General Information/How to use this table : The genes that encode for many of the enzymes in the cytochrome 450 system, by convention, are labeled with the abbreviation CYP. The first number that follows designates the gene family, the capital letter the sub-family and the last number designates the individual gene. Each gene codes for a specific gene in the CYP450 system. These genes are found on a number of different chromosomes. The following tables are provided by Molecular Testing Labs to provide you with a listing of the specific drugs whose primary physiologic metabolism is dependent on the enzymes coded by the indicated genes (Table #1); known substances that inhibit the action of these specific enzymes (Table #2) and substances that will induce or augment the activity of these enzymes (Table #3). By utilizing the results of the genetic testing and the information provided within these three tables, the healthcare provider can tailor a precise and individualized drug regimen for the patient that maximizes the benefit and minimizes the risk to the patient. As clinical research continues, more information will become available and Molecular Testing Labs is committed to informing the healthcare providers of the most current information available and providing the most complete line of this type testing available. TM TM Table #1: Primary Substrates (primary enzyme for metabolism) CYP2C19 Psychotropics: amitriptyline citalopram clobazam clomipramine diazepam escitalopram flunitrazapam fluvoxamine Luvox {fluoxetine} imipramine moclobemide modafinil Provigil sertraline trimipramine Anticonvulsants: mephenytoin phenytoin Proton Pump Inhibitors: {esomeprazole} Dexlansoprazole lansoprazole omeprazole {pantoprazole} rabeprazole Antibiotics/ Antifungals: voriconazole Hormones/Steroids drospirenone Antiviral Agents: nelfinavir voriconazole Others: carisoprodol Soma cilostazol clopidogrel (p) Plavix cyclophosphophamide (p) ifosphosphamide (p) nelfinavir proguanil (p) Malarone prasugrel propranolol R-warfarin Ticagrelor CYP2C9 Psychotropics: fluoxetine fluvoxamine Luvox {sertraline} valproic acid NSAIDS: aceclofenac celecoxib Celebrex diclofenac flurbiprofen ibuprofen indomethacin lornoxicam meloxicam {naproxen} piroxicam suprofen tenoxicam Hypoglycemics: chlorpropamide glipizide Glucotrol Glimepiride Amaryl glyburide DiaBeta nateglinide Starlix {rosiglitazone} {Avandia} tolbutamide Orinase Others: bosentan candesartan Atacand fluvastatin Lescol irbesartan losartan Cozaar (p) phenobarbital phenytoin sulfa drugs {tamoxifen} warfarin tetrahydrocannabinol (marijauna) torsemide Tomide italics = brand name bold = potent CYP2D6 Psychotropics: amphetamines amitriptyline aripiprazole atomoxetine benztropine chlorpromazine {citalopram} clomipramine clozapine desipramine doxepin duloxetine fluoxetine fluvoxamine Luvox galantamine haloperidol imipramine iloperidone mirtazapine modafinil nefazodone Provigil nortripyline olanzapine paroxetine perphenazine pimozide protriptyline risperidone {sertraline} tetrabenazine thioridazine trimipramine venlafaxine ^Cough Medicines Dextromethorphan Others: cevimeline dolesetron(p) doxorubicin drospirenone encainide ethinyl estradiol MDMA (ecstasy) metoclopramide Reglan mexiletine phenacetin proprafenone quinidine Rythmol {ranitidine} {Zantac} tamoxifen(p) tiotropium tolterodine Detrol Tropisetron Analgesics: acetaminophen Tylenol Antibiotics/ Antifungals: terbinafine Antihistamines: chlorpheniramine diphenhydramine hydroxyzine Atarax Beta Blockers: chlorpropamide carveodilol metoprolol propranolol timolol Chemotherapeutic Agents: gefitinib CYP3A4,5 Psychotropics: alprazolam amitriptyline aripiprazole buspirone carbamazepine citalopram {clomipramine} {clozapine} {diazepam} estazolam eszopiclone Lunesta fluoxetine fluvoxamine Luvox haloperidol midazolam nefazodone pimozide quetiapine risperidone sertraline trazodone triazolam zaleplon Sonata {ziprasidone} zolpidem Ambien Drugs of Abuse/ Treatment/ Opiates: Drugs of codeine(p) Abuse/Treatment: dextromethorphan hydrocodone (p) {oxycodone} tramadol {brackets} = minor or less potent (p) = pro-drug buprenorphine cocaine fentanyl ketamine methadone oxycodone phencyclidine PCP Antibiotics/ Antifungals: macrolides (not azithromycin) itraconazole ketoconazole telithromycin Ketek Anticonvulsants: carbamazepine ethosuximide felbamate tiagabine Gabitril Zonisamide Zonegran Antihistamines: Yellow Highlight = FDA/EMA recommends PGx tests for these drugs ^ = entire class or group COMT Psychotropics: tranylcypromine agomelatine trazodone amisulpride trifluoperazine amitriptyline triflupromazine amoxapine trimipramine aripiprazole venlafaxine chlorpromazine ziprasidone chlorprothixene citalopram Asthma clomipramine Parkinson’s clozapine Medication: Therapeutics: desipramine fluticasone entacapone desvenlafaxine Flovent tolcapone doxepin salmeterol droperidol Serevent duloxetine zileuton escitalopram Zyflo fluoxetine ^Calcium Channel fluphenazine CYP1A2 fluspirilene Blockers fluvoxamine Psychotropics: haloperidol asenapine Hormones/Chemo imipramine caffeine iron therapeutics: clozapine isocarboxazid duloxetine cortisols lithium fluvoxamine desogestrel (p) loxapine frovatriptan ethinyl estradiol l-tryptophan melatonin gefitinib maprotiline mirtazapine OCs mesoridazine olanzapine progestins/progesterone methadone vincristine and methotrimeprazine phenacetin pimozide others methylphenidate propranolol minaprine ramelteon Others: mirtazapine riluzole moclobemide aprepitant zolmitriptan morphine Emend nefazodone cinacalcet Parkinson’s nicotine esomeprazole nortriptyline Therapeutics: granisetron olanzapine nateglinide rasagiline paliperidone nelfinavir ropinirole paroxetine Starlix perazine omeprazole Others: perphenazine pioglitazone aprepitant phenelzine Actos cinacalcet pimozide quinidine deferasirox pipotiazine sildenafil dexlansoprazole prochlorperazine erlotinib promazine Statins: flutamide (atorvastatin,lovastatin, protriptyline leflunomide quetiapine simvastatin) mexiletine reboxetine ticagrelor ondansetron remoxipride tolterodine palonosetron risperidone Detrol R-warfarin sertindole Sirolimus ropivacaine sertraline Tacrolimus theophylline sulpiride thiabendazole tacrine tizanidine thioproperazine triamterene thioridazine zileuton thiothixene Desloratadine Clarinex fexofenadine Allegra loratadine Claritin OPRM1 Opioid Analgesics: amphetamine bupropion butorphanol codeine dezocine ethanol fentanyl heroin hydromorphone meperidine methadone morphine nalbuphine naloxone naltrexone oxycodone opioid pentazocine propoxyphene tramadol Nicotinics: nicotine varenicline Chemotherapeutics: SLCO1B1 Chemotherapeutic Agents: arsenic atrasentan methotrexate SN-38 Statins: atorvastatin cerivastatin lovastatin pitavastatin pravastatin rosuvastatin simvastatin Antihypertension: bosentan enalaprilat olmesartan valsartan Others: benzylpenicillin caspofungin repaglinide troglitazone sulfate Carboplatin Docetaxel Paclitaxel The FDA requires that many of these drugs, which are highlighted in yellow, are labeled with pharmacogenetic information and recommends that the patient be given a molecular pharmacological test prior to taking these drugs. Data Tables : Across the top of each of these three tables are the names of genes in the CYP450 system. These genes code for a number of enzymes that have been found to be clinically significant and affect the metabolism of well over half of all prescribed drugs as well as a number of other substances and toxins. They are also genes for which we can detect various polymorphisms that cause clinically significant alterations in the body’s ability to metabolize these substances. By taking into account the results of the patient’s genetic tests, considering other medications and substances the patient might be taking and integrating that information along with the information found in all three of these tables, the healthcare provider can make an informed and custom tailored determination whether and how to alter the dosing of an individual drug or whether to consider a different drug altogether. Table #2: Inhibitors (reduces or blocks the ability of the enzyme to metabolize the substrates) CYP2C19 artemisinin chloramphenicol delavirdine efavirenz esomeprazole felbamate {fluconazole} {fluoxetine} fluvoxamine indomethacin inh modafinil Provigil omeprazole Prilosec CYP2C9 oral contraceptives oxcarbazepine ticlopidine topiramate voriconazole amiodarone anastrazole cimetidine