b'LYNPARZA (olaparib) tablets, for oral use 3Postmarketing Experience Females and Males of Reproductive Potential The following adverse reactions have been identied during post-approval use of Lynparza.Lynparza can cause fetal harm when administered to a pregnant woman [see Use in Specic Because these reactions are reported voluntarily from a population of uncertain size, it is not alwaysPopulations (8.1) in the full Prescribing Information].possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Pregnancy TestingImmune System Disorders: Hypersensitivity including angioedema. Verify pregnancy status in females of reproductive potential prior to initiating treatment with Skin and subcutaneous tissue disorders: Erythema nodosum, rash, dermatitis. Lynparza.DRUG INTERACTIONS ContraceptionUse with Anticancer Agents FemalesClinical studies of Lynparza with other myelosuppressive anticancer agents, including DNAAdvise females of reproductive potential to use effective contraception during treatment with damaging agents, indicate a potentiation and prolongation of myelosuppressive toxicity. Lynparza and for 6 months following the last dose.Effect of Other Drugs on Lynparza Males Strong and Moderate CYP3A Inhibitors Based on ndings in genetic toxicity and animal reproduction studies, advise male patients with Coadministration of CYP3A inhibitors can increase olaparib concentrations, which may increasefemale partners of reproductive potential or who are pregnant to use effective contraception during the risk for adverse reactions [see Clinical Pharmacology (12.3) in the full Prescribing Information].treatment and for 3 months following the last dose of Lynparza. Advise male patients not to donate Avoid coadministration of strong or moderate CYP3A inhibitors. If the strong or moderate inhibitorsperm during therapy and for 3 months following the last dose of Lynparza [see Use in Specic must be coadministered, reduce the dose of Lynparza [see Dosage and Administration (2.4) in thePopulations (8.1) and Nonclinical Toxicology (13.1) in the full Prescribing Information]. full Prescribing Information].Pediatric Use Strong and Moderate CYP3A Inducers Safety and effectiveness of Lynparza have not been established in pediatric patients.Concomitant use with a strong or moderate CYP3A inducer decreased olaparib exposure,Geriatric Use which may reduce Lynparza efcacy [see Clinical Pharmacology (12.3) in the full PrescribingOf the 2901 patients with advanced solid tumors who received Lynparza as a single agent, Information]. Avoid coadministration of strong or moderate CYP3A inducers. 680 (23%) patients were aged 65 years, and this included 206 (7%) patients who were aged USE IN SPECIFIC POPULATIONS 75 years. Thirteen (0.4%) patients were aged 85 years. PregnancyOf the 535 patients with advanced solid tumors who received Lynparza tablets 300 mg orally twice daily in combination with bevacizumab (PAOLA-1), 204 (38%) patients were aged 65 years, and Risk Summary this included 31 (6%) patients who were aged 75 years.Based on ndings in animals and its mechanism of action [see Clinical Pharmacology (12.1) inOfthe398patientswithadvancedsolidtumorswhoreceivedLynparzatablets300mg the full Prescribing Information], Lynparza can cause fetal harm when administered to a pregnantorally twice daily in combination with abiraterone and prednisone or prednisolone (PROpel), woman. There are no available data on Lynparza use in pregnant women to inform the drug- 268 (67%) patients were aged 65 years, and this included 95 (24%) patients who were aged associated risk. In an animal reproduction study, the administration of olaparib to pregnant rats75 years.during the period of organogenesis caused teratogenicity and embryo-fetal toxicity at exposuresNo overall differences in the safety or effectiveness of Lynparza were observed between these below those in patients receiving the recommended human dose of 300 mg twice daily (see Data).patients and younger patients.Apprise pregnant women of the potential hazard to the fetus and the potential risk for loss of the pregnancy. Renal ImpairmentTheestimatedbackgroundriskofmajorbirthdefectsandmiscarriagefortheindicatedNo dosage modication is recommended in patients with mild renal impairment (CLcr 51 population is unknown. The estimated background risk in the U.S. general population of majorto80mL/minestimatedbyCockcroft-Gault).ReduceLynparzadosageto200mgtwice birth defects is 2-4%; and the risk for spontaneous abortion is approximately 15-20% in clinicallydailyinpatientswithmoderaterenalimpairment(CLcr31to50mL/min)[seeDosage recognized pregnancies. and Administration (2.5) in the full Prescribing Information]. There are no data in patients with Data severe renal impairment or end-stage disease(CLcr 30 mL/min) [see Clinical Pharmacology Animal Data (12.3) in the full Prescribing Information].In a fertility and early embryonic development study in female rats, olaparib was administeredHepatic Impairmentorally for 14 days before mating through to Day 6 of pregnancy, which resulted in increasedNo adjustment to the starting dose is required in patients with mild or moderate hepatic post-implantation loss at a dose level of 15 mg/kg/day (with maternal systemic exposuresimpairment (Child-Pugh classication A and B). There are no data in patients with severe approximately 7% of the human exposure (AUC 0-24h ) at the recommended dose). hepatic impairment (Child-Pugh classication C) [see Clinical Pharmacology (12.3) in the full Inanembryo-fetaldevelopmentstudy,pregnantratsreceivedoraldosesof0.05andPrescribing Information].0.5 mg/kg/day olaparib during the period of organogenesis. A dose of 0.5 mg/kg/day (with maternalsystemicexposuresapproximately0.18%ofhumanexposure(AUC 0-24h )attheDistributed by:recommended dose) caused embryo-fetal toxicities including increased post-implantation lossAstraZeneca Pharmaceuticals LPand major malformations of the eyes (anophthalmia, microphthalmia), vertebrae/ribs (extra rib orWilmington, DE 19850ossication center; fused or absent neural arches, ribs, and sternebrae), skull (fused exoccipital),AstraZeneca 2023and diaphragm (hernia). Additional abnormalities or variants included incomplete or absent11/23 US-82507 11/23ossication (vertebrae/sternebrae, ribs, limbs) and other ndings in the vertebrae/sternebrae, pelvic girdle, lung, thymus, liver, ureter, and umbilical artery. Some ndings noted above in the eyes, ribs, and ureter were observed at a dose of 0.05 mg/kg/day olaparib at lower incidence.Lactation Risk SummaryNo data are available regarding the presence of olaparib in human milk, or on its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in the breastfed infants from Lynparza, advise a lactating woman not to breastfeed during treatment with Lynparza and for one month after receiving the last dose.'