Zejula

Treatment with Zejula should be initiated and supervised by a physician experienced in the use of anticancer medicinal products. Posology First-line ovarian cancer maintenance treatment The recommended starting dose of Zejula is 200 mg (two 100-mg capsules), taken once daily.

8). Recurrent ovarian cancer maintenance treatment The dose is three 100 mg hard capsules once daily, equivalent to a total daily dose of 300 mg. Patients should be encouraged to take their dose at approximately the same time each day.

Bedtime administration may be a potential method for managing nausea. 3 It is recommended that treatment should be continued until disease progression or toxicity. Missing dose If patients miss a dose, they should take their next dose at its regularly scheduled time.

Dose adjustments for adverse reactions The recommended dose modifications for adverse reactions are listed in Tables 1, 2 and 3. In general, it is recommended to first interrupt the treatment (but no longer than 28 consecutive days) to allow the patient to recover from the adverse reaction and then restart at the same dose.

In the case that the adverse reaction recurs, it is recommended to interrupt the treatment and then resume at the lower dose. If adverse reactions persist beyond a 28-day dose interruption, it is recommended that Zejula be discontinued.

If adverse reactions are not manageable with this strategy of dose interruption and reduction, it is recommended that Zejula be discontinued.

Table 1:

Recommended dose modifications for adverse reactions Starting dose level 200 mg 300 mg First dose reduction 100 mg/day 200 mg/day (two 100-mg capsules) Second dose reduction Discontinue Zejula. 100 mg/daya (one 100-mg capsule) a If further dose reduction below 100 mg/day is required, discontinue Zejula.

Table 2:

Dose modifications for non-haematologic adverse reactions Non-haematologic CTCAE ≥Grade 3 treatment-related adverse reaction where prophylaxis is not considered feasible or adverse reaction persists despite treatment First occurrence: • Withhold Zejula for a maximum of 28 days or until resolution of adverse reaction.

• Resume Zejula at a reduced dose level per Table 1. Second occurrence: • Withhold Zejula for a maximum of 28 days or until resolution of adverse reaction. • Resume Zejula at a reduced dose or discontinue per Table 1. CTCAE ≥Grade 3 treatment-related adverse reaction lasting more than 28 days while patient is administered Zejula 100 mg/day Discontinue treatment.

Summary of the safety profile Adverse reactions of all grades occurring in ≥10% of the 851 patients receiving Zejula monotherapy in the pooled PRIMA (either 200 mg or 300 mg starting dose) and NOVA trials were nausea, anaemia, thrombocytopenia, fatigue, constipation, vomiting, headache, insomnia, platelet count decreased, neutropenia, abdominal pain, decreased appetite, diarrhoea, dyspnoea, hypertension, asthenia, dizziness, neutrophil count decreased, cough, arthralgia, back pain, white blood cell count decreased, and hot flush.

The most common serious adverse reactions >1% (treatment-emergent frequencies) were thrombocytopenia and anaemia. Tabulated list of adverse reactions The following adverse reactions have been identified based on clinical trials and post-marketing surveillance in patients receiving Zejula monotherapy (see Table 4).

Frequencies of occurrence of undesirable effects are based on pooled adverse events data generated from the PRIMA and NOVA studies (fixed starting dose of 300 mg/day) where patient exposure is known and defined as: Very common: ≥1/10 Common: ≥1/100 to <1/10 Uncommon: ≥1/1,000 to <1/100 Rare: ≥1/10,000 to <1/1,000 Very rare: <1/10,000 Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

02. a Based on niraparib clinical trial data. This is not limited to pivotal ENGOT-OV16 monotherapy study. b Includes hypersensitivity, drug hypersensitivity, anaphylactoid reaction, drug eruption, angioedema, and urticaria. c Includes memory impairment, concentration impairment.

The adverse reactions noted in the group of patients who were administered a 200 mg starting dose of Zejula based on baseline weight or platelet count were of similar or lesser frequency compared to the group administered a fixed starting dose of 300 mg (Table 4).

See below for specific information regarding frequency of thrombocytopenia, anaemia and neutropenia. Description of selected adverse reactions Haematologic adverse reactions (thrombocytopenia, anaemia, neutropenia) including clinical diagnoses and/or laboratory findings generally occurred early during niraparib treatment with the incidence decreasing over time.

8). 2). 2). If a patient develops severe persistent haematologic toxicity including pancytopenia that does not resolve within 28 days following interruption, Zejula should be discontinued. 8). 8). 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 patients had a history of bone marrow suppression. 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. 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. 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.

2). Zejula should be discontinued in case of hypertensive crisis or if medically significant hypertension cannot be adequately controlled with antihypertensive therapy. 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.

1. 6).