Gefitinib is metabolized by CYP3A4. Strong inducers (e.g., rifampicin, phenytoin, carbamazepine, St. John’s wort) may decrease plasma levels of Gefitinib, while strong inhibitors (e.g., ketoconazole, itraconazole) may increase exposure. Dose adjustment may be required.

The recommended daily dose of Gefitinib is 250 mg orally, with or without food. Higher doses do not improve response but increase toxicity.

Dosage Modifications: Withhold treatment for up to 14 days following adverse effects such as:

Acute onset or worsening pulmonary symptoms (dyspnea, cough, fever)

≥ Grade 2 ALT and/or AST elevations
≥ Grade 3 diarrhea

Severe or worsening ocular disorders including keratitis
≥ Grade 3 skin reactions

Treatment may be resumed when adverse effects resolve or improve to Grade 1. Permanently discontinue for confirmed interstitial lung disease, severe hepatic impairment, gastrointestinal perforation, or persistent ulcerative keratitis.

Co-administration with CYP3A4 Inducers: In the absence of severe adverse reactions, increase dose to 500 mg daily. Resume 250 mg daily after discontinuation of the strong CYP3A4 inducer.

Gefitinib is contraindicated in patients with severe hypersensitivity to Gefitinib or to any of its components.

The most common adverse events reported at the recommended 250 mg daily dose are diarrhea, rash, acne, dry skin, nausea, and vomiting. The 500 mg dose showed a higher frequency of these adverse events.

Pregnancy: Category D. Gefitinib may cause fetal harm when administered to a pregnant woman. Animal studies have shown placental transfer. There are no adequate and well-controlled studies in pregnant women. If used during pregnancy, patients should be apprised of the potential hazard to the fetus.

Lactation: It is not known whether Gefitinib is excreted in human milk. Use in nursing mothers is not recommended.

Pulmonary Toxicity: Cases of interstitial lung disease (ILD) have been observed in about 1% of patients. Patients may present with dyspnea, cough, and fever, which can become severe and require hospitalization.

Hepatotoxicity: Asymptomatic increases in liver transaminases have been reported. Periodic liver function tests (ALT, AST, bilirubin, alkaline phosphatase) are recommended. Discontinue Gefitinib if changes are severe.

Information for Patients: Patients should seek medical advice promptly if they develop severe or persistent diarrhea, nausea, anorexia, vomiting, pulmonary symptoms, eye irritation, or any new symptom.

Gefitinib has shown low acute toxicity up to 500 mg in clinical studies. At higher doses (up to 1000 mg/day), adverse events such as diarrhea and rash occur more frequently and severely. Overdose should be managed symptomatically, with special attention to severe diarrhea.

Store at temperatures not exceeding 30°C, in a dry place, protected from light and moisture. Keep out of the reach of children.