Iressa (Gefitinib)

Gefitinib is indicated for cancers driven by EGFR mutations, primarily within the non‑small cell lung cancer pathway.

• EGFR mutation‑positive non‑small cell lung cancer: improves progression‑free survival as first‑line targeted therapy in adult patients.
• Metastatic non‑small cell lung cancer after prior chemotherapy: provides an oral option for patients whose disease harbours EGFR activating mutations.
• Pancreatic cancer (investigational): being studied for potential benefit in patients with EGFR‑dependent tumor biology.

• Gefitinib binds competitively to the intracellular ATP‑binding site of the epidermal growth factor receptor (EGFR) tyrosine kinase. By inhibiting autophosphorylation, it blocks downstream signaling cascades such as the MAPK, PI3K/AKT and STAT pathways, which are essential for tumor cell proliferation, survival and angiogenesis. The selective inhibition is most effective in cells that express activating EGFR mutations. Consequently, tumor growth is curtailed and apoptosis may be promoted.

Gefitinib may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Diarrhea: watery stools that may be mild to moderate.
• Skin rash: erythematous eruption often on the face or trunk.
• Nausea: feeling of sickness, sometimes with vomiting.
• Loss of appetite: reduced desire to eat.
• Fatigue: generalized tiredness.
• Dry skin: itching or flaking.

Serious or Rare Side Effects

• Interstitial lung disease: inflammation of lung tissue that can be life‑threatening.
• Hepatic toxicity: elevated liver enzymes or hepatitis.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Ocular disorders: blurred vision or corneal ulceration.
• QT interval prolongation: cardiac rhythm disturbance.
• Severe hepatic failure: liver failure requiring medical intervention.

When prescribing Gefitinib, clinicians should observe several safety measures to minimize risk.

• Monitor liver function: perform baseline and periodic hepatic enzyme tests.
• Assess pulmonary status: watch for new or worsening respiratory symptoms.
• Evaluate skin condition: manage rash promptly to prevent infection.
• Review concomitant medications: avoid strong CYP3A4 inhibitors that increase exposure.
• Counsel patients on pregnancy risk: drug may be harmful; advise effective contraception.
• Store at ambient temperature: keep tablets below 25 °C in the original container, protected from moisture.

Gefitinib interacts with several medicines that can alter its plasma concentration or toxicity profile.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): may raise gefitinib levels and increase toxicity.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): may lower gefitinib exposure, reducing efficacy.
• Antacids that raise gastric pH (e.g., aluminum‑magnesium hydroxide): can reduce absorption of gefitinib.

Moderate Interactions (Monitor Closely)

• Warfarin: may enhance anticoagulant effect, requiring INR monitoring.
• Oral contraceptives: gefitinib may reduce hormonal efficacy, consider alternative contraception.
• H2‑blockers or proton pump inhibitors: may modestly decrease gefitinib absorption.
• Statins (e.g., simvastatin): potential for increased statin exposure, monitor for myopathy.