Non-small cell lung cancer, Metastatic, first-line therapy, EGFR exon 19 deletions or exon 21 substitution mutations.

Gefitinib, a tyrosine-kinase inhibitor of activating mutations of epidermal growth factor receptors (EGFR), prevents the autophosphorylation, thereby inhibiting downstream signally and blocking EGFR-dependent proliferation. Its affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than affinity for wild-type EGFR.

Absorption Tmax, oral: 3 to 7 hours. Bioavailabililty, oral: 60%. Effects of Food: No significant effect on bioavailability. Distribution
Protein binding, serum albumin and alfa-1-acid glycoprotein: 90%. Vd: 1400 L. Metabolism
Liver: primarily. Metabolites: 8 metabolites including O-desmethyl gefitinib: 1/14 of the potency of gefitinib. Substrate of CYP3A4 (mainly), CYP2D6, and P-gp. Inhibitor of CYP2C19 and CYP2D6. Excretion
Renal: Less than 4%. Fecal: 86%. Elimination Half Life
48 hours .

Specific contraindications have not been determined.

Fetal risk cannot be ruled out. Avoid using gefitinib during pregnancy.

Infant risk cannot be ruled out.

Central nervous system: Insomnia (15%), fatigue (14%)
Dermatologic: Dermatological reaction (47% to 58%), skin rash (52%), xeroderma (24%), pruritus (18%), paronychia (14%), acne vulgaris (11%), alopecia (5% to 11%)
Gastrointestinal: Diarrhea (29% to 47%; grades 3/4: 3%), anorexia (19% to 20%), nausea (17% to 18%), decreased appetite (17%), vomiting (13% to 14%), stomatitis (7% to 13%), constipation (12%)
Genitourinary: Proteinuria (8% to 35%)
Hepatic: Increased serum AST (8% to 40%; grades 3/4: 2% to 3%), increased serum ALT (11% to 38%; grades 3/4: 2% to 5%)
Neuromuscular & skeletal: Weakness (18%)

Non-small cell lung cancer, Metastatic, first-line therapy, EGFR exon 19 deletions or exon 21 substitution mutations:
250 mg QD without regard to food until disease progression or unacceptable toxicity;
do not administer a missed dose within 12 hours of the next dose.
[Patients with difficulty swallowing, NG tube]:
Immerse tablets in 4 to 8 ounces of water and stir for about 15 minutes.
Drink immediately, or via NG tube.
Rinse container with another 4 to 8 ounces of water and drink immediately.

Safety and efficacy in pediatric patients have not been established.

Due to minimal renal excretion (<4% of gefitinib and metabolites) the need for dosage adjustment is unlikely.
Use has not been studied in patients with CrCl ?20 mL/minute.

ALT and/or AST elevations (grade 2 or higher):
Withhold treatment for up to 14 days;
may resume treatment when fully resolved or improved to grade 1.
Severe hepatic impairment: Permanently discontinue.
[Concomitant strong CYP3A4 inducer, in the absence of severe adverse effects]:
Increase gefitinib to 500 mg once daily;
7 days after discontinuation of the strong CYP3A4 inducer, resume gefitinib 250 mg once daily.

Store at a controlled room temperature between 20 and 25°C.