General Information/How to use this table :

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