How Long Does It Take For Zejula To Start Working

What is Zejula and how is it used?

Zejula is a prescription medicine used to treat the symptoms of Ovarian Cancer. Zejula may be used lone or with other medications.

Zejula belongs to a grade of drugs called Antineoplastics, PARP Inhibitors.

Information technology is not known if Zejula is safe and effective in children.

What are the possible side effects of Zejula?

Zejula may cause serious side effects including:

• hives,
• difficulty animate,
• swelling of your face, lips, tongue, or pharynx,
• fever,
• frequent infections,
• weakness,
• tiredness,
• shortness of breath,
• weight loss,
• blood in your urine or stools,
• easy bruising,
• unusual bleeding,
• pounding heartbeats,
• fluttering in your breast,
• sores or white patches in or around your mouth,
• trouble swallowing or talking,
• dry out mouth,
• bad breath,
• altered sense of taste,
• pain or called-for when yous urinate,
• severe headache,
• blurred vision, and
• pounding in your cervix or ears
• Get medical assist right away, if you lot have whatsoever of the symptoms listed to a higher place.
• The most common side effects of Zejula include:
• indigestion,
• breadbasket pain,
• loss of appetite,
• nausea,
• airsickness,
• constipation,
• diarrhea,
• irregular heartbeats,
• shortness of breath,
• abnormal liver function or other blood tests,
• little or no urination,
• changes in the color of your urine,
• painful urination,
• dry mouth,
• oral cavity sores,
• altered sense of taste,
• back pain,
• musculus or joint pain,
• headache,
• dizziness,
• anxiety,
• slumber problems,
• tiredness,
• cough,
• sore throat, and
• rash

Tell the doctor if you take any side effect that bothers you or that does not get away.

These are not all the possible side effects of Zejula. For more than information, ask your doc or chemist.

Phone call your doctor for medical advice about side effects. You may written report side furnishings to FDA at i-800-FDA-1088.

Description

Niraparib is an orally available poly(ADP-ribose) polymerase (PARP) inhibitor.

The chemical proper noun for niraparib tosylate monohydrate is ii-{four-[(3S)-piperidin-three-yl]phenyl}-2Hindazole 7-carboxamide 4-methylbenzenesulfonate hydrate (i:ane:1). The molecular formula is C₂₆H₃₀Northward_ivO₅S and it has a molecular weight of 510.61 amu. The molecular structure is shown below:

Niraparib tosylate monohydrate is a white to off-white, not-hygroscopic crystalline solid. Niraparib solubility is pH independent below the pKa of ix.95, with an aqueous free base of operations solubility of 0.vii 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 gratis base equally the active ingredient. The inactive ingredients in the sheathing fill are magnesium stearate and lactose monohydrate. The capsule shell consists of titanium dioxide, gelatin in the white capsule body; and FD&C Bluish #i, FD&C Ruby-red #3, FD&C Yellow #5 and gelatin in the royal capsule cap. The black printing ink consists of shellac, dehydrated booze, isopropyl booze, butyl alcohol, propylene glycol, purified h2o, potent ammonia solution, potassium hydroxide and black iron oxide. The white printing ink consists of shellac, dehydrated alcohol, isopropyl alcohol, butyl booze, propylene glycol, sodium hydroxide, povidone and titanium oxide.

INDICATIONS

First-Line Maintenance Handling Of Advanced Ovarian Cancer

ZEJULA is indicated for the maintenance treatment of developed patients with advanced epithelial ovarian, fallopian tube, or principal peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy.

Maintenance Treatment Of Recurrent Germline BRCA-Mutated Ovarian Cancer

ZEJULA is indicated for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (one thousandBRCAmut) recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a consummate or partial response to platinum-based chemotherapy.

DOSAGE AND ADMINISTRATION

Patient Selection

Maintenance Handling Of Recurrent Germline BRCA-Mutated Ovarian Cancer

Select patients for the maintenance treatment of recurrent ovarian cancer with ZEJULA based on the presence of deleterious or suspected deleterious germline BRCA mutations [run into Clinical Studies].

An FDA-approved test for the detection of deleterious or suspected deleterious germline BRCA mutations is non currently bachelor.

Recommended Dosage

Continue handling with ZEJULA until illness progression or unacceptable toxicity.

Instruct patients to take their dose of ZEJULA at approximately the aforementioned time each day. Advise patients to swallow each sheathing whole and non to chew, shell, or split ZEJULA prior to swallowing. ZEJULA may exist taken with or without food. Bedtime administration may be a potential method for managing nausea.

In the instance 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 non exist taken.

First-Line Maintenance Treatment Of Advanced Ovarian Cancer

• For patients weighing <77 kg (<170 lbs) OR with a platelet count of <150,000/mcL, the recommended dosage is 200 mg (2 100-mg capsules) taken orally once daily.
• For patients weighing ≥77 kg (≥170 lbs) AND who have a platelet count ≥150,000/mcL, the recommended dosage is 300 mg (three 100-mg capsules) taken orally once daily.

