Lynparza Prescribing Information

1 US-54700. HIGHLIGHTS OF Prescribing Information Prostate cancer These highlights do not include all the Information needed to use Lynparza safely for the treatment of adult patients with deleterious or suspected deleterious germline and effectively. See full Prescribing Information for Lynparza . or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior Lynparza (olaparib) tablets, for oral use treatment with enzalutamide or abiraterone. Select patients for therapy based on an Initial Approval: 2014 FDA-approved companion diagnostic for Lynparza .

2 ( , ). --------------------------------- DOSAGE AND ADMINISTRATION -------------------------------- ------------------------------------ RECENT MAJOR CHANGES ----------------------------------- Indications and Usage (1) 5/2020 Recommended dosage is 300 mg taken orally twice daily with or without food. See Dosage and Administration (2) 12/2020 Full Prescribing Information for the recommended duration. ( ). Warnings and Precautions, Myelodysplastic Syndrome/Acute Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing Myeloid Leukemia ( ) 3/2021 hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

3 ( ). Warnings and Precautions, Venous Thromboembolic Events ( ) 5/2020 For moderate renal impairment (CLcr 31-50 mL/min), reduce Lynparza dosage to 200 mg orally twice daily. ( ). ------------------------------------ INDICATIONS AND USAGE ------------------------------------ Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: ------------------------------- DOSAGE FORMS AND STRENGTHS ------------------------------ Ovarian cancer Tablets: 150 mg, 100 mg (3). for the maintenance treatment of adult patients with deleterious or suspected --------------------------------------- CONTRAINDICATIONS -------------------------------------- deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, None.

4 (4). fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an --------------------------------- WARNINGS AND PRECAUTIONS -------------------------------- FDA-approved companion diagnostic for Lynparza . ( , ) Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in in combination with bevacizumab for the maintenance treatment of adult patients approximately of patients exposed to Lynparza monotherapy and the majority of with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who events had a fatal outcome.

5 Monitor patients for hematological toxicity at baseline and are in complete or partial response to first-line platinum-based chemotherapy monthly thereafter. Discontinue if MDS/AML is confirmed. ( ). and whose cancer is associated with homologous recombination deficiency Pneumonitis: Occurred in of patients exposed to Lynparza , and some cases were (HRD)-positive status defined by either: fatal. Interrupt treatment if pneumonitis is suspected. Discontinue if pneumonitis is a deleterious or suspected deleterious BRCA mutation, and/or confirmed. ( ). genomic instability. Embryo-Fetal Toxicity: Can cause fetal harm. Advise of the potential risk to a fetus and Select patients for therapy based on an FDA-approved companion diagnostic for to use effective contraception.

6 ( , , ). Lynparza ( , ). Venous thromboembolic events including pulmonary embolism occurred in 7%. for the maintenance treatment of adult patients with recurrent epithelial ovarian, of patients with mCRPC. Monitor patients for signs and symptoms of venous fallopian tube or primary peritoneal cancer, who are in complete or partial response to thrombosis and pulmonary embolism and treat as medically appropriate. ( ). platinum-based chemotherapy. ( ). for the treatment of adult patients with deleterious or suspected deleterious germline -------------------------------------- ADVERSE REACTIONS -------------------------------------- BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with Most common adverse reactions ( 10%) in clinical trials: three or more prior lines of chemotherapy.

7 Select patients for therapy based on an as a single agent were nausea, fatigue (including asthenia), anemia, vomiting, FDA-approved companion diagnostic for Lynparza . ( , ) diarrhea, decreased appetite, headache, dysgeusia, cough, neutropenia, dyspnea, Breast cancer dizziness, dyspepsia, leukopenia, and thrombocytopenia. ( ). for the treatment of adult patients with deleterious or suspected deleterious in combination with bevacizumab were nausea, fatigue (including asthenia), anemia, gBRCAm, HER2-negative metastatic breast cancer who have been treated with lymphopenia, vomiting, diarrhea, neutropenia, leukopenia, urinary tract infection, and chemotherapy in the neoadjuvant, adjuvant or metastatic setting.

8 Patients with headache. ( ). hormone receptor (HR)-positive breast cancer should have been treated with a prior To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933. endocrine therapy or be considered inappropriate for endocrine therapy. Select or FDA at 1-800-FDA-1088 or patients for therapy based on an FDA-approved companion diagnostic for Lynparza . ( , ) --------------------------------------- DRUG INTERACTIONS -------------------------------------- Pancreatic cancer Strong or moderate CYP3A inhibitors: Avoid concomitant use. If concomitant use for the maintenance treatment of adult patients with deleterious or suspected cannot be avoided, reduce Lynparza dosage.

9 ( , , ). deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has Strong or moderate CYP3A inducers: Avoid concomitant use. ( , ). not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion --------------------------------- USE IN SPECIFIC POPULATIONS -------------------------------- diagnostic for Lynparza . ( , ) Lactation: Advise women not to breastfeed. ( ). See 17 for PATIENT COUNSELING Information and Medication Guide. Revised: 6/2021. FULL Prescribing Information : CONTENTS* 8 USE IN SPECIFIC POPULATIONS. 1 INDICATIONS AND USAGE Pregnancy First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer Lactation First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer in Females and Males of Reproductive Potential Combination with Bevacizumab Pediatric Use Maintenance Treatment of Recurrent Ovarian Cancer Geriatric Use Advanced Germline BRCA-mutated Ovarian Cancer After 3 or More Lines of Renal Impairment Chemotherapy Hepatic Impairment Germline BRCA-mutated HER2-negative Metastatic Breast Cancer 11 DESCRIPTION.

10 First-Line Maintenance Treatment of Germline BRCA-mutated Metastatic 12 CLINICAL PHARMACOLOGY. Pancreatic Adenocarcinoma Mechanism of Action HRR Gene-mutated Metastatic Castration-Resistant Prostate Cancer Pharmacodynamics 2 DOSAGE AND ADMINISTRATION. Pharmacokinetics Patient Selection 13 NONCLINICAL TOXICOLOGY. Recommended Dosage Carcinogenesis, Mutagenesis, Impairment of Fertility Dosage Modifications for Adverse Reactions 14 CLINICAL STUDIES. Dosage Modifications for Concomitant Use with Strong or Moderate First-Line Maintenance Treatment of BRCA-mutated Advanced Ovarian Cancer CYP3A Inhibitors First-line Maintenance Treatment of HRD-positive Advanced Ovarian Cancer in Dosage Modifications for Renal Impairment Combination with Bevacizumab 3 DOSAGE FORMS AND STRENGTHS.