Niraparib is an oral, once-daily medication used as a maintenance treatment for certain types of ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. It belongs to a class of drugs known as poly(ADP-ribose) polymerase (PARP) inhibitors.

PARP is an enzyme that helps repair damaged DNA in cells. By inhibiting this enzyme, PARP inhibitors like niraparib prevent cancer cells from repairing their DNA, leading to the death of these cells and a halt or slowing of tumor growth. They are particularly effective against cancers that already have defects in their DNA repair mechanisms, such as those with mutations in the BRCA1 and BRCA2 genes.

Niraparib (Zejula) is a highly selective poly ADP-ribose polymerase (PARP) enzyme inhibitor that detects and repairs damaged DNA.

Niraparib Uses:

• Ovarian, fallopian tube, or primary peritoneal cancer:
  • In patients who are in complete or partial response to platinum-based chemotherapy, maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer is necessary.

Niraparib (Zejula) Dose in Adults

Note:

• It's a pill taken every day to help treat certain types of ovarian, fallopian tube, and primary peritoneal cancers.
• Works by stopping cancer cells from fixing their damaged DNA, which causes them to die.
• Helps patients who've had certain chemotherapy treatments.
• Common side effects: tiredness, stomach upset, and low blood counts.
• Some people feel like throwing up when taking it. So, doctors might give another medicine to help prevent this feeling.

Niraparib (Zejula) Dose in the treatment of Recurrent Ovarian, fallopian tube, or primary peritoneal cancer (maintenance treatment):

• Standard Dose: Take 300 mg by mouth once every day. Keep taking it until the disease gets worse or if side effects become too hard to handle. Start this medicine within 8 weeks after finishing the last chemotherapy that had platinum in it.

Reduced Dose (not the usual method but sometimes used):

• If you weigh less than 77 kg (about 170 lbs) OR if your platelet count is less than 150,000/mm:
  • Start with a lower dose: 200 mg by mouth once every day.
  • After 2-3 months, if you're not having problems with low blood counts, your doctor might increase it to the regular 300 mg dose.

If You Miss a Dose or Throw Up After Taking It:

• Don't take an extra dose that day.
• Just take your next dose as usual the next day.

Niraparib (Zejula) Dose in Childrens

Not indicated for use in children.

Pregnancy Risk Category: D

• Animal tests to see if niraparib affects pregnancy haven't been done.
• But, because of how the medicine works, it might harm an unborn baby.
• Before starting niraparib, women should have a pregnancy test to make sure they're not pregnant.
• If a woman can have a baby, she should use effective birth control while taking niraparib and for 6 months after the last dose.

Use of Niraparib while breastfeeding

• We're not sure if niraparib gets into breast milk.
• Because it might have harmful effects, it's advised not to breastfeed while taking this medicine and for 1 month after the last dose.

Niraparib (Zejula) Dose in Kidney Disease:

• If your kidney function is between 30 to less than 90 mL/minute (measured using the Cockcroft-Gault formula), you don't need to change the dose.
• If your kidney function is less than 30 mL/minute (which means your kidneys are not working well), there are no specific dose adjustments recommended because it hasn't been studied in people with severe kidney problems.
• For people with end-stage kidney disease (ESRD), there are also no specific dose adjustments recommended because it hasn't been studied in this group.

Niraparib (Zejula) Dose in Liver disease:

Dosing Based on Liver Function:

• If you have a slight liver problem (mild impairment), you can take Niraparib as usual without changing the dose.
• If you have moderate to severe liver problems, there's no specific advice on how to adjust the dose. This is because it hasn't been studied in people with these levels of liver problems.

Common Side Effects of Niraparib (Zejula):

• Cardiovascular:
  • Hypertension
• Central Nervous System:
  • Fatigue
  • Insomnia
  • Headache
  • Dizziness
  • Anxiety
• Dermatologic:
  • Skin Rash
• Gastrointestinal:
  • Nausea
  • Constipation
  • Vomiting
  • Decreased Appetite
  • Mucositis
  • Stomatitis
  • Dyspepsia
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Thrombocytopenia
  • Anemia
  • Neutropenia
  • Leukopenia
• Hepatic:
  • Increased Serum AST
  • Increased Serum ALT
• Neuromuscular & Skeletal:
  • Weakness
  • Back Pain
• Respiratory:
  • Nasopharyngitis
  • Dyspnea
  • Cough

Less Common Side Effects Of Niraparib (Zejula):

• Cardiovascular:
  • Palpitations
  • Peripheral Edema
  • Tachycardia
• Central Nervous System:
  • Depression
• Endocrine & Metabolic:
  • Hypokalemia
  • Increased Gamma-Glutamyl Transferase
  • Weight Loss
• Gastrointestinal:
  • Dysgeusia
  • Xerostomia
• Hepatic:
  • Increased Serum Alkaline Phosphatase
• Ophthalmic:
  • Conjunctivitis
• Renal:
  • Increased Serum Creatinine
• Respiratory:
  • Bronchitis
  • Epistaxis

Contraindications to Niraparib (Zejula):

• The manufacturer hasn't listed any specific conditions or situations where you shouldn't take Niraparib.

