TAGRISSO PRESCRIBING INFORMATION

1 US-23584 HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese highlights do not include all the INFORMATION needed to use TAGRISSO safely and effectively. See full PRESCRIBING INFORMATION for (osimertinib) tablets, for oral useInitial Approval: 2015--------------------------------- RECENT MAJOR CHANGES --------------------------------Indicati ons and Usage ( ) 4/2018 Dosage and Administration ( ) 4/2018 Warnings and Precautions ( , ) 4/2018--------------------------------- INDICATIONS AND USAGE ---------------------------------TAGRISS O is a kinase inhibitor indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.

2 ( , ) the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy. ( , )----------------------------- DOSAGE AND ADMINISTRATION ------------------------------Recommende d dosage: 80 mg orally once daily, with or without food. ( )--------------------------- DOSAGE FORMS AND STRENGTHS -----------------------------Tablets: 80 mg and 40 mg. (3)----------------------------------- CONTRAINDICATIONS ------------------------------------None . (4)----------------------------- WARNINGS AND PRECAUTIONS ------------------------------ Interstitial Lung Disease (ILD)/Pneumonitis: Occurred in of patients .

3 Permanently discontinue TAGRISSO in patients diagnosed with ILD/Pneumonitis.( ) QTc Interval Prolongation: Monitor electrocardiograms and electrolytes in patients who have a history or predisposition for QTc prolongation, or those who are taking medications that are known to prolong the QTc interval. Withhold then restart at a reduced dose or permanently discontinue TAGRISSO . ( , ) Cardiomyopathy: Occurred in of patients . Conduct cardiac monitoring, including left ventricular ejection fraction (LVEF) assessment in patients with cardiac risk factors.

4 ( , ) Keratitis: Promptly refer patients with signs and symptoms of keratitis to an ophthalmologist for evaluation. ( ) Embryo-Fetal Toxicity: TAGRISSO can cause fetal harm. Advise females of potential risk to the fetus and to use effective contraception during treatment with TAGRISSO and for 6 weeks after final dose. Advise males to use effective contraception for 4 months, after the last dose of TAGRISSO . ( , , )----------------------------------- ADVERSE REACTIONS ------------------------------------Most common adverse reactions ( 20%) were diarrhea, rash, dry skin, nail toxicity, stomatitis, fatigue and decreased appetite.

5 ( )To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or or FDA at 1-800-FDA-1088 or DRUG INTERACTIONS ------------------------------------Stro ng CYP3A Inducers: Avoid if possible. If not possible, increase TAGRISSO to 160 mg daily in patients receiving a strong CYP3A4 inducer. ( , )----------------------------- USE IN SPECIFIC POPULATIONS ------------------------------Lactation: Do not breastfeed. ( )See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient : 8/2018 FULL PRESCRIBING INFORMATION .

6 CONTENTS*1 INDICATIONS AND USAGE First-line Treatment of EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC) Previously Treated EGFR T790M Mutation-Positive Metastatic NSCLC2 DOSAGE AND ADMINISTRATION Patient Selection Recommended Dosage Regimen Administration to patients Who Have Difficulty Swallowing Solids Dosage Modifications3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS Interstitial Lung Disease/Pneumonitis QTc Interval Prolongation Cardiomyopathy Keratitis Embryo-Fetal Toxicity 6 ADVERSE REACTIONS Clinical Trials Experience7 DRUG INTERACTIONS Effect of Other Drugs on Osimertinib Effect of Osimertinib on Other Drugs Drugs

7 That Prolong the QTc Interval8 USE IN SPECIFIC POPULATIONS Pregnancy Lactation Females and Males of Reproductive Potential Pediatric Use Geriatric Use Renal Impairment Hepatic Impairment11 DESCRIPTION12 CLINICAL PHARMACOLOGY Mechanism of Action Pharmacodynamics Pharmacokinetics13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES Previously Untreated EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer Previously Treated EGFR T790M Mutation-Positive Metastatic Non-Small Cell Lung Cancer16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full PRESCRIBING INFORMATION are not (osimertinib) tablets, for oral use2 FULL PRESCRIBING INFORMATION1 INDICATIONS AND First-line Treatment of EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)

8 TAGRISSO is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test [see Dosage and Administration ( )]. Previously Treated EGFR T790M Mutation-Positive Metastatic NSCLCTAGRISSO is indicated for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy [see Dosage and Administration ( )].

9 2 DOSAGE AND Patient SelectionSelect patients for the first-line treatment of metastatic EGFR-positive NSCLC with TAGRISSO based on the presence of EGFR exon 19 deletions or exon 21 L858R mutations in tumor or plasma specimens [see Clinical Studies (14)]. If these mutations are not detected in a plasma specimen, test tumor tissue if patients for the treatment of metastatic EGFR T790M mutation-positive NSCLC with TAGRISSO following progression on or after EGFR TKI therapy based on the presence of an EGFR T790M mutation in tumor or plasma specimens [see Clinical Studies (14)].

10 Testing for the presence of the T790M mutation in plasma specimens is recommended only in patients for whom a tumor biopsy cannot be obtained. If this mutation is not detected in a plasma specimen, re-evaluate the feasibility of biopsy for tumor tissue on FDA-approved tests for the detection of EGFR mutations is available at Recommended Dosage RegimenThe recommended dosage of TAGRISSO is 80 mg tablet once a day until disease progression or unacceptable toxicity. TAGRISSO can be taken with or without a dose of TAGRISSO is missed, do not make up the missed dose and take the next dose as Administration to patients Who Have Difficulty Swallowing SolidsDisperse tablet in 60 mL (2 ounces) of non-carbonated water only.