Drug interactions with the tyrosine kinase inhibitors

imatinib, dasatinib and nilotinib

Table from the following article: Haouala A, Widmer N, Duchosal MA, Montemurro M, Buclin T,
Decosterd LA. Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib.
Blood 2010. http://dx.doi.org/10.1182/blood-2010-07-294330

Legend:
The Table (in 17 parts) summarizes observed or potential drug interactions between TKIs and
commonly concomitantly prescribed drugs or classical interacting agents (lines) sorted according to
the ATC classification. The arrows and indicate an increase or decrease of drug concentration
respectively. Boldface text outlines interactions reported in the literature (reference number), whereas
standard characters represent potential interactions predicted from theoretical considerations (but not
yet reported in the literature). Absence of interaction means that a clinical study concluded to the
absence of interaction (reference number), and a box shaded in grey means that no interaction is
either reported or theoretically expected

Disclaimer:
This table summarizes potential drug interactions between some commonly prescribed drugs (lines)
and three tyrosine kinase inhibtors (columns). Each cell indicates the type of interaction expected
when the drug is taken together with the corresponding tyrosine kinase inhibitor. The data presented
are however only indicative and do not replace clinical judgment necessary when treating patients with
multiple drugs. Not all interactions are expected to have clinical significance and/or to imply dosage
adjustment. It is also of importance to check regularly for updated literature on this topic.

References:
See full article.
 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Alimentary tract and metabolism

Imatinib Dasatinib Nilotinib

Inhibition of Pgp by omeprazole :

Omeprazole dasatinib absorption
imatinib exposure

Inhibition of Pgp by esomeprazole :

PPI

Esomeprazole dasatinib absorption

imatinib exposure

Inhibition of Pgp by pantoprazole:

Pantoprazole dasatinib absorption
imatinib exposure

Inhibition of CYP 3A4 and Pgp by

cimetidine :
Inhibition of CYP 3A4 by cimetidine :
H2-antagonists

Cimetidine imatinib exposure dasatinib absorption

nilotinib exposure
Inhibition of hOCT1 by cimetidine :
imatinib intracellular exposure

Inhibition of Pgp by ranitidine :

dasatinib absorption
imatinib exposure
Ranitidine
Inhibition of hOCT1 by ranitidine :
imatinib intracellular exposure
Antiemetics

QT interval QT interval
Metoclopramide (additive effect) (additive effect)
monitor ECG monitor ECG

Insulin

Inhibition of hOCT1 by metformin :

Metformin
imatinib intracellular exposure

Inhibition of CYP 3A4 and 2C9 by

Inhibition of CYP 3A4 by dasatinib:
imatinib: Inhibition of CYP 3A4 and 2C9 by
glibenclamide exposure
Glibenclamide glibenclamide exposure nilotinib:
Inhibition of Pgp by glibenclamide :
Inhibition of Pgp by glibenclamide : glibenclamide exposure
dasatinib exposure
imatinib exposure
Antidiabetic drugs

Acarbose

Inhibition of CYP 2C9 by imatinib: Inhibition of CYP 2C9 by nilotinib:

Rosiglitazone
rosiglitazone exposure rosiglitazone exposure

Inhibition of CYP 3A4 and 2C9 by Inhibition of CYP 3A4 and 2C9 by
Inhibition of CYP 3A4 by dasatinib:
Pioglitazone imatinib: nilotinib:
pioglitazone exposure
pioglitazone exposure pioglitazone exposure

Inhibition of CYP 3A4 and 2C9 by Inhibition of CYP 3A4 and 2C9 by
Inhibition of CYP 3A4 by dasatinib:
Nateglinide imatinib: nilotinib:
nateglinide exposure
nateglinide exposure nateglinide exposure

Inhibition of CYP 3A4 and 2C8 by Inhibition of CYP 3A4 and 2C8 by
Inhibition of CYP 3A4 by imatinib:
Repaglinide dasatinib: nilotinib:
pioglitazone exposure
pioglitazone exposure pioglitazone exposure

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Blood and blood forming organs

Imatinib Dasatinib Nilotinib

a

Inhibition of CYP 3A4 by

Antiplatelet drug

dasatinib:
Inhibition of CYP 3A4 and Inhibition of CYP 3A4 by
clopidogrel exposure
2C19 by imatinib: nilotinib:
Clopidogrel clopidogrel bioactivation
clopidogrel exposure clopidogrel exposure
Thrombocytopenic effect of
clopidogrel bioactivation clopidogrel bioactivation
dasatinib:
risk of bleeding

