Gefitinib (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- GEFITINIB
- IRESSA
Indications and Usage
Gefitinib tablets are indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test [see Clinical Studies (14)]. Limitation of Use: Safety and efficacy of gefitinib tablets have not been established in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations [seeClinical Studies (14)].
Contraindications
None.
Adverse Reactions
The following adverse drug reactions are discussed in more detail in other sections of the labeling: Interstitial Lung Disease [see Warnings and Precautions (5.1)] Hepatotoxicity [see Warnings and Precautions (5.2)] Gastrointestinal Perforation [see Warnings and Precautions (5.3)] Severe or Persistent Diarrhea [see Warnings and Precautions (5.4)] Ocular Disorders including Keratitis [see Warnings and Precautions (5.5)] Bullous and Exfoliative Skin Disorders [see Warning and Precautions (5.6)]
Mechanism of Action
The epidermal growth factor receptor (EGFR) is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation. Some EGFR activating mutations (exon 19 deletion or exon 21 point mutation L858R) within NSCLC cells have been identified as contributing to the promotion of tumor cell growth, blocking of apoptosis, increasing the production of angiogenic factors and facilitating the processes of metastasis. Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signaling and blocking EGFR-dependent proliferation. Gefitinib binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. Gefitinib also inhibits IGF and PDGF-mediated signaling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized.
Overdosage
Twenty three patients were treated weekly with doses from 1500 mg to 3500 mg, and gefitinib tablets exposure did not increase with increasing dose. Adverse events were mostly mild to moderate in severity, and were consistent with the known safety profile of gefitinib tablets. In the event of suspected overdose, interrupt gefitinib tablets, institute supportive care, and observe until clinical stabilization. There are no specific measures/treatments that should be taken following gefitinib tablets overdosing.