Written by: Michelle Phillips, PharmD, University of Rochester Medical Center
Description: 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).
Background: 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 mg 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
- Commercially insured patients
- 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.