Niraparib

Keep all appointments with your doctor and the laboratory. Your doctor will check your blood pressure regularly and order certain lab tests before and during your treatment to check your body's response to niraparib.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Contraindications

None

Cautions

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with fatal outcome, reported; discontinue drug if MDS/AML is confirmed

May cause bone marrow suppression resulting in hematologic toxicities (eg, thrombocytopenia, anemia, neutropenia); do not initiate until patients have recovered from hematological toxicities caused by previous chemotherapy (grade ≤1); monitor complete blood cell counts weekly for the first month, monthly for the next 11 months of treatment, and periodically after this time (also see Dosage Modifications)

Hypertension and hypertensive crisis reported; monitor BP and HR 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 (see Pregnancy)

You should not use niraparib if you are pregnant. Avoid pregnancy for at least 6 months after you stop using this medicine.

You should not breast-feed while using this medicine and for at least 1 month after your last dose.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Medicines used to treat cancer are very strong and can have many side effects. Before using niraparib, make sure you understand all the risks and benefits. It is important for you to work closely with your doctor during your treatment.

Take niraparib exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

niraparib usually comes with patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the capsules whole. Do not crush, break, chew, or open it. You may take niraparib with or without food.

Take niraparib at the same time each day.

Dosing

The dose of niraparib will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of niraparib. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (capsules):
  • For maintenance treatment of ovarian cancer, fallopian tube cancer, or primary peritoneal cancer:
    • Adults—300 milligrams (mg) (three 100 mg capsules) once a day. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of niraparib, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood tests may be needed to check for unwanted effects.

Using niraparib while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 6 months after the last dose of niraparib. If you think you have become pregnant while using the medicine, tell your doctor right away.

niraparib may cause bone marrow problems, such as myelodysplastic syndrome or acute myeloid leukemia. Check with your doctor right away if you have a fever, blood in the urine or stool, chills, unusual bleeding, bruising, tiredness, or weakness, or weight loss.

Niraparib can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

If you plan to have children, talk with your doctor before using niraparib. Some men using niraparib have become infertile (unable to have children).

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Niraparib is a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor, which is highly selective for PARP-1 and PARP-2. PARP-1 and PARP-2 are involved in detecting DNA damage and promote repair (Mirza 2016). Inhibiting PARP enzymatic activity results in DNA damage, apoptosis and cell death. Niraparib induces cytotoxicity in tumor cell lines with and without BRCA1/2 deficiencies.

Distribution

Vd/F: 1,074 L

Metabolism

Metabolized by carboxylesterases to an inactive metabolite, which subsequently undergoes glucuronidation.

Excretion

Urine (~48% [at 21 days]; 11% [pooled samples collected over 6 days] as unchanged drug); Feces (~39% [at 21 days]; 19% [pooled samples collected over 6 days] as unchanged drug)

Time to Peak

Within 3 hours

Half-Life Elimination

36 hours

Protein Binding

83%

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience back pain, nausea, vomiting, constipation, diarrhea, abdominal pain, heartburn, change in taste, insomnia, anxiety, rhinitis, pharyngitis, mouth irritation, mouth sores, dry mouth, lack of appetite, muscle pain, or joint pain. Have patient report immediately to prescriber signs of infection, signs of a urinary tract infection (hematuria, burning or painful urination, polyuria, fever, lower abdominal pain, or pelvic pain), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), severe headache, severe dizziness, passing out, vision changes, weight loss, abnormal heartbeat, abdominal edema, shortness of breath, or severe loss of strength and energy (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

300 mg orally once a day
Duration of Therapy: Until disease progression or unacceptable toxicity

Comments:
-Initiate treatment with this drug no later than 8 weeks after a patient's most recent platinum-containing regimen.
-Bedtime administration may be a potential method for managing nausea.

Use: Maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

ADVERSE REACTIONS (ARs): Consider treatment interruption, dose reduction, and/or treatment discontinuation to manage ARs.
-FIRST DOSE REDUCTION: 200 mg orally once a day
-SECOND DOSE REDUCTION: 100 mg orally once a day
-FURTHER DOSE REDUCTION BELOW 100 MG/DAY REQUIRED: Discontinue treatment.

NON-HEMATOLOGIC ARs:
GRADE 3 OR GREATER AR WHERE PROPHYLAXIS IS NOT CONSIDERED FEASIBLE OR AR PERSISTS DESPITE TREATMENT:
-Withhold treatment for a maximum of 28 days or until resolution or AR.
-Resume treatment at a reduced dose; up to 2 dose reductions are permitted.
GRADE 3 OR GREATER TREATMENT-RELATED AR LASTING MORE THAN 28 DAYS WHILE PATIENT IS ADMINISTERED DOSE OF 100 MG/DAY: Discontinue treatment.

HEMATOLOGIC ARs: Monitor complete blood counts weekly for the first month, monthly for the next 11 months of treatment and periodically afterwards.
PLATELET COUNT LESS THAN 100,000/mcL:
FIRST OCCURRENCE:
-Withhold treatment for a maximum of 28 days and monitor blood counts weekly until platelet counts return to 100,000/mcL or more.
-Resume treatment at same or reduced dose.
-If platelets less than 75,000/mcL, resume at a reduced dose.
SECOND OCCURRENCE:
-Withhold treatment for a maximum of 28 days and monitor blood counts weekly until platelet counts return to 100,000/mcL or more.
-Resume treatment at a reduced dose.
-Discontinue treatment if the platelet count has not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg once a day.

NEUTROPHILS LESS THAN 1000/mcL OR HEMOGLOBIN LESS THAN 8 g/dL:
-Withhold treatment for a maximum of 28 days and monitor blood counts weekly until neutrophil counts return to 1500/mcL or more OR hemoglobin returns to 9 g/dL or more.
-Resume treatment at a reduced dose.
-Discontinue treatment if neutrophils and/or hemoglobin have not returned to acceptable levels within 28 days of the dose interruption period, or if the patient has already undergone dose reduction to 100 mg once a day.

HEMATOLOGIC ADVERSE REACTION REQUIRING TRANSFUSION:
-Consider platelet transfusion for patients with platelet counts 10,000/mcL or less.
-If there are other risk factors such as co-administration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a higher platelet count.
-Resume treatment at a reduced dose.

MYELODYSPLASTIC SYNDROME OR ACUTE MYELOID LEUKEMIA (MDS/AML) IS CONFIRMED: Discontinue treatment.