For the maintenance treatment of avant-garde ovarian cancer, patients should start treatment with ZEJULA no afterward than 12 weeks after their most recent platinum-containing regimen.

Maintenance Treatment Of Recurrent Germline BRCA-Mutated Ovarian Cancer

The recommended dosage of ZEJULA is 300 mg (three 100-mg capsules) taken orally once daily.

For the maintenance treatment of recurrent ovarian cancer, patients should get-go treatment with ZEJULA no later on than 8 weeks after their most recent platinum-containing regimen.

Dosage Adjustments For Adverse Reactions

To manage adverse reactions, consider break of treatment, dose reduction, or dose discontinuation. The recommended dose modifications for agin reactions are listed in Tables 1, two, and 3.

Table i. Recommended Dose Modifications for Adverse Reactions

Starting Dose Level	200 mg	300 mg
First dose reduction	100 mg/daya (one 100-mg capsule)	200 mg/solar day (two 100-mg capsules)
2d dose reduction	Discontinue ZEJULA.	100 mg/daya (ane 100-mg capsule)
a If farther dose reduction below 100 mg/day is required, discontinue ZEJULA.

Table two. Dose Modifications for Not-Hematologic Agin Reactions

Non-hematologic CTCAE ≥Grade 3 agin reaction that persists despite medical management	Withhold ZEJULA for a maximum of 28 days or until resolution of adverse reaction. Resume ZEJULA at a reduced dose per Table 1.
CTCAE ≥Grade 3 treatment-related adverse reaction lasting more than 28 days while patient is administered ZEJULA 100 mg/mean solar day	Discontinue ZEJULA.
CTCAE = Common Terminology Criteria for Agin Events.

Table three. Dose Modifications for Hematologic Adverse Reactions

Monitor complete blood counts weekly for the offset month, monthly for the adjacent 11 months of treatment, and periodically after this time [see WARNINGS AND PRECAUTIONS].
Platelet count <100,000/mcL	First occurrence: Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until platelet counts render to ≥100,000/mcL. Resume ZEJULA at same or reduced dose per Table one. If platelet count is <75,000/mcL, resume at a reduced dose. Second occurrence: Withhold ZEJULA for a maximum of 28 days and monitor claret counts weekly until platelet counts return to ≥100,000/mcL. Resume ZEJULA at a reduced dose per Table 1. Discontinue ZEJULA if the platelet count has not returned to acceptable levels within 28 days of the dose pause catamenia or if the patient has already undergone dose reduction to 100 mg once daily.a
Neutrophil <1,000/mcL or hemoglobin <eight g/dL	Withhold ZEJULA for a maximum of 28 days and monitor blood counts weekly until neutrophil counts render to ≥1,500/mcL or hemoglobin returns to ≥9 g/dL. Resume ZEJULA at a reduced dose per Table 1. Discontinue ZEJULA if neutrophils and/or hemoglobin have not returned to acceptable levels inside 28 days of the dose suspension menstruum or if the patient has already undergone dose reduction to 100 mg once daily.a
Hematologic adverse reaction requiring transfusion	For patients with platelet count ≤10,000/mcL, platelet transfusion should exist considered. If there are other risk factors such as coadministration of anticoagulation or antiplatelet drugs, consider interrupting these drugs and/or transfusion at a college platelet count. Resume ZEJULA at a reduced dose.
a If myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) is confirmed, discontinue ZEJULA [see WARNINGS AND PRECAUTIONS].

Dosage Adjustment For Hepatic Harm

Moderate Hepatic Harm

For patients with moderate hepatic harm, reduce the starting dosage of ZEJULA to 200 mg one time daily. Monitor patients for hematologic toxicity and reduce the dose further, if needed [see Dosage Adjustments For Adverse Reactions, Use In Specific Populations, CLINICAL PHARMACOLOGY].

HOW SUPPLIED

Dosage Forms And Strengths

100-mg sheathing having a white body with "100 mg" printed in black ink, and a purple cap with "Niraparib" printed in white ink.

Storage And Handling

ZEJULA is available as capsules having a white body printed with "100 mg" in black ink, and a purple cap printed with "Niraparib" in white ink.

Each capsule contains 100 mg of niraparib free base.

ZEJULA capsules are packaged as

30-count bottles NDC 69656-103-30

Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between fifteen°C to 30°C (59°F to 86°F) [meet USP Controlled Room Temperature].

Manufactured for: GlaxoSmithKline, Durham, NC 27701. Revised: Dec 2022

SLIDESHOW

Skin Cancer Symptoms, Types, Images See Slideshow

Side Effects & Drug Interactions

SIDE Effects

The following clinically significant adverse reactions are described elsewhere in the labeling:

• MDS/AML [see WARNINGS AND PRECAUTIONS]
• Bone marrow suppression [see WARNINGS AND PRECAUTIONS]
• Hypertension and cardiovascular furnishings [run into WARNINGS AND PRECAUTIONS]
• Posterior reversible encephalopathy syndrome [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of some other drug and may non reverberate the rates observed in practise.

