What are the common side effects of niraparib (Zejula) and how are they managed?

Niraparib Side Effects and Management

Niraparib causes significant hematologic toxicity, particularly thrombocytopenia (34% grade ≥3), which is substantially higher than other PARP inhibitors and requires individualized starting dose based on baseline body weight and platelet count to minimize toxicity while maintaining efficacy. 1

Hematologic Toxicities (Most Common and Serious)

Thrombocytopenia

• Grade ≥3 thrombocytopenia occurs in 28.7-33.8% of patients receiving niraparib, making it the most problematic hematologic toxicity 1, 2
• This is dramatically higher than olaparib (1-2% grade ≥3) or rucaparib (2.4% grade ≥3) 1, 3
• Individualized starting dose is critical: Use 200 mg daily (instead of 300 mg) for patients with baseline body weight <77 kg OR baseline platelet count <150,000/μL 1, 4
• This dose modification reduces grade ≥3 thrombocytopenia while maintaining progression-free survival benefit 4
• Management approach: Hold niraparib for grade 3/4 thrombocytopenia, then reduce dose upon recovery 1
• Discontinue permanently for persistent thrombocytopenia or significant bleeding despite dose reduction 1
• Rare cases of persistent, irreversible thrombocytopenia have been reported even months after treatment 5

Anemia

• Grade ≥3 anemia occurs in 25.3-31% of patients 1, 6, 2
• Transfusion is indicated for symptomatic relief and/or hemoglobin <8 g/dL 1
• Dose reduction is required with evidence of repeated anemia to avoid multiple transfusions 1
• Growth factor support may be offered per ASCO guidelines for progressive anemia 1
• Drug holding alone without dose modification will result in recurrence upon reinstitution 1

Neutropenia

• Grade ≥3 neutropenia occurs in 19.6% of patients [1, @19@]
• Prophylactic growth factor is NOT indicated for daily PARP inhibitor therapy 1
• Hold niraparib for grade 4 neutropenia lasting ≥5-7 days or grade 3 with fever 1
• Short-acting growth factor (e.g., 3 days of neupogen) may be used during drug hold to support patient safety 1
• Do not restart niraparib until fever resolves, granulocyte count ≥1,000/dL, and 48-72 hours have elapsed since last growth factor dose 1

Non-Hematologic Toxicities

Gastrointestinal Effects

• Nausea occurs in the majority of patients but is typically low-grade (grade ≥3 in only 4.9% despite high overall incidence) [1, @19@]
• Many patients experience tachyphylaxis of nausea symptoms over the first treatment cycle 1
• Dose reduction is indicated for: persistent nausea requiring daily antiemetic intervention, causing reduced performance status, and/or resulting in >5% weight loss 1
• Once-daily dosing at night may help alleviate gastrointestinal symptoms 2

Fatigue

• Occurs in 42-63% of patients (any grade), with grade ≥3 in 8.2% 1, 2
• May be multifactorial due to cytopenias, nausea-related stress, or persistent low-grade events 1
• Special attention should be paid to cumulative low-grade adverse events with daily continuous administration 1

Cardiovascular Effects

• Hypertension, tachycardia, and palpitations require monitoring 6
• Patients should be monitored for hypertension throughout treatment 6

Rare but Serious Toxicities

Myelodysplastic Syndrome/Acute Myelogenous Leukemia

• Overall risk is 0.9% across all niraparib-treated patients 6
• Evaluate for treatment-related MDS/AML in patients with persistent cytopenia despite drug hold 1
• Use low threshold for bone marrow evaluation, especially with persistent multilineage cytopenia 1
• Early hematology consultation is recommended where appropriate 1

Pneumonitis

• Drug-induced pneumonitis occurs in approximately 2% of patients 3
• Life-threatening cases have been reported despite not being documented in phase III trials 7
• This is an emerging side effect requiring heightened awareness with first-line maintenance use 7

Dose Modification Patterns

• Dose interruptions occur in 62-80% of patients receiving niraparib 2
• Dose reductions occur in 47-71% of patients 2
• Treatment discontinuation due to adverse events occurs in 14.7% of patients 4
• Following dose modification, 200 mg becomes the most commonly administered dose 4
• Patients requiring dose reduction to 200 mg or 100 mg maintain progression-free survival benefit consistent with those remaining at 300 mg 4

Monitoring Requirements

• Complete blood count monitoring is mandatory throughout treatment 3
• Baseline assessment of body weight and platelet count determines starting dose 1, 4
• Type and screen availability with transfusion support readiness is required 3
• Blood pressure monitoring for cardiovascular toxicity 6

Quality of Life Considerations

Despite the significant toxicity profile, niraparib does not negatively impact health-related quality of life compared to placebo when adverse events are appropriately managed 3