Lynparza 100 mg and 150 mg Film-Coated Tablets

4.8    Undesirable effects

Update to risk of MDS/AML from SOLO1 (7 year follow up) and PAOLA-1 (5 year follow up)

5.1 Pharmacodynamic properties

Update to OS data from descriptive analysis performed at seven years after the last patient was randomized

Update to TSFT data 

2.      What you need to know before you take Lynparza

[...]

• if you notice yellowing of your skin or the whites of your eyes, abnormally dark urine (brown coloured), pain on the right side of your stomach area (abdomen), tiredness, feeling less hungry than usual or unexplained nausea and vomiting contact your doctor immediately as this may indicate problems with your liver.

[...]

4.      Possible side effects

[...]

Common side effects that may show up in blood tests

• low white blood cell count (lymphopenia) which may decrease your ability to fight infection and may be associated with fever
• decrease in the number of platelets in blood (thrombocytopenia) ‑ you may notice the following symptoms

o  bruising or bleeding for longer than usual if you hurt yourself

•  increase in blood creatinine ‑ this test is used to check how your kidneys are working.
•  abnormal liver function tests.

[...]

Not known (cannot be estimated from available data)

• signs of liver problems, such as yellowing of your skin or the whites of your eyes (jaundice), nausea or vomiting, pain on the right side of your stomach area (abdomen), dark urine (brown coloured), feeling less hungry than usual, tiredness.

[...]

6.      Contents of the pack and other information

This leaflet was last revised in 0508/2023

4.4    Special warnings and precautions for use

[...]

Hepatotoxicity

Cases of hepatotoxicity have been reported in patients treated with olaparib (see section 4.8). If clinical symptoms or signs suggestive of hepatotoxicity develop, prompt clinical evaluation of the patient and measurement of liver function tests should be performed. In case of suspected drug-induced liver injury (DILI), treatment should be interrupted. In case of severe DILI treatment discontinuation should be considered as clinically appropriate.

[...]

4.8    Undesirable effects

Inclusion of "Hepatobiliary disorders" in "table 1 list of adverse reactions"

10.    DATE OF REVISION OF THE TEXT

 30^th March24^th August 2023

5.      PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

[..]

OPINION Study

[..]

Olaparib, when used as maintenance therapy, demonstrated clinical activity in patients with non-gBRCAm PSR ovarian cancer. At the final overall survival time of primary PFS analysis (DCO 17 September 2021), the OS data were 52.330% mature.

A summary of the primary PFS and OS secondary objective outcome for patients with non-gBRCAm PSR ovarian cancer in OPINION is presented in Table 7.

Table 7 Summary of key objective outcome for progression free survival: non-gBRCAm patients with PSR ovarian cancer in OPINION

Olaparib tablets 300 mg bd

PFS (75% maturity) (DCO 2 October 2020)

Number of events: total number of patients (%)

210: 279 (75.3)

Median PFS (95% CI), months^a

9.2 (7.6, 10.9)

OS (52.3% maturity) (DCO 17 September 2021)

Number of events: total number of patients (%)

146: 279 (52.3)

Median OS (95% CI), months^a

32.7 (29.5, 35.3)

^a Calculated using the Kaplan-Meier technique.

Confidence intervals for median PFS and OS were was derived based on Brookmeyer Crowley method.

bd Twice daily; PFS Progression-free survival; OS Overall survival; DCO Data cut off; CI Confidence interval.

[..]

10.    DATE OF REVISION OF THE TEXT

26^th January 2023 16^th December 2022

Update to the product information following the approval of a new indication;

Lynparza is indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated (see section 5.1)

Update to the product information following the approval of a new indication;

Lynparza is indicated in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with mCRPC in whom chemotherapy is not clinically indicated (see section 5.1)

Section 4.2 Posology and method of administration - section Important differences in posology between Lynparza tablets and capsules removed:

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.

Section 5.1 Pharmacodynamic properties - references to capsules removed.

Section 10. Date of revision of the text - revision date updated to 01 September 2022.

Update to section 3. How to take Lynparza due to removal of capsules formulation:

Your doctor has prescribed Lynparza film-coated tablets for you. Please note Lynparza is also

available as a 50 mg capsule.

• The doses of Lynparza tablets and capsules are not the same.

• Taking the wrong dose or a capsule instead of a tablet could lead to Lynparza not working

properly or to more side effects.

