Haematological toxicity: Haematological toxicity has been reported in patients treated with olaparib, 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 within normal range or 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.
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.
Pneumonitis: Pneumonitis has been reported in a small number of patients receiving olaparib, and some reports have been fatal. The 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 a radiological abnormality occurs, 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), olaparib 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 (FC tab)/400 mg (hard cap) twice daily.
Interactions: Olaparib co-administration 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 olaparib should be reduced (see Dosage & Administration and Interactions).
Olaparib co-administration with strong or moderate CYP3A inducers is not recommended (see Interactions). In the event that a patient already receiving olaparib requires treatment with a strong or moderate CYP3A inducer, the prescriber should be aware that the efficacy of olaparib may be substantially reduced (see Interactions).
Hard cap: In the event that a patient already receiving olaparib requires treatment with a P-gp inhibitor, careful monitoring of olaparib associated adverse events and management of those events via the dose reduction strategy is recommended (see Dosage & Administration).
Myelodysplastic syndrome/Acute myeloid leukaemia: FC tab: 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% and 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 >2 years; data with longer durations of exposure are limited. 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 agents and radiotherapy. The majority of reports were in germline breast cancer susceptibility gene 1 or 2 (gBRCA1/2) mutation carriers. The incidence of MDS/AML cases was similar among gBRCA1m and gBRCA2m patients (1.7% and 1.4%, respectively). Some of the patients had a history of previous cancer 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.
Hard cap: Myelodysplastic syndrome/Acute Myeloid Leukaemia (MDS/AML) have been reported in a small number of patients who received Lynparza alone or in combination with other anti-cancer drugs; the majority of cases have been fatal. The duration of therapy with olaparib in patients who developed MDS/AML varied from < 6 months to > 2 years. The cases were typical of secondary MDS/cancer therapy-related AML. All patients had potential contributing factors for the development of MDS/AML; the majority of cases were in gBRCA mutation carriers and some of the patients had a history of previous cancer or of bone marrow dysplasia. All had received previous platinum-containing chemotherapy regimens and many had also received other DNA damaging agents and radiotherapy. If MDS and/or AML are confirmed while on treatment with Lynparza, it is recommended that the patient be treated appropriately. If additional anticancer therapy is recommended, Lynparza should be discontinued and not given in combination with other anticancer therapy.
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.
Use in Pregnancy: 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 1 month 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 Use in Pregnancy & Lactation).