Lynparza Special Precautions

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 anti-cancer 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 Adverse Reactions).
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 incidence of 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 Adverse Reactions). The majority of events had a fatal outcome. The duration of therapy with Lynparza in patients who developed MDS/AML varied from < 6 months to > 4 years. All patients had potential contributing factors for the development of MDS/AML, having received previous chemotherapy with platinum agents. Many had also received other DNA damaging treatments. The majority of reports were in germline BRCA mutation (gBRCAm) carriers and some of the patients had a history of more than one primary malignancy or of bone marrow dysplasia. If MDS and/or AML are confirmed while on treatment with Lynparza, it is recommended that Lynparza should be discontinued and the patient be treated appropriately.
Venous Thromboembolic Events: Hard capsule: Venous thromboembolic events, including 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 Adverse Reactions). Monitor patients for clinical signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate.
Pneumonitis: Pneumonitis has been reported in <1.0% patients treated with Lynparza monotherapy 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). When Lynparza was used in clinical studies in combination with other therapies there have been events with a fatal outcome. 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.
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 (FC tablet); 400 mg twice daily (Hard capsule).
Lynparza should not be taken during pregnancy. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a foetus. Women of childbearing potential should be advised that they must use effective contraception during Lynparza treatment and for one month after receiving the last dose of Lynparza (see Use in Pregnancy & Lactation).
FC tablet: Male patients and their female partners of childbearing potential should be advised that they must use effective contraception during Lynparza treatment and for 3 months after receiving the last dose of Lynparza (see Use in Pregnancy & Lactation).
Interactions with other medicinal products: Co-administration of Lynparza with strong or moderate CYP3A inhibitors is not recommended (see Interactions). If a strong or moderate CYP3A inhibitor must be co-administered, the dose of Lynparza should be reduced (see Dosage & Administration).
Co-administration of Lynparza 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 Interactions).
Effects on ability to drive and use machines: No studies to establish the effects of olaparib on the ability to drive and use machinery have been conducted. However, during treatment with Lynparza, asthenia, fatigue, and dizziness have been reported and those patients who experience these symptoms should observe caution when driving or using machines.
Use in Lactation: The excretion of olaparib in milk has not been studied in animals or in breast-feeding mothers. Breast-feeding mothers are advised not to breast-feed during treatment with Lynparza and for one month after receiving the last dose of Lynparza (see Use in Pregnancy & Lactation).