILLICITS 5-Fluoro-NPB-22 Negative ng/ml Yes 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) Negative ng/ml Yes Page: 9 of 15

10 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 Negative ng/ml No Ethyl Glucuronide (Ethanol) Negative ng/ml No Ethyl Sulfate (Ethanol) Negative ng/ml No 15. CleanAssure ANTI-INFLAMMATORY / NSAIDs Celecoxib Negative ng/ml No Cetirizine Negative ng/ml No Chlorpheniramine Negative ng/ml No Colchicine Negative ng/ml No Desloratadine Negative ng/ml No Diclofenac Negative ng/ml No Diphenhydramine Negative ng/ml No Etodolac Negative ng/ml No Febuxostat Negative ng/ml No Fexofenadine Negative ng/ml No Hydroxychloroquine Negative ng/ml No Hydroxyzine Negative ng/ml No Ibuprofen Negative ng/ml No Indomethacin Negative ng/ml No Loratadine Negative ng/ml No Meloxicam Negative ng/ml No Montelukast Negative ng/ml No Naproxen Negative ng/ml No Olopatadine Negative ng/ml No Oxipurinol Negative ng/ml No Piroxicam Negative ng/ml No Promethazine Negative ng/ml No Sumatriptan Negative ng/ml No Tofacitinib Negative ng/ml No Page: 10 of 15

11 16. CleanAssure CARDIOVASCULAR Acebutolol Negative ng/ml No Alpha-hydroxymetoprolol Positive ng/ml No Amiodarone Negative ng/ml No Amlodipine Negative ng/ml No Apixaban Negative ng/ml No Atenolol Negative ng/ml No Atorvastatin Negative ng/ml No Atorvastatin Lactone Negative ng/ml No Benazepril Negative ng/ml No Bisoprolol Negative ng/ml No Candesartan Negative ng/ml No Candesartan Cilexetil Negative ng/ml No Carvedilol Negative ng/ml No Cilostazol Negative ng/ml No Clopidogrel Negative ng/ml No Dabigatran Negative ng/ml No Diltiazem Negative ng/ml No Dipyridamole Negative ng/ml No Doxazosin Negative ng/ml No Dronedarone Negative ng/ml No Eletriptan Negative ng/ml No Enalaprilat Negative ng/ml No Ezetimibe Negative ng/ml No Fenofibric Acid Negative ng/ml No Flecainide Negative ng/ml No Gemfibrozil Negative ng/ml No Glimepiride Negative ng/ml No Hydrochlorothiazide Negative ng/ml No Irbesartan Negative ng/ml No Labetalol Negative ng/ml No Lisinopril Negative ng/ml No Losartan Negative ng/ml No Metoprolol Positive ng/ml No N-Desethylamiodarone Negative ng/ml No Nadolol Negative ng/ml No Nifedipine Negative ng/ml No Olmesartan Acid Negative ng/ml No Pentoxifylline Negative ng/ml No Page: 11 of 15

12 Propranolol Negative ng/ml No Ranolazine Negative ng/ml No Rivaroxaban Negative ng/ml No Simvastatin Negative ng/ml No Telmisartan Negative ng/ml No Terazosin Negative ng/ml No Ticagrelor Negative ng/ml No Valsartan Negative ng/ml No Verapamil Negative ng/ml No Warfarin Positive ng/ml No 17. CleanAssure ANTIBIOTICS / UTIs Darifenacin Negative ng/ml No Itraconazole Negative ng/ml No Nitrofurantoin Negative ng/ml No 18. CleanAssure GASTROINTESTINAL / DIETARY Biotin Negative ng/ml No Famotidine Negative ng/ml No Hyoscyamine Negative ng/ml No Lansoprazole Negative ng/ml No Metoclopramide Negative ng/ml No Omeprazole Negative ng/ml No Inconsistent Result Omeprazole Acid Negative ng/ml No Inconsistent Result Pantoprazole Negative ng/ml No Ranitidine Positive ng/ml No Inconsistent Result 19. CleanAssure DIABETIC Glipizide Negative ng/ml No Glyburide Negative ng/ml No Linagliptin Negative ng/ml No Metformin Negative ng/ml No Nateglinide Negative ng/ml No Pioglitazone Negative ng/ml No Repaglinide Negative ng/ml No Rosiglitazone Negative ng/ml No Saxagliptin Negative ng/ml No Sitagliptin Negative ng/ml No Page: 12 of 15

13 20. CleanAssure DIURETICS / INCONTINENCE Acetazolamide Negative ng/ml No Alfuzosin Negative ng/ml No Canrenone Negative ng/ml No Chlorothiazide Negative ng/ml No Furosemide Positive ng/ml No Indapamide Negative ng/ml No Solifenacin Negative ng/ml No Torsemide Negative ng/ml No Triamterene Negative ng/ml No 21. CleanAssure PDE (Phosphodiesterase Inhibitors) Sildenafil Negative ng/ml No Tadalafil Negative ng/ml No Vardenafil Negative ng/ml No 22. CleanAssure CORTICOSTEROIDS / HORMONE THERAPY Budesonide Negative ng/ml No Dexamethasone Negative ng/ml No Finasteride Negative ng/ml No Levothyroxine Negative ng/ml No Prednisolone Negative ng/ml No Raloxifene Negative ng/ml No 23. CleanAssure ANTI-NEOPLASTICS / CANCER THERAPY Methotrexate Negative ng/ml No Ondansetron Negative ng/ml No 24. CleanAssure DEMENTIA (Parkinson's/Alzheimer's) Donepezil Negative ng/ml No Rivastigmine Negative ng/ml No Ropinirole Negative ng/ml No Page: 13 of 15

14 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: 14 of 15

15 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. Reviewed By: 07/12/ :57 Date: Page: 15 of 15

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