Warnings and precautions

Suppression of bone marrow

• Anemia and neutropenia are common events in grade 3, 4 and 5. They rarely need to be discontinued.
• For the first month, check blood counts weekly, then every other week for 11 months, and then follow-up thoroughly.
• You should not start niraparib until your hematologic toxicities due to prior chemotherapy have resolved to grade 1 and lower.
• Hematologic toxicities may require treatment interruption, dose reduction or discontinuation.
• If hematologic toxicities persist after a niraparib interruption, discontinue use and consult hematology.
• A reduced initial dose strategy is recommended to reduce hematologic toxicities and maintain efficacy for patients with low bodyweight (77 kg) and low baseline platelets (150,000/mm3).

Cardiovascular effects

• Niraparib can cause high blood pressure and, in extreme cases, a severe increase in blood pressure.
• Some patients have experienced very high blood pressure levels, and in rare situations, they had to stop taking the medicine because of this.
• It's important to check blood pressure and heart rate regularly: once a month for the first year and less often after that.
• Patients with heart issues, like chest pain, irregular heartbeats, or high blood pressure, should be watched closely.
• If someone's blood pressure gets too high, they might need blood pressure medicine or a change in their Niraparib dose.

Gastrointestinal toxicities:

• Niraparib has a moderate emetic potency.
• Antiemetics can be used to prevent nausea or vomiting.
• Consider giving niraparib to your bedtime routine in order to reduce nausea and vomiting.
• Reports of nausea, vomiting, constipation, and mucositis/stomatitis include:

Secondary malignancy

• Niraparib has been linked to a rare but serious condition where the bone marrow produces abnormal blood cells or develops a type of blood cancer, called MDS/AML.
• Some people who got this had fatal outcomes.
• Those affected had taken Niraparib for different times, from less than a month to up to 2 years.
• All these patients had received earlier treatments, including platinum-based chemotherapy.
• If someone taking Niraparib is diagnosed with MDS/AML, they should stop the medicine.

Niraparib: Drug Interaction

Monitoring parameters:

Blood Tests (CBC with differential)

• Every week for the first month.
• Once a month for the next 11 months.
• Every so often after that.

Pregnancy Test

• For women who could get pregnant, do this test before starting Niraparib.

Blood Pressure & Heart Rate

• Check monthly for the first year.
• Less often after the first year.

Medicine Adherence

• Keep an eye on if the medicine is being taken as prescribed.

How to administer Niraparib (Zejula)?

When to Take:

• Take it around the same time every day.

How to Take:

• You can take it with or without food.
• Don't break or chew the capsules. Swallow them whole.

Side Effects:

• Niraparib might make you feel like throwing up.
• You might need another medicine to help prevent this feeling (antiemetics).

Tip:

• Taking it at bedtime might help reduce the chances of feeling sick.

Mechanism of action of Niraparib (Zejula):

• Niraparib is a drug that blocks something called PARP enzymes.
• These enzymes, known as PARP-1 and PARP-2, usually help fix damaged DNA in our cells.
• When you take Niraparib, it stops these enzymes from doing their job.
• This leads to DNA damage, which can make cancer cells die.
• Niraparib can harm tumor cells, whether they have BRCA1/2 problems or not.

Distribution:

• Niraparib spreads throughout the body and is stored in a space of about 1,074 liters.

Protein Binding:

• About 83% of Niraparib attaches to proteins in the blood.

Metabolism:

• It goes through a process in the body where it changes into an inactive form with the help of enzymes called carboxylesterases. After that, it's turned into a different form through glucuronidation.

Bioavailability:

• Around 73% of the drug gets into the bloodstream when taken by mouth.

Half-Life:

• It takes about 36 hours for half of the Niraparib in the body to be eliminated.

Time to Peak:

• After taking it, Niraparib reaches its highest level in the blood within about 3 hours.

Excretion:

• It leaves the body mainly through urine (about 48% after 21 days) and also in feces (about 39% after 21 days). Some of it stays in the same form it was when first taken.

International Brands of Niraparib:

• Zejula

Niraparib Brand Names in Pakistan:

Not available.