Gefitinib is 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.

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 signalling and blocking EGFR-dependent proliferation. Gefitinib's binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. It also inhibits IGF and PDGF-mediated signalling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized.

Recommended dose: 250 mg Gefitinib orally once daily with or without food until disease progression or unacceptable toxicity. One should not take a missed dose within 12 hours of the next dose.

Administration to Patients who have Difficulty Swallowing Solids: Gefitinib tablets should be immersed in 4 to 8 ounces of water by dropping the tablet into the water, and stirred for approximately 15 minutes. The liquid should be immediately drunk or administered through a nasogastric tube. The container should be rinsed with 4 to 8 ounces of water and immediately drunk or administered through the nasogastric tube.

CYP3A4 Inducer: Drugs that are strong inducers of CYP3A4 increase the metabolism of Gefitinib and decrease Gefitinib plasma concentrations. Gefitinib should be increased to 500 mg daily in patients receiving a strong CYP3A4 inducer (e.g., rifampicin, phenytoin, or tricyclic antidepressant) and should be resumed at 250 mg 7 days after discontinuation of the strong inducer.

CYP3A4 Inhibitor: Drugs that are strong inhibitors of CYP3A4 (e.g., ketoconazole and itraconazole) decrease Gefitinib metabolism and increase Gefitinib plasma concentrations.

It is contraindicated in patients with known hypersensitivity to Gefitinib or any other components of this drug.

The most common side effects of this tablet are: interstitial lung disease, hepatotoxicity, gastrointestinal perforation, severe or persistent diarrhea, ocular disorders including keratitis, and bullous and exfoliative skin disorders.

There are no adequate and well-controlled studies in pregnant women using Gefitinib. If it is used during pregnancy or if the patient becomes pregnant while receiving this drug, she should be apprised of the potential hazard to the fetus or potential risk for loss of the pregnancy. It is not known whether Gefitinib is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from Gefitinib, women should be advised to discontinue breastfeeding during treatment with Gefitinib.

Interstitial lung disease (ILD): ILD or ILD-like adverse drug reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or pulmonary fibrosis) occurred in 1.3% of the 2,462 patients who received Gefitinib across clinical trials. Gefitinib should be withheld and promptly investigated for ILD in any patient who presents with worsening of respiratory symptoms such as dyspnea, cough and fever. It should be permanently discontinued if ILD is confirmed.

Hepatotoxicity: Patients receiving Gefitinib across clinical trials: 11.4% of patients had increased alanine aminotransferase (ALT), 7.9% of patients had increased aspartate aminotransferase (AST), and 2.7% of patients had increased bilirubin. Periodic liver function testing should be obtained. Gefitinib should be withheld in patients with worsening liver function and discontinued in patients with severe hepatic impairment.

Gastrointestinal Perforation: Gastrointestinal perforation occurred in three (0.1%) of the 2,462 Gefitinib-treated patients across clinical trials. It should be permanently discontinued in patients who develop gastrointestinal perforation.

Severe or Persistent Diarrhea: Grade 3 or 4 diarrhea occurred in 3% of 2,462 Gefitinib-treated patients across clinical trials. It should be withheld for severe or persistent (up to 14 days) diarrhea.

Ocular Disorders including Keratitis: Ocular disorders [keratitis (0.1%), corneal erosion and aberrant eyelash growth (0.2%), conjunctivitis, blepharitis and dry eye (6.7%)] occurred in the 2,462 Gefitinib-treated patients across clinical trials. It should be interrupted or discontinued for severe or worsening ocular disorders.

Bullous and Exfoliative Skin Disorders: Bullous conditions including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme have been reported from treatment with Gefitinib. Erythema multiforme and dermatitis bullous have been reported in two patients (0.08%) across NSCLC trials. Gefitinib treatment should be interrupted or discontinued if the patient develops severe bullous, blistering or exfoliating conditions.

Pediatric Use: The safety and effectiveness of Gefitinib in pediatric patients have not been established.

Renal Impairment: No clinical studies were conducted with Gefitinib in patients with severe renal impairment.

Hepatic Impairment: Adverse reactions should be monitored when Gefitinib is administered to patients with moderate and severe hepatic impairment.

Targeted Cancer Therapy

Store between 20-25°C. Store in a cool and dry place, away from sunlight. Keep out of the reach of children.