Identification

Name
Afatinib
Accession Number
DB08916
Type
Small Molecule
Groups
Approved
Description

Afatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor in the form of a dimaleate salt available as Boehringer Ingelheim's brand name Gilotrif [Label]. For oral use, afatinib tablets are a first-line (initial) treatment for patients with metastatic non-small cell lung cancer (NSCLC) with common epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test [4]. Gilotrif (afatinib) is the first FDA-approved oncology product from Boehringer Ingelheim [4].

Structure
Thumb
Synonyms
  • Afatinibum
External IDs
BIBW 2992 / BIBW-2992 / BIBW2992
Product Ingredients
IngredientUNIICASInChI Key
Afatinib dimaleateV1T5K7RZ0B850140-73-7USNRYVNRPYXCSP-JUGPPOIOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GilotrifTablet, film coated20 mg/1OralBoehringer Ingelheim2013-07-12Not applicableUs
GilotrifTablet, film coated40 mg/1OralBoehringer Ingelheim2013-07-12Not applicableUs
GilotrifTablet, film coated30 mg/1OralBoehringer Ingelheim2013-07-12Not applicableUs
GiotrifTablet20 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2014-01-17Not applicableCanada
GiotrifTablet40 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2014-01-17Not applicableCanada
GiotrifTablet30 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2014-01-17Not applicableCanada
Categories
UNII
41UD74L59M
CAS number
850140-72-6
Weight
Average: 485.938
Monoisotopic: 485.162995603
Chemical Formula
C24H25ClFN5O3
InChI Key
ULXXDDBFHOBEHA-CWDCEQMOSA-N
InChI
InChI=1S/C24H25ClFN5O3/c1-31(2)8-3-4-23(32)30-21-11-17-20(12-22(21)34-16-7-9-33-13-16)27-14-28-24(17)29-15-5-6-19(26)18(25)10-15/h3-6,10-12,14,16H,7-9,13H2,1-2H3,(H,30,32)(H,27,28,29)/b4-3+/t16-/m0/s1
IUPAC Name
(2E)-N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[(3S)-oxolan-3-yloxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide
SMILES
CN(C)C\C=C\C(=O)NC1=C(O[C@H]2CCOC2)C=C2N=CN=C(NC3=CC(Cl)=C(F)C=C3)C2=C1

Pharmacology

Indication

Afatinib is a kinase inhibitor indicated as monotherapy [3] for the first-line [Label] treatment of (a) Epidermal Growth Factor Receptor (EGFR) TKI (tyrosine kinase inhibitor)-naive adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have non-resistant EGFR mutations as detected by an FDA-approved test [Label], and (b) adult patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy [Label].

Recently, as of January 2018, the US FDA approved a supplemental New Drug Application for Boehringer Ingelheim's Gilotrif (afatinib) for the first line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have non-resistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test [4]. The new label includes data on three additional EGFR mutations: L861Q, G719X and S768I [4].

Associated Conditions
Pharmacodynamics

Aberrant ErbB signaling triggered by receptor mutations, and/or amplification, and/or receptor ligand overexpression contributes to the malignant phenotype [3]. Mutation in EGFR defines a distinct molecular subtype of lung cancer [3].

In non-clinical disease models with ErbB pathway deregulation, afatinib as a single agent effectively blocks ErbB receptor signaling resulting in tumor growth inhibition or tumor regression [3]. NSCLC tumors with common activating EGFR mutations (Del 19, L858R) and several less common EGFR mutations in exon 18 (G719X) and exon 21 (L861Q) are particularly sensitive to afatinib treatment in non-clinical and clinical settings [3]. Limited non-clinical and/or clinical activity was observed in NSCLC tumors with insertion mutations in exon 20 [3].

The acquisition of a secondary T790M mutation is a major mechanism of acquired resistance to afatinib and gene dosage of the T790M-containing allele correlates with the degree of resistance in vitro [3]. The T790M mutation is found in approximately 50% of patients' tumors upon disease progression on afatinib, for which T790M targeted EGFR TKIs may be considered as a next line treatment option [3]. Other potential mechanisms of resistance to afatinib have been suggested preclinically and MET gene amplification has been observed clinically [3].

At the same time, the effect of multiple doses of afatinib (50 mg once daily) on cardiac electrophysiology and the QTc interval was evaluated in an open-label, single-arm study in patients with relapsed or refractory solid tumors [Label]. Ultimately, no large changes in the mean QTc interval (i.e., >20 ms) were detected in the study [Label].

Mechanism of action

Afatinib is a potent and selective, irreversible ErbB family blocker [3]. Afatinib covalently binds to and irreversibly blocks signaling from all homo and heterodimers formed by the ErbB family members EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4 [3].

In particular, afatinib covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling [Label]. Certain mutations in EGFR, including non-resistant mutations in its kinase domain, can result in increased autophosphorylation of the receptor, leading to receptor activation, sometimes in the absence of ligand binding, and can support cell proliferation in NSCLC [Label]. Non-resistant mutations are defined as those occurring in exons constituting the kinase domain of EGFR that lead to increased receptor activation and where efficacy is predicted by 1) clinically meaningful tumor shrinkage with the recommended dose of afatinib and/or 2) inhibition of cellular proliferation or EGFR tyrosine kinase phosphorylation at concentrations of afatinib sustainable at the recommended dosage according to validated methods [Label]. The most commonly found of these mutations are exon 21 L858R substitutions and exon 19 deletions [Label].

Moreover, afatinib demonstrated inhibition of autophosphorylation and/or in vitro proliferation of cell lines expressing wild-type EGFR and in those expressing selected EGFR exon 19 deletion mutations, exon 21 L858R mutations, or other less common non-resistant mutations, at afatinib concentrations achieved in patients [Label]. In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2 [Label].

TargetActionsOrganism
AEpidermal growth factor receptor
inhibitor
Human
AReceptor tyrosine-protein kinase erbB-2
inhibitor
Human
AReceptor tyrosine-protein kinase erbB-4
inhibitor
Human
Absorption

Following oral administration, time to peak plasma concentration (Tmax) is 2 to 5 hours [Label]. Maximum concentration (Cmax) and area under the concentration-time curve from time zero to infinity (AUC0-∞) values increased slightly more than dose proportional in the range of 20 to 50 mg [Label]. The geometric mean relative bioavailability of 20 mg tablets was 92% as compared to an oral solution [Label].

Additionally, systemic exposure to afatinib is decreased by 50% (Cmax) and 39% (AUC0-∞), when administered with a high-fat meal compared to administration in the fasted state [3]. Based on population pharmacokinetic data derived from clinical trials in various tumor types, an average decrease of 26% in AUCss was observed when food was consumed within 3 hours before or 1 hour after taking afatinib [3].

