Written by: Michelle Phillips, PharmD, University of Rochester Medical Center
The purpose of this PQI is to highlight key criteria for appropriate monitoring, dosing, and administration to improve the dispensing and management of patients taking niraparib (Zejula).
Niraparib is indicated for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Additional indication in patients with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status (BRCA+ or BRCA- with Genomic Instability Positive (GIS+) disease). Niraparib efficacy is particularly pronounced in patients with BRCA1/2 mutations but also yields therapeutic benefit in those without germline BRCA mutations.
Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred, respectively, in 3%, 1%, and 2% of patients. Retrospective analysis of the pivotal phase III NOVA clinical trial reveals most dose adjustments occurred within 3 months and did not appear to compromise efficacy.
- Verify dose on initial fill—labeled starting dose is 300 mg once daily
- Consider starting at 200 mg daily for patients with baseline weight < 77 kg or baseline platelets < 150K.
- In practice, it has been seen at starting doses of 100 once daily as well
- Ensure patients should start treatment with niraparib no later than 8 weeks after their most recent platinum-containing regimen
- Consider bevacizumab discontinuation before initiation of treatment with niraparib
- Ensure appropriate monitoring:
- CBC weekly x 4 weeks, monthly x 11 months, then periodically
- Heart rate and BP monthly x 12 months, then periodically
- Discontinue for any adverse effect that has not resolved within 28 days or grade ≥ 3 while on 100 mg/day.
Dose Adjustments for hematologic toxicity: **MINIMUM dose 100 mg/day**
|Platelets < 100 K|
(Monitor CBC weekly until resolved)
|1st Occurrence: HOLD* until platelets ≥ 100 K|
Resume same dose
However, if < 75K, reduce dose by 100 mg
2nd Occurrence: HOLD* until platelets ≥ 100K
Reduce by 100 mg/day
|ANC < 1.0 or|
Hg < 8 g/dL
(Monitor CBC weekly until resolved)
|HOLD* until ANC ≥ 1.5 or Hg ≥ 9 g/dL|
Reduce dose by 100 mg/day
|* Hold for maximum of 28 days. Discontinue if not resolved within 28 days or if dose reduction needed beyond 100 mg/day.|
- Provide Oral Chemotherapy Education (OCE) Sheet
- Take once daily, with or without food
- Taking at bedtime may minimize nausea
- Moderate to high emetogenic risk per NCCN guidelines
- Advise patients of warnings:
- Myelodysplastic syndrome/Acute myeloid leukemia
- Bone marrow suppression
- Cardiovascular effects (hypertension, tachycardia)
- Embryo-fetal toxicity
- Consider weekly home blood pressure and heart rate monitoring
- Recommend stool softeners/laxatives as needed for constipation
- Recommend home antiemetic as needed for nausea/vomiting
- 5HT-3 such as: Ondansetron
- Quick start and bridge program—offers 15 day supply while awaiting insurance authorization (up to 5 refills)
- Commercially insured patients
- $0 copay, up to $26,000 per year
- Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. NEJM. 2016; 375 (22): 2154 – 64.
- Moore KN, Mirsa MR, Matulonia UA. The poly (ADP ribose) polymerase inhibitor niraparib: Management of toxicities. 2018; 149: 214 – 220.
- National Comprehensive Cancer Network. Antiemesis (Version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf Accessed May 17, 2018.
- National Comprehensive Cancer Network. Ovarian cancer (Version 2.2018). https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf Accessed May 15, 2018.
- Niraparib incidence and management of thrombocytopenia. TESARO Response letter; 2018.
- Retrospective analaysis of the NOVA trial to assess potential predictors for early dose modification. TESARO Response Letter; 2018.
- Gonzalez A, Mirza MR, et al. A Prospective Evaluation of tolerability of niraparib dosing based upon baseline body weight and platelet count. Annals of Oncology (2018) 29 (suppl_8): vii332-vii358.10.1093/annonc/mdy285
- ZEJULA [Package Insert]. Waltham, MA: Tesaro, Inc; 2019