QuickView for Gefitinib (compound)

Summary
General Info

PubChem

PubChem Compound 11719266

Name:	gefitinib
PubChem Compound ID:	11719266
Molecular formula:	C₂₂H₂₄ClFN₄O₃
Molecular weight:	445.905 g/mol

DrugBank

Identification

Name:	gefitinib
Name (isomeric):	DB00317
Drug Type:	small molecule
Synonyms:	ZD-1839; ZD1839
Brand:	Iressa, Tarceva, Irressat
Category:	Antineoplastic Agents, Protein Kinase Inhibitors
CAS number:	184475-35-2

Pharmacology

Indication:	For the continued treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of either platinum-based or docetaxel chemotherapies.
Pharmacology:	Gefitinib inhibits the intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including the tyrosine kinases associated with the epidermal growth factor receptor (EGFR-TK). EGFR is expressed on the cell surface of many normal cells and cancer cells.
Mechanism of Action:	Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the E... show more » Gefitinib inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. Thus the function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited; and malignant cells are inhibited. Gefitinib is the first selective inhibitor of the EGFR tyrosine kinase which is also referred to as Her1 or ErbB-1. EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. Overexpression leads to inappropriate activation of the apoptotic Ras signal transduction cascade, eventually leading to uncontrolled cell proliferation. show less «
Absorption:	Absorbed slowly after oral administration with mean bioavailability of 60%.
Protein binding:	90% primarily to serum albumin and alpha 1-acid glycoproteins.
Biotransformation:	Primarily hepatic via CYP3A4. Three sites of biotransformation have been identified: metabolism of the N-propoxymorpholino-group, demethylation of the methoxy-substituent on the quinazoline, and oxidative defluorination of the halogenated phenyl group.
Route of elimination:	Elimination is by metabolism (primarily CYP3A4) and excretion in feces. Excretion is predominantly via the feces (86%), with renal elimination of drug and metabolites accounting for less than 4% of the administered dose.
Half Life:	48 hours
Clearance:	595 mL/min
Toxicity:	The acute toxicity of gefitinib up to 500 mg in clinical studies has been low. In non-clinical studies, a single dose of 12,000 mg/m² (about 80 times the recommended clinical dose on a mg/m² basis) was lethal to rats. Half this dose caused no mortality in mice. Symptoms of overdose include diarrhea and skin rash.
Affected organisms:	Humans and other mammals

Interactions

Food interaction:

Take without regard to meals.

Avoid fresh grapefruit and its juice during therapy as grapefruit may increase serum product levels.

Drug interaction:

Topotecan	The BCRP/ABCG2 inhibitor, Gefitnib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Gefitinib is initiated, discontinued or dose changed.
Dihydroquinidine barbiturate	The CYP3A4 inducer, dihydroquinidine barbiturate, may decrease the serum concentration and therapeutic effects of gefitinib.
Heptabarbital	The CYP3A4 inducer, heptabarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Carbamazepine	The CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of gefitinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of gefitinib if voriconazole is initiated, discontinued or dose changed.

Topotecan	The BCRP/ABCG2 inhibitor, Gefitnib, may increase the bioavailability and serum concentration of oral Topotecan. Monitor for change in the therapeutic and adverse effects of Topotecan if Gefitinib is initiated, discontinued or dose changed.
Dihydroquinidine barbiturate	The CYP3A4 inducer, dihydroquinidine barbiturate, may decrease the serum concentration and therapeutic effects of gefitinib.
Heptabarbital	The CYP3A4 inducer, heptabarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Carbamazepine	The CYP3A4 inducer, carbamazepine, may decrease the serum concentration and therapeutic effects of gefitinib.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of gefitinib by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of gefitinib if voriconazole is initiated, discontinued or dose changed.
Butalbital	The CYP3A4 inducer, butalbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Telithromycin	Telithromycin may reduce clearance of Gefitinib. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Gefitinib if Telithromycin is initiated, discontinued or dose changed.
Talbutal	The CYP3A4 inducer, talbutal, may decrease the serum concentration and therapeutic effects of gefitinib.
Aprobarbital	The CYP3A4 inducer, aprobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Hexobarbital	The CYP3A4 inducer, hexobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Anisindione	Gefitinib may increase the anticoagulant effect of anisindione.
Rifampin	Rifampin reduces levels and efficacy of gefitinib
Ritonavir	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Methohexital	The CYP3A4 inducer, methohexital, may decrease the serum concentration and therapeutic effects of gefitinib.
Clarithromycin	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Primidone	The CYP3A4 inducer, primidone, may decrease the serum concentration and therapeutic effects of gefitinib.
Butabarbital	The CYP3A4 inducer, butabarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Secobarbital	The CYP3A4 inducer, secobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Dicumarol	Gefitinib may increase the anticoagulant effect of dicumarol.
Acenocoumarol	Gefitinib may increase the anticoagulant effect of acenocoumarol.
Pentobarbital	The CYP3A4 inducer, pentobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Quinidine barbiturate	The CYP3A4 inducer, quinidine barbiturate, may decrease the serum concentration and therapeutic effects of gefitinib.
Trastuzumab	Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Phenobarbital	The CYP3A4 inducer, phenobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Ketoconazole	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Butethal	The CYP3A4 inducer, butethal, may decrease the serum concentration and therapeutic effects of gefitinib.
Ethotoin	The CYP3A4 inducer, ethotoin, may decrease the serum concentration and therapeutic effects of gefitinib.
St. John's Wort	The CYP3A4 inducer, St. John's Wort, may decrease the serum concentration and therapeutic effects of gefitinib.
Methylphenobarbital	The CYP3A4 inducer, methylphenobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Mephenytoin	The CYP3A4 inducer, mephenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.
Erythromycin	This CYP3A4 inhibitor increases levels/toxicity of gefitinib
Phenytoin	The CYP3A4 inducer, phenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.
Amobarbital	The CYP3A4 inducer, amobarbital, may decrease the serum concentration and therapeutic effects of gefitinib.
Warfarin	Gefitinib may increase the anticoagulant effect of warfarin.
Itraconazole	Itraconazole, a strong CYP3A4 inhibitor, may decrease the metabolism of gefitinib. Monitor for changes in the therapeutic and adverse effects of gefitinib if itraconazole is initiated, discontinued or dose changed.
Fosphenytoin	The CYP3A4 inducer, fosphenytoin, may decrease the serum concentration and therapeutic effects of gefitinib.

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Targets

Epidermal growth factor receptor

Enzymes

Cytochrome P450 3A4

Cytochrome P450 2D6

Transporters

Multidrug resistance protein 1

ATP-binding cassette sub-family G member 2