Inhibition of CYP 2C9 by Thrombocytopenic effect of Inhibition of CYP 2C9 by

imatinib: dasatinib: nilotinib:
Acenocoumarol
anticoagulation risk of bleeding anticoagulation
monitor PT/INR monitor PT/INR

Inhibition of CYP 2C9 by

Inhibition of CYP 2C9 by Thrombocytopenic effect of
nilotinib:
imatinib: dasatinib:
Phenprocoumon anticoagulation
anticoagulation risk of bleeding
monitor PT/INR
monitor PT/INR

Inhibition of CYP 2C9 by Inhibition of CYP 2C9 by

Thrombocytopenic effect of
imatinib: nilotinib:
dasatinib:
Warfarin anticoagulation anticoagulation
risk of bleeding
monitor PT/INR monitor PT/INR
a
Anticoagulants

Thrombocytopenic effect of
Inhibition of Pgp by dasatinib:
heparin: risk of bleeding
Heparin
imatinib exposure Inhibition of Pgp by heparin:
dasatinib exposure

Thrombocytopenic effect of
dasatinib:
Enoxaparin
risk of bleeding

Thrombocytopenic effect of
Nadroparin dasatinib:
risk of bleeding

Thrombocytopenic effect of
Dalteparin dasatinib:
risk of bleeding

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Cardiovascular system

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 and Pgp by

Inhibition of CYP 3A4 by dasatinib: Inhibition of CYP 3A4 and Pgp by
imatinib:
verapamil exposure nilotinib: verapamil exposure
verapamil exposure
Verapamil Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by
Inhibition of CYP 3A4 and Pgp by
verapamil: verapamil:
Calcium channel blockers

verapamil:
dasatinib exposure nilotinib exposure
imatinib exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by nilotinib:
Inhibition of CYP 3A4 by dasatinib:
imatinib: diltiazem exposure diltiazem exposure
diltiazem exposure
Diltiazem Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by
Inhibition of CYP 3A4 and Pgp by
diltiazem: diltiazem:
diltiazem: dasatinib exposure
imatinib exposure nilotinib exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
Inhibition of CYP3A4 by nilotinib:
Nifedipine imatinib: dasatinib:
nifedipine exposure
nifedipine exposure nifedipine exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
Inhibition of CYP 3A4 by nilotinib:
Amlodipine imatinib: dasatinib:
amlodipine exposure
amlodipine exposure amlodipine exposure

Molsidomine
NO precursors

Isosorbid
Inhibition of CYP 3A4 by imatinib: Inhibition of CYP 3A4 by dasatinib: Inhibition of CYP 3A4 by nilotinib:
mononitrate
ISMN exposure ISMN exposure ISMN exposure
(ISMN)
Isosorbid
Inhibition of CYP 3A4 by imatinib: Inhibition of CYP 3A4 by dasatinib: Inhibition of CYP 3A4 by nilotinib:
dinitrate
ISDN exposure ISDN exposure ISMN exposure
(ISDN)

Nitroglycerine

Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by

imatinib: dasatinib:
HMG-CoA reductase inhibitors

Inhibition of CYP 3A4 by nilotinib:

Simvastatin simvastatin exposure simvastatin exposure
simvastatin exposure
Inhibition of Pgp by simvastatin: Inhibition of Pgp by simvastatin:
imatinib exposure dasatinib exposure

Pravastatin

Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 by dasatinib:
imatinib: Inhibition of CYP 3A4 by nilotinib:
atorvastatin exposure
Atorvastatin atorvastatin exposure atorvastatin exposure
Inhibition of Pgp by atorvastatin:
Inhibition of Pgp by atorvastatin:
dasatinib exposure
imatinib exposure

Rosuvastatin

Inhibition of CYP 3A4 and Pgp by

Inhibition of Pgp and CYP 3A4 by
imatinib:
Inhibition of CYP 3A4 by dasatinib: nilotinib: amiodarone exposure
amiodarone exposure
amiodarone exposure Inhibition of CYP 3A4 by
Inhibition of CYP3A4 and Pgp by
Antiarrhythmic drugs

