ZEFTIGLO

Indications

• Non-small cell lung cancer (NSCLC) with EGFR mutations
• Locally advanced or metastatic NSCLC
• First-line treatment in EGFR mutation-positive NSCLC

Dosage

Children: Refer to BNF for Children for specific dosing guidelines.

Adults: Refer to BNF for specific dosing guidelines.

Mechanism of action

Gefitinib selectively binds to the tyrosine kinase domain of the epidermal growth factor receptor (EGFR), inhibiting its phosphorylation and subsequent downstream signaling pathways. This leads to decreased cell proliferation, increased apoptosis, and inhibition of tumor growth in cancer cells that express mutant forms of EGFR.

Pharmacodynamics

Gefitinib's pharmacodynamics involve the inhibition of EGFR-mediated signaling pathways, which are crucial for cellular growth and survival. This inhibition leads to reduced cell viability and induced apoptosis in tumors harboring activating mutations in the EGFR gene. The drug has shown efficacy particularly in patients with NSCLC who possess specific activating mutations in the EGFR gene, such as exon 19 deletions or the L858R point mutation.

Pharmacokinetics

Gefitinib is well absorbed after oral administration, with peak plasma concentrations occurring about 3 to 7 hours post-dose. It has a volume of distribution of approximately 1,200 L, indicating extensive tissue distribution. The drug is primarily metabolized in the liver via cytochrome P450 enzymes, particularly CYP3A4, and has a half-life of about 48 hours, allowing for once-daily dosing. The elimination of gefitinib is primarily through feces, with renal excretion accounting for a minor fraction.

Contra-indications

• Hypersensitivity to gefitinib or any of the excipients
• Severe hepatic impairment

Adverse effects

• Diarrhea
• Rash
• Nausea
• Vomiting
• Anorexia
• Dry skin
• Pruritus
• Fatigue
• Interstitial lung disease
• Hepatotoxicity

Interactions

• Strong CYP3A4 inhibitors may increase gefitinib levels
• CYP3A4 inducers may decrease gefitinib levels
• Concomitant use with warfarin may increase INR

Precautions

• Monitor for symptoms of interstitial lung disease
• Assess liver function regularly
• Use caution in patients with a history of pulmonary disease
• Avoid use in patients with severe hepatic impairment

Pregnancy

Gefitinib is not recommended during pregnancy due to potential harm to the fetus.

Breast-feeding

It is not known whether gefitinib is excreted in human milk; caution should be exercised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets: 250 mg