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CYP2C9 Master Drug List Warfarin Celecoxib Ibuprofen Meloxicam Diclofenac Naproxen Glyburide Glipizide Tolbutamide Glimepiride Phenytoin Fluvastatin Rosuvastatin Losartan Coumadin Celebrex Advil, Motrin Mobic Cataflam, Voltaren XR Aleve Diabeta Glucotrol Orinase Amaryl Dilantin Lescol Crestor Cozaar LAB NOTES CYP2C9 is a liver enzyme that metabolizes approximately 10% of all drugs, including warfarin, phenytoin, non-steroidal anti-inflammatory drugs (NSAIDs), and antihyperglycemic sulphonylureas. Detecting variants of the CYP2C9 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of CYP2C9 substrates. Roughly 3% of the population are 2C9 Poor Metabolizers (PMs), meaning they have no 2C9 enzymatic activity. Another 36% of the population are considered Intermediate Metabolizers (IMs) with decreased activity. Both IMs and PMs exhibit decreased metabolic activity, which puts them at risk for side effects to drugs normally inactivated by 2C9. With respect to warfarin, 2C9 deficiency can lead to increased bleeding risk, decreased dose requirement, and a longer time to reach stable therapy. The combination of CYP2C9 genotyping with VKORC1 - the target of warfarin’s effect – and with patient physical characteristics can accurately estimate a patient’s warfarin sensitivity level, dose requirement, and ultimately provide practitioners with better guidance for optimal INR interpretation and management. PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories CYP2C19 Master Drug List CYP2C19 Clopidogrel** Citalopram Escitalopram Imipramine Sertraline Diazepam Omeprazole Esomeprazole Pantoprazole Rabeprazole Lansoprazole Nelfinavir Methadone (active portion) Carisoprodol** Voriconazole Plavix Celexa Lexapro, various Tofranil Zoloft Valium Prilosec Nexium Protonix Aciphex Prevacid Viracept Various brands Soma Vfend **indicates prodrug LAB NOTES CYP2C19 is a liver enzyme responsible for metabolizing 10-15% of medications, including clopidogrel, proton pump inhibitors, and many antidepressants. Detecting variants of the CYP2C19 gene that cause altered CYP2C19 enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of medications metabolized by CYP2C19. Roughly 2% of the population are 2C19 Poor Metabolizers (PMs), meaning they have no 2C19 enzymatic activity. Another 30% of the population are considered Intermediate Metabolizers (IMs) with decreased activity. Still another 28% of people are UltraRapid Metabolizers. Both IMs and PMs exhibit decreased metabolic activity, which puts them at risk for side effects to drugs normally inactivated by 2C19 (e.g.,sertraline, diazepam), or lack of efficacy for drugs requiring activation by 2C19 (e.g., prodrugs such as clopidogrel). The FDA required clopidogrel to be labeled with a box warning indicating that PM patients taking clopidogrel are at increased risk of thrombotic events due to failure to convert clopidogrel to its activate component. CYP2C19 UMs are the other extreme, having higher than normal enzymatic activity. UMs are at increased risk of failure to active drugs because they clear the drugs too rapidly to benefit from a standard dose. UMs are also at risk of toxic side effects from prodrugs, such as bleeding on clopidogrel, because they convert the drug into an active form more so than expected. PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories CYP2D6 Master Drug List Pain Management Codeine** Oxycodone** Hydrocodone** Tramadol** Various brands Oxycontin, various Various brands Ultram, various Cardiology Carvedilol Metoprolol Propanolol Nebivolol Timolol Propafenone Flecainide Coreg Toprol-XL Inderal, various Bystolic Blocadren Rythmol Tambocor Other Loratadine Donepezil Dextromethorphan Tamoxifen** Fesoterodine Tamulosin Claritin Aricept Various brands Various brands Toriaz Flomax Psychiatry Antidepressants Fluoxetine Fluvoxamine Paroxetine Venlafaxine Duloxetine Maprotiline Mirtazapine Amitriptyline Clomipramine Desipramine Doxepin Imipramine Nortriptyline Trimipramine Prozac Luvox Paxil Effexor Cymbalta Ludiomil Remeron Various brands Ananfranil Norpramin Sinequan Tofranil Pamelor, Aventyl Surmontil Antipsychotics Haloperidol Risperidone Aripiprazole Zuclopenthixol Perphenazine Thioridazine Iloperidine Chlorpromazine Atomoxetine Amphetamine Haldol Risperdal Abilify Various brands Trilafon Mellaril Fanapt Thorazine Strattera Adderall **indicates prodrug LAB NOTES CYP2D6 is a liver enzyme responsible for metabolizing roughly 25% of all drugs, including opioids, many antidepressants, antipsychotics, beta-blockers, and tamoxifen. Detecting variants of the CYP2D6 