Generic Name and Formulations:
Osimertinib 40mg, 80mg; tabs.
Indications for TAGRISSO:
Treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy.
80mg once daily until disease progression or unacceptable toxicity. If swallowing difficulty, may disperse tab in 2oz (60mL) of non-carbonated water only; stir and swallow immediately, then rinse container with 4–8oz water and drink immediately; or if administration via NG tube is required, disperse tab in 15mL of non-carbonated water and use an additional 15mL of water to transfer any residues to the syringe; give resulting 30mL via NG tube as instructed with appropriate water flushes (~30mL). Concomitant strong CYP3A4 inducers (if use is unavoidable): increase dose to 160mg daily; resume at 80mg 3 weeks after discontinuing CYP3A4 inducer. Dose modification: see full labeling.
Confirm presence of T790M mutation prior to treatment initiation. Permanently discontinue if interstitial lung disease (ILD)/pneumonitis is confirmed; QTc interval prolongation with signs/symptoms of life-threatening arrhythmia; symptomatic CHF or persistent, asymptomatic LV dysfunction that does not resolve within 4 weeks; or if no improvement within 3 weeks. Withhold dose if worsening respiratory symptoms indicative of ILD occur; if QTc interval >500msec on ≥2 separate ECGs; or adverse reactions of Grade ≥3 severity. Monitor ECGs and electrolytes periodically in patients with congenital long QTc syndrome, CHF, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval. Conduct cardiac monitoring (including LVEF at baseline and during treatment in patients with cardiac risk factors). Evaluate if signs/symptoms of keratitis occur. ESRD. Severe hepatic impairment. Embryo-fetal toxicity. Females of reproductive potential should use effective contraception during and for 6 weeks after final dose; males (with female partners of reproductive potential) should use effective contraception during and for 4 months after final dose. Pregnancy. Nursing mothers: not recommended (during and for 2 weeks after final dose).
Antagonized by strong CYP3A inducers (eg, phenytoin, rifampin, carbamazepine, St. John’s Wort); avoid; if use is unavoidable, increase Tagrisso dose (see Adults). Potentiates BCRP substrates (eg, rosuvastatin, sulfasalazine, topotecan); monitor closely for related toxicity.
Diarrhea, rash, dry skin, nail toxicity, fatigue, lab abnormalities; possibly infertility.