Volume of distribution

The volume of distribution of afatinib recorded in healthy male volunteers is documented as 4500 L [2]. Such a high volume of distribution in plasma suggests a potentially high tissue distribution [2].

Protein binding

In vitro binding of afatinib to human plasma proteins is approximately 95% [3]. Afatinib binds to proteins both non-covalently (traditional protein binding) and covalently [3].

Metabolism

Enzyme-catalyzed metabolic reactions play a negligible role for afatinib in vivo [3]. Covalent adducts to proteins were the major circulating metabolites of afatinib [3].

Route of elimination

In humans, excretion of afatinib is primarily via the feces [3]. Following administration of an oral solution of 15 mg afatinib, 85.4% of the dose was recovered in the feces and 4.3% in urine [3]. The parent compound afatinib accounted for 88% of the recovered dose [3].

Half life

Afatinib is eliminated with an effective half-life of approximately 37 hours [3]. Thus, steady-state plasma concentrations of afatinib were achieved within 8 days of multiple dosing of afatinib resulting in an accumulation of 2.77-fold (AUC0-∞) and 2.11-fold (Cmax) [3]. In patients treated with afatinib for more than 6 months, a terminal half-life of 344 h was estimated [3].

Clearance

The apparent total body clearance of afatinib as recorded in healthy male volunteers is documented as being a high geometric mean of 1530 mL/min [2].

Toxicity

Most common adverse reactions (≥20%) are diarrhea, rash/dermatitis, acneiform, stomatitis, paronychia, dry skin, decreased appetite, pruritus [Label].

Conversely, overdose in 2 healthy adolescents involving the ingestion of 360 mg each of afatinib (as part of a mixed drug ingestion) was associated with adverse events of nausea, vomiting, asthenia, dizziness, headache, abdominal pain and elevated amylase (< 1.5 times ULN) [3]. Both individuals recovered from these adverse events [3].

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Epidermal growth factor receptorL861Q(A;A) / (A;T) / (G;G) / (G;T)T > A or GEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.Details
Epidermal growth factor receptorL858R(G;G) / (G;T)T > GEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.Details
Epidermal growth factor receptorG719A/C(T;T) / (G;T) / (A;A) / (A;G) / (C;C) / (C;G)G > A or C or TEffect Directly StudiedThe presence of this polymorphism in EGFR is associated with a higher response rate to afatinib.Details

