Treatment with Lynparza should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
Patient Selection: Select patients for treatment with Lynparza based on the presence of deleterious or suspected deleterious BRCA mutations, or genomic instability based on the indication, biomarker, and sample type (Table 16). (See Table 16.)
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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: First-line maintenance treatment of BRCA-mutated advanced 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.
First-line maintenance treatment of HRD positive advanced ovarian cancer in combination with bevacizumab: Continue Lynparza treatment until disease progression, unacceptable toxicity, or completion of 2 years of treatment. 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 healthcare provider can derive further benefit from continuous Lynparza treatment, can be treated beyond 2 years.
When used with Lynparza, the recommended dose of bevacizumab is 15 mg/kg every three weeks. Bevacizumab should be given for a total of 15 months including the period given with chemotherapy and given as maintenance. Refer to the Prescribing Information for bevacizumab when used in combination with Lynparza for more information.
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.
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, whichever occurs first. Patients with hormone receptor-positive breast cancer should continue concurrent treatment with endocrine therapy as per local guidelines.
gBRCA1/2-mutated HER2-negative metastatic breast cancer: It is recommended that treatment be continued until progression of the underlying disease or unacceptable toxicity.
First-line maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma: It is recommended that treatment be continued until disease progression or unacceptable toxicity.
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).
BRCA or ATM mutated Metastatic Castration-Resistant Prostate Cancer: It is recommended that treatment be continued until disease progression or unacceptable toxicity. Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
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.