Lynparza Dosage/Direction for Use

Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Hard capsule: Patients must have confirmation of a breast cancer susceptibility gene (BRCA) mutation (germline or tumour) before Lynparza treatment is initiated. BRCA mutation status should be determined by an experienced laboratory using a validated test method (see Pharmacology: Pharmacodynamics under Actions).
There are limited data in patients with somatic BRCA-mutated tumours.
Patients should start treatment with Lynparza no later than 8 weeks after completion of their final dose of the platinum-containing regimen.
Dosage in adults: The recommended dose of Lynparza is 400 mg (eight 50 mg capsules) taken twice daily, equivalent to a total daily dose of 800 mg.
Lynparza should be taken on an empty stomach (at least 1 hour after a meal). Once Lynparza is taken, refrain from eating for 2 hours.
It is recommended that treatment be continued until progression of the underlying disease.
FC tablet: 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 gBRCAm 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.
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 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 Pharmacology: Pharmacodynamics under Actions).
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.
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.
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.
Hard capsule: The recommended dose reduction is to 200 mg twice daily (equivalent to a total daily dose of 400 mg).
If a further dose reduction is required, then reduction to 100 mg twice daily (equivalent to a total daily dose of 200 mg) is recommended.
FC tablet: 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.
Hard capsule: If a strong CYP3A inhibitor must be co-administered, the recommended Lynparza dose reduction is to 150 mg taken twice daily (equivalent to a total daily dose of 300 mg). If a moderate CYP3A inhibitor must be co-administered, the recommended Lynparza dose reduction is to 200 mg taken twice daily (equivalent to a total daily dose of 400 mg) (see Precautions and Interactions).
FC tablet: 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 Precautions and Interactions).
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: Hard capsule: For patients with moderate renal impairment (creatinine clearance 31-50 ml/min) the recommended dose of Lynparza is 300 mg twice daily (equivalent to a total daily dose of 600 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 Pharmacology: Pharmacokinetics under Actions).
FC tablet: 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 Pharmacology: Pharmacokinetics under Actions).
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 Pharmacology: Pharmacokinetics under Actions). 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: FC tablet: 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.