In a pooled rubber population of patients (n = one,314) with advanced ovarian, fallopian tube, or chief peritoneal cancer treated with ZEJULA monotherapy including PRIMA (northward = 484), NOVA (n = 367), and another clinical trial (n = 463) , the most mutual agin reactions >10% were nausea (65%), thrombocytopenia (threescore%), anemia (56%), fatigue (55%), constipation (39%), musculoskeletal pain (36%), abdominal hurting (35%), vomiting (33%), neutropenia (31%), decreased appetite (24%), leukopenia (24%), indisposition (23%), headache (23%), dyspnea (22%), rash (21%), diarrhea (18%), hypertension (17%), cough (16%), dizziness (xiv%), acute kidney injury (13%), urinary tract infection (12%), and hypomagnesemia (11%).

First-Line Maintenance Treatment Of Advanced Ovarian Cancer

The rubber of ZEJULA for the treatment of patients with advanced ovarian cancer post-obit first-line treatment with platinum-based chemotherapy was studied in the PRIMA trial, a placebo-controlled, double-blind study in which 728 patients received niraparib or placebo. Amongst patients who received ZEJULA, the median duration of treatment was 11.1 months (range: 0.03 to 29 months).

All Patients Receiving ZEJULA in PRIMA

Serious adverse reactions occurred in 32% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were thrombocytopenia (sixteen%), anemia (6%), and small intestinal obstruction (2.9%). Fatal adverse reactions occurred in 0.4% of patients, including abdominal perforation and pleural effusion (1 patient each). MDS/AML occurred in ane.ii% of patients receiving ZEJULA.

Permanent discontinuation due to adverse reactions occurred in 12% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >ane% of patients who received ZEJULA included thrombocytopenia (3.vii%), anemia (1.9%), and nausea and neutropenia (1.2% each).

Adverse reactions led to dose reduction or interruption in 80% of patients, almost oftentimes from thrombocytopenia (56%), anemia (33%), and neutropenia (twenty%).

Tabular array 4 and Table five summarize the common adverse reactions and aberrant laboratory findings, respectively, observed in all patients treated with ZEJULA in the PRIMA study.

Table 4. Adverse Reactions Reported in ≥10% of All Patients Receiving ZEJULA in PRIMA^a

Adverse Reaction	Grades one-4b		Grades 3-4b
	ZEJULA (north = 484) %	Placebo (n = 244) %	ZEJULA (due north = 484) %	Placebo (n = 244) %
Claret and lymphatic arrangement disorders
Thrombocytopenia	66	five	39	0.4
Anemia	64	eighteen	31	2
Neutropeniac	42	8	21	1
Leukopeniad	28	9	five	0.iv
Gastrointestinal disorders
Nausea	57	28	i	ane
Constipation	forty	20	1	0.4
Vomiting	22	12	1	i
General disorders and administration site atmospheric condition
Fatigue	51	41	3	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	39	38	1	0
Nervous organization disorders
Headache	26	15	0.4	0
Dizziness	19	xiii	0	0.iv
Psychiatric disorders
Insomnia	25	15	one	0.4
Respiratory, thoracic, and mediastinal disorders
Dyspnea	22	xiii	0.4	1
Cough	xviii	xv	0	0.4
Metabolism and nutrition disorders
Decreased appetite	19	8	1	0
Vascular disorders
Hypertension	18	vii	6	1
Investigations
AST/ALT pinnacle	fourteen	7	3	0.8
Renal and urinary disorders
Acute kidney injurye	12	5	0.2	0
AST/ALT = Aspartate transaminase/alanine aminotransferase. a All adverse reactions in the table consist of grouped preferred terms except for nausea, vomiting, decreased ambition, headache, and insomnia, which are unmarried preferred terms. b Mutual Terminology Criteria for Adverse Events version 4.02. c Includes neutropenia, neutropenic infection, neutropenic sepsis, and febrile neutropenia. d Includes leukopenia, lymphocyte count decreased, lymphopenia, and white blood cell count decreased. e Includes blood creatinine increased, claret urea increased, acute kidney injury, renal failure, and blood creatine increased.