Interactions

Drug Interactions
DrugInteractionDrug group
AbemaciclibThe serum concentration of Afatinib can be increased when it is combined with Abemaciclib.Approved, Investigational
AcetaminophenThe serum concentration of Afatinib can be increased when it is combined with Acetaminophen.Approved
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Afatinib.Approved
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Afatinib.Experimental
AlbendazoleThe serum concentration of Afatinib can be increased when it is combined with Albendazole.Approved, Vet Approved
AldosteroneThe serum concentration of Afatinib can be decreased when it is combined with Aldosterone.Experimental, Investigational
AlectinibThe serum concentration of Afatinib can be increased when it is combined with Alectinib.Approved, Investigational
AlfentanilThe serum concentration of Afatinib can be increased when it is combined with Alfentanil.Approved, Illicit
AmantadineThe serum concentration of Afatinib can be increased when it is combined with Amantadine.Approved
Aminohippuric acidThe serum concentration of Afatinib can be increased when it is combined with Aminohippuric acid.Approved, Investigational
AmiodaroneThe serum concentration of Afatinib can be increased when it is combined with Amiodarone.Approved, Investigational
AmitriptylineThe serum concentration of Afatinib can be increased when it is combined with Amitriptyline.Approved
AmlodipineThe serum concentration of Afatinib can be increased when it is combined with Amlodipine.Approved
AmprenavirThe serum concentration of Afatinib can be decreased when it is combined with Amprenavir.Approved, Investigational
AmsacrineThe serum concentration of Afatinib can be increased when it is combined with Amsacrine.Approved, Investigational
AncestimThe risk or severity of cytotoxicity can be increased when Ancestim is combined with Afatinib.Approved, Investigational, Withdrawn
ApalutamideThe serum concentration of Afatinib can be decreased when it is combined with Apalutamide.Approved, Investigational
AstemizoleThe serum concentration of Afatinib can be increased when it is combined with Astemizole.Approved, Withdrawn
AtazanavirThe serum concentration of Afatinib can be increased when it is combined with Atazanavir.Approved, Investigational
AtenololThe serum concentration of Afatinib can be increased when it is combined with Atenolol.Approved
AtorvastatinThe serum concentration of Afatinib can be increased when it is combined with Atorvastatin.Approved
AzelastineThe serum concentration of Afatinib can be increased when it is combined with Azelastine.Approved
AzithromycinThe serum concentration of Afatinib can be increased when it is combined with Azithromycin.Approved
BepridilThe serum concentration of Afatinib can be increased when it is combined with Bepridil.Approved, Withdrawn
BevacizumabBevacizumab may increase the cardiotoxic activities of Afatinib.Approved, Investigational
BiperidenThe serum concentration of Afatinib can be increased when it is combined with Biperiden.Approved, Investigational
BoceprevirThe serum concentration of Afatinib can be increased when it is combined with Boceprevir.Approved, Withdrawn
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Afatinib.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Afatinib.Approved, Investigational
BromocriptineThe serum concentration of Afatinib can be increased when it is combined with Bromocriptine.Approved, Investigational
BuprenorphineThe serum concentration of Afatinib can be increased when it is combined with Buprenorphine.Approved, Illicit, Investigational, Vet Approved
BuspironeThe serum concentration of Afatinib can be increased when it is combined with Buspirone.Approved, Investigational
CabazitaxelThe serum concentration of Afatinib can be increased when it is combined with Cabazitaxel.Approved
CaffeineThe serum concentration of Afatinib can be increased when it is combined with Caffeine.Approved
CanagliflozinThe serum concentration of Afatinib can be increased when it is combined with Canagliflozin.Approved
CandesartanThe serum concentration of Afatinib can be increased when it is combined with Candesartan.Experimental
Candesartan cilexetilThe serum concentration of Afatinib can be increased when it is combined with Candesartan cilexetil.Approved
CaptoprilThe serum concentration of Afatinib can be increased when it is combined with Captopril.Approved
CarbamazepineThe serum concentration of Afatinib can be decreased when it is combined with Carbamazepine.Approved, Investigational
CarvedilolThe serum concentration of Afatinib can be increased when it is combined with Carvedilol.Approved, Investigational
CaspofunginThe serum concentration of Afatinib can be increased when it is combined with Caspofungin.Approved
ChloroquineThe serum concentration of Afatinib can be increased when it is combined with Chloroquine.Approved, Investigational, Vet Approved
ChlorpromazineThe serum concentration of Afatinib can be increased when it is combined with Chlorpromazine.Approved, Investigational, Vet Approved
ChlorpropamideThe serum concentration of Afatinib can be increased when it is combined with Chlorpropamide.Approved, Investigational
ChlorprothixeneThe serum concentration of Afatinib can be increased when it is combined with Chlorprothixene.Approved, Investigational, Withdrawn
CholesterolThe serum concentration of Afatinib can be increased when it is combined with Cholesterol.Approved, Investigational
Cholic AcidThe serum concentration of Afatinib can be decreased when it is combined with Cholic Acid.Approved
CilazaprilThe serum concentration of Afatinib can be increased when it is combined with Cilazapril.Approved
CimetidineThe serum concentration of Cimetidine can be increased when it is combined with Afatinib.Approved, Investigational
CiprofloxacinThe serum concentration of Ciprofloxacin can be increased when it is combined with Afatinib.Approved, Investigational
CitalopramThe serum concentration of Afatinib can be increased when it is combined with Citalopram.Approved
ClarithromycinThe serum concentration of Afatinib can be increased when it is combined with Clarithromycin.Approved
ClofazimineThe serum concentration of Afatinib can be increased when it is combined with Clofazimine.Approved, Investigational
ClomipramineThe serum concentration of Afatinib can be increased when it is combined with Clomipramine.Approved, Investigational, Vet Approved
ClotrimazoleThe serum concentration of Afatinib can be decreased when it is combined with Clotrimazole.Approved, Vet Approved
CobicistatThe serum concentration of Afatinib can be increased when it is combined with Cobicistat.Approved
ColchicineThe serum concentration of Afatinib can be increased when it is combined with Colchicine.Approved
ColforsinThe serum concentration of Afatinib can be increased when it is combined with Colforsin.Experimental, Investigational
CrizotinibThe serum concentration of Afatinib can be increased when it is combined with Crizotinib.Approved
CurcuminThe serum concentration of Afatinib can be increased when it is combined with Curcumin.Approved, Investigational
CyclophosphamideThe serum concentration of Afatinib can be increased when it is combined with Cyclophosphamide.Approved, Investigational
CyclosporineThe serum concentration of Afatinib can be increased when it is combined with Cyclosporine.Approved, Investigational, Vet Approved
CymarinCymarin may decrease the cardiotoxic activities of Afatinib.Experimental
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Afatinib.Approved
DaclatasvirThe serum concentration of Afatinib can be increased when it is combined with Daclatasvir.Approved, Investigational
DactinomycinThe serum concentration of Afatinib can be increased when it is combined with Dactinomycin.Approved, Investigational
DapagliflozinThe serum concentration of Dapagliflozin can be increased when it is combined with Afatinib.Approved
DasatinibThe serum concentration of Afatinib can be increased when it is combined with Dasatinib.Approved, Investigational
DaunorubicinThe serum concentration of Afatinib can be decreased when it is combined with Daunorubicin.Approved
DesipramineThe serum concentration of Afatinib can be increased when it is combined with Desipramine.Approved, Investigational
DeslanosideDeslanoside may decrease the cardiotoxic activities of Afatinib.Approved
