Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Haematologic adverse reactions
Haematologic adverse reactions (thrombocytopenia, anaemia, neutropenia) have been reported in patients treated with Zejula (see section 4.8). Patients with lower body weight or lower baseline platelet count may be at increased risk of Grade 3+ thrombocytopenia (see section 4.2).
Testing complete blood counts weekly for the first month, followed by monthly monitoring for the next 10 months of treatment and periodically after this time is recommended to monitor for clinically significant changes in any haematologic parameter during treatment (see section 4.2).

If a patient develops severe persistent haematologic toxicity including pancytopenia that does not resolve within 28 days following interruption, Zejula should be discontinued.

Due to the risk of thrombocytopenia, anticoagulants and medicinal products known to reduce the thrombocyte count should be used with caution (see section 4.8).

Myelodysplastic syndrome/acute myeloid leukaemia

Cases of myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome, have been observed in patients treated with Zejula monotherapy or combination therapy in clinical trials and postmarketing (see section 4.8).

In clinical trials, the duration of Zejula treatment in patients prior to developing MDS/AML varied from 0.5 months to > 4.9 years. The cases were typical of secondary, cancer therapy-related MDS/AML. All patients had received platinum-containing chemotherapy regimens and many had also received other DNA damaging agents and radiotherapy. Some of the patients had a history of bone marrow suppression. In the NOVA trial, the incidence of MDS/AML was higher in the gBRCAmut cohort (7.4%) than in the non-gBRCAmut cohort (1.7%).
For suspected MDS/AML or prolonged haematological toxicities, the patient should be referred to a haematologist for further evaluation. If MDS/AML is confirmed Zejula treatment should be discontinued and the patient treated appropriately.

Hypertension, including hypertensive crisis

Hypertension, including hypertensive crisis, has been reported with the use of Zejula (see section 4.8).
Pre-existing hypertension should be adequately controlled before starting Zejula treatment. Blood pressure should be monitored at least weekly for two months, monitored monthly afterwards for the first year and periodically thereafter during treatment with Zejula. Home blood pressure monitoring may be considered for appropriate patients with instruction to contact their health care provider in case of rise in blood pressure.

Hypertension should be medically managed with antihypertensive medicinal products as well as adjustment of the Zejula dose (see section 4.2), if necessary. In the clinical programme, blood pressure measurements were obtained on Day 1 of each 28-day cycle while the patient remained on Zejula. In most cases, hypertension was controlled adequately using standard antihypertensive treatment with or without Zejula dose adjustment (see section 4.2). Zejula should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy.

Posterior reversible encephalopathy syndrome (PRES)

There have been reports of PRES in patients receiving Zejula (see section 4.8). PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizures, headache, altered mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI).

In case of PRES, it is recommended to discontinue Zejula and to treat specific symptoms including hypertension. The safety of reinitiating Zejula therapy in patients previously experiencing PRES is not known.

Pregnancy/contraception

Zejula should not be used during pregnancy or in women of childbearing potential not willing to use highly effective contraception during therapy and for 6 months after receiving the last dose of Zejula (see section 4.6). A pregnancy test should be performed on all women of childbearing potential prior to treatment.

Hepatic impairment

Patients with severe hepatic impairment could have increased exposure of niraparib based on data from patients with moderate hepatic impairment and should be carefully monitored (see section and 5.2).

Lactose

Zejula film-coated tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.





Effects on Driving

4.7    Effects on ability to drive and use machines

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