Table 5. Abnormal Laboratory Findings in ≥25% of All Patients Receiving ZEJULA in PRIMA

Aberrant Laboratory Finding	Grades 1-4		Grades three-4
	ZEJULA (n = 484) %	Placebo (due north = 244) %	ZEJULA (n = 484) %	Placebo (due north = 244) %
Decreased hemoglobin	87	66	29	1
Decreased platelets	74	13	37	0
Decreased leukocytes	71	36	9	0
Increased glucose	66	57	three	3
Decreased neutrophils	66	25	23	1
Decreased lymphocytes	51	29	7	3
Increased alkaline phosphatase	46	21	i	0
Increased creatinine	xl	23	0	0
Decreased magnesium	36	34	1	0
Increased aspartate aminotransferase	35	17	1	0.4
Increased alanine aminotransferase	29	17	2	1

Patients Receiving ZEJULA with Dose Based on Baseline Weight or Platelet Count in PRIMA

Among patients who received ZEJULA with the dose based on weight and platelet count, the median duration of treatment was 11 months (range: 1 day to 16 months).

Serious adverse reactions occurred in 27% of patients receiving ZEJULA. Serious agin reactions in >2% of patients were anemia (eight%), and thrombocytopenia (7%). No fatal agin reactions occurred.

Permanent discontinuation due to adverse reactions occurred in 14% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >2% of patients who received ZEJULA included thrombocytopenia and anemia (3% each) and nausea (two.iv%).

Adverse reactions led to dose reduction or interruption in 72% of patients, virtually frequently from thrombocytopenia (40%), anemia (23%), and neutropenia (15%).

Table six and Table 7 summarize agin reactions and abnormal laboratory findings in the group of patients who received ZEJULA.

Table 6. Adverse Reactions Reported in ≥ten% of Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMA^a

Adverse Reaction	Grades ane-4b		Grades 3-ivb
	ZEJULA (north = 169) %	Placebo (n = 86) %	ZEJULA (n = 169) %	Placebo (n = 86) %
Blood and lymphatic organization disorders
Thrombocytopenia	54	5	21	1
Anemia	50	28	23	1
Neutropeniac	36	8	15	1
Leukopeniad	28	11	5	0
Gastrointestinal disorders
Nausea	53	21	1	0
Constipation	31	15	1	one
Vomiting	17	9	0	1
General disorders and assistants site atmospheric condition
Fatigue	48	36	3	0
Nervous system disorders
Headache	22	17	1	0
Dizziness	14	13	0	0
Psychiatric disorders
Insomnia	21	14	0	0
Metabolism and nutrition disorders
Decreased ambition	19	5	1	0
Respiratory, thoracic, and mediastinal disorders
Dyspnea	18	10	0	i
Vascular disorders
Hypertension	17	9	5	2
Renal and urinary disorders
Acute kidney injurye	12	5	ane	0
a All adverse reactions in the table consist of grouped preferred terms except for nausea, vomiting, decreased appetite, headache, and insomnia, which are single preferred terms. b Mutual Terminology Criteria for Agin Events version iv.02. c Includes neutropenia, neutropenic infection, neutropenic sepsis, and febrile neutropenia. d Includes leukopenia, lymphocyte count decreased, lymphopenia, and white claret cell count decreased.

Table 7. Abnormal Laboratory Findings in ≥25% of All Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMA

Abnormal Laboratory Finding	Grades ane-iv		Grades 3-four
	ZEJULA (n = 169) %	Placebo (n = 86) %	ZEJULA (n = 169) %	Placebo (n = 86) %
Decreased hemoglobin	81	70	21	0
Decreased leukocytes	lxx	36	vi	0
Decreased platelets	63	15	18	0
Increased glucose	63	56	2	1
Decreased neutrophils	60	27	15	0
Decreased lymphocytes	52	thirty	5	iv
Decreased magnesium	44	30	0	0
Increased alkaline phosphatase	43	17	one	0
Increased creatinine	41	22	0	0
Increased aspartate aminotransferase	31	19	1	0
Increased alanine aminotransferase	28	fifteen	2	2

Maintenance Treatment Of Recurrent Germline BRCA-Mutated Ovarian Cancer

The rubber of monotherapy with ZEJULA 300 mg once daily has been studied in 136 patients with platinum-sensitive recurrent gBRCAmut ovarian, fallopian tube, and chief peritoneal cancer in the NOVA trial. The percentages of patients who experienced adverse reactions in NOVA that led to dose reduction and dose suspension were 79% and 68%, respectively, well-nigh ofttimes from thrombocytopenia (41% and 35%, respectively) and anemia (23% and xx%, respectively). The permanent discontinuation rate due to adverse reactions in NOVA was 13%. The median exposure to ZEJULA in these patients was 367 days.

Table eight and Table 9 summarize the common adverse reactions and abnormal laboratory findings, respectively, observed in patients treated with ZEJULA in the grandBRCAmut cohort in NOVA.

