niraparib

nye-RAP-a-rib

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

High Alert

Maintenance treatment of deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to platinum-based chemotherapy.
Maintenance treatment of advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who are in a complete or partial response to first-line platinum-based chemotherapy.

Acts as a poly (ADP-ribose) polymerase (PARP-1 and PARP-2) inhibitor; results in DNA damage, apoptosis, and cell death.

Therapeutic effects:

Decreased progression of ovarian, fallopian tube, or primary peritoneal cancer and improved survival.

Absorption: 73% absorbed following oral administration.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized by carboxylesterases to an inactive metabolite; 48% excreted in urine (11% as unchanged drug), 39% in feces (19% as unchanged drug).

Half-Life: 36 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3 hr	24 hr

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Ischemic heart disease, arrhythmias, or hypertension;
Severe renal impairment (CCr <30 mL/min);
Previous use of platinum chemotherapy agents or radiation (↑ risk of secondary myelodysplastic syndrome or acute myeloid leukemia);
Moderate or severe hepatic impairment (↓ dose in moderate hepatic impairment);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

CV: palpitations, hypertension

Derm: rash

GI: ↑liver enzymes, abdominal pain/distention, constipation, diarrhea, dry mouth, dyspepsia, nausea, stomatitis, vomiting

GU: urinary tract infection, ↓fertility (males)

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia, MYELODYSPLASTIC SYNDROME (MDS)/ACUTE MYELOID LEUKEMIA (AML), pancytopenia

Metab: ↓appetite

MS: arthralgia, myalgia

Neuro: anxiety, dizziness, dysgeusia, fatigue, headache, insomnia, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)

Resp: cough, dyspnea

Drug-drug:

None reported.

Maintenance Treatment of Recurrent Germline BRCA-Mutated Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

PO (Adults ): 300 mg once daily until disease progression or unacceptable toxicity. Treatment should be started within 8 wk after most recent platinum-containing regimen.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 200 mg once daily until disease progression or unacceptable toxicity. Treatment should be started within 8 wk after most recent platinum-containing regimen.

Maintenance Treatment of Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

PO (Adults ≥77 kg AND platelet count ≥150,000/mm³): 300 mg once daily until disease progression or unacceptable toxicity. Treatment should be started within 12 wk after most recent platinum-containing regimen.
PO (Adults <77 kg OR platelet count <150,000/mm³): 200 mg once daily until disease progression or unacceptable toxicity. Treatment should be started within 12 wk after most recent platinum-containing regimen.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 200 mg once daily until disease progression or unacceptable toxicity. Treatment should be started within 12 wk after most recent platinum-containing regimen.

Tablets: 100 mg; 200 mg; 300 mg
In combination with: abiraterone (Akeega). See Appendix [not included in this PDA edition].

Monitor for signs and symptoms of MDS or AML (weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness, blood in urine or stool, low blood cell counts, need for blood transfusions) periodically during therapy.
Monitor BP and HR weekly for first 2 mo, then monthly for first year, and periodically during therapy. Closely monitor patients with cardiovascular disorders, especially coronary artery disease, cardiac arrhythmias, and hypertension. Manage hypertension with antihypertensive medications and adjustment of niraparib dose, if necessary.
Monitor for signs and symptoms of PRES (seizure, headache, altered mental status, visual disturbance, cortical blindness, with or without associated hypertension). If symptoms occur, promptly discontinue niraparib.

Lab Test Considerations:

Patient selection is based on either deleterious or suspected deleterious BRCA mutation and/or genomic instability score. Information on FDA-approved tests for the detection of either deleterious or suspected deleterious BRCA mutation or genomic instability for this indication is available at https://www.fda.gov/companiondiagnostics.Verify negative pregnancy test before starting therapy.
- Monitor CBC weekly for first mo, monthly for next 11 mo, and periodically during therapy. Do not start niraparib until recovery of hematological toxicity from previous chemotherapy has recovered. If platelet count <100,000 /mm³/L:First occurrence: Hold niraparib for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000 /mm³/L. Resume at same or ↓ dose. If platelet count <75,000/ mm³/L, resume at a ↓ dose. Second occurrence: Hold niraparib for a maximum of 28 days and monitor blood counts weekly until platelet counts return to ≥100,000/mm³. Resume at a ↓ dose. Discontinue niraparib if platelet count has not returned to acceptable levels within 28 days of the dose interruption period or if dose already ↓ to 100 mg once daily. For platelet count ≤10,000/mm³/L, consider platelet transfusion. If other risk factors such as coadministration of anticoagulation or antiplatelet drugs exist, consider interrupting these drugs and/or transfusion. Resume therapy at a ↓ dose.
- If neutrophil count <1000/mm³ or hemoglobin <8 g/dL, hold niraparib for a maximum of 28 days and monitor blood counts weekly until neutrophil counts return to ≥1500/mm³ or hemoglobin returns to ≥9 g/dL. Resume at a ↓ dose. Discontinue therapy if neutrophil count and/or hemoglobin have not returned to acceptable levels within 28 days of dose interruption or if dose already ↓ to 100 mg once daily.
- May cause anemia.
- May cause ↑ AST and ALT.

Do not confuse niraparib with neratinib or nilotinib.
For the maintenance treatment of advanced ovarian cancer, start therapy with no later than 12 wk after most recent platinum-containing regimen.
Dose Modification Recommendations: First dose reduction: If taking 200 mg once daily, ↓ to 100 mg once daily. If taking 300 mg once daily, ↓ to 200 mg once daily. Second dose reduction: If taking 200 mg once daily, discontinue niraparib. If taking 300 mg once daily, ↓to 100 mg/day. If further dose ↓ below 100 mg/day is required, discontinue niraparib.
For nonhematologic adverse reactions: If nonhematologic CTCAE ≥Grade 3 adverse reaction persists despite medical management, hold niraparib for a maximum of 28 days or until resolution of adverse reaction. Resume niraparib at a reduced dose. Discontinue therapy if CTCAE ≥Grade 3 treatment-related adverse reaction lasts >28 days while taking 100 mg once daily.
PO: Administer once daily, at the same time each day, without regard to food. Nausea may be minimized by administering at bedtime. DNC: Swallow tablets whole; do not crush or chew.

Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes. Instruct patient to take niraparib as directed at the same time each day. Do not stop therapy without consulting health care professional. If a dose is missed or patient vomits after dose, omit and take next dose at scheduled time; do not double doses.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Advise patient to notify health care professional if symptoms of MDS or AML (weakness, fever, feeling tired, weight loss, shortness of breath, blood in urine or stool, frequent infections, unusual bruising or bleeding) occur.
Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose and to avoid breastfeeding during and for 1 mo after last dose of therapy. Inform male patients niraparib may impair fertility.

Decreased progression of ovarian, fallopian tube, or primary peritoneal cancer and improved survival.

Zejula

NDC Code

69656- TESARO, Inc.
- 69656-103- ZEJULA
  - 69656-103-30- 30 CAPSULE in 1 BOTTLE (69656-103-30)

69656- TESARO, Inc.
- 69656-103- ZEJULA
  - 69656-103-90- 90 CAPSULE in 1 BOTTLE (69656-103-90)

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