Niraparib (Zejula)

General information

Class/mechanism: PARP inhibitor. Niraparib inhibits poly(ADP-ribose) polymerase (PARP) enzymes PARP-1 and PARP-2, which are involved in DNA repair. Inhibiting PARP-1 and PARP-2 may result in formation of PARP-DNA complexes, DNA damage, apoptosis, and cell death. PARP proteins utilize base-excision repair (BER) to identify and repair single strand DNA breaks.
Route: PO
Extravasation: n/a

• IUPHAR/BPS

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Ovarian cancer

Patient drug information

• Niraparib (Zejula) package insert

History of changes in FDA indication

Ovarian cancer - PARTIALLY WITHDRAWN

• 2017-03-27: Initial approval for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. (Based on NOVA)
• 2019-10-23: Approved for patients with advanced ovarian, fallopian tube, or primary peritoneal cancer treated with three or more prior chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD)-positive status. HRD is defined by either a deleterious or suspected deleterious BRCA mutation, or genomic instability in patients with disease progression greater than six months after response to the last platinum-based chemotherapy. (Based on QUADRA)
  • 2022-09-14: Indication voluntarily withdrawn by the manufacturer; awaiting FDA withdrawal notice.
• 2020-04-29: Approved for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy. (Based on PRIMA_OV)

History of changes in EMA indication

• 2017-11-16: Initial marketing authorization as Zejula. Zejula is indicated as monotherapy for the maintenance treatment of adult patients with platinum-sensitive relapsed high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. (Based on NOVA)
• 2020-10-27: Extension of indication to include the use of Zejula as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

History of changes in Health Canada indication

• 2019-06-27: Initial notice of compliance

History of changes in PMDA indication

• 2020-09-29: Newly indicated for the maintenance treatment of ovarian cancer in patients who have received first chemotherapy.
• 2020-09-29: Newly indicated for the maintenance treatment of recurrent ovarian cancer in patients who are in a complete or partial response to platinum-based chemotherapy.
• 2020-09-29: Newly indicated for the treatment of homologous recombination deficiency (HRD)-positive recurrent ovarian cancer in patients who are in a complete or partial response to platinum-based chemotherapy.

Also known as

• Code name: MK-4827
• Brand name: Niranib, Zejula