Table 8. Adverse Reactions Reported in ≥10% of Patients Receiving ZEJULA in NOVA gBRCAmut Cohort

Adverse Reaction	Grades ane-4a		Grades 3-iva
	ZEJULA (north = 136) %	Placebo (northward = 65) %	ZEJULA (n = 136) %	Placebo (n = 65) %
Gastrointestinal disorders
Nausea	77	34	v	3
Vomiting	twoscore	15	iv	0
Constipation	38	18	0.7	ii
Dyspepsia	17	12	0	0
Dry rima oris	xiii	3	0.7	0
Blood and lymphatic system disorders
Thrombocytopeniab	71	v	38	ii
Anemiac	52	8	33	0
Neutropeniad	31	9	21	three
General disorders and administration site conditions
Fatiguee	61	35	eight	ii
Nervous system disorders
Headache	35	viii	0.seven	0
Dizziness	18	9	0	0
Dysgeusia	13	2	0	0
Metabolism and nutrition disorders
Decreased appetite	22	14	0	0
Vascular disorders
Hypertension	21	eight	8	five
Psychiatric disorders
Insomnia	xviii	half dozen	0.7	0
Anxiety	10	11	0.7	0
Respiratory, thoracic, and mediastinal disorders
Dyspnea	17	5	two	0
Cough	xvi	two	0	0
Nasopharyngitis	13	5	0	0
Musculoskeletal and connective tissue disorders
Back hurting	16	eleven	0.7	0
Infections and infestations
Urinary tract infection	11	ix	0	ii
Skin and subcutaneous tissue disorders
Rash	10	2	0	0
a Common Terminology Criteria for Adverse Events version 4.02. b Includes platelet count decreased. c Includes hemoglobin decreased. d Includes neutrophil count decreased. east Includes asthenia, malaise, lethargy.

The following adverse reactions accept been identified in ≥1 to <ten% of the 136 patients receiving ZEJULA in the yardBRCAmut cohort of the NOVA trial and not included in the table: palpitations (9%), mucositis/stomatitis (9%), MDS/AML (7%), tachycardia (vii%), and bronchitis (4%).

Table ix. Abnormal Laboratory Findings in ≥25% of Patients Receiving ZEJULA in NOVA

Abnormal Laboratory Finding	Grades one-4		Grades 3-4
	ZEJULA (n = 136) %	Placebo (due north = 65) %	ZEJULA (n = 136) %	Placebo (north = 65) %
Decrease in hemoglobin	85	62	32	0
Decrease in platelet count	81	25	38	2
Decrease in white blood cell count	71	37	9	ii
Subtract in absolute neutrophil count	56	34	23	3
Increase in aspartate aminotransferase	35	25	0.seven	0
Increase in alanine aminotransferase	25	15	0.7	2

Postmarketing Feel

The following agin reactions have been identified during postapproval use of ZEJULA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably gauge their frequency or plant a causal relationship to drug exposure.

Blood and Lymphatic System Disorders

Pancytopenia.

Immune System Disorders

Hypersensitivity (including anaphylaxis).

Nervous Organisation Disorders

Posterior reversible encephalopathy syndrome (PRES).

Psychiatric Disorders

Confusional state/disorientation, hallucination, cognitive damage (e.m., memory impairment, concentration impairment).

Respiratory, Thoracic, and Mediastinal Disorders

Non-infectious pneumonitis.

Skin and Subcutaneous Tissue Disorders

Photosensitivity.

Vascular Disorders

Hypertensive crunch.

DRUG INTERACTIONS

No Information Provided

WARNINGS

Included as office of the "PRECAUTIONS" Section

PRECAUTIONS

Myelodysplastic Syndrome/Astute Myeloid Leukemia

Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), including cases with a fatal outcome, accept been reported in patients who received ZEJULA.

In PRIMA, MDS/AML occurred in 6 out of 484 (1.2%) patients treated with ZEJULA and in 3 out of 244 (i.ii%) patients treated with placebo [run across Agin REACTIONS]. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer therapy-related AML varied from 3.7 months to ii.5 years.

In NOVA, of patients inside the 1000BRCAmut accomplice, MDS/AML occurred in 10 out of 136 (seven%) patients treated with ZEJULA and in two out of 65 (3%) patients treated with placebo [see ADVERSE REACTIONS]. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer-therapy related AML varied from three.6 months to 5.9 years.

All patients who developed secondary MDS/cancer-therapy–related AML had received previous chemotherapy with platinum agents and/or other Dna-damaging agents, including radiotherapy.

For suspected MDS/AML or prolonged hematological toxicities, refer the patient to a hematologist for further evaluation. Discontinue ZEJULA if MDS/AML is confirmed.

Bone Marrow Suppression

Hematologic adverse reactions, including thrombocytopenia, anemia, neutropenia, and/or pancytopenia have been reported in patients treated with ZEJULA [see Adverse REACTIONS].

In PRIMA, the overall incidences of ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 39%, 31%, and 21%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in 4%, 2%, and ii%, respectively, of patients. In patients who were administered a starting dose of ZEJULA based on baseline weight or platelet count, ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 22%, 23%, and 15%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in 3%, 3%, and 2%, respectively, of patients.