delavirdine efavirenz fenofibrate Tricor fluconazole {fluoxetine} fluvoxamine fluvastatin isoniazid ketoconazole leflunomide modafiinil phenylbutazone {sertraline} sulfamethoxazole sulfaphenazole tamoxifen teniposide valproic acid voriconazole Vfend {zafirlukast}, {Accolate} 5-fluorouracil CYP2D6 amiodarone {amitriptyline} bupropion celecoxib chlorpheniramine chlorpromazine cimetidine cinacalcet {citalopram} chlorpheniramine clomipramine {desipramine} diphenhydramine doxepin duloxetine {fluvoxamine} fluoxetine CYP3A4,5 goldenseal halofantrine haloperidol {hydroxyzine} imipramine methadone metoclopramide moclobemide paroxetine pimozide propafenone quinidine/quinine ritonavir {sertraline} terbinafine thioridazine ticlopidine amiodarone amprenavir aprepitant -initially atazanavir Reyataz {cimetidine} ciprofloxacin clarithromycin delavirdine diltiazem doxycycline echinacea enoxacin erythromycin fluconazole fluvoxamine grapefruit juice indinavir itraconazole ketoconazole miconazole nefazodone nelfinavir ritonavir and boosted PIs saquinavir telithromycin verapamil voriconazole CYP1A2 cimetidine ciprofloxacin clinafloxacin enoxacin fluvoxamine furafylline interferon methoxsalen mexiletine norfloxacin oral contraceptives rofecoxib thiabendazole ticlopidine vemurafenib Table #3: Inducers (increases the ability of the enzyme to metabolize the substrates) CYP2C19 ginko biloba rifampin St John’s Wort CYP2C9 aprepitant-long term barbiturates bosentan carbamazepine rifampin-chronic ritonavir and boosted Pis St John’s Wort-long term CYP2D6 rifampin CYP3A4,5 aprepitant -long term barbiturates bosanten carbamazepine efavirenz felbamate glucocorticoids modafinil nafcillin nevirapine {oxcarbazepine} phenytoin primidone rifampins St John’s Wort pioglitazone Actos topiramate at >200 mg/d CYP1A2 cigarette smoking montelukast moricizine omeprazole phenobarbital phenytoin SLCO1B1 atazanavir/ritonavir clotrimazole cyclosporine cyclosporine A eltrombopag gemfibrozil glibenclamide lithocholate lopinavir/ritonavir mifepristone paclitaxel pioglitazone repaglinide rifampicin rifamycin SV ritonavir rosiglitazone saquinavir,ritonavir saquinavir/ritonavir sirolimus tacrolimus tipranavir/ritonavir troglitazone SLCO1B1 Inducers (not characterized) Table #1: For each of the drugs listed here, it is vital to recognize whether the drug, as taken, is an active drug or a pro-drug that must be metabolized to an active form before having a clinical effect. These pro-drugs are indicated by the entry “(p)” following the name of the drug. If the substance is an active drug, it exerts its physiologic effect on the body directly and will be metabolized to less active intermediates, primarily by the enzyme coded by the gene at the top of the column where that drug appears. Thus a genetic polymorphism on this gene which inhibits this gene’s activity will allow the level of the active drug to increase over what would be seen with normal dosing in a patient with a “normal” or what is termed “wild type” genotype for this particular gene. Conversely, if the patient carries a polymorphism that induces or increases the activity of this enzyme, the active form will be metabolized more rapidly to less active intermediates and the patient will receive a reduced benefit or no benefit at all from the drug when administered at a conventional dose and frequency. Table #2 : Lists the names of these genes in the CYP450 system across the top of the columns. The medications and substances listed below each gene are known to inhibit the enzyme activity associated with the gene indicated. This results in a similar effect on the metabolism of drugs by this enzyme that would be caused by a genetic polymorphism that inhibits the activity of the indicated enzyme. Table #3: Lists drugs and substances known to induce the enzymatic activity associated the indicated genes. Molecular Testing Labs is committed to providing you the most current and complete information in this new and exciting field of medicine. Please contact us with questions and let us know how we can best help you take the best care possible for your patients. TM [email protected] • (360) 693-8850 • 2700 NE Andresen Rd., Suite E3 • Vancouver, WA 98661 • www.moleculartestinglabs.com