Posology : מינונים

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 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 and BRCA1/2 or ATM Gene- mutated Metastatic Castration-Resistant Prostate Cancer and Metastatic Pancreatic Adenocarcinoma 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.

Patients receiving Lynparza for mCRPC should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
Genetic counselling for patients tested for mutations in BRCA1/2 genes should be performed according to local regulations.

Treatment of mCRPC in combination with abiraterone and prednisone or prednisolone: No genomic testing is required prior to using Lynparza in combination with abiraterone and prednisone or prednisolone for the treatment of patients with mCRPC.

For First-Line Maintenance Treatment of HRD Positive Advanced Ovarian Cancer in Combination with Bevacizumab Select patients with advanced ovarian cancer who are in complete or partial response to first-line platinum-based chemotherapy for maintenance treatment with Lynparza in combination with bevacizumab associated with HRD positive status based on either deleterious or suspected deleterious BRCA mutation and/or genomic instability.

Posology
Lynparza is available as 100 mg and 150 mg tablets.

The recommended dose of Lynparza in monotherapy or in combination with bevacizumab for ovarian cancer or in combination with abiraterone and prednisone or prednisolone for prostate cancer or endocrine therapy 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.

Lynparza monotherapy
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.

Lynparza in combination with abiraterone and prednisone or prednisolone: When Lynparza is used in combination with abiraterone for the treatment of patients with mCRPC, the dose of abiraterone is 1000 mg orally once daily (see section 5.1). Abiraterone should be given with prednisone or prednisolone 5 mg orally twice daily. Please refer to the full product information for abiraterone.

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.

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.

Monotherapy treatment of gBRCA1/2-mutated HER2-negative metastatic breast cancer: It is recommended that treatment be continued until progression of the underlying disease 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 section 5.1).

Adjuvant Treatment of Germline BRCA-mutated HER2-negative High Risk Early Breast Cancer Continue treatment for a total of 1 year, or until disease recurrence, or unacceptable toxicity, whichever occurs first. Patients receiving Lynparza for hormone receptor positive HER2-negative breast cancer should continue concurrent treatment with endocrine therapy as per current clinical practice guidelines.

First-line maintenance treatment of germline BRCA-mutated metastatic pancreatic adenocarcinoma
Continue treatment until disease progression or unacceptable toxicity.

First-Line Maintenance Treatment of 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.

Monotherapy treatment of BRCA1/2 or ATM Gene-mutated Metastatic Castration-Resistant Prostate Cancer
Continue treatment until disease progression or unacceptable toxicity.

Treatment of mCRPC 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 and prednisone or prednisolone. Treatment with a gonadotropin-releasing hormone (GnRH) analogue should be continued during treatment in all patients, or patients should have had prior bilateral orchiectomy. Please refer to the product information for abiraterone.

There are no efficacy or safety data on retreatment with Lynparza in prostate cancer patients (see section 5.1).

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 section 4.8).
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 sections 4.4 and 4.5).

Special populations
Elderly
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 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 section 5.2).
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 section 5.2). 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 section 5.2).

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.