Gefitinib

IRESSA

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Pronunciation: ge-FI-ti-nib (eye-RES-sa)

Gefitinib ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Gefitinib ballicule

What it isOral first-generation EGFR tyrosine kinase inhibitor that reversibly blocks ATP binding in the EGFR kinase domain.

Why this oneFirst-line therapy for metastatic non-small cell lung cancer harboring sensitizing EGFR mutations (exon 19 deletions or L858R).

What limits itCan cause interstitial lung disease (occasionally fatal) and hepatotoxicity, and its absorption falls sharply when gastric pH is raised by PPIs or H2 blockers.

Gefitinib molecular structure (skeletal formula) — Molecular structure: Gefitinib

FDA label

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FDA dosing	Population	Start	Target	Max
Metastatic NSCLC, first-line, EGFR exon 19 deletion or exon 21 L858R mutation	Adults	250 mg QD	Continue until disease progression or unacceptable toxicity	250 mg QD (500 mg QD only with concomitant strong CYP3A4 inducer)

Renal Undefined

Hepatic No baseline dose adjustment stated; monitor for adverse reactions in moderate-severe impairment (AUC +263%/+166%); discontinue for severe (treatment-emergent) hepatic impairment

Strong CYP3A4 inducer: increase to 500 mg QD (absent severe ADR); resume 250 mg QD 7 days after inducer discontinued

Instructions

With or without food; do not take a missed dose within 12 h of the next dose
Difficulty swallowing: disperse tablet in 4-8 oz water, stir ~15 min, drink immediately (or give via NG tube); rinse container with 4-8 oz water and drink
Withhold up to 14 days for: acute/worsening pulmonary symptoms, Grade >=2 ALT/AST, Grade >=3 diarrhea, severe/worsening ocular disorders, Grade >=3 skin reactions; resume when resolved to <=Grade 1
Permanently discontinue for: confirmed ILD, severe hepatic impairment, GI perforation, persistent ulcerative keratitis

Available strengths

tab 250 mg

Cautions

Interstitial lung disease (1.3%, some fatal) - withhold for worsening respiratory symptoms; discontinue if ILD confirmed
Hepatotoxicity (fatal 0.04%) - periodic LFTs
GI perforation (0.1%) - discontinue
Severe or persistent diarrhea
Ocular disorders incl. keratitis - withhold for severe/worsening; discontinue for persistent ulcerative keratitis
Bullous/exfoliative skin disorders incl. TEN, SJS, erythema multiforme
Embryo-fetal toxicity - contraception during treatment and >=2 weeks after

Adverse reactions

Skin reactions and diarrhea (>20%, > placebo)

Pregnancy Can cause fetal harm (mechanism + animal data: fetotoxicity/neonatal death below recommended human dose); advise risk

Lactation Discontinue breastfeeding during treatment (gefitinib 11-19x higher in rat milk than blood)

Cost

Gefitinib (IRESSA)

Strength		#/mo	generic $/mo	CostPlus
250 mg	tab	30 qd		offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Gefitinib is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry2022

NO BOXED WARNINGS

Principal riskNo FDA boxed warning.

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk3 / 4

Legacy pregnancy categoryD

Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.

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