For: Ovarian Cancer, Fallopian Tube Cancer, Peritoneal Cancer
Zejula (niraparib) is an oral, poly ADP-ribose polymerase (PARP) inhibitor for the treatment of patients with ovarian, fallopian tube, or primary peritoneal cancer. ZEJULA- niraparib capsule
TESARO, Inc.
1 INDICATIONS AND USAGE
ZEJULA� is 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.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
The recommended dose of ZEJULA as monotherapy is 300 mg (three 100 mg capsules) taken orally once daily.
Instruct patients to take their dose of ZEJULA at approximately the same time each day. Each capsule should be swallowed whole. ZEJULA may be taken with or without food. Bedtime administration may be a potential method for managing nausea.
Patients should start treatment with ZEJULA no later than 8 weeks after their most recent platinum-containing regimen.
ZEJULA treatment should be continued until disease progression or unacceptable toxicity.
In the case of a missed dose of ZEJULA, instruct patients to take their next dose at its regularly scheduled time. If a patient vomits or misses a dose of ZEJULA, an additional dose should not be taken.
2.2 Dose Adjustments for Adverse Reactions
To manage adverse reactions, consider interruption of treatment, dose reduction, or dose discontinuation. The recommended dose modifications for adverse reactions are listed in Tables 1, 2 and 3.
DOSAGE FORMS AND STRENGTHS
100 mg capsule having a white body with "100 mg" printed in black ink, and a purple cap with "Niraparib" printed in white ink.
DESCRIPTION
Niraparib is an orally available poly(ADP-ribose) polymerase (PARP) inhibitor.
The chemical name for niraparib tosylate monohydrate is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole 7-carboxamide 4-methylbenzenesulfonate hydrate (1:1:1). The molecular formula is C26 H30 N4 O5 S and it has a molecular weight of 510.61 amu. The molecular structure is shown below:
Chemical Structure
(click image for full-size original)
Niraparib tosylate monohydrate is a white to off-white, non-hygroscopic crystalline solid. Niraparib solubility is pH independent below the pKa of 9.95, with an aqueous free base solubility of 0.7 mg/mL to 1.1 mg/mL across the physiological pH range.
Each ZEJULA capsule contains 159.4 mg niraparib tosylate monohydrate equivalent to 100 mg niraparib free base as the active ingredient. The inactive ingredients in the capsule fill are magnesium stearate and lactose monohydrate. The capsule shell consists of titanium dioxide, gelatin in the white capsule body; and FD&C Blue #1, FD&C Red #3, FD&C Yellow #5 and gelatin in the purple capsule cap. The black printing ink consists of shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, purified water, strong ammonia solution, potassium hydroxide and black iron oxide. The white printing ink consists of shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, sodium hydroxide, povidone and titanium oxide.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Niraparib is an inhibitor of poly(ADP-ribose) polymerase (PARP) enzymes, PARP-1 and PARP-2, which play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency that had either mutated or wild type BRCA1/2.