Amiodarone Inhibition of CYP 3A4 and Pgp by amiodarone:

amiodarone:
amiodarone: nilotinib exposure
imatinib exposure
dasatinib exposure QT interval (additive effect)

Inhibition of hOCT1 by amiodarone :
=> monitor ECG
imatinib intracellular exposure
Inhibition of CYP 3A4 by
imatinib: Inhibition of CYP 3A4 by
quinidine exposure dasatinib: Inhibition of CYP 3A4 by
Quinidine Inhibition of Pgp by quinidine: quinidine exposure nilotinib:
imatinib exposure Inhibition of Pgp by quinidine: quinidine exposure
Inhibition of hOCT1 by quinidine : dasatinib exposure
imatinib intracellular exposure

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Furosemide Absence of interaction

Inhibition of CYP 2C9 by imatinib: Inhibition of CYP 2C9 by nilotinib:

Torasemide
Diuretics

torasemide exposure torasemide exposure

Hydrochlorothiazide

Inhibition of Pgp by Inhibition of Pgp by

Spironolactone spironolactone: spironolactone:
imatinib exposure dasatinib exposure
Inhibition of CYP 2D6 by
Inhibition of Pgp by metoprolol: Inhibition of CYP 2D6 by nilotinib:
Metoprolol imatinib:
dasatinib exposure metoprolol exposure
metoprolol exposure
Inhibition of CYP 2D6 by Inhibition of CYP 3A4 by
Inhibition of CYP 2D6 by nilotinib:
Beta blockers

Bisoprolol imatinib: dasatinib:

bisoprolol exposure
bisoprolol exposure bisoprolol exposure
Inhibition of CYP 2C9 and 2D6 by
imatinib: Inhibition of CYP 2C9 and 2D6
Inhibition of Pgp by carvedilol:
Carvedilol carvedilol exposure by nilotinib:
dasatinib exposure
Inhibition of Pgp by carvedilol: carvedilol exposure
imatinib exposure

Atenolol Absence of interaction

Inhibition of CYP 2D6 by imatinib:

captopril exposure Inhibition of Pgp by captopril: Inhibition of CYP 2D6 by nilotinib:
Captopril
Inhibition of Pgp by captopril: dasatinib exposure captopril exposure
imatinib exposure
Inhibition of CYP 3A4 by imatinib:
ACE inhibitors

enalapril exposure Inhibition of Pgp by enalapril: Inhibition of CYP 3A4 by nilotinib:

Enalapril
Inhibition of Pgp by enalapril: dasatinib exposure enalapril exposure
imatinib exposure

Ramipril

Inhibition of Pgp by imatinib:

lisinopril exposure Inhibition of Pgp by lisinopril:
Lisinopril
Inhibition of Pgp by lisinopril: dasatinib exposure
imatinib exposure
Inhibition of CYP 2C9 and 3A4 by
Inhibition of CYP 3A4 by Inhibition of CYP 2C9 and 3A4 by
imatinib:
AT II receptor

dasatinib: nilotinib:
losartan exposure and
blockers

Losartan losartan exposure losartan exposure and

losartan bioactivation
Inhibition of Pgp by losartan: losartan bioactivation
Inhibition of Pgp by losartan:
dasatinib exposure
imatinib exposure

Candesartan

QT interval
glycosides

(additive effect)
Cardiac

QT interval
digoxin absorption monitor ECG
Digoxin (additive effect)
(unknown mechanism) Inhibition of Pgp by nilotinib:
monitor ECG
digoxin exposure

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Hormonal preparations

Imatinib Dasatinib Nilotinib

Prednisone
Corticosteroids

Induction of CYP 3A4 by Induction of CYP 3A4 by Induction of CYP 3A4 by

Dexamethasone dexamethasone : dexamethasone : dexamethasone :
imatinib exposure dasatinib exposure nilotinib exposure

Betamethasone

Induction of UGTs by
imatinib :
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
Thyroid therapy

levothyroxine
Levothyroxine levothyroxine: levothyroxine:
Inhibition of CYP 3A4 by
dasatinib exposure nilotinib exposure
levothyroxine:
imatinib exposure

