LYNPARZA FILM-COATED TABLET 100MG [SIN15663P]

Product Info

LYNPARZA FILM-COATED TABLET 100MG

[SIN15663P]

4.1 Therapeutic indications

Ovarian cancer

Lynparza is indicated as monotherapy for the:

• maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

• maintenance treatment of adult patients with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy.

Lynparza in combination with bevacizumab is indicated for the:

• maintenance treatment of adult patients with advanced (FIGO stages III and IV) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete response or partial response) following completion of first-line platinum-based chemotherapy in combination with bevacizumab and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either a BRCA1/2 mutation and/or genomic instability (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Breast cancer

Lynparza is indicated:

• for the adjuvant treatment of adult patients with germline BRCA-mutated HER2-negative high risk early breast cancer who have previously been treated with neoadjuvant or adjuvant chemotherapy (see sections 4.2 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

• as monotherapy for the treatment of adult patients with germline BRCA-mutated HER2-negative metastatic breast cancer who have previously been treated with chemotherapy. These patients could have received chemotherapy in the neoadjuvant, adjuvant or metastatic setting.

Adenocarcinoma of the pancreas

Lynparza is indicated as monotherapy for the:

• maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas whose disease has not progressed on a minimum of 16 weeks of first-line platinum-based chemotherapy. Germline BRCA mutation must be confirmed before LYNPARZA treatment is initiated.

Prostate cancer

Lynparza is indicated as monotherapy for the:

• treatment of adult patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene BRCA1/2 and/or ataxia telangiectasia (ATM)-mutations (germline and/or somatic) who have progressed following a prior new hormonal agent.

Lynparza in combination with abiraterone and prednisone or prednisolone is indicated for the:

• treatment of adult patients with metastatic castration-resistant prostate cancer in whom chemotherapy is not clinically indicated (see Section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

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 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.

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.

4.3 Contraindications

None.