In NOVA, ≥Grade 3 thrombocytopenia, anemia, and neutropenia were reported in 29%, 25%, and 20%, respectively, of patients receiving ZEJULA. Discontinuation due to thrombocytopenia, anemia, and neutropenia occurred in iii%, i%, and ii%, respectively, of patients.

Practice not outset ZEJULA until patients accept recovered from hematological toxicity caused by previous chemotherapy (≤Grade 1). Monitor consummate blood counts weekly for the first calendar month, monthly for the next eleven months of handling, and periodically after this time. If hematological toxicities practice not resolve within 28 days following interruption, discontinue ZEJULA and refer the patient to a hematologist for further investigations, including bone marrow analysis and claret sample for cytogenetics [see DOSAGE AND Assistants].

Hypertension And Cardiovascular Furnishings

Hypertension and hypertensive crunch have been reported in patients treated with ZEJULA [see Agin REACTIONS].

In PRIMA, Grade 3 to four hypertension occurred in half-dozen% of patients treated with ZEJULA compared with 1% of placebo-treated patients with a median time from starting time dose to first onset of 43 days (range: 1 to 531 days) and with a median elapsing of 12 days (range: 1 to 61 days). There were no discontinuations due to hypertension.

In NOVA, Grade 3 to 4 hypertension occurred in 9% of patients treated with ZEJULA compared with 2% of placebo-treated patients with a median time from first dose to start onset of 77 days (range: four to 504 days) and with a median duration of fifteen days (range: i to 86 days). Discontinuation due to hypertension occurred in <1% of patients.

Monitor claret pressure and heart rate at least weekly for the first ii months, then monthly for the first twelvemonth and periodically thereafter during treatment with ZEJULA. Closely monitor patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Medically manage hypertension with antihypertensive medications and adjustment of the dose of ZEJULA, if necessary [run into DOSAGE AND ADMINISTRATION, Nonclinical Toxicology].

Posterior Reversible Encephalopathy Syndrome

Posterior reversible encephalopathy syndrome (PRES) occurred in 0.1% of two,165 patients treated with ZEJULA in clinical trials and has also been described in postmarketing reports [see Agin REACTIONS]. Signs and symptoms of PRES include seizure, headache, contradistinct mental status, visual disturbance, or cortical blindness, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging.

Monitor all patients treated with ZEJULA for signs and symptoms of PRES. If PRES is suspected, promptly discontinue ZEJULA and administrate advisable treatment. The condom of reinitiating ZEJULA in patients previously experiencing PRES is not known.

Embryo-Fetal Toxicity

Based on its mechanism of action, ZEJULA can cause fetal damage when administered to a meaning woman [see CLINICAL PHARMACOLOGY]. ZEJULA has the potential to crusade teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (e.g., bone marrow) [see Bone Marrow Suppression, Nonclinical Toxicology]. Due to the potential adventure to a fetus based on its mechanism of action, animal developmental and reproductive toxicology studies were not conducted with niraparib.

Apprise pregnant women of the potential chance to a fetus. Propose females of reproductive potential to use constructive contraception during treatment and for six months after the last dose of ZEJULA [see Use In Specific Populations].

Allergic Reactions To FD&C Yellow No. 5 (Tartrazine)

ZEJULA capsules contain FD&C Yellow No. v (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons. Although the overall incidence of FD&C Yellowish No. 5 (tartrazine) sensitivity in the full general population is low, it is oftentimes seen in patients who also have aspirin hypersensitivity.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Myelodysplastic Syndrome/Astute Myeloid Leukemia

Suggest patients to contact their healthcare provider if they feel weakness, feeling tired, fever, weight loss, frequent infections, bruising, bleeding easily, breathlessness, claret in urine or stool, and/or laboratory findings of low blood cell counts or a need for claret transfusions. This may be a sign of hematological toxicity or MDS or AML, which has been reported in patients treated with ZEJULA [see WARNINGS AND PRECAUTIONS].

Bone Marrow Suppression

Advise patients that periodic monitoring of their blood counts is required. Advise patients to contact their healthcare provider for new onset of haemorrhage, fever, or symptoms of infection [see WARNINGS AND PRECAUTIONS].

Hypertension And Cardiovascular Effects

Advise patients to undergo blood pressure level and eye charge per unit monitoring at least weekly for the first ii months, then monthly for the first year of treatment and periodically thereafter. Advise patients to contact their healthcare provider if blood pressure is elevated [see WARNINGS AND PRECAUTIONS].

Posterior Reversible Encephalopathy Syndrome

Inform patients that they are at take chances of developing posterior reversible encephalopathy syndrome (PRES) that can present with signs and symptoms including seizure, headaches, contradistinct mental status, or vision changes. Advise patients to contact their healthcare provider if they develop any of these signs or symptoms [meet WARNINGS AND PRECAUTIONS].