Carbimazole
Antineoplastic

Inhibition of CYP 2D6 and Inhibition of CYP 3A4 by Induction of CYP 2B6 by
3A4 by imatinib: dasatinib: nilotinib:
agents

cyclophosphamide cyclophosphamide cyclophosphamide

Cyclophosphamide
exposure exposure exposure
cyclophosphamide cyclophosphamide cyclophosphamide
bioactivation bioactivation bioactivation
Antiestrogen

Inhibition of CYP 2D6 and Inhibition of CYP 3A4 by Inhibition of CYP 2D6 and
agent

3A4 by imatinib: dasatinib: 3A4 by nilotinib:

Tamoxifen
tamoxifen exposure tamoxifen exposure tamoxifen exposure
tamoxifen bioactivation tamoxifen bioactivation tamoxifen bioactivation

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Anti-infectives

Imatinib Dasatinib Nilotinib

Penicillins

Amoxicillin

Flucloxacillin
Cephalosporins

Cfuroxime

Cefpodoxime

Ceftriaxone

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and Pgp Inhibition of CYP 3A4
Clarithromycin Pgp by clarithromycin: by clarithromycin: by clarithromycin:
imatinib exposure dasatinib exposure nilotinib exposure
Macrolides

Azithromycin

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and Pgp Inhibition of CYP 3A4
Erythromycin Pgp by erythromycin: by erythromycin: by erythromycin:
imatinib exposure dasatinib exposure nilotinib exposure
Tertracyclines

Doxycyclin

QT interval
(additive effect) QT interval
Inhibition of Pgp by
monitor ECG (additive effect)
Ciprofloxacin ciprofloxacin:
Inhibition of Pgp by monitor ECG
imatinib exposure
ciprofloxacin:
dasatinib exposure
Quinolones

Inhibition of Pgp by levofloxacin: QT interval

imatinib exposure
Levofloxacin Inhibition of hOCT1 by
levofloxacine :
imatinib intracellular exposure
QT interval
(additive effect)
(additive effect)
monitor ECG
monitor ECG
Inhibition of Pgp by levofloxacin:
dasatinib exposure

QT interval QT interval
(additive effect) (additive effect)
Norfloxacin
monitor ECG monitor ECG
Sulfonamides

Inhibition of CYP 2C9 by Inhibition of CYP 2C9

Co-trimoxazole imatinib: by nilotinib:
co-trimoxazole co-trimoxazole

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by
Itraconazole Pgp by itraconazole: itraconazole: itraconazole:
imatinib exposure dasatinib exposure nilotinib exposure

Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by

fluconazole: fluconazole:
Inhibition of CYP 3A4 and
dasatinib exposure nilotinib exposure
Pgp by fluconazole:
Fluconazole QT interval QT interval
imatinib exposure
(additive effect) (additive effect)
monitor ECG monitor ECG
Azoles

Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 by voriconazole:
voriconazole:
Inhibition of CYP 3A4 by dasatinib exposure
nilotinib exposure
Voriconazole voriconazole: QT interval
QT interval
imatinib exposure (additive effect)
(additive effect)
monitor ECG
monitor ECG
Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by
ketoconazole: ketoconazole:
Inhibition of CYP 3A4 and
dasatinib exposure nilotinib exposure
Ketoconazole Pgp by ketoconazole:
QT interval QT interval
imatinib exposure
(additive effect) (additive effect)
monitor ECG monitor ECG
Allylamine

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and 2C9 by

Inhibition of CYP 3A4 by dasatinib:
Terbinafine 2C9 by imatinib: nilotinib:
terbinafine exposure
terbinafine exposure terbinafine exposure
Nitroimidazole

Metronidazole

Aciclovir Absence of interaction

Antiviral/Nucleoside analog

Valaciclovir Absence of interaction

Inhibition of hOCT1 by
ganciclovir :
Ganciclovir
imatinib intracellular
exposure
Inhibition of hOCT1 by
ganciclovir :
Valganciclovir
imatinib intracellular
exposure
Antimycobacterials

Induction of CYP 3A4 by Induction of CYP 3A4 by

Induction of CYP 3A4 by rifampicine:
Rifampicine rifampicine: rifampicine:
dasatinib exposure
imatinib exposure nilotinib exposure

