Posology : מינונים

4.2      Posology and method of administration

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.
However, for those patients who weigh ≥ 77 kg and have baseline platelet count ≥ 150,000/μL, the recommended starting dose of Zejula is 300 mg (three 100-mg capsules), taken once daily (see section 4.4 and 4.8).


ZEJULA-SPC-0223-V1                                 Page 1 of 22
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.

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/day* (one 100-mg capsule)
*
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     First occurrence: adverse reaction where prophylaxis is not considered    • Withhold Zejula for a maximum of feasible or adverse reaction persists despite treatment     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              Discontinue treatment.
lasting more than 28 days while patient is administered
Zejula 100 mg/day

*CTCAE=Common Terminology Criteria for Adverse Events


ZEJULA-SPC-0223-V1                           Page 2 of 22
Table 3: Dose modifications for haematologic adverse reactions
Haematologic adverse reactions have been observed during the treatment with Zejula especially during the initial phase of the treatment. It is therefore recommended to monitor complete blood counts (CBCs) weekly during the first month of treatment and modify the dose as needed. After the first month, it is recommended to monitor CBCs monthly and periodically after this time (see section 4.4). Based on individual laboratory values, weekly monitoring for the second month may be warranted.
•       For patients with platelet count ≤ 10,000/μL, platelet transfusion should be considered. If there are other risk
Haematologic adverse reaction factors for bleeding such as co-administration of requiring transfusion or anticoagulation or antiplatelet medicinal products,
haematopoietic growth factor consider interrupting these substances and/or support transfusion at a higher platelet count.
•       Resume Zejula at a reduced dose.
First occurrence:
•       Withhold Zejula for a maximum of 28 days and monitor blood counts weekly until platelet counts return to
≥ 100,000/µL.
•       Resume Zejula at same or reduced dose per Table 1 based on clinical evaluation.
•       If platelet count is < 75,000/μL at any time, resume at a reduced dose per Table 1.
Platelet count < 100,000/μL            Second occurrence:
•       Withhold Zejula for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥ 100,000/µL.
•       Resume Zejula at a reduced dose per Table 1.
•       Discontinue Zejula if the platelet count has not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg QD.
•       Withhold Zejula for a maximum of 28 days and monitor blood counts weekly until neutrophil counts return to ≥ 1,500/µL or haemoglobin returns to ≥ 9 g/dL.
Neutrophil < 1,000/µL or               •       Resume Zejula at a reduced dose per Table 1.
Haemoglobin < 8 g/dL                   •       Discontinue Zejula if neutrophils and/or haemoglobin have not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg QD.
Confirmed diagnosis of myelodysplastic syndrome (MDS)
•       Permanently discontinue Zejula.
or acute myeloid leukaemia
(AML)

Patients with low body weight in recurrent ovarian cancer maintenance treatment Approximately 25% of patients in the NOVA study weighed less than 58 kg, and approximately 25% of patients weighed more than 77 kg. The incidence of Grade 3 or 4 adverse reactions (ADRs) was greater among low body weight patients (78%) than high body weight patients (53%). Only 13% of low body weight patients remained at a dose of 300 mg beyond Cycle 3. A starting dose of 200 mg for patients weighing less than 58 kg may be considered.

Elderly
No dose adjustment is necessary for elderly patients (≥ 65 years). There are limited clinical data in patients aged 75 or over.

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Renal impairment
No dose adjustment is necessary for patients with mild to moderate renal impairment. There are no data in patients with severe renal impairment or end stage renal disease undergoing haemodialysis; use with caution in these patients (see section 5.2).

Hepatic impairment
No dose adjustment is needed in patients with mild to moderate hepatic impairment. There are no data in patients with severe hepatic impairment; use with caution in these patients (see section 5.2).

Patients with ECOG performance status 2 to 4
Clinical data are not available in patients with ECOG performance status 2 to 4.

Paediatric population
The safety and efficacy of niraparib in children and adolescents below 18 years of age have not yet been established. No data are available.

Method of administration

Zejula is for oral use. The capsules should be swallowed whole with water. The capsules should not be chewed or crushed.

Zejula can be taken without regard to meals.