Dosing Instructions

Inform patients on how to take ZEJULA [meet DOSAGE AND Administration]. ZEJULA should be taken once daily. Instruct patients that if they miss a dose of ZEJULA not to accept an extra dose to make up for the one that they missed. They should take their side by side dose at the regularly scheduled time. Each sheathing should exist swallowed whole. ZEJULA may be taken with or without food. Bedtime administration may be a potential method for managing nausea.

Embryo-Fetal Toxicity

Advise females to inform their healthcare provider if they are meaning or become pregnant. Inform female patients of the risk to a fetus and potential loss of the pregnancy [come across WARNINGS AND PRECAUTIONS, Use In Specific Populations].

Contraception

Advise females of reproductive potential to utilize effective contraception during handling with ZEJULA and for at least 6 months subsequently receiving the last dose [see Utilise In Specific Populations].

Lactation

Suggest patients not to breastfeed while taking ZEJULA and for 1 month after the terminal dose [see Use In Specific Populations].

Allergic Reactions To FD&C Yellow No. v (Tartrazine)

Suggest patients that ZEJULA capsules contain FD&C Xanthous No. five (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible persons or in patients who also have aspirin hypersensitivity [see WARNINGS AND PRECAUTIONS].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Harm Of Fertility

Carcinogenicity studies have not been conducted with niraparib.

Niraparib was clastogenic in an in vitro mammalian chromosomal abnormality assay and in an in vivo rat os marrow micronucleus analysis. This clastogenicity is consequent with genomic instability resulting from the primary pharmacology of niraparib and indicates potential for genotoxicity in humans. Niraparib was non mutagenic in a bacterial contrary mutation assay (Ames) test.

Fertility studies in animals have not been conducted with niraparib. In repeat-dose oral toxicity studies, niraparib was administered daily for upwardly to 3 months' elapsing in rats and dogs. Reduced sperm, spermatids, and germ cells in epididymides and testes were observed at doses ≥10 mg/kg and ≥1.5 mg/kg in rats and dogs, respectively. These dose levels resulted in systemic exposures approximately 0.3 and 0.012 times, respectively, the human exposure (AUC0-24h) at the recommended dose of 300 mg daily. There was a trend toward reversibility of these findings 4 weeks subsequently dosing was stopped.

Employ In Specific Populations

Pregnancy

Risk Summary

Based on its mechanism of activeness, ZEJULA tin can cause fetal harm when administered to pregnant women [come across CLINICAL PHARMACOLOGY]. At that place are no data regarding the apply of ZEJULA in meaning women to inform the drug-associated risk. ZEJULA has the potential to cause teratogenicity and/or embryo-fetal death since niraparib is genotoxic and targets actively dividing cells in animals and patients (east.m., bone marrow) [see WARNINGS AND PRECAUTIONS, Nonclinical Toxicology]. Due to the potential risk to a fetus based on its mechanism of action, fauna developmental and reproductive toxicology studies were not conducted with niraparib. Apprise pregnant women of the potential risk to a fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background take chances of major nativity defects and miscarriage in clinically recognized pregnancies is 2% to iv% and xv% to xx%, respectively.

Lactation

Risk Summary

No data are available regarding the presence of niraparib or its metabolites in homo milk, or on its effects on the breastfed child or milk product. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with ZEJULA and for 1 month after receiving the final dose.

Females And Males Of Reproductive Potential

ZEJULA tin cause fetal damage when administered to a pregnant woman [see Pregnancy].

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating treatment with ZEJULA.

Contraception

Females

Advise females of reproductive potential to use constructive contraception during handling with ZEJULA and for at least for 6 months following the last dose.

Infertility

Males

Based on beast studies, ZEJULA may impair fertility in males of reproductive potential [see Nonclinical Toxicology].

Pediatric Use

The condom and effectiveness of ZEJULA have not been established in pediatric patients.

Geriatric Use

In PRIMA, 39% of patients were aged 65 years or older and 10% were aged 75 years or older. In NOVA, 35% of patients were anile 65 years or older and 8% were aged 75 years or older. No overall differences in safety and effectiveness of ZEJULA were observed betwixt these patients and younger patients merely greater sensitivity of some older individuals cannot exist ruled out.

Renal Impairment

No dose adjustment is necessary for patients with balmy (CLcr: 60 to 89 mL/min) to moderate (CLcr: 30 to 59 mL/min) renal impairment. The degree of renal impairment was adamant by creatinine clearance as estimated by the Cockcroft-Gault equation. The condom of ZEJULA in patients with severe renal harm or end-stage renal disease undergoing hemodialysis is unknown.

Hepatic Damage

For patients with moderate hepatic impairment, reduce the starting dosage of niraparib to 200 mg once daily [come across DOSAGE AND Administration]. Niraparib exposure increased in patients with moderate hepatic impairment [total bilirubin ≥1.v x upper level of normal (ULN) to 3.0 x ULN and any aspartate transaminase (AST) level]. Monitor patients for hematologic toxicity and reduce the dose further, if needed [come across DOSAGE AND Administration].