Isoniazide

Ethambutol

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 and Pgp by

Inhibition of CYP 3A4 by ritonavir:
ritonavir:
nilotinib exposure
dasatinib exposure
Ritonavir QT interval
QT interval
(additive effect)
(additive effect)
monitor ECG
monitor ECG
Inhibition of CYP 3A4 and Pgp by
imatinib: Inhibition of CYP 3A4 and Pgp by
Inhibition of CYP 3A4 by dasatinib:
Saquinavir saquinavir exposure nilotinib:
saquinavir exposure
Inhibition of hOCT1 by saquinavir : saquinavir exposure
imatinib intracellular exposure
Inhibition of CYP 3A4 by
Protease inhibitors

Inhibition of CYP 3A4 by darunavir: Inhibition of CYP 3A4 by darunavir:

Darunavir darunavir:
dasatinib exposure nilotinib exposure
imatinib exposure
Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 and Pgp by
Inhibition of CYP 3A4 by dasatinib:
Atazanavir imatinib: nilotinib:
atazanavir exposure
atazanavir exposure atazanavir exposure

Inhibition of CYP 3A4 and Pgp by

Inhibition of CYP 3A4 and Pgp by
imatinib: Inhibition of CYP 3A4 by dasatinib:
nilotinib:
tipranavir exposure tipranavir exposure
Tipranavir tipranavir exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by tipranavir:
Inhibition of CYP 3A4 by tipranavir:
tipranavir: dasatinib exposure
nilotinib exposure
imatinib exposure

Inhibition of CYP 3A4 and Pgp by

imatinib: Inhibition of CYP 3A4 and Pgp by
Inhibition of CYP 3A4 by dasatinib:
Indinavir indinavir exposure nilotinib:
indinavir exposure
Inhibition of hOCT1 by indinavir : indinavir exposure
imatinib intracellular exposure
transcriptase inhibitors

Inhibition of hOCT1 by
nucleotide reverse

Lamivudine lamivudine :
Nucleoside and

imatinib intracellular exposure

Emtricitabine

Zidovudine

Inhibition of CYP 3A4 by imatinib:

Inhibition of CYP 3A4 by dasatinib: Inhibition of CYP 3A4 by nilotinib:
efavirenz exposure
efavirenz exposure efavirenz exposure
Non-nucleoside reverse transcriptase

Induction of CYP 3A4 by

Efavirenz Induction of CYP 3A4 by efavirenz: Induction of CYP 3A4 by efavirenz:
efavirenz:
dasatinib exposure nilotinib exposure
imatinib exposure

Inhibition of CYP 3A4 by imatinib:

Inhibition of CYP 3A4 by dasatinib: Inhibition of CYP 3A4 by nilotinib:
inhibitors

nevirapine exposure
nevirapine exposure nevirapine exposure
Induction of CYP 3A4 by
Nevirapine Induction of CYP 3A4 by nevirapine: Induction of CYP 3A4 by nevirapine:
nevirapine:
dasatinib exposure nilotinib exposure
imatinib exposure

Inhibition of CYP 2C9 and 3A4 by

Inhibition of CYP 2C9 and 3A4 by
imatinib: Inhibition of CYP 3A4 by dasatinib:
nilotinib:
etravirine exposure etravirine exposure
Etravirine etravirine exposure
Induction of CYP 3A4 by Induction of CYP 3A4 by etravirine:
Induction of CYP 3A4 by etravirine:
etravirine: dasatinib exposure
nilotinib exposure
imatinib exposure

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 by imatinib: Inhibition of CYP 3A4 by

quinidine exposure dasatinib:
Inhibition of CYP 3A4 by
Inhibition of CYP 2D6 and Pgp by quinidine exposure
nilotinib:
Quinine quinidine: Inhibition of CYP 3A4 by
quinidine exposure
imatinib exposure dasatinib:
Inhibition of hOCT1 by quinine : quinidine exposure
imatinib intracellular exposure

Inhibition of Pgp by chloroquine: Inhibition of Pgp by chloroquine: QT interval

imatinib exposure dasatinib exposure (additive effect)
Chloroquine
Inhibition of hOCT1 by chloroquine : QT interval monitor ECG
imatinib intracellular exposure (additive effect)
monitor ECG
Antimalarial drugs

Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 and
Inhibition of CYP 3A4 and Pgp by dasatinib:
Ppg by nilotinib:
imatinib: mefloquine exposure
mefloquine exposure
Mefloquine mefloquine exposure Inhibition of Pgp by mefloquine:
QT interval
Inhibition of Pgp by mefloquine: dasatinib exposure
(additive effect)
imatinib exposure QT interval
monitor ECG
(additive effect)
monitor ECG

Inhibition of CYP 2C19 and Pgp by

imatinib:
Proguanil
proguanil exposure
proguanil bioactivation

Atovaquone

Doxycycline

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Immunomodulating agents

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 and
imatinib: dasatinib:
Pgp by nilotinib:
ciclosporin exposure ciclosporin exposure
ciclosporin exposure
Ciclosporin Inhibition of Pgp and CYP 3A4 by Inhibition of CYP3A4 and
Inhibition of CYP3A4 by
ciclosporin: Pgp by ciclosporin:
ciclosporin:
imatinib exposure dasatinib exposure
nilotinib exposure

Inhibition of CYP 3A4 by

dasatinib:
Inhibition of CYP 3A4 by imatinib: Inhibition of CYP 3A4 and
tacrolimus exposure
Tacrolimus tacrolimus exposure Pgp by nilotinib:
Inhibition of Pgp by
Inhibition of Pgp by tacrolimus: tacrolimus exposure
tacrolimus:
imatinib exposure
dasatinib exposure

Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and
Sirolimus imatinib: dasatinib: Pgp by nilotinib:
Immunosuppressants

sirolimus exposure sirolimus exposure sirolimus exposure

Inhibition of CYP 3A4 and Pgp by Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and
Everolimus imatinib: dasatinib: Pgp by nilotinib:
everolimus exposure everolimus exposure everolimus exposure

Mycophenolate
mofetil

Methotrexate

Azathioprine

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Musculo-skeletal system

Imatinib Dasatinib Nilotinib

Thrombocytopenic effect of
Aspirin dasatinib:
risk of bleeding

Inhibition of CYP 2C9 by Inhibition of CYP 2C8 by Inhibition of CYP 2C8 and 2C9
Ibuprofen imatinib: dasatinib: by nilotinib:
ibuprofen exposure ibuprofen exposure ibuprofen exposure

Inhibition of CYP 2C9 by Inhibition of CYP 2C8 by Inhibition of CYP 2C8 and 2C9
NSAIDs

Mefenacid imatinib: dasatinib: by nilotinib:

mefenacid exposure mefenacid exposure mefenacid exposure

Induction of CYP 3A4 by Induction of CYP 3A4 by Induction of CYP 3A4 by

Metamizole metamizole: metamizole : metamizole :
imatinib exposure dasatinib exposure nilotinib exposure

Inhibition of CYP 2C9 by

Inhibition of CYP 2C8 by
imatinib:
dasatinib: Inhibition of CYP 2C8 and 2C9
diclofenac exposure
diclofenac exposure and by nilotinib:
Diclofenac Inhibition of Pgp by
Inhibition of Pgp by diclofenac exposure
diclofenac:
diclofenac:
imatinib exposure
dasatinib exposure
preparations
Antigout

Allopurinol

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Nervous system

Imatinib Dasatinib Nilotinib

Inhibition of CYP 2D6 by QT interval QT interval

Fluoxetine imatinib: (additive effect) (additive effect)
fluoxetine exposure monitor ECG monitor ECG

Inhibition of CYP 2D6 by Inhibition of CYP 2D6 by

Fluvoxamine imatinib: nilotinib:
fluvoxamine exposure fluvoxamine exposure
SSRI

Inhibition of CYP 2D6 by Inhibition of CYP 2D6 by

Paroxetine imatinib: nilotinib:
paroxetine exposure paroxetine exposure
Inhibition of CYP 3A4 and Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and 2D6
Citalopram 2D6 by imatinib: dasatinib: by nilotinib:
citalopram exposure citalopram exposure citalopram exposure
Inhibition of CYP 3A4 and Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and 2D6
Sertraline 2D6 by imatinib: dasatinib: by nilotinib:
sertraline exposure sertraline exposure sertraline exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and 2D6
dasatinib: by nilotinib:
Inhibition of CYP 3A4 and
venlafaxine exposure venlafaxine exposure
Venlafaxine 2D6 by imatinib:
QT interval QT interval
venlafaxine exposure
(additive effect) (additive effect)
SSNRI

monitor ECG monitor ECG

Inhibition of CYP 2D6 by Inhibition of CYP 2D6 by

Duloxetine imatinib: nilotinib:
duloxetine exposure duloxetine exposure
Tetracyclic