DesloratadineThe serum concentration of Afatinib can be increased when it is combined with Desloratadine.Approved, Investigational
DexamethasoneThe serum concentration of Afatinib can be decreased when it is combined with Dexamethasone.Approved, Investigational, Vet Approved
DexniguldipineThe serum concentration of Afatinib can be increased when it is combined with Dexniguldipine.Experimental
DexverapamilThe serum concentration of Afatinib can be increased when it is combined with Dexverapamil.Experimental
DigitoxinDigitoxin may decrease the cardiotoxic activities of Afatinib.Approved, Investigational
DigoxinThe serum concentration of Afatinib can be decreased when it is combined with Digoxin.Approved
Digoxin Immune Fab (Ovine)Digoxin Immune Fab (Ovine) may decrease the cardiotoxic activities of Afatinib.Approved
DihydroergotamineThe serum concentration of Afatinib can be increased when it is combined with Dihydroergotamine.Approved, Investigational
DiltiazemThe serum concentration of Afatinib can be increased when it is combined with Diltiazem.Approved, Investigational
DipyridamoleThe serum concentration of Afatinib can be increased when it is combined with Dipyridamole.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Afatinib.Approved, Investigational
DoxazosinThe serum concentration of Afatinib can be increased when it is combined with Doxazosin.Approved
DoxepinThe serum concentration of Afatinib can be increased when it is combined with Doxepin.Approved, Investigational
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Afatinib.Approved, Investigational
DoxorubicinThe serum concentration of Afatinib can be decreased when it is combined with Doxorubicin.Approved, Investigational
DronabinolThe serum concentration of Afatinib can be increased when it is combined with Dronabinol.Approved, Illicit
DronedaroneThe serum concentration of Afatinib can be increased when it is combined with Dronedarone.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Afatinib.Approved
EltrombopagThe serum concentration of Afatinib can be increased when it is combined with Eltrombopag.Approved
EmopamilThe serum concentration of Afatinib can be increased when it is combined with Emopamil.Experimental
EnalaprilThe serum concentration of Afatinib can be increased when it is combined with Enalapril.Approved, Vet Approved
EnasidenibThe serum concentration of Afatinib can be increased when it is combined with Enasidenib.Approved, Investigational
EnzalutamideThe serum concentration of Afatinib can be increased when it is combined with Enzalutamide.Approved
ErgonovineThe serum concentration of Afatinib can be increased when it is combined with Ergonovine.Approved
ErgotamineThe serum concentration of Afatinib can be increased when it is combined with Ergotamine.Approved
ErythromycinThe serum concentration of Afatinib can be increased when it is combined with Erythromycin.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Afatinib can be increased when it is combined with Estramustine.Approved, Investigational
EstriolThe serum concentration of Afatinib can be decreased when it is combined with Estriol.Approved, Investigational, Vet Approved
EstroneThe serum concentration of Afatinib can be decreased when it is combined with Estrone.Approved
EtoposideThe serum concentration of Afatinib can be increased when it is combined with Etoposide.Approved
EtravirineThe serum concentration of Afatinib can be increased when it is combined with Etravirine.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Afatinib.Approved
FelodipineThe serum concentration of Afatinib can be increased when it is combined with Felodipine.Approved, Investigational
FentanylThe serum concentration of Afatinib can be increased when it is combined with Fentanyl.Approved, Illicit, Investigational, Vet Approved
FexofenadineThe serum concentration of Afatinib can be increased when it is combined with Fexofenadine.Approved, Investigational
FidaxomicinThe serum concentration of Afatinib can be increased when it is combined with Fidaxomicin.Approved
FluconazoleThe serum concentration of Afatinib can be increased when it is combined with Fluconazole.Approved, Investigational
FluoxetineThe serum concentration of Afatinib can be increased when it is combined with Fluoxetine.Approved, Vet Approved
FlupentixolThe serum concentration of Afatinib can be increased when it is combined with Flupentixol.Approved, Investigational, Withdrawn
FluphenazineThe serum concentration of Afatinib can be increased when it is combined with Fluphenazine.Approved
FlurazepamThe serum concentration of Afatinib can be increased when it is combined with Flurazepam.Approved, Illicit, Investigational
Fluticasone propionateThe serum concentration of Fluticasone propionate can be increased when it is combined with Afatinib.Approved
FluvoxamineThe serum concentration of Afatinib can be increased when it is combined with Fluvoxamine.Approved, Investigational
GallopamilThe serum concentration of Afatinib can be increased when it is combined with Gallopamil.Investigational
GefitinibThe serum concentration of Afatinib can be increased when it is combined with Gefitinib.Approved, Investigational
GenisteinThe serum concentration of Afatinib can be increased when it is combined with Genistein.Investigational
GitoformateGitoformate may decrease the cardiotoxic activities of Afatinib.Experimental
GlecaprevirThe serum concentration of Afatinib can be increased when it is combined with Glecaprevir.Approved, Investigational
GlyburideThe serum concentration of Afatinib can be increased when it is combined with Glyburide.Approved
GlycerinThe serum concentration of Afatinib can be increased when it is combined with Glycerin.Approved, Investigational
Gramicidin DThe serum concentration of Afatinib can be increased when it is combined with Gramicidin D.Approved
GrepafloxacinThe serum concentration of Afatinib can be increased when it is combined with Grepafloxacin.Approved, Investigational, Withdrawn
HaloperidolThe serum concentration of Afatinib can be increased when it is combined with Haloperidol.Approved
HydrocortisoneThe serum concentration of Hydrocortisone can be increased when it is combined with Afatinib.Approved, Vet Approved
IbuprofenThe serum concentration of Afatinib can be increased when it is combined with Ibuprofen.Approved
IdelalisibThe serum concentration of Afatinib can be increased when it is combined with Idelalisib.Approved
ImatinibThe serum concentration of Afatinib can be increased when it is combined with Imatinib.Approved
ImipramineThe serum concentration of Afatinib can be increased when it is combined with Imipramine.Approved
IndinavirThe serum concentration of Afatinib can be decreased when it is combined with Indinavir.Approved
IndomethacinThe serum concentration of Afatinib can be increased when it is combined with Indomethacin.Approved, Investigational
IsavuconazoleThe serum concentration of Afatinib can be increased when it is combined with Isavuconazole.Approved, Investigational
IsavuconazoniumThe serum concentration of Afatinib can be increased when it is combined with Isavuconazonium.Approved, Investigational
IsradipineThe serum concentration of Afatinib can be increased when it is combined with Isradipine.Approved, Investigational
ItraconazoleThe serum concentration of Afatinib can be increased when it is combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Afatinib can be increased when it is combined with Ivacaftor.Approved
IvermectinThe serum concentration of Afatinib can be increased when it is combined with Ivermectin.Approved, Investigational, Vet Approved
KetamineThe serum concentration of Afatinib can be increased when it is combined with Ketamine.Approved, Vet Approved
KetoconazoleThe serum concentration of Afatinib can be increased when it is combined with Ketoconazole.Approved, Investigational
LamivudineThe serum concentration of Lamivudine can be increased when it is combined with Afatinib.Approved, Investigational
LamotrigineThe serum concentration of Lamotrigine can be increased when it is combined with Afatinib.Approved, Investigational
Lanatoside CLanatoside C may decrease the cardiotoxic activities of Afatinib.Experimental
LansoprazoleThe serum concentration of Afatinib can be increased when it is combined with Lansoprazole.Approved, Investigational
LapatinibThe serum concentration of Afatinib can be increased when it is combined with Lapatinib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Afatinib.Approved
