LYNPARZA FILM-COATED TABLET 150MG

ASTRAZENECA SINGAPORE PTE LTD

ASTRAZENECA SINGAPORE PTE LTD

Therapeutic

Prescription Only

TABLET, FILM COATED

**4.2 Posology and method of administration** Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. **Detection of _BRCA_, _ATM_ gene mutations and/or genomic instability:** Gene mutation and/or genomic instability status should be determined by an experienced laboratory using a validated test method. **Monotherapy maintenance treatment of newly diagnosed advanced _BRCA_-mutated ovarian cancer:** Patients must have confirmation of a breast cancer susceptibility gene ( _BRCA_) mutation (identified by either germline or tumour testing) before Lynparza treatment is initiated. **First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab:** Patients must have confirmation of either deleterious or suspected deleterious _BRCA1/2_ mutation and/or genomic instability before Lynparza treatment is initiated. **Adjuvant treatment of germline _BRCA_-mutated HER2-negative high risk early breast cancer:** Patients must have confirmation of a _BRCA_ mutation (identified by germline testing) before Lynparza treatment is initiated. **Metastatic HER2-negative breast cancer:** Patients must have confirmation of a _BRCA_ mutation (identified by germline testing) before Lynparza treatment is initiated. **Maintenance treatment of patients with g _BRCA_ m metastatic adenocarcinoma of the pancreas who are in response to first-line platinum-based chemotherapy:** Patients must have confirmation of a deleterious or suspected deleterious _BRCA_ mutation (identified by germline testing) before LYNPARZA treatment is initiated. **Monotherapy treatment of HRR-gene _BRCA1/2_ and/or _ATM_-mutated metastatic castration-resistant prostate cancer (mCRPC):** Patients must have confirmation of _BRCA1/2_ and/or _ATM_ gene mutation (using either tumour DNA from a tissue sample, ctDNA obtained from a plasma sample or germline DNA obtained from a blood or another non-tumour sample) before Lynparza treatment is initiated. _BRCA1/2_ and/or _ATM_ genetic status should be determined by an experienced laboratory using a validated test method. **Dosage in adults** Lynparza is available as 100 mg and 150 mg tablets. The recommended dose of Lynparza as monotherapy and in combination with bevacizumab for ovarian cancer or in combination with abiraterone and prednisone or prednisolone for prostate cancer is 300 mg (two 150 mg tablets) taken twice daily, equivalent to a total daily dose of 600 mg. The 100 mg tablet is available for dose reduction. **Duration of treatment** **Monotherapy maintenance treatment of newly diagnosed advanced _BRCA_-mutated ovarian cancer:** patients can continue treatment for 2 years or until disease progression. Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous treatment, can be treated beyond 2 years. **Platinum-sensitive relapsed ovarian cancer:** it is recommended that treatment be continued until progression of the underlying disease. **First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab:** patients can continue treatment for 2 years or until disease progression. Patients with a complete response (no radiological evidence of disease) at 2 years should stop treatment. Patients with evidence of disease at 2 years, who in the opinion of the treating physician can derive further benefit from continuous Lynparza treatment, can be treated beyond 2 years. When Lynparza is used in combination with bevacizumab, refer to the Prescribing Information for bevacizumab for recommended dosing information (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **Adjuvant treatment of germline _BRCA_-mutated HER2-negative high risk early breast cancer:** it is recommended that patients are treated for a total of 1 year, or until disease recurrence, or unacceptable toxicity, whichever occurs first. Patients with hormone receptor-positive breast cancer should continue concurrent treatment with endocrine therapy as per local guidelines. **Metastatic HER2-negative breast cancer:** it is recommended that treatment be continued until progression of the underlying disease. **Maintenance following first-line treatment of metastatic adenocarcinoma of the pancreas:** it is recommended that treatment be continued until progression of the underlying disease. **Monotherapy treatment of HRR-gene _BRCA1/2_ and/or _ATM_-mutated metastatic castration-resistant prostate cancer:** it is recommended that treatment be continued until progression of the underlying disease. **Treatment of metastatic castration-resistant prostate cancer in combination with abiraterone and prednisone or prednisolone:** it is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity. When Lynparza is used in combination with abiraterone, refer to the Prescribing Information for abiraterone for recommended dosing information (see section 5.1 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Lynparza is also available as a 50 mg capsule. Refer to the capsules label for specific dosing information. Lynparza capsules (50 mg) should not be substituted for Lynparza tablets (100 mg and 150 mg) on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. **Missing dose** If a patient misses a dose of Lynparza, they should take their next normal dose at its scheduled time. **Dose adjustments** _**For adverse events**_ Treatment may be interrupted to manage adverse events and dose reduction can be considered. The recommended dose reduction is to 250 mg (one 150 mg tablet and one 100 mg tablet) twice daily (equivalent to a total daily dose of 500 mg). If a further dose reduction is required, then reduction to 200 mg (two 100 mg tablets) twice daily (equivalent to a total daily dose of 400 mg) is recommended. **_Co-administration with CYP3A inhibitors_** Concomitant use of strong or moderate CYP3A inhibitors is not recommended and alternative agents should be considered. If a strong CYP3A inhibitor must be co-administered, the recommended Lynparza dose reduction is to 100 mg (one 100 mg tablet) taken twice daily (equivalent to a total daily dose of 200 mg). If a moderate CYP3A inhibitor must be co-administered, the recommended Lynparza dose reduction is to 150 mg (one 150 mg tablet) taken twice daily (equivalent to a total daily dose of 300 mg) (see sections 4.4 and 4.5 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). **Special patient populations** _**Children or adolescents:**_ Lynparza is not indicated for use in paediatric patients, as safety and efficacy of Lynparza in children and adolescents have not been established. _**Elderly (>65 years):**_ No adjustment in starting dose is required for elderly patients. There are limited clinical data in patients aged 75 years and over. _**Renal impairment:**_ For patients with moderate renal impairment (creatinine clearance 31 – 50 ml/min) the recommended dose of Lynparza is 200 mg (two 100 mg tablets) twice daily (equivalent to a total daily dose of 400 mg). Lynparza is not recommended for patients with severe renal impairment or end-stage renal disease (creatinine clearance ≤30 ml/min), as safety and pharmacokinetics have not been studied in these patients. Lynparza can be administered to patients with mild renal impairment (creatinine clearance 51 – 80 ml/min) with no dose adjustment (see section 5.2 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). _**Hepatic impairment:**_ Lynparza can be administered to patients with mild or moderate hepatic impairment (Child-Pugh classification A or B) with no dose adjustment (see section 5.2 – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_). Lynparza is not recommended for use in patients with severe hepatic impairment (Child-Pugh classification C), as safety and pharmacokinetics have not been studied in these patients. **Method of administration** For oral use. Lynparza tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Lynparza tablets can be taken with or without food.