US-17452 --------------------------------- DOSAGE …

1 US-17452 HIGHLIGHTS OF PRESCRIBING INFORMATIONT hese highlights do not include all the information needed to use lynparza safely and effectively. See full prescribing information for (olaparib) tablets, for oral useInitial Approval: 2014------------------------------------ -- RECENT MAJOR CHANGES -------------------------------------Ind ications and Usage ( ) 1/2018 DOSAGE and Administration ( ) 1/2018 Warnings and Precautions (5) 1/2018---------------------------------- ---- INDICATIONS AND USAGE --------------------------------------Ly nparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:Ovarian cancer for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy.

2 ( ) for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for lynparza . ( , )Breast cancer in patients with deleterious or suspected deleterious gBRCAm, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy.

3 Select patients for therapy based on an FDA-approved companion diagnostic for lynparza . ( , )----------------------------------- DOSAGE AND ADMINISTRATION ---------------------------------- To avoid substitution errors and overdose, do not substitute lynparza tablets with lynparza capsules on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. ( ) Recommended tablet dose is 300 mg taken orally twice daily with or without food. ( ) Continue treatment until disease progression or unacceptable toxicity. ( ) For adverse reactions, consider dose interruption or dose reduction. ( ) For moderate renal impairment (CLcr 31-50 mL/min), reduce dose to 200 mg twice daily.

4 ( ) --------------------------------- DOSAGE FORMS AND STRENGTHS --------------------------------Tablets: 150 mg, 100 mg (3)------------------------------------- ---- CONTRAINDICATIONS ---------------------------------------- None. (4)----------------------------------- WARNINGS AND PRECAUTIONS ---------------------------------- Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML): Occurred in < of patients exposed to lynparza monotherapy and the majority of events had a fatal outcome. Monitor patients for hematological toxicity at baseline and monthly thereafter. Discontinue if MDS/AML is confirmed. ( ) Pneumonitis: Occurred in <1% of patients exposed to lynparza , and some cases were fatal.

5 Interrupt treatment if pneumonitis is suspected. Discontinue if pneumonitis is confirmed. ( ) Embryo-Fetal Toxicity: lynparza can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. ( , , ) ---------------------------------------- ADVERSE REACTIONS ---------------------------------------- Most common adverse reactions ( 20%) in clinical trials were anemia, nausea, fatigue (including asthenia), vomiting, neutropenia, leukopenia, nasopharyngitis/upper respiratory tract infection/influenza, respiratory tract infection, diarrhea, arthralgia/myalgia, dysgeusia, headache, dyspepsia, decreased appetite, constipation and stomatitis.

6 ( ) Most common laboratory abnormalities ( 25%) were decrease in hemoglobin, increase in mean corpuscular volume, decrease in lymphocytes, decrease in leukocytes, decrease in absolute neutrophil count, increase in serum creatinine and decrease in platelets. ( )To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or DRUG INTERACTIONS ---------------------------------------- CYP3A Inhibitors: Avoid concomitant use of strong or moderate CYP3A inhibitors. If the inhibitor cannot be avoided, reduce the olaparib dose. ( , , ) CYP3A Inducers: Avoid concomitant use of strong or moderate CYP3A inducers as decreased efficacy can occur.

7 ( , )----------------------------------- USE IN SPECIFIC POPULATIONS ----------------------------------Lactat ion: Advise women not to breastfeed. ( )See 17 for PATIENT COUNSELING INFORMATION and MEDICATION GUIDER evised: 1/2018 FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE Maintenance Treatment of Recurrent Ovarian Cancer Advanced gBRCA-mutated Ovarian Cancer After 3 or More Lines of Chemotherapy Germline BRCA-mutated HER2-negative Metastatic Breast Cancer2 DOSAGE AND ADMINISTRATION Important Administration Instructions Recommended Dosing Patient Selection for gBRCAm Advanced Ovarian Cancer Patient Selection for gBRCAm HER2-negative Metastatic Breast Cancer Dose Adjustments for Adverse Reactions Dose Modifications for Use with CYP3A Inhibitors Dose Modifications for Patients with Renal Impairment3 DOSAGE FORMS AND STRENGTHS4

8 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS Myelodysplastic Syndrome/Acute Myeloid Leukemia Pneumonitis Embryo-Fetal Toxicity6 ADVERSE REACTIONS Clinical Trial Experience Postmarketing Experience7 DRUG INTERACTIONS Anticancer Agents Drugs That May Increase Olaparib Plasma Concentrations Drugs That May Decrease Olaparib Plasma Concentrations8 USE IN SPECIFIC POPULATIONS Pregnancy Lactation Females and Males of Reproductive Potential Pediatric Use Geriatric Use Hepatic Impairment Renal Impairment10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY Mechanism of Action Pharmacodynamics Pharmacokinetics13 NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES Maintenance Treatment of Recurrent Ovarian Cancer Advanced gBRCA-mutated Ovarian Cancer Treated with 3 or More Prior Lines of Chemotherapy Treatment of gBRCAm HER2-negative Metastatic Breast Cancer16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Storage17 PATIENT COUNSELING INFORMATION*Sections or subsections omitted from the full prescribing information are not (olaparib)

9 Tablets, for oral use2 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND Maintenance Treatment of Recurrent Ovarian CancerLynparza is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in a complete or partial response to platinum-based Advanced gBRCA-mutated Ovarian Cancer After 3 or More Lines of ChemotherapyLynparza is indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) advanced ovarian cancer who have been treated with three or more prior lines of chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for lynparza .

10 [see DOSAGE and Administration ( )]. Germline BRCA-mutated HER2-negative Metastatic Breast CancerLynparza is indicated in patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer, who have been treated with chemotherapy in the neoadjuvant, adjuvant, or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for lynparza [see DOSAGE and Administration ( )].2 DOSAGE AND Important Administration InstructionsLynparza is also available as a 50 mg capsule.