Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: GlaxoSmithKline (Ireland) Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland
Zejula is indicated:
Treatment with Zejula should be initiated and supervised by a physician experienced in the use of anticancer medicinal products.
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).
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.
If patients miss a dose, they should take their next dose at its regularly scheduled time.
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 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. |
* CTCAE=Common Terminology Criteria for Adverse Events
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. | |
| Haematologic adverse reaction requiring transfusion or haematopoietic growth factor support | • For patients with platelet count ≤10,000/μL, platelet transfusion should be considered. If there are other risk factors for bleeding such as co-administration of anticoagulation or antiplatelet medicinal products, consider interrupting these substances and/or transfusion at a higher platelet count. • Resume Zejula at a reduced dose. |
| Platelet count <100,000/μL | 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. |
| 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. | |
| Neutrophil <1,000/µL or Haemoglobin <8 g/dL | • 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. • Resume Zejula at a reduced dose per Table 1. • 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) or acute myeloid leukaemia (AML) | • Permanently discontinue Zejula. |
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.
No dose adjustment is necessary for elderly patients (≥65 years). There are limited clinical data in patients aged 75 or over.
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).
No dose adjustment is needed in patients with mild hepatic impairment (either aspartate aminotransferase (AST) > upper limit of normal (ULN) and total bilirubin (TB) ≤ ULN or any AST and TB > 1.0 x – 1,5 x ULN). For patients with moderate hepatic impairment (any AST and TB > 1.5 x – 3 x ULN) the recommended starting dose of Zejula is 200 mg once daily. There are no data in patients with severe hepatic impairment (any AST and TB > 3 x ULN); use with caution in these patients (see sections 4.4 and 5.2).
Clinical data are not available in patients with ECOG performance status 2 to 4.
The safety and efficacy of niraparib in children and adolescents below 18 years of age have not yet been established. No data are available.
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.
There is no specific treatment in the event of Zejula overdose, and symptoms of overdose are not established. In the event of an overdose, physicians should follow general supportive measures and should treat symptomatically.
3 years.
Do not store above 30°C.
Aclar/PVC/aluminium foil perforated unit dose blisters in cartons of 84 × 1, 56 × 1 and 28 × 1 hard capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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