LetermovirThe serum concentration of Afatinib can be increased when it is combined with Letermovir.Approved, Investigational
LevetiracetamThe serum concentration of Levetiracetam can be increased when it is combined with Afatinib.Approved, Investigational
LevofloxacinThe serum concentration of Afatinib can be increased when it is combined with Levofloxacin.Approved, Investigational
LevothyroxineThe serum concentration of Afatinib can be decreased when it is combined with Levothyroxine.Approved
LidocaineThe serum concentration of Afatinib can be increased when it is combined with Lidocaine.Approved, Vet Approved
LiothyronineThe serum concentration of Afatinib can be decreased when it is combined with Liothyronine.Approved, Vet Approved
LiotrixThe serum concentration of Afatinib can be decreased when it is combined with Liotrix.Approved
LomerizineThe serum concentration of Afatinib can be increased when it is combined with Lomerizine.Experimental
LomitapideThe serum concentration of Afatinib can be increased when it is combined with Lomitapide.Approved, Investigational
LoperamideThe serum concentration of Afatinib can be increased when it is combined with Loperamide.Approved
LopinavirThe serum concentration of Afatinib can be increased when it is combined with Lopinavir.Approved
LoratadineThe serum concentration of Afatinib can be increased when it is combined with Loratadine.Approved, Investigational
LosartanThe serum concentration of Afatinib can be increased when it is combined with Losartan.Approved
LovastatinThe serum concentration of Afatinib can be increased when it is combined with Lovastatin.Approved, Investigational
LumacaftorThe serum concentration of Afatinib can be decreased when it is combined with Lumacaftor.Approved
MaprotilineThe serum concentration of Afatinib can be increased when it is combined with Maprotiline.Approved, Investigational
MebendazoleThe serum concentration of Afatinib can be increased when it is combined with Mebendazole.Approved, Vet Approved
MefloquineThe serum concentration of Afatinib can be increased when it is combined with Mefloquine.Approved, Investigational
Megestrol acetateThe serum concentration of Afatinib can be increased when it is combined with Megestrol acetate.Approved, Investigational, Vet Approved
MeprobamateThe serum concentration of Afatinib can be increased when it is combined with Meprobamate.Approved, Illicit
MethadoneThe serum concentration of Afatinib can be increased when it is combined with Methadone.Approved
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Afatinib.Approved, Vet Approved
MetildigoxinMetildigoxin may decrease the cardiotoxic activities of Afatinib.Experimental
MibefradilThe serum concentration of Afatinib can be increased when it is combined with Mibefradil.Investigational, Withdrawn
MiconazoleThe serum concentration of Afatinib can be increased when it is combined with Miconazole.Approved, Investigational, Vet Approved
MidazolamThe serum concentration of Afatinib can be decreased when it is combined with Midazolam.Approved, Illicit
MifepristoneThe serum concentration of Afatinib can be decreased when it is combined with Mifepristone.Approved, Investigational
MitomycinThe serum concentration of Afatinib can be increased when it is combined with Mitomycin.Approved
MitoxantroneThe serum concentration of Afatinib can be decreased when it is combined with Mitoxantrone.Approved, Investigational
MorphineThe serum concentration of Afatinib can be increased when it is combined with Morphine.Approved, Investigational
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Afatinib.Approved
NaltrexoneThe serum concentration of Afatinib can be increased when it is combined with Naltrexone.Approved, Investigational, Vet Approved
NaringeninThe serum concentration of Afatinib can be increased when it is combined with Naringenin.Experimental
NefazodoneThe serum concentration of Afatinib can be decreased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Afatinib can be decreased when it is combined with Nelfinavir.Approved
NeostigmineThe serum concentration of Afatinib can be increased when it is combined with Neostigmine.Approved, Vet Approved
NicardipineThe serum concentration of Afatinib can be increased when it is combined with Nicardipine.Approved, Investigational
NifedipineThe serum concentration of Afatinib can be decreased when it is combined with Nifedipine.Approved
NiguldipineThe serum concentration of Afatinib can be increased when it is combined with Niguldipine.Experimental
NilotinibThe serum concentration of Afatinib can be increased when it is combined with Nilotinib.Approved, Investigational
NimodipineThe serum concentration of Afatinib can be increased when it is combined with Nimodipine.Approved, Investigational
NisoldipineThe serum concentration of Afatinib can be increased when it is combined with Nisoldipine.Approved
NitrazepamThe serum concentration of Afatinib can be increased when it is combined with Nitrazepam.Approved
NitrendipineThe serum concentration of Afatinib can be increased when it is combined with Nitrendipine.Approved, Investigational
NorethisteroneThe serum concentration of Afatinib can be decreased when it is combined with Norethisterone.Approved
OleandrinOleandrin may decrease the cardiotoxic activities of Afatinib.Experimental, Investigational
OmeprazoleThe serum concentration of Afatinib can be increased when it is combined with Omeprazole.Approved, Investigational, Vet Approved
OuabainOuabain may decrease the cardiotoxic activities of Afatinib.Approved
P-NitrophenolThe serum concentration of Afatinib can be increased when it is combined with P-Nitrophenol.Experimental
PaclitaxelThe serum concentration of Afatinib can be increased when it is combined with Paclitaxel.Approved, Vet Approved
Palmitic AcidThe serum concentration of Afatinib can be increased when it is combined with Palmitic Acid.Approved, Experimental
PantoprazoleThe serum concentration of Afatinib can be increased when it is combined with Pantoprazole.Approved
ParoxetineThe serum concentration of Afatinib can be increased when it is combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Afatinib.Approved
PerindoprilThe serum concentration of Afatinib can be increased when it is combined with Perindopril.Approved
PeruvosidePeruvoside may decrease the cardiotoxic activities of Afatinib.Experimental
PhenobarbitalThe serum concentration of Afatinib can be decreased when it is combined with Phenobarbital.Approved, Investigational
PibrentasvirThe serum concentration of Afatinib can be increased when it is combined with Pibrentasvir.Approved, Investigational
PimozideThe serum concentration of Afatinib can be increased when it is combined with Pimozide.Approved
PitolisantThe serum concentration of Afatinib can be decreased when it is combined with Pitolisant.Approved, Investigational
Platelet Activating FactorThe serum concentration of Afatinib can be decreased when it is combined with Platelet Activating Factor.Experimental
PonatinibThe serum concentration of Afatinib can be increased when it is combined with Ponatinib.Approved, Investigational
PosaconazoleThe serum concentration of Afatinib can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Afatinib can be increased when it is combined with Pravastatin.Approved
PrazosinThe serum concentration of Afatinib can be increased when it is combined with Prazosin.Approved
PrednisoneThe serum concentration of Afatinib can be increased when it is combined with Prednisone.Approved, Vet Approved
ProbenecidThe serum concentration of Afatinib can be increased when it is combined with Probenecid.Approved, Investigational
ProgesteroneThe serum concentration of Afatinib can be decreased when it is combined with Progesterone.Approved, Vet Approved
PromethazineThe serum concentration of Afatinib can be increased when it is combined with Promethazine.Approved, Investigational
PropafenoneThe serum concentration of Afatinib can be increased when it is combined with Propafenone.Approved
PropranololThe serum concentration of Propranolol can be increased when it is combined with Afatinib.Approved, Investigational
ProscillaridinProscillaridin may decrease the cardiotoxic activities of Afatinib.Experimental
ProtriptylineThe serum concentration of Afatinib can be increased when it is combined with Protriptyline.Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Afatinib.Approved
