Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Haematological toxicity
Haematological toxicity has been reported in patients treated with Lynparza, including clinical diagnoses and/or laboratory findings of generally mild or moderate (CTCAE grade 1 or 2) anaemia, neutropenia, thrombocytopenia and lymphopenia. Patients should not start treatment with Lynparza until they have recovered from haematological toxicity caused by previous anticancer therapy (haemoglobin, platelet and neutrophil levels should be ≤CTCAE grade 1).
Baseline testing, followed by monthly monitoring, of complete blood counts is recommended for the first 12 months of treatment and periodically after this time to monitor for clinically significant changes in any parameter during treatment (see section 4.8).

If a patient develops severe haematological toxicity or blood transfusion dependence, treatment with Lynparza should be interrupted and appropriate haematological testing should be initiated. If the blood parameters remain clinically abnormal after 4 weeks of Lynparza dose interruption, bone marrow analysis and/or blood cytogenetic analysis are recommended.

Myelodysplastic syndrome/Acute myeloid leukaemia
The overall incidence of myelodysplastic syndrome/acute myeloid leukaemia (MDS/AML) in patients treated in clinical trials with Lynparza monotherapy, including long-term survival follow- up, was <1.5%, with higher incidence in patients with BRCAm platinum-sensitive relapsed ovarian cancer who had received at least two prior lines of platinum chemotherapy and were followed up for 5 years (see section 4.8). The majority of events had a fatal outcome. The duration of therapy with olaparib in patients who developed MDS/AML varied from <6 months to >4 years.
If MDS/AML is suspected, the patient should be referred to a haematologist for further investigations, including bone marrow analysis and blood sampling for cytogenetics. If, following investigation for prolonged haematological toxicity, MDS/ AML is confirmed, Lynparza should be discontinued and the patient treated appropriately.

Venous Thromboembolic Events
Venous thromboembolic events, predominantly events of pulmonary embolism, have occurred in patients treated with Lynparza and had no consistent clinical pattern. A higher incidence was observed in patients with metastatic castration-resistant prostate cancer, who also received androgen deprivation therapy, compared with other approved indications (see section 4.8).
Monitor patients for clinical signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.
Patients with a prior history of VTE may be more at risk of a further occurrence and should be monitored appropriately.

Pneumonitis
Pneumonitis, including events with a fatal outcome, has been reported in <1.0% of patients treated with Lynparza in clinical studies. Reports of pneumonitis had no consistent clinical pattern and were confounded by a number of pre-disposing factors (cancer and/or metastases in lungs, underlying pulmonary disease, smoking history, and/or previous chemotherapy and radiotherapy). If patients present with new or worsening respiratory symptoms such as dyspnoea, cough and fever, or an abnormal chest radiologic finding is observed, Lynparza treatment should be interrupted and prompt investigation initiated. If pneumonitis is confirmed, Lynparza treatment should be discontinued and the patient treated appropriately.

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.

Embryofoetal toxicity
Based on its mechanism of action (PARP inhibition), Lynparza could cause foetal harm when administered to a pregnant woman. Nonclinical studies in rats have shown that olaparib causes adverse effects on embryofoetal survival and induces major foetal malformations at exposures below those expected at the recommended human dose of 300 mg twice daily.


Pregnancy/contraception
Lynparza should not be used during pregnancy. Women of childbearing potential must use two forms of reliable contraception before starting Lynparza treatment, during therapy and for 6 months after receiving the last dose of Lynparza. Two highly effective and complementary forms of contraception are recommended. Male patients and their female partners of childbearing potential should use reliable contraception during therapy and for 3 months after receiving the last dose of Lynparza (see section 4.6).

Interactions
Lynparza co-administration with strong or moderate CYP3A inhibitors is not recommended (see section 4.5). If a strong or moderate CYP3A inhibitor must be co-administered, the dose of Lynparza should be reduced (see sections 4.2 and 4.5).
Lynparza co-administration with strong or moderate CYP3A inducers is not recommended. In the event that a patient already receiving Lynparza requires treatment with a strong or moderate CYP3A inducer, the prescriber should be aware that the efficacy of Lynparza may be substantially reduced (see section 4.5).

Sodium
This medicinal product contains less than 1 mmol sodium (23 mg) per 100 mg or 150 mg tablet, that is to say essentially “sodium-free”.

Effects on Driving

4.7 Effects on ability to drive and use machines
Lynparza has moderate influence on the ability to drive and use machines. Patients who take Lynparza may experience fatigue, asthenia or dizziness. Patients who experience these symptoms should observe caution when driving or using machines.