Osimatab

• Non-Small Cell Lung Cancer (NSCLC):
• First-line treatment of patients with metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations.
• Treatment of patients with metastatic NSCLC with EGFR T790M mutation-positive disease, detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.
• Off-label:
• Occasionally used in clinical trials or compassionate use for other EGFR-mutated solid tumors.

• Route: Oral (film-coated tablets).
• Adults:
• Recommended dose: 80 mg once daily, taken orally with or without food.
• Continue treatment until disease progression or unacceptable toxicity.
• Elderly:
• No dose adjustment required based on age alone.
• Renal Impairment:
• No dose adjustment necessary for mild to moderate impairment.
• Severe impairment: Use with caution; clinical data limited.
• Hepatic Impairment:
• Mild to moderate hepatic impairment: No dose adjustment needed.
• Severe hepatic impairment: Use with caution.
• Pediatrics:
• Safety and efficacy not established; not recommended.

Osimertinib is a third-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that selectively targets both EGFR sensitizing mutations (exon 19 deletions and exon 21 L858R mutations) and the EGFR T790M resistance mutation. By covalently binding to the cysteine-797 residue in the ATP-binding site of mutant EGFR, osimertinib inhibits autophosphorylation of the receptor, blocking downstream signaling pathways involved in cell proliferation and survival. This results in inhibition of tumor growth and induction of cancer cell apoptosis.

• Absorption:
• Peak plasma concentration reached in 6 hours post oral administration.
• Absolute bioavailability not fully determined; food has no clinically significant effect.
• Distribution:
• Volume of distribution approximately 2,700 L; extensive tissue distribution.
• Metabolism:
• Primarily metabolized by CYP3A4 and CYP3A5 to active metabolites, including AZ5104, which has similar pharmacologic activity.
• Half-life:
• Terminal half-life approximately 48 hours.
• Elimination:
• Excreted mainly via feces (~68%) and urine (~14%).

• Pregnancy:
• FDA pregnancy category D (positive evidence of human fetal risk). Osimertinib can cause fetal harm; avoid use during pregnancy. Women of reproductive potential should use effective contraception.
• Lactation:
• Unknown if osimertinib is excreted in human milk; breastfeeding is not recommended during treatment and for at least 2 weeks after last dose.

• EGFR tyrosine kinase inhibitor (third generation).

• Known hypersensitivity to osimertinib or any of its excipients.

• Interstitial Lung Disease (ILD)/Pneumonitis:
• Serious and potentially fatal ILD/pneumonitis can occur. Monitor for respiratory symptoms; discontinue if ILD is suspected.
• QT Interval Prolongation:
• May prolong QT interval; monitor ECG and electrolytes, especially in patients with risk factors.
• Cardiomyopathy:
• Monitor cardiac function (e.g., ejection fraction) periodically.
• Hepatotoxicity:
• Monitor liver function tests; discontinue or reduce dose if severe abnormalities develop.
• Eye Disorders:
• Cases of keratitis, dry eye, and other ocular toxicities reported; monitor and manage appropriately.
• Embryo-Fetal Toxicity:
• High risk; advise contraception.

• Common:
• Diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue, decreased appetite, cough.
• Serious (Less Common):
• Interstitial lung disease/pneumonitis, QT prolongation, cardiomyopathy, hepatotoxicity, keratitis.
• Onset & Severity:
• Skin and gastrointestinal side effects often occur within weeks of starting therapy. Serious adverse effects may develop at any time.

• CYP3A4 Inhibitors:
• May increase osimertinib plasma concentrations; avoid strong inhibitors or monitor closely.
• CYP3A4 Inducers:
• May decrease plasma concentrations; co-administration is not recommended.
• Drugs that prolong QT interval:
• Use cautiously due to additive risk of QT prolongation.
• P-glycoprotein (P-gp) substrates:
• Possible interaction; monitor accordingly.

• Osimertinib is now standard first-line therapy for EGFR-mutated metastatic NSCLC per NCCN, ESMO, and FDA approvals.
• New guidelines emphasize early testing for T790M mutation to optimize treatment sequencing.
• Increased awareness of ILD risk has prompted detailed monitoring recommendations.
• No major changes in dose or indication since initial approval.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep in original container tightly closed.
• Do not freeze.