QuercetinThe serum concentration of Afatinib can be increased when it is combined with Quercetin.Experimental, Investigational
QuetiapineThe serum concentration of Quetiapine can be increased when it is combined with Afatinib.Approved
QuinacrineThe serum concentration of Afatinib can be increased when it is combined with Quinacrine.Approved, Investigational
QuinidineThe serum concentration of Afatinib can be increased when it is combined with Quinidine.Approved, Investigational
QuinineThe serum concentration of Afatinib can be increased when it is combined with Quinine.Approved
RanitidineThe serum concentration of Afatinib can be increased when it is combined with Ranitidine.Approved
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Afatinib.Approved, Investigational
ReboxetineThe serum concentration of Afatinib can be increased when it is combined with Reboxetine.Approved, Investigational
RegorafenibThe serum concentration of Afatinib can be increased when it is combined with Regorafenib.Approved
ReserpineThe serum concentration of Afatinib can be decreased when it is combined with Reserpine.Approved, Investigational
RifampicinThe serum concentration of Afatinib can be decreased when it is combined with Rifampicin.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Afatinib.Approved, Investigational
RilpivirineThe serum concentration of Afatinib can be increased when it is combined with Rilpivirine.Approved
RitonavirThe serum concentration of Afatinib can be decreased when it is combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Afatinib can be increased when it is combined with Rolapitant.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Afatinib.Approved
RucaparibThe serum concentration of Afatinib can be increased when it is combined with Rucaparib.Approved, Investigational
SaquinavirThe serum concentration of Afatinib can be decreased when it is combined with Saquinavir.Approved, Investigational
ScopolamineThe serum concentration of Afatinib can be increased when it is combined with Scopolamine.Approved, Investigational
SelegilineThe serum concentration of Afatinib can be increased when it is combined with Selegiline.Approved, Investigational, Vet Approved
SertralineThe serum concentration of Afatinib can be increased when it is combined with Sertraline.Approved
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Afatinib.Approved
SimeprevirThe serum concentration of Afatinib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Afatinib can be increased when it is combined with Simvastatin.Approved
SirolimusThe serum concentration of Afatinib can be decreased when it is combined with Sirolimus.Approved, Investigational
SitagliptinThe serum concentration of Sitagliptin can be increased when it is combined with Afatinib.Approved, Investigational
SorafenibThe serum concentration of Afatinib can be increased when it is combined with Sorafenib.Approved, Investigational
SpironolactoneThe serum concentration of Afatinib can be decreased when it is combined with Spironolactone.Approved
St. John's WortThe serum concentration of Afatinib can be decreased when it is combined with St. John's Wort.Approved, Investigational, Nutraceutical
StaurosporineThe serum concentration of Afatinib can be increased when it is combined with Staurosporine.Experimental
StreptozocinThe serum concentration of Afatinib can be decreased when it is combined with Streptozocin.Approved, Investigational
SulfasalazineThe serum concentration of Afatinib can be increased when it is combined with Sulfasalazine.Approved
SulfinpyrazoneThe serum concentration of Afatinib can be increased when it is combined with Sulfinpyrazone.Approved
SumatriptanThe serum concentration of Sumatriptan can be increased when it is combined with Afatinib.Approved, Investigational
SunitinibThe serum concentration of Afatinib can be increased when it is combined with Sunitinib.Approved, Investigational
TacrineThe serum concentration of Afatinib can be increased when it is combined with Tacrine.Investigational, Withdrawn
TacrolimusThe serum concentration of Afatinib can be decreased when it is combined with Tacrolimus.Approved, Investigational
TamoxifenThe serum concentration of Afatinib can be decreased when it is combined with Tamoxifen.Approved
Taurocholic AcidThe serum concentration of Afatinib can be increased when it is combined with Taurocholic Acid.Experimental
TelaprevirThe serum concentration of Afatinib can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelmisartanThe serum concentration of Afatinib can be increased when it is combined with Telmisartan.Approved, Investigational
TemsirolimusThe serum concentration of Afatinib can be increased when it is combined with Temsirolimus.Approved
TerazosinThe serum concentration of Afatinib can be increased when it is combined with Terazosin.Approved
TerfenadineThe serum concentration of Afatinib can be increased when it is combined with Terfenadine.Approved, Withdrawn
TeriflunomideThe serum concentration of Afatinib can be increased when it is combined with Teriflunomide.Approved
TesmilifeneThe serum concentration of Afatinib can be decreased when it is combined with Tesmilifene.Investigational
TestosteroneThe serum concentration of Afatinib can be increased when it is combined with Testosterone.Approved, Investigational
Testosterone cypionateThe serum concentration of Afatinib can be increased when it is combined with Testosterone cypionate.Approved
Testosterone enanthateThe serum concentration of Afatinib can be increased when it is combined with Testosterone enanthate.Approved
Testosterone undecanoateThe serum concentration of Afatinib can be increased when it is combined with Testosterone undecanoate.Approved, Investigational
TetrandrineThe serum concentration of Afatinib can be increased when it is combined with Tetrandrine.Experimental
TicagrelorThe serum concentration of Afatinib can be increased when it is combined with Ticagrelor.Approved
TolvaptanThe serum concentration of Afatinib can be increased when it is combined with Tolvaptan.Approved
TopiramateThe serum concentration of Topiramate can be increased when it is combined with Afatinib.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Afatinib.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Afatinib.Approved, Investigational
TrazodoneThe serum concentration of Afatinib can be decreased when it is combined with Trazodone.Approved, Investigational
TrifluoperazineThe serum concentration of Afatinib can be increased when it is combined with Trifluoperazine.Approved, Investigational
TriflupromazineThe serum concentration of Afatinib can be increased when it is combined with Triflupromazine.Approved, Vet Approved
TrimethoprimThe serum concentration of Afatinib can be decreased when it is combined with Trimethoprim.Approved, Vet Approved
TrimipramineThe serum concentration of Afatinib can be increased when it is combined with Trimipramine.Approved
TroleandomycinThe serum concentration of Afatinib can be increased when it is combined with Troleandomycin.Approved
VelpatasvirThe serum concentration of Afatinib can be increased when it is combined with Velpatasvir.Approved, Investigational
VemurafenibThe serum concentration of Afatinib can be increased when it is combined with Vemurafenib.Approved
VenlafaxineThe serum concentration of Afatinib can be increased when it is combined with Venlafaxine.Approved
VerapamilThe serum concentration of Afatinib can be increased when it is combined with Verapamil.Approved
VinblastineThe serum concentration of Afatinib can be decreased when it is combined with Vinblastine.Approved
VincristineThe serum concentration of Afatinib can be decreased when it is combined with Vincristine.Approved, Investigational
VincristineThe excretion of Vincristine can be decreased when combined with Afatinib.Approved, Investigational
VinorelbineThe serum concentration of Afatinib can be increased when it is combined with Vinorelbine.Approved, Investigational
VoacamineThe serum concentration of Afatinib can be increased when it is combined with Voacamine.Approved, Investigational
VoxilaprevirThe serum concentration of Afatinib can be increased when it is combined with Voxilaprevir.Approved, Investigational
ZimelidineThe serum concentration of Afatinib can be increased when it is combined with Zimelidine.Withdrawn
Food Interactions
  • When given with a high-fat meal, Cmax decreases by 50% and AUC by 39% relative to the fasted state.

