Zejula

Zejula Uses, Dosage, Side Effects, Food Interaction and all others data.

Zejula is an orally active PARP inhibitor developed by Tesaro to treat ovarian cancer. FDA approval on March 2017.

Cardiovascular Effects:Zejula has the potential to cause effects on pulse rate and blood pressure in patients receiving the recommended dose, which may be related to pharmacological inhibition of the dopamine transporter (DAT), norepinephrine transporter (NET) and serotonin transporter (SERT).In the NOVA study, mean pulse rate and blood pressure increased over baseline in the niraparib arm relative to the placebo arm at all on-study assessments. Mean greatest increases from baseline in pulse rate on treatment were 24.1 and 15.8 beats/min in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in systolic blood pressure on treatment were 24.5 and 18.3 mmHg in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in diastolic blood pressure on treatment were 16.5 and 11.6 mmHg in the niraparib and placebo arms, respectively.Cardiac ElectrophysiologyThe potential for QTc prolongation with niraparib was evaluated in a randomized, placebo-controlled trial in cancer patients (367 patients on niraparib and 179 patients on placebo). No large changes in the mean QTc interval (>20 ms) were detected in the trial following the treatment of niraparib 300 mg once daily.

Zejula
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Zejula
Availability	Prescription only
Generic	Niraparib
Niraparib Other Names	Niraparib
Related Drugs	carboplatin, doxorubicin, cisplatin, paclitaxel, Avastin, bevacizumab, Lynparza, Zejula, Alymsys, Zirabev
Weight	100mg,
Type	Capsule, Oral Capsule
Formula	C₁₉H₂₀N₄O
Weight	Average: 320.396 Monoisotopic: 320.16371128
Protein binding	Niraparib is 83.0% bound to human plasma proteins.
Groups	Approved, Investigational
Therapeutic Class
Manufacturer	GlaxoSmithKline UK
Available Country	Australia, United Kingdom, United States,
Last Updated:	September 19, 2023 at 7:00 am

Uses

Zejula is a poly-ADP ribose polymerase inhibitor used to treat recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer responding to platinum based chemotherapy.

Zejula is indicated for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy

Zejula is also used to associated treatment for these conditions: Fallopian Tube Cancer, Ovarian Epithelial Cancer, Primary Peritoneal Cancer

How Zejula works

Zejula 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. Zejula 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.

Food Interaction

Take at the same time every day.
Take with or without food.

Zejula Drug Interaction

Moderate: paclitaxel protein-bound, lactobacillus acidophilus, doxorubicin, aspirin, cabozantinib, lactobacillus rhamnosus gg, apixaban, olaparibUnknown: acetaminophen, calcium carbonate, multivitamin with minerals, loratadine, duloxetine, leuprolide, loperamide, loperamide, levothyroxine, dronabinol, ascorbic acid, cholecalciferol

Zejula Disease Interaction

Moderate: cardiovascular disorders, liver dysfunction, MDS/AML, pancytopenia, renal impairment

Volume of Distribution

The average (±SD) apparent volume of distribution (Vd/F) was 1220 (±1114) L.

Elimination Route

The absolute bioavailability of niraparib is approximately 73%. Following oral administration of niraparib, peak plasma concentration, Cmax, is reached within 3 hours. Concomitant administration of a high fat meal (800-1,000 calories with approximately 50% of total caloric content of the meal from fat) did not significantly affect the pharmacokinetics of niraparib.
Following a single-dose administration of 300 mg niraparib, the mean (±SD) peak plasma concentration (Cmax) was 804 (± 403) ng/mL. The systemic exposures (Cmax and AUC) of niraparib increased in a dose proportional manner with daily doses ranging 30 mg (0.1 times the approved recommended dosage) to 400 mg (1.3 times the approved recommended dosage). The accumulation ratio of niraparib exposure following 21 days of repeated daily doses was approximately 2 fold for doses ranging from 30 mg to 400 mg.

Half Life

Following multiple daily doses of 300 mg niraparib, the mean half-life (t1/2) is 36 hours.

Clearance

the apparent total clearance (CL/F) of niraparib was 16.2 L/h in cancer patients.

Elimination Route

Following administration of a single oral 300 mg dose of radio-labeled niraparib, the average percent recovery of the administered dose over 21 days was 47.5% (range 33.4% to 60.2%) in urine, and 38.8% (range 28.3% to 47.0%) in feces.