Always take this medicine exactly as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Update to section 6. Contents of the pack and other information - revision date updated to 09/2022.

1.      What Lynparza is and what it is used for - addition of new indication:

Lynparza is used for the treatment of 

(...)

• a type of breast cancer (BRCA-mutated, HER2-negative) when the cancer has not spread to other parts of the body and treatment is going to be given after surgery (treatment after surgery is called adjuvant therapy). You should have received chemotherapy medicines before or after surgery. If your cancer is hormone-receptor positive your doctor may also prescribe hormonal treatment.
•  A test is used to find out whether you have BRCA-mutated breast cancer.

2.      What you need to know before you take Lynparza - Contraception, pregnancy and breast‑feeding section updated:

Female patients

•  You should not take Lynparza if you are pregnant or might become pregnant. This is because it may harm an unborn baby.
•  You should not become pregnant while taking this medicine. If you are having sex, you should use two effective methods of contraception while taking this medicine and for 61 months after taking the last dose of Lynparza. It is not known whether Lynparza may affect the effectiveness of some hormonal contraceptives. Please tell your doctor if you are taking a hormonal contraceptive, as your doctor may recommend the addition of a non‑hormonal contraceptive method.
•  You should have a pregnancy test before starting Lynparza, at regular times during treatment and 61 months after taking the last dose of Lynparza. If you become pregnant during this time, you must talk to your doctor straight away.
• It is not known whether Lynparza passes into breast milk. Do not breast‑feed if you are taking Lynparza and for 1 month after taking the last dose of Lynparza. If you are planning to breast‑feed, tell your doctor.

4.      Possible side effects - update to very common and common side effects that may show up in blood tests:

Very common side effects that may show up in blood tests

• decrease in the number of platelets in blood (thrombocytopenia) ‑ you may notice the following symptoms
•   bruising or bleeding for longer than usual if you hurt yourself
• low white blood cell count (leukopenia or neutropenia) which may decrease your ability to fight infection and may be associated with fever.

Common side effects that may show up in blood tests:

• decrease in the number of platelets in blood (thrombocytopenia) ‑ you may notice the following symptoms
• bruising or bleeding for longer than usual if you hurt yourself
• low white blood cell count (lymphopenia) which may decrease your ability to fight infection and may be associated with fever
• increase in blood creatinine ‑ this test is used to check how your kidneys are working.

4.      Possible side effects - update to rare side effects:

Rare (may affect up to 1 in 1,000 people)

• Painful inflammation of the fatty tissue under the skin (erythema nodosum).
• Facial swelling (angioedema).

6.      Contents of the pack and other information - revision date updated to 08/2022

Section 4.1 Therapeutic indications – addition of new indication:

Breast cancer

Lynparza is indicated as:

• monotherapy or in combination with endocrine therapy for the adjuvant treatment of adult patients with germline BRCA1/2-mutations who have HER2-negative, high risk early breast cancer previously treated with neoadjuvant or adjuvant chemotherapy (see sections 4.2 and 5.1).

Section 4.2 Posology and method of administration – Patient selection subsection updated to include new indication:

Adjuvant treatment of germline BRCA-mutated high risk early breast cancer

Before Lynparza treatment is initiated for adjuvant treatment of HER2 negative high risk early breast cancer, patients must have confirmation of deleterious or suspected deleterious gBRCA1/2 mutation using a validated test (see section 5.1).

Section 4.2 Posology and method of administration – Posology subsection updated to include endocrine therapy:

 The recommended dose of Lynparza in monotherapy or in combination with bevacizumab 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 in combination with endocrine therapy

Please refer to the full product information of the endocrine therapy combination partner(s) (aromatase inhibitor/anti-oestrogen agent and/or LHRH) for the recommended posology.

Section 4.2 Posology and method of administration – Duration of treatment subsection updated to include endocrine therapy:

 Adjuvant treatment of germline BRCA-mutated high risk early breast cancer

It is recommended that patients are treated for up to 1 year, or until disease recurrence, or unacceptable toxicity, whichever occurs first.

Section 4.8 Undesirable effects – updates to tabulated list of adverse reactions:

Section 5.1 Pharmacodynamic properties – addition of OlympiA study under Adjuvant treatment of germline BRCA-mutated high risk early breast cancer heading

Section 10. Date of revision of a text - revision date updated to 02 August 2022