Zejula

Dosage Forms & Strengths

capsule

• 100mg

Ovarian Cancer

Indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy

300 mg PO qDay; continue until disease progression or unacceptable toxicity

Also see Administration

Dosage Modifications

Dose reductions

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

Nonhematologic adverse reactions

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

Hematologic adverse reactions

• Platelet count <1000,000/mcL
  • First occurrence: Withhold niraparib up to 28 days and monitor blood cell counts weekly until platelets ≥100,000/mcL; resume at same or reduced dose; if platelet count is <75,000/mcL, resume at reduced dose
  • Second occurrence: Withhold niraparib up to 28 days and monitor blood cell counts weekly until platelets ≥100,000/mcL; 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 <1000/mcL or hemoglobin <8 g/dL
  • Withhold niraparib up to 28 days and monitor blood cell counts weekly until neutrophils ≥1500/mcL or hemoglobin ≥9 g/dL; 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 ≤10,000/mcL: Consider platelet transfusion
  • If other risk factors exist (eg anticoagulants, antiplatelets), consider interrupting anticoagulants or antiplatelet drugs and/or transfuse at a higher platelet count
  • Resume niraparib at a reduced dose

Renal impairment

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

Hepatic impairment

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

Safety and efficacy not established

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

You should start taking niraparib no longer than 8 weeks after your most recent chemotherapy treatment with a platinum medicine (cisplatin, oxaliplatin, carboplatin).

You may take niraparib with or without food. Take the medicine at the same time each day.

Niraparib is usually taken once a day until your body no longer responds to the medication.

Niraparib may be taken at bedtime it upsets your stomach.

Do not crush, chew, break, or open a niraparib capsule. Swallow it whole.

If you vomit shortly after taking a niraparib capsule, do not take another one. Wait until your next scheduled dose and take the regular amount of medicine at that time.

Niraparib can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Your blood pressure and heart rate will also need to be checked often.

Store at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

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

Niraparib tosylate has the following uses:

Niraparib tosylate is a poly(ADP-ribose) polymerase (PARP) inhibitor indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of niraparib in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of niraparib in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Anemia or
• Bone marrow problems (eg, acute myeloid leukemia, myelodysplastic syndrome) or
• Heart disease or
• Heart rhythm problems (eg, arrhythmia) or
• Hypertension (high blood pressure) or
• Neutropenia (low number of white blood cells) or
• Thrombocytopenia (low number of platelets)—Use with caution. May make these conditions worse.

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 this medicine 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 this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine 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 this medicine. Some men using this medicine 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.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of a urinary tract infection (UTI) like blood in the urine, burning or pain when passing urine, feeling the need to pass urine often or right away, fever, lower stomach pain, or pelvic pain.
• Signs of bleeding like throwing up blood or throw up that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; vaginal bleeding that is not normal; bruises without a reason or that get bigger; or any bleeding that is very bad or that you cannot stop.
• Signs of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
• Feeling very tired or weak.
• Weight loss.
• A heartbeat that does not feel normal.
• Swelling of belly.
• Shortness of breath.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Hard stools (constipation).
• Loose stools (diarrhea).
• Belly pain or heartburn.
• Mouth irritation or mouth sores.
• Dry mouth.
• Not hungry.
• Feeling tired or weak.
• Muscle or joint pain.
• Back pain.
• Headache.
• Dizziness.
• Change in taste.
• Not able to sleep.
• Anxiety.
• Nose or throat irritation.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Usual Adult Dose for Ovarian Cancer:

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.

Usual Adult Dose for Fallopian Tube Cancer:

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.

Usual Adult Dose for Peritoneal Cancer:

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.

Get emergency medical help if you have signs of an allergic reaction to Zejula: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• pounding heartbeats or fluttering in your chest;

• sores or white patches in or around your mouth, trouble swallowing or talking, dry mouth, bad breath, altered sense of taste;

• pain or burning when you urinate;

• increased blood pressure - severe headache, blurred vision, pounding in your neck or ears, anxiety, nosebleed;

• low blood cell counts - fever, chills, flu-like symptoms, swollen gums, mouth sores, skin sores, rapid heart rate, pale skin, easy bruising, unusual bleeding, feeling light-headed; or

• signs of a bone marrow disorder - fever, weakness, tiredness, feeling short of breath, weight loss, blood in your urine or stools.

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common Zejula side effects may include:

• indigestion, stomach pain, loss of appetite, nausea, vomiting;

• constipation, diarrhea;

• irregular heartbeats, feeling short of breath;

• abnormal liver function tests;

• dry mouth, mouth sores;

• altered sense of taste;

• back pain, muscle or joint pain;

• feeling tired;

• headache, dizziness, anxiety;

• sleep problems (insomnia);

• sore throat; or

• rash.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Applies to niraparib: oral capsule

General

The most commonly reported adverse reactions (incidence 20% or greater) were
decreased hemoglobin (85%), decreased platelet count (82%), nausea (74%), decreased white blood cell count (66%), thrombocytopenia (61%), fatigue/asthenia (57%), decreased absolute neutrophil count (53%), anemia (50%), constipation (40%), increased AST (36%), vomiting (34%), abdominal pain/distention (33%), neutropenia (30%), increased ALT (28%), insomnia (27%), headache (26%), decreased appetite (25%), nasopharyngitis (23%), rash (21%), diarrhea (20%), dyspnea (20%), hypertension (20%), and mucositis/stomatitis (20%).[Ref]

Hematologic

Very common (10% or more): Decreased hemoglobin (85%), decreased platelet count (82%), decreased white blood cell count (66%), thrombocytopenia (61%), decreased absolute neutrophil count (53%), anemia (50%), neutropenia (30%), leukopenia (17%)[Ref]

Gastrointestinal

Very common (10% or more): Nausea (74%), constipation (40%), vomiting (34%), abdominal pain/distention (33%), diarrhea (20%), mucositis/stomatitis (20%), dyspepsia (18%), dry mouth (10%)[Ref]

Other

Very common (10% or more): Fatigue/asthenia (57%)
Common (1% to 10%): Peripheral edema[Ref]

Hepatic

Very common (10% or more): Increased AST (36%), Increased ALT (28%), AST/ALT elevation (10%)
Common (1% to 10%): Increased gamma-glutamyl transferase, increased blood alkaline phosphatase[Ref]

Psychiatric

Very common (10% or more): Insomnia (27%), anxiety (11%)
Common (1% to 10%): Depression[Ref]

Nervous system

Very common (10% or more): Headache (26%), dizziness (18%), dysgeusia (10%)[Ref]

Metabolic

Very common (10% or more): Decreased appetite (25%)
Common (1% to 10%): Hypokalemia, decreased weight[Ref]

Respiratory

Very common (10% or more): Nasopharyngitis (23%), dyspnea (20%), cough (16%)
Common (1% to 10%): Bronchitis, epistaxis[Ref]

Dermatologic

Very common (10% or more): Rash (21%)[Ref]

Cardiovascular

Very common (10% or more): Hypertension (20%), palpitations (10%)
Common (1% to 10%): Tachycardia
Frequency not reported: Hypertensive crisis[Ref]

Musculoskeletal

Very common (10% or more): Myalgia (19%), back pain (18%), arthralgia (13%)[Ref]

Genitourinary

Very common (10% or more): Urinary tract infection (13%)[Ref]

Ocular

Common (1% to 10%): Conjunctivitis[Ref]

Renal

Common (1% to 10%): Increased blood creatinine[Ref]

Oncologic

Uncommon (0.1% to 1%): Myelodysplastic Syndrome/Acute Myeloid Leukemia[Ref]

Some side effects of Zejula may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.