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and 2D6
agent

Mirtazapine 2D6 by imatinib: dasatinib: by nilotinib :

mirtazapine exposure mirtazapine exposure mirtazapine exposure

QT interval
(additive effect)
Inhibition of CYP 2D6 by QT interval
monitor ECG
Trimipramine imatinib: (additive effect)
Inhibition of CYP 2D6 by
Tricyclic agents

trimipramine exposure monitor ECG

nilotinib:
trimipramine exposure
Inhibition of CYP 3A4 by
Inhibition of CYP 3A4 and 2D6
dasatinib:
by nilotinib:
Inhibition of CYP 3A4 and amitriptyline exposure
amitriptyline exposure
Amitriptyline 2D6 by imatinib: QT interval
QT interval
amitriptyline exposure (additive effect)
(additive effect)
monitor ECG
monitor ECG
Phenothiazines

Inhibition of CYP 2D6 by

Inhibition of CYP 2D6 by
imatinib:
Levomepromazine nilotinib:
levomepromazine
levomepromazine exposure
exposure

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib
Imatinib
Inhibition of CYP 3A4 by
Zolpidem imatinib:
zolpidem exposure
Z-drugs
Inhibition of CYP 3A4 by
Zaleplon imatinib:
zaleplon exposure
Inhibition of CYP 3A4 by
Zopiclon imatinib:
zopiclon exposure
Inhibition of CYP 3A4 by
Alprazolam imatinib:
alprazolam exposure
Inhibition of CYP 3A4 by
Bromazepam imatinib:
bromazepam exposure
Inhibition of CYP 3A4 by
Clonazepam imatinib:
clonazepam exposure
Benzodiazepines
Oxazepam
Lorazepam
Inhibition of CYP 3A4 by
Diazepam imatinib:
diazepam exposure
Inhibition of CYP 3A4 by
imatinib:
midazolam exposure
Inhibition of Pgp by midazolam:
Midazolam imatinib exposure
Inhibition of hOCT1 by
midazolam :
imatinib intracellular exposure
Inhibition of CYP 2C9 and
Barbiturates
2C19 by imatinib:
phenobarbital exposure
Phenobarbital
Induction of CYP 3A4 by
phenobarbital:
imatinib exposure
Dasatinib Nilotinib
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
zolpidem exposure zolpidem exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
zaleplon exposure zaleplon exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
zopiclon exposure zopiclon exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
alprazolam exposure alprazolam exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
bromazepam exposure bromazepam exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
clonazepam exposure clonazepam exposure
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by
dasatinib: nilotinib:
diazepam exposure diazepam exposure
Inhibition of CYP 3A4 by
dasatinib: Inhibition of CYP 3A4 by
midazolam exposure nilotinib:
Inhibition of Pgp by midazolam: midazolam exposure
dasatinib exposure
Inhibition of CYP 2C9 by
Induction of CYP 3A4 by nilotinib:
phenobarbital: phenobarbital exposure
dasatinib exposure Induction of CYP 3A4 by
phenobarbital:
nilotinib exposure
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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Inhibition of CYP 3A4 by
dasatinib:
Inhibition of CYP 3A4 and 2D6 QT interval
haloperidol exposure
Haloperidol by imatinib: (additive effect)
QT interval
haloperidol exposure monitor ECG
(additive effect)
Antipsychotic agents

monitor ECG
Inhibition of CYP 3A4 by Inhibition of CYP 3A4 and 2D6
Inhibition of CYP 3A4 and 2D6
dasatinib: by nilotinib:
Clozapine by imatinib:
clozapine exposure clozapine exposure
clozapine exposure

Olanzapine

Inhibition of CYP 2D6 by QT interval QT interval

Risperidone imatinib: (additive effect) (additive effect)
risperidone exposure monitor ECG monitor ECG

Induction of CYP 3A4 by Induction of CYP 3A4 by Induction of CYP 3A4 by

Phenytoin phenytoin : phenytoin : phenytoin :
imatinib exposure dasatinib exposure nilotinib exposure

