Niraparib

Niraparib is used to treat recurrent or advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Niraparib is available under the following different brand names: Zejula.

Dosages of Niraparib:

Dosage Forms and Strengths

Capsules

• 100 mg

Dosage Considerations – Should be Given as Follows:

Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Indicated for maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy
• 300 mg orally once daily; continue until disease progression or unacceptable toxicity
• Start treatment no later than 8 weeks after the most recent platinum-containing regimen

Advanced Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

• Indicated for the treatment of adults with advanced ovarian, fallopian tube, or primary peritoneal cancer who have been treated with 3 prior or more chemotherapy regimens and whose cancer is associated with homologous recombination deficiency (HRD) positive status defined by either: a deleterious or suspected deleterious BRCA mutation, or genomic instability and who progressed more than 6 months after responding to the last platinum-based chemotherapy
• 300 mg orally once daily; continue until disease progression or unacceptable toxicity

Dosage Modifications

Dose reductions

• First dose reduction: 200 mg/day
• Second dose reduction: 100 mg/day
• Discontinue if further dose reduction less than 100 mg/day is required

Nonhematologic adverse reactions

• Grade 3 and greater reactions where prophylaxis is not considered feasible or adverse reaction persists despite treatment: Withhold up to 28 days or until resolution of adverse reactions; resume at a reduced dose (up to 2 dose reductions are permitted)
• Grade 3 and greater reactions lasting more than 28 days and taking niraparib 100 mg/day: Discontinue treatment

Hematologic adverse reactions

• Platelet count less than 1000,000/mcL
  • First occurrence: Withhold up to 28 days and monitor blood cell counts weekly until platelets 100,000/mcL or greater; resume at same or reduced dose; if the platelet count is less than 75,000/mcL, resume at reduced dose
  • Second occurrence: Withhold up to 28 days and monitor blood cell counts weekly until platelets 100,000/mcL or greater; resume at reduced dose; discontinue if platelet count has not returned to acceptable levels within 28 days or if the patient is already on 100 mg/day

• Neutrophil count less than 1000/mcL or hemoglobin is less than 8 g/dL
  • Withhold up to 28 days and monitor blood cell counts weekly until neutrophils 1500/mcL or greater or hemoglobin 9 g/dL or greater; resume at reduced dose
  • Discontinue if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days or if the patient is already on 100 mg/day
• Hematologic adverse reaction requiring transfusion
  • Platelet count up to 10,000/mcL: Consider platelet transfusion
  • If other risk factors exist (e.g. anticoagulants, antiplatelets), consider interrupting anticoagulants or antiplatelet drugs and/or transfuse at a higher platelet count
  • Resume at a reduced dose

Renal impairment

• Mild-to-moderate (CrCl 30 mL/minute or greater): No dose adjustment is required
• Severe or ESRD: Not studied

Hepatic impairment

• Mild: No dose adjustment required
• Moderate or severe: Not studied

Dosing Considerations

Patient selection for treatment of advanced ovarian cancer after 3 prior or more chemotherapy regimens

• Select patients for treatment of advanced ovarian cancer associated with HRD positive status based on either deleterious or suspected deleterious BRCA mutation and/or genomic instability score (GIS)
• 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: http://www.fda.gov/CompanionDiagnostics
• Safety and efficacy not established in pediatric patients

Common side effects of Niraparib include:

• Nausea
• Low blood platelets (thrombocytopenia)
• Fatigue/weakness
• Anemia
• Constipation
• Vomiting
• Abdominal pain/distention
• Low white blood cell counts (neutropenia, leukopenia)
• Insomnia
• Headache
• Runny or stuffy nose
• Rash
• High blood pressure (hypertension)
• Inflammation of the mouth and lips
• Inflammation of mucus membranes
• Diarrhea
• Heartburn/indigestion
• Muscle pain
• Back pain
• Dizziness
• Cough
• Urinary tract infection (UTI)
• Joint pain
• Anxiety
• Palpitations
• Dry mouth
• AST/ALT elevation
• Changes in taste

Postmarketing side effects of niraparib reported include:

• Immune system disorders: Hypersensitivity (including anaphylaxis)
• Nervous system disorders: Posterior reversible encephalopathy syndrome (PRES)
• Psychiatric disorders: Confusional state/disorientation, hallucination
• Respiratory, thoracic, and mediastinal disorders: Non-infectious pneumonitis
• Skin and SC tissue disorders: Photosensitivity

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider or pharmacist first.

• Niraparib Topical has no listed severe interactions with other drugs.
• Niraparib Topical has no listed serious interactions with other drugs.
• Niraparib Topical has no listed moderate interactions with other drugs.
• Niraparib Topical has no listed mild interactions with other drugs.

Warnings

• This medication contains niraparib. Do not take Zejula if you are allergic to niraparib or any ingredients contained in this drug.
• Keep out of reach of children. In case of overdose, get medical help or contact a Poison Control Center immediately.

Contraindications

• None

Effects of Drug Abuse

• No information is available.

Short-Term Effects

• See "What Are Side Effects Associated with Using Niraparib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Niraparib?"

Cautions

• Bone marrow suppression

Pregnancy and Lactation

• Niraparib has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells into animals and patients (e.g., bone marrow). A pregnancy test is recommended for females of reproductive potential before initiating niraparib. Based on animal studies, niraparib may impair fertility in males of reproductive potential.
• Females of reproductive potential are advised to use effective contraception during treatment with niraparib and for at least 6 months following the last dose.
• No data are available regarding the presence of niraparib or its metabolites in human milk, or on its effects on the breastfed infant or milk production. Owing to the potential for serious adverse reactions in breastfed infants, lactating women are advised not to breastfeed during treatment with niraparib and for 1 month after receiving the final dose.
  • Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome, reported; discontinue drug if MDS/AML is confirmed
  • Hypertension and hypertensive crisis reported; monitor blood pressure and heart rate monthly for the first year and periodically thereafter during treatment; medically manage hypertension with antihypertensive medications and niraparib dose adjustment
  • Based on its mechanism of action, can cause fetal harm if administered to a pregnant woman
    • May cause bone marrow suppression resulting in hematologic toxicities (e.g., thrombocytopenia, anemia, neutropenia)
    • Do not initiate until patients have recovered from hematological toxicities caused by previous chemotherapy (grade up to 1)
    • Monitor complete blood cell counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time