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:

• With a moderate emetic potential, Niraparib is associated.
• To prevent nausea and vomiting, antiemetics may be necessary.

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

P/O:

• Continue until disease progression or unacceptable toxicity, 300 mg once daily.
• Following the most recent platinum-containing regimen, begin treatment no later than 8 weeks.

• Reduced initial dosing strategy (off-label):

  • Patients weighing <77 kg & with baseline platelets <150,000/mm³:
  • Initially 200 mg orally once a day.
  • After 2-3 months, in the absence of hematologic toxicity, consider escalating the dose to the usual dose of 300 mg once daily.

• Missed/vomited doses:

  • An additional dose should not be taken that day if a dose is missed or vomited. Resume dosing with the next scheduled daily dose.

Niraparib (Zejula) Dose in Childrens

Not indicated for use in children.

Pregnancy Risk Category: D

• Although animal reproduction studies have not been done, it is possible that fetal harm could be caused by niraparib during pregnancy.
• It is important to have pregnancies tested before starting treatment. Effective contraception should also be used during and for at least six months after the last dose.

Use of Niraparib while breastfeeding

• It is unknown if breast milk contains niraparib.
• Due to the possibility of adverse events, breastfeeding is not recommended during treatment and for at least one month after the last dose.

Niraparib (Zejula) Dose in Kidney Disease:

• Renal Impairment:
  •  Using the Cockcroft-Gault formula, Adult Renal function is estimated

• CrCl 30 to <90 mL/minute:

  • No dosage adjustment is necessary.

• CrCl <30 mL/minute:

  •  In the manufacturer's labeling, there are no dosage adjustments provided (has not been studied).

• End-stage renal disease (ESRD):

  • In the manufacturer's labeling, there are no dosage adjustments provided (has not been studied).

Niraparib (Zejula) Dose in Liver disease:

• Using the National Cancer Institute Organ Dysfunction Working Group Criteria, Hepatic function is estimated

• Mild impairment:

  • No dosage adjustment is necessary.

• Moderate to severe impairment:

  • In the manufacturer's labeling, there are no dosage adjustments provided  (has not been studied).

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):

• There are no contraindications in the manufacturer's labeling.

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

  • In addition to hypertension of grade 3 or 4, Hypertension and hypertensive crise have been reported. (In rare cases, hypertension must be discontinued).
  • Every month for the first year, and every other month thereafter, check blood pressure and heart beat.
  • Patients with cardiac conditions (especially arrhythmias, coronary insufficiency, and hypertension) need to be closely monitored.
  • Hypertension should be treated with antihypertensives, niraparib dosage adjustment if needed.

• 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

  • There have been rare reports of myelodysplastic syndrome/acute meeloid leukemia (MDS/AML), some even fatal.
  • Before the invention of MDS/AML the treatment duration for niraparib was 1 to 2 years.
  • All patients had previously received chemotherapy, which included platinum-based regimens.
  • Stop using niraparib when MDS/AML is confirmed.

Niraparib: Drug Interaction

Monitoring parameters:

• CBC with differential (weekly the first month, then monthly the next 11 months, and then periodically thereafter).
• Pregnancy test (prior treatment; for females with reproductive potential).
• Every month, check blood pressure and heart beat. You should also check for compliance.

How to administer Niraparib (Zejula)?

P/O:

• Either with or without food, administer at approximately the same time each day.
• Swallow capsules wholly.
• Niraparib is associated with a moderate emetic potential.
• To prevent nausea and vomiting, Antiemetics may be necessary.
• To diminish the potential for nausea and vomiting, consider administering at bedtime.

Mechanism of action of Niraparib (Zejula):

• Niraparib, a poly (ADPribose polymerase) polymerase inhibitor (PARP), is highly selective for PARP-1 & PARP-2. PARP-1 & PARP-2 play an important role in DNA damage detection and repair.
• Inhibiting PARP enzyme activity causes DNA damage, cell death and apoptosis.
• Niraparib induces both cytotoxicity in tumor cells and BRCA1/2 deficiency in tumor cell lines.

Distribution:

• V : 1,074 L

Protein binding:

• 83 Percent.

Metabolism:

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

Bioavailability:

• ~73 percent.

Half-life elimination:

• 36 hours

Time to peak:

• Within 3 hours

Excretion:

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

International Brands of Niraparib:

• Zejula

Niraparib Brand Names in Pakistan:

No Brands Available in Pakistan.