Inhibition of CYP 2C9 and 2C19 Inhibition of CYP 2C9 by

by imatinib: nilotinib:
valproic acid exposure Inhibition of CYP 3A4 by valproic acid exposure
Valproic acid Inhibition of CYP 3A4 by valproic valproic acid : Inhibition of CYP 3A4 by
acid: dasatinib exposure valproic acid :
imatinib exposure nilotinib exposure
Antiseizure drugs

Induction of CYP 3A4 and Pgp Induction of CYP 3A4 and Induction of CYP 3A4 by
Carbamazepine by carbamazepine: Pgp by carbamazepine: carbamazepine:
imatinib exposure dasatinib exposure nilotinib exposure

Lamotrigine

Gabapentin

Induction of CYP 3A4 by Induction of CYP 3A4 by Induction of CYP 3A4 by

Topiramate topiramate : topiramate : topiramate :
imatinib exposure dasatinib exposure nilotinib exposure

Levetiracetam
Antimaniac
drug

Lithium
Aminoketone

Induction of CYP 2B6 by

nilotinib:
Bupropion bupropion exposure
bupropion bioactivation

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Imatinib Dasatinib Nilotinib

Morphine

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and

Inhibition of CYP 3A4 by
2D6 by imatinib : 2D6 by nilotinib :
Tramadol dasatinib :
tramadol exposure tramadol exposure
tramadol exposure
tramadol bioactivation tramadol bioactivation

Inhibition of CYP 3A4 by

QT interval
nilotinib :
Inhibition of CYP 3A4 by (additive effect)
methadone exposure
imatinib : Inhibition of CYP 3A4 by
Induction of CYP 2B6 by
Methadone methadone exposure dasatinib :
nilotinib:
Inhibition of Pgp by methadone exposure
methadone exposure
methadone: Inhibition of Pgp by methadone:
QT interval
Opioids

imatinib exposure. dasatinib exposure.

(additive effect)

Hydromorphone

Inhibition of CYP 3A4 and Inhibition of CYP 3A4 and

Inhibition of CYP 3A4 by
2D6 by imatinib : 2D6 by nilotinib :
Oxycodone dasatinib :
oxycodone exposure oxycodone exposure
oxycodone exposure
oxycodone bioactivation oxycodone bioactivation

Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 by dasatinib:
Buprenorphine imatinib : nilotinib:
buprenorphine exposure
buprenorphine exposure buprenorphine exposure

Inhibition of o-
glucuronidation
Other

Acetaminophen by imatinib :
acetaminophen
exposure

Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by

imatinib: Inhibition of CYP 3A4 by dasatinib: nilotinib:
Dihydroergotamine
dihydroergotamine dihydroergotamine exposure dihydroergotamine
Antimigraine
preparations

exposure exposure

Sumatriptan

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Respiratory system

Imatinib Dasatinib Nilotinib

Inhibition of Pgp by nilotinib:

Cetirizin
cetirizin exposure

Inhibition of Pgp by nilotinib:

Levocetirizin
H1-antagonists

cetirizin exposure

Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by

Inhibition of Pgp by nilotinib:
Loratadin imatinib : dasatinib:
loratadin exposure
loratadin exposure loratadin exposure

Fexofenadin
Anti asthma drugs

Salbutamol

Theophylline

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 Haouala et al Drug interactions with the tyrosine kinase inhibitors imatinib, dasatinib and nilotinib

Miscellaneous

Imatinib Dasatinib Nilotinib

Induction of CYP 3A4 by St Induction of CYP 3A4 by St Induction of CYP 3A4 by St

Johns wort: Johns wort: Johns wort:
St Johns wort
imatinib exposure dasatinib exposure nilotinib exposure

Inhibition of CYP 3A4 and Pgp Inhibition of CYP 3A4 and Pgp Inhibition of CYP 3A4 by
Grapefruit by grapefruit: by grapefruit: grapefruit:
imatinib exposure dasatinib exposure nilotinib exposure

Inhibition of CYP 3A4 by Inhibition of CYP 3A4 by

Inhibition of CYP 3A4 by licorice:
licorice: licorice:
Licorice imatinib exposure
dasatinib exposure nilotinib exposure

a
TKIs in general can cause thrombocytopenia, which is usually of no clinical relevance, please take that into
consideration when coadministrating with anticoagulant medication.

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