Lynparza Dosage/Direction for Use

Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Detection of BRCA and other HRR gene mutations: Gene mutation status should be determined by an experienced laboratory using a validated test method.
Detection of BRCA1/2 mutations: Before Lynparza treatment is initiated for first-line maintenance treatment of high-grade epithelial ovarian cancer (EOC), fallopian tube cancer (FTC) or primary peritoneal cancer (PPC), patients must have confirmation of deleterious or suspected deleterious germline and/or somatic mutations in the breast cancer susceptibility genes (BRCA) 1 or 2 using a validated test.
There is no requirement for BRCA1/2 testing prior to using Lynparza for the maintenance treatment of relapsed EOC, FTC or PPC who are in a complete or partial response to platinum-based therapy.
For germline breast cancer susceptibility genes (gBRCA1/2) mutated human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, patients must have confirmation of a deleterious or suspected deleterious gBRCA1/2 mutation before Lynparza treatment is initiated. gBRCA1/2 mutation status should be determined by an experienced laboratory using a validated test method. Data demonstrating clinical validation of tumour BRCA1/2 tests in breast cancer are not currently available.
Genetic counselling for patients tested for mutations in BRCA1/2 genes should be performed according to local regulations.
Maintenance following first-line treatment of metastatic adenocarcinoma of the pancreas: Patients must have confirmation of a BRCA mutation (identified by germline testing) before Lynparza treatment is initiated.
HRR-gene mutated metastatic castration-resistant prostate cancer (mCRPC): Patients must have confirmation of a homologous recombination repair (HRR) 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. HRR genetic status should be determined by an experienced laboratory using a validated test method.
Posology: 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.
Patients with platinum-sensitive relapsed (PSR) high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy should start treatment with Lynparza no later than 8 weeks after completion of their final dose of the platinum-containing regimen.
Duration of treatment: Monotherapy maintenance treatment of newly diagnosed advanced BRCA-mutated ovarian cancer: Patients can continue treatment until radiological disease progression, unacceptable toxicity or for up to 2 years if there is no radiological evidence of disease after 2 years of 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.
Maintenance treatment of platinum sensitive relapsed ovarian cancer: For patients with platinum sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer, it is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity.
Maintenance treatment of newly diagnosed 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).]
gBRCA1/2-mutated HER2-negative metastatic breast cancer: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity.
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 mutated metastatic castration-resistant prostate cancer: It is recommended that treatment be continued until progression of the underlying disease.
There are no efficacy or safety data on maintenance retreatment with Lynparza following first or subsequent relapse in ovarian cancer patients or on retreatment of breast cancer patients (see Pharmacology: Pharmacodynamics under Actions).
Important differences in posology between Lynparza tablets and capsules: Lynparza tablets (100 mg and 150 mg) should not be substituted for Lynparza capsules (50 mg) on a milligram-to-milligram basis due to differences in the dosing and bioavailability of each formulation. Therefore, the specific dose recommendations for each formulation should be followed.
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 reactions: Treatment may be interrupted to manage adverse reactions such as nausea, vomiting, diarrhoea, and anaemia and dose reduction can be considered (see Adverse Reactions).
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.
Dose adjustments for 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 Precautions and Interactions).
Special populations: Elderly: No adjustment in starting dose is required for elderly patients.
Renal impairment: For patients with moderate renal impairment (creatinine clearance 31 to 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) (see Pharmacology: Pharmacokinetics under Actions).
Lynparza can be administered in patients with mild renal impairment (creatinine clearance 51 to 80 ml/min) with no dose adjustment.
Lynparza is not recommended for use in 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 may only be used in patients with severe renal impairment if the benefit outweighs the potential risk, and the patient should be carefully monitored for renal function and adverse events.
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.
Non-Caucasian patients: There are limited clinical data available in non-Caucasian patients. However, no dose adjustment is required on the basis of ethnicity (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: The safety and efficacy of Lynparza in children and adolescents have not been established.
No data are available.
Method of administration: Lynparza is for oral use.
Lynparza tablets should be swallowed whole and not chewed, crushed, dissolved or divided. Lynparza tablets may be taken without regard to meals.