References

General References
  1. Wind S, Schnell D, Ebner T, Freiwald M, Stopfer P: Clinical Pharmacokinetics and Pharmacodynamics of Afatinib. Clin Pharmacokinet. 2017 Mar;56(3):235-250. doi: 10.1007/s40262-016-0440-1. [PubMed:27470518]
  2. Stopfer P, Marzin K, Narjes H, Gansser D, Shahidi M, Uttereuther-Fischer M, Ebner T: Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers. Cancer Chemother Pharmacol. 2012 Apr;69(4):1051-61. doi: 10.1007/s00280-011-1803-9. Epub 2011 Dec 27. [PubMed:22200729]
  3. Electronic Medicines Compendium: Giotrif 30 mg film-coated tablets Monograph [Link]
  4. Boehringer Ingelheim: FDA approves new indication for Gilotrif® in EGFR mutation-positive NSCLC [Link]
External Links
KEGG Drug
D09724
PubChem Compound
10184653
PubChem Substance
175427153
ChemSpider
8360155
BindingDB
50322823
ChEBI
61390
ChEMBL
CHEMBL1173655
PharmGKB
PA165981154
HET
0WM
Drugs.com
Drugs.com Drug Page
Wikipedia
Afatinib
ATC Codes
L01XE13 — Afatinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4g5j
FDA label
Download (427 KB)
MSDS
Download (26.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentGlioblastomas1
1Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Lung Cancers1
1CompletedTreatmentHNSCC1
1CompletedTreatmentHead and Neck Carcinoma / Squamous Cell Cancer1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers / Liver Diseases1
1CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)4
1CompletedTreatmentNeoplasms14
1CompletedTreatmentNeoplasms, Breast1
1CompletedTreatmentNeoplasms, Breast / Stomach Neoplasms1
1RecruitingOtherPancreatic Cancer Metastatic1
1RecruitingTreatmentAdvanced Malignant Solid Neoplasm / Bile Duct Carcinoma / Recurrent Malignant Solid Neoplasm / Recurrent Pancreatic Carcinoma / Solid Neoplasms / Stage III Pancreatic Cancer / Stage III Pancreatic Cancer AJCC v6 and v7 / Stage IVA Pancreatic Cancer / Stage IVB Pancreatic Cancer1
1RecruitingTreatmentBrain Cancer1
1RecruitingTreatmentNon-Small Cell Lung Carcinoma (NSCLC)1
1RecruitingTreatmentRecurrent Non-Small Cell Lung Carcinoma / Stage IIIA Non-Small Cell Lung Cancer / Stage IIIb Non-small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer1
1RecruitingTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1TerminatedTreatmentMetastatic Disease1
1WithdrawnTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
1, 2Not Yet RecruitingTreatmentEGFR Mutation Positive Non Small Cell Lung Cancer1
1, 2RecruitingOtherAdvanced Breast Cancer / Advanced Lung Cancer / Brain Cancer / Cancer, Breast / Lung Cancers1
1, 2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Neoplasms, Colorectal / Neoplasms, Gastrointestinal / Neoplasms, Pancreatic1
1, 2RecruitingTreatmentNeuroectodermal Tumors / Rhabdomyosarcomas1
1, 2TerminatedTreatmentSquamous Cell Carcinoma of the Head and Neck (SCCHN)1
1, 2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentEGFR Gene Mutations / Neoplasms, Lung1
2Active Not RecruitingTreatmentEGFR / Her-2 / Lung Cancer Non-Small Cell Cancer (NSCLC)1
2Active Not RecruitingTreatmentFocus of Study Instead1
2Active Not RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC) / Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma / Salivary Gland Squamous Cell Carcinoma / Stage III Salivary Gland Cancer / Stage III Squamous Cell Carcinoma of the Hypopharynx / Stage III Squamous Cell Carcinoma of the Larynx / Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage III Squamous Cell Carcinoma of the Oropharynx / Stage III Verrucous Carcinoma of the Larynx / Stage III Verrucous Carcinoma of the Oral Cavity / Stage IV Squamous Cell Carcinoma of the Hypopharynx / Stage IV Squamous Cell Carcinoma of the Larynx / Stage IVA Salivary Gland Cancer / Stage IVA Squamous Cell Carcinoma of the Larynx / Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVA Squamous Cell Carcinoma of the Oropharynx / Stage IVA Verrucous Carcinoma of the Larynx / Stage IVA Verrucous Carcinoma of the Oral Cavity / Stage IVB Salivary Gland Cancer / Stage IVB Squamous Cell Carcinoma of the Larynx / Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVB Squamous Cell Carcinoma of the Oropharynx / Stage IVB Verrucous Carcinoma of the Larynx / Stage IVB Verrucous Carcinoma of the Oral Cavity / Stage IVC Salivary Gland Cancer / Stage IVC Squamous Cell Carcinoma of the Larynx / Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity / Stage IVC Squamous Cell Carcinoma of the Oropharynx / Stage IVC Verrucous Carcinoma of the Larynx / Stage IVC Verrucous Carcinoma of the Oral Cavity / Tongue Cancer1
2Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2Active Not RecruitingTreatmentMetastatic Cancers1
2Active Not RecruitingTreatmentNeoplasms, Breast1
2Active Not RecruitingTreatmentNeoplasms, Lung1
2CompletedDiagnosticNeoplasms, Breast1
2CompletedTreatmentCarcinoma, Squamous Cell of Head and Neck2
2CompletedTreatmentGliomas1
2CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)7
2CompletedTreatmentLung Cancers1
2CompletedTreatmentMetastatic Colorectal Cancers1
2CompletedTreatmentNeoplasms1
2CompletedTreatmentNeoplasms Metastasis / Neoplasms, Breast1
2CompletedTreatmentNeoplasms, Breast3
2CompletedTreatmentNeoplasms, Colorectal2
2CompletedTreatmentNeoplasms, Head and Neck / Squamous Cell Carcinoma (SCC)1
2CompletedTreatmentProstatic Neoplasms1
2CompletedTreatmentRefractory Cancer1
2CompletedTreatmentUnilateral HER2 Positive Breast Cancer1
2Not Yet RecruitingTreatmentChordomas1
2Not Yet RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentAdvanced Malignant Neoplasm / Advanced Malignant Solid Neoplasm / Bladder Carcinoma / Carcinoma, Breast / Carcinoma, Colorectal / Carcinoma, Pancreatic / Cervical Carcinoma / Colon Carcinoma / Endometrial Carcinoma / Gastric Carcinoma / Gliomas / Head and Neck Carcinoma / Liver and Intrahepatic Bile Duct Carcinoma / Lung, Carcinoma / Malignant Lymphomas / Malignant Uterine Neoplasm / Melanoma / Oesophageal Carcinoma / Ovarian Carcinoma / Plasma Cell Myeloma / Prostate Cancer / Rectal Carcinoma / Recurrent Bladder Carcinoma / Recurrent Breast Carcinoma / Recurrent Cervical Carcinoma / Recurrent Colon Carcinoma / Recurrent Colorectal Carcinoma / Recurrent Esophageal Carcinoma / Recurrent Gastric Carcinoma / Recurrent Gliomas / Recurrent Head and Neck Carcinoma / Recurrent Liver Carcinoma / Recurrent Lung Carcinoma / Recurrent Lymphoma / Recurrent Malignant Solid Neoplasm / Recurrent Melanoma / Recurrent Ovarian Carcinoma / Recurrent Pancreatic Carcinoma / Recurrent Plasma Cell Myeloma / Recurrent Prostate Carcinoma / Recurrent Rectal Carcinoma / Recurrent Skin Carcinoma / Recurrent Solid Neoplasm / Recurrent Thyroid Gland Carcinoma / Recurrent Uterine Corpus Carcinoma / Refractory Lymphomas / Refractory Malignant Neoplasm / Refractory Malignant Solid Neoplasm / Refractory Plasma Cell Myeloma / Renal Carcinoma / Skin Carcinoma / Solid Neoplasms / Thyroid Gland Carcinoma / Uterine Corpus Cancer1
