Afatin

• Approved Indications:
• Treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring activating EGFR mutations (e.g., exon 19 deletions, exon 21 L858R substitution).
• Treatment of locally advanced or metastatic squamous NSCLC after progression on platinum-based chemotherapy.
• Off-label Uses:
• Investigational treatment of other solid tumors with ErbB family receptor alterations.

• Adults:
• Starting dose: 40 mg orally once daily, with or without food.
• Dose reductions in 10 mg decrements to a minimum of 20 mg daily may be required for toxicity management.
• Dose increases up to 50 mg daily considered if tolerated.
• Continue treatment until disease progression or unacceptable toxicity.
• Pediatrics:
• Safety and efficacy not established.
• Elderly:
• No initial dose adjustment; monitor for toxicity.
• Renal/Hepatic Impairment:
• Use with caution in severe renal or hepatic impairment; no dose adjustment recommended for mild to moderate impairment.
• Administration Route:
• Oral; swallow tablets whole with water.

Afatinib is an irreversible inhibitor of the ErbB family tyrosine kinases, including EGFR (ErbB1), HER2 (ErbB2), and ErbB4. It covalently binds to these receptors' kinase domains, inhibiting autophosphorylation and downstream signaling pathways essential for tumor cell proliferation and survival. This blockade induces apoptosis and inhibits tumor growth, particularly in tumors with activating EGFR mutations.

• Absorption: Peak plasma concentrations within 2–5 hours after oral dosing.
• Bioavailability: Approximately 92%.
• Distribution: Large volume of distribution (~2600 L); high plasma protein binding (>95%).
• Metabolism: Minimal CYP450 involvement; primarily metabolized by nonenzymatic processes.
• Elimination: Excreted mainly unchanged in feces (~85%) and urine (~4%).
• Half-life: Approximately 37 hours.

• Pregnancy: FDA category D — evidence of fetal risk. Use only if benefits justify potential risks. Animal studies showed embryotoxicity.
• Lactation: Unknown if excreted in human milk; breastfeeding not recommended during treatment.

• Antineoplastic agent
• Tyrosine kinase inhibitor (ErbB family)

• Hypersensitivity to afatinib or formulation components.
• Severe hepatic impairment (lack of data).
• Known interstitial lung disease.

• Risk of interstitial lung disease—monitor respiratory symptoms and discontinue if suspected.
• Diarrhea management essential to prevent dehydration; dose adjustments may be required.
• Monitor for dermatologic toxicities.
• Liver function monitoring advised.
• Caution in cardiac patients due to rare QT prolongation.

• Common: Diarrhea, rash, stomatitis, paronychia, dry skin, nausea, fatigue.
• Serious: Interstitial lung disease, severe diarrhea, hepatotoxicity, keratitis, cardiac arrhythmias.

• Substrate of P-glycoprotein; inhibitors may increase afatinib levels.
• Minimal CYP450 interactions.
• Avoid coadministration with other EGFR inhibitors or QT-prolonging drugs without monitoring.

• Recommended as first-line for EGFR-mutant metastatic NSCLC.
• New indications for squamous NSCLC post-chemotherapy.
• Emphasis on early adverse event management for optimal dosing.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original container until use.
• Keep out of reach of children.