gene that cause altered CYP2D6 enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of medications metabolized by CYP2D6. Roughly 10% of the population are 2D6 Poor Metabolizers (PMs), meaning they have no 2D6 enzymatic activity. Another 35% of the population are considered Intermediate Metabolizers (IMs) with decreased activity. Still another 1-3% of people are Ultra-Rapid Metabolizers. Both IMs and PMs exhibit decreased metabolic activity, which puts them at risk for side effects to drugs normally inactivated by 2D6 (e.g., venlafaxine, metoprolol), or lack of efficacy for drugs requiring activation by 2D6 (e.g., prodrugs such as opioids, tamoxifen). UMs are the other extreme, having higher than normal enzymatic activity. UMs are at increased risk of failure to active drugs because they clear the drugs too rapidly to benefit from a standard dose. UMs are also at risk of toxic side effects from prodrugs because they convert the drug into an active form more so than expected. PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories CYP1A2 Master Drug List Psychiatry Olanzapine Clozapine Imipramine Clomipramine Mirtazapine Bupropion Duloxetine Promazine Asenapine Zyprexa Clozaril Tofranil Anafranil Remeron Wellbutrin Cymbalta Sparine Saphris Other Ropivicaine Lidocaine Theophylline Frovatriptan Zolmipitran Triamterene Flutamide Tizanidine Tacrine Cyclobenzaprine Rasagiline Ropinirole Caffeine 17-beta estradiol Various brands Various brands Aerolate Frova Zomig Dyrenium Eulexin Zanaflex Cognex Flexeril Azilect Requip LAB NOTES CYP1A2 is a liver enzyme that metabolizes many medications, including theophylline, diazepam, caffeine, many antidepressants, and antipsychotics. CYP1A2 enzymatic activity can be induced by several medications, substrates, and constituents of tobacco smoke. CYP1A2 can also be inhibited by several medications. Detecting inherited variants of the CYP1A2 gene that cause altered enzymatic activity, particularly in the presence of an inducer, can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP1A2 medications. PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories CYP3A4 and CYP3A5 Master Drug List PSYCHIATRY Benzodiazepines Alprazolam Midazolam Triazolam Xanax Versed Halcion Antipsychotics Quetiapine Ziprasidone Buspirone Lurasidone Carbamazepine Seroquel Geodon Buspar Latuda Various brands Antidepressants Desvenlafaxine Vilazodone Trazadone Nefazadone Reboxetine Nortriptyline Pristiq Viibryd Desyrel Serzone Edronax Pamelor, Aventyl CARDIOLOGY Quinidine Ticareglor Rivaroxaban Various brands Brilinta Xarelto Statins Atorvastatin Lovastatin Mevastatin Simvastatin Lipitor, Caduet Mevacor, Advicor Compactin Zocor, Vytorin, Simcor UROLOGY Sildenafil Tidalafil Alfuzosin Doxazosin Finasteride Dutasteride Viagra Cialis Uroxatral Cardura Procar Avodart OTHER Antimicrobials/antivirals Clarithromycin Erythromycin Telithromycin Indinavir Nelfinavir Ritonavir Saquinavir Biaxin E-Mycin Ketek Crixivan Viracept Norvir Fortovase Steroids Estradiol Hydrocortisone Progesterone Testosterone Various brands Various brands Various brands Various brands Chemotherapeutics Vincristine Docetaxel Oncovin Taxotere Pain Management Cyclobenzaprine Fentanyl Alfentanil Flexeril Actiq, Duragesic Alfenta Immunosuppressants Cyclosporine Tacrolimus Gengraf Prograf Other Guanfacine Eletriptan Zolpidem Intuniv Relpax Ambien Ca Channel Blockers Amiodipine Diltiazem Felodipine Lercanidipine Nifedipine Nisoldipine Nitrendipine Verapamil Norvasc Cardizem Plendil Zanidip Adalat Sular Various brands Various brands LAB NOTES CYP3A4 is a liver enzyme that, in concert with CYP3A5, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A4 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories dosages of 3A4 substrates. Roughly 4-10% of the general population possesses inherited differences in 3A4 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A4. CYP3A4 and CYP3A5 Master Drug List (continued) CYP3A5 is a liver enzyme that, in concert with CYP3A4, metabolizes approximately 50% of medications, including many of the statins, benzodiazepines, antibiotics, and antipsychotics. Detecting variants of the CYP3A5 gene that cause altered enzymatic activity can identify patients who may be at increased risk of having adverse drug reactions while taking standard dosages of 3A5 substrates. More than half of the general population (60-80%) possesses inherited differences in 3A5 that cause decreased metabolism. These Decreased Metabolizers may be at increased risk for dose-dependent side effects to drugs normally inactivated by 3A5. PGXL Master Drug List 062013 © 2012-3 by PGXL Laboratories