2RecruitingTreatmentCarcinoma, Squamous Cell of Head and Neck1
2RecruitingTreatmentDistal Urethral Cancer / Metastatic Bladder Cancer / Proximal Urethral Cancer / Recurrent Bladder Cancer / Recurrent Urethral Cancer / Stage III Bladder Cancer / Stage III Urethral Cancer / Stage IV Urethral Cancer / Ureteral Cancer1
2RecruitingTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach1
2RecruitingTreatmentGastroesophageal Junction Cancer / Malignant Neoplasm of Stomach1
2RecruitingTreatmentGastrointestinal Carcinoma, Non-colon / Non-Small Cell Lung Carcinoma (NSCLC) / Transitional Cell Carcinoma / Upper Aerodigestive Tract Carcinoma1
2RecruitingTreatmentHER2/Neu+ Uterine Serous Carcinoma1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)3
2RecruitingTreatmentLung Cancers1
2RecruitingTreatmentPenile Squamous Cell Carcinoma (PSCC)1
2RecruitingTreatmentRare Tumor / Refractory Tumors1
2RecruitingTreatmentSquamous Cell Cancers of the Head and Neck1
2RecruitingTreatmentSquamous Cell Carcinoma of Esophagus1
2RecruitingTreatmentTriple Negative Breast Cancer (TNBC)1
2RecruitingTreatmentTumors, Solid1
2RecruitingTreatmentUrologic Neoplasms1
2SuspendedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentBreast Cancer Metastatic1
2TerminatedTreatmentLung Cancers1
2TerminatedTreatmentNeoplasms1
2TerminatedTreatmentNon-small-cell Lung Cancer With Somatic EGFR Mutations1
2Unknown StatusTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2WithdrawnTreatmentEsophageal Cancers / Gastrooesophageal Cancer / Her-2 Positive Gastric Cancer1
2WithdrawnTreatmentLung Cancers1
2WithdrawnTreatmentSmall Cell Lung Carcinoma1
2, 3RecruitingTreatmentRecurrent Non-Small Cell Lung Carcinoma / Stage IV Non-Small Cell Lung Cancer1
3Active Not RecruitingTreatmentHead and Neck Squamous Cell Carcinoma (HNSCC)1
3Active Not RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
3Active Not RecruitingTreatmentNeoplasms, Head and Neck1
3CompletedTreatmentAdenocarcinomas / Lung Cancer Non-Small Cell Cancer (NSCLC)2
3CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)6
3CompletedTreatmentNeoplasms, Breast1
3CompletedTreatmentNeoplasms, Head and Neck / Squamous Cell Carcinoma (SCC)1
3TerminatedTreatmentNeoplasms, Head and Neck2
4Active Not RecruitingTreatmentErbB Receptors / Lung Cancer Non-Small Cell Cancer (NSCLC)1
4CompletedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
4TerminatedTreatmentErbB Receptors / Lung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableActive Not RecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)2
Not AvailableApproved for MarketingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)3
Not AvailableCompletedNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableCompletedNot AvailableNeoplasms1
Not AvailableCompletedTreatmentEGFR Mutations / Lung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableRecruitingNot AvailableLung Cancer Non-Small Cell Cancer (NSCLC)1
Not AvailableRecruitingOtherEGFR Gene Mutations / Non-Small Cell Adenocarcinoma / Tyrosine kinase mutation1
Not AvailableUnknown StatusDiagnosticEGFR Mutation Positive Non-small Cell Lung Cancer1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral20 mg/1
Tablet, film coatedOral30 mg/1
Tablet, film coatedOral40 mg/1
TabletOral20 mg
TabletOral30 mg
TabletOral40 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6251912No1998-07-292018-07-29Us
US8426586No2009-10-102029-10-10Us
USRE43431No2002-01-222022-01-22Us
US8545884No2009-12-192029-12-19Us
US9539258No2006-11-092026-11-09Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0128 mg/mLALOGPS
logP3.77ALOGPS
logP3.76ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)12.49ChemAxon
pKa (Strongest Basic)8.81ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area88.61 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity131.38 m3·mol-1ChemAxon
Polarizability50.07 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8717
Caco-2 permeable-0.5342
P-glycoprotein substrateSubstrate0.744
P-glycoprotein inhibitor IInhibitor0.6776
P-glycoprotein inhibitor IIInhibitor0.9036
Renal organic cation transporterNon-inhibitor0.7154
CYP450 2C9 substrateNon-substrate0.7919
CYP450 2D6 substrateNon-substrate0.8034
CYP450 3A4 substrateSubstrate0.7504
CYP450 1A2 substrateNon-inhibitor0.5236
CYP450 2C9 inhibitorNon-inhibitor0.7294
CYP450 2D6 inhibitorNon-inhibitor0.7625
CYP450 2C19 inhibitorNon-inhibitor0.5877
CYP450 3A4 inhibitorNon-inhibitor0.6486
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7096
Ames testNon AMES toxic0.5695
CarcinogenicityNon-carcinogens0.8692
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.5643 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8956
hERG inhibition (predictor II)Inhibitor0.7228
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Diazanaphthalenes
Sub Class
Benzodiazines
Direct Parent
Quinazolinamines
Alternative Parents
N-arylamides / Aniline and substituted anilines / Chlorobenzenes / Fluorobenzenes / Aminopyrimidines and derivatives / Alkyl aryl ethers / Imidolactams / Aryl chlorides / Aryl fluorides / Tetrahydrofurans
show 14 more
Substituents
Quinazolinamine / N-arylamide / Aniline or substituted anilines / Alkyl aryl ether / Halobenzene / Fluorobenzene / Aminopyrimidine / Chlorobenzene / Aryl chloride / Imidolactam
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, tertiary amino compound, aromatic ether, enamide, furans, monochlorobenzenes, quinazolines (CHEBI:61390)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. Known ligands include EGF, TG...
Gene Name
EGFR
Uniprot ID
P00533
Uniprot Name
Epidermal growth factor receptor
Molecular Weight
134276.185 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane signaling receptor activity
Specific Function
Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, alt...
Gene Name
ERBB2
Uniprot ID
P04626
Uniprot Name
Receptor tyrosine-protein kinase erbB-2
Molecular Weight
137909.27 Da
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that plays an essential role as cell surface receptor for neuregulins and EGF family members and regulates development of the heart, the central nervous system and the mamma...
Gene Name
ERBB4
Uniprot ID
Q15303
Uniprot Name
Receptor tyrosine-protein kinase erbB-4
Molecular Weight
146806.865 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da

Drug created on July 17, 2013 15:59 / Updated on August 14, 2018 04:31