For patients with balmy hepatic impairment (total bilirubin <1.5 10 ULN and any AST level or bilirubin ≤ ULN and AST > ULN), no dose adjustment is needed.

The recommended dose of ZEJULA has not been established for patients with severe hepatic impairment (full bilirubin >3.0 x ULN and any AST level) [encounter CLINICAL PHARMACOLOGY].

Overdose & Contraindications

OVERDOSE

No Data provided

CONTRAINDICATIONS

None.

CLINICAL PHARMACOLOGY

Machinery Of Action

Niraparib is an inhibitor of PARP enzymes, including PARP-one and PARP-2, that play a role in Dna repair. In vitro studies accept shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic action and increased germination of PARP-DNA complexes resulting in DNA damage, apoptosis, and prison cell expiry. Increased niraparib-induced cytotoxicity was observed in tumor jail cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human being cancer cell lines with deficiencies in BRCAi/two and in human patient-derived xenograft tumor models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCAi/2.

Pharmacodynamics

The pharmacodynamic response of niraparib has non been characterized.

Hypertension And Cardiovascular Effects

Niraparib has the potential to cause furnishings on pulse charge per unit and blood pressure in patients receiving the recommended dose, which may exist related to pharmacological inhibition of the dopamine transporter (DAT), norepinephrine transporter (Net), and serotonin transporter (SERT) [run into Nonclinical Toxicology].

In the PRIMA study, mean pulse charge per unit and blood pressure increased over baseline in the niraparib arm relative to the placebo arm at well-nigh on-written report assessments. Mean greatest increases from baseline in pulse charge per unit on treatment were 22.4 and 14.0 beats/min in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in systolic claret pressure on treatment were 24.4 and 19.half dozen mmHg in the niraparib and placebo arms, respectively. Hateful greatest increases from baseline in diastolic blood pressure on treatment were 15.nine and 13.ix mmHg in the niraparib and placebo arms, respectively.

In the NOVA written report, mean pulse rate and blood pressure increased over baseline in the niraparib arm relative to the placebo arm at all on-written report assessments. Mean greatest increases from baseline in pulse rate on treatment were 24.i and 15.eight beats/min in the niraparib and placebo artillery, respectively. Mean greatest increases from baseline in systolic claret pressure level on treatment were 24.5 and eighteen.iii mmHg in the niraparib and placebo arms, respectively. Mean greatest increases from baseline in diastolic blood pressure on handling were sixteen.five and eleven.half dozen mmHg in the niraparib and placebo arms, respectively.

Cardiac Electrophysiology

The potential for QTc prolongation with niraparib was evaluated in a randomized, placebo-controlled trial in patients with cancer (367 patients on niraparib and 179 patients on placebo). No large changes in the mean QTc interval (>twenty ms) were detected in the trial post-obit the treatment of niraparib 300 mg once daily.

Pharmacokinetics

Following a single-dose administration of 300 mg niraparib, the mean (±SD) peak plasma concentration (Cmax) was 804 (±403) ng/mL. The exposure (Cmax and AUC) of niraparib increased in a dose-proportional fashion with daily doses ranging from 30 mg (0.1 times the approved recommended dose) to 400 mg (1.3 times the canonical recommended dose). The accumulation ratio of niraparib exposure following 21 days of repeated daily doses was approximately 2-fold for doses ranging from 30 to 400 mg.

Absorption

The absolute bioavailability of niraparib is approximately 73%. Following oral administration of niraparib, peak plasma concentration, Cmax, is reached inside three hours.

Concomitant administration of a loftier-fat meal (800 to i,000 calories with approximately fifty% of full caloric content of the repast from fat) did not significantly touch on the pharmacokinetics of niraparib.

Distribution

Niraparib is 83.0% leap to human plasma proteins. The average (±SD) credible volume of distribution (Vd/F) was i,220 (±1,114) L. In a population pharmacokinetic analysis, the Vd/F of niraparib was 1,074 L in patients with cancer .

Elimination

Following multiple daily doses of 300 mg of niraparib, the mean half-life (t1/2) is 36 hours. In a population pharmacokinetic assay, the apparent full clearance (CL/F) of niraparib was 16.2 Fifty/h in patients with cancer.

Metabolism

Niraparib is metabolized by carboxylesterases (CEs) to form a major inactive metabolite, which subsequently undergoes glucuronidation.

Excretion

Post-obit administration of a unmarried 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 carrion. In pooled samples nerveless over vi days, unchanged niraparib deemed for 11% and 19% of the administered dose recovered in urine and feces, respectively.

Specific Populations

Historic period (18 to 65 years), race/ethnicity, and mild to moderate renal harm (CLcr ≥30 to xc mL/min) had no clinically pregnant effect on the pharmacokinetics of niraparib.

The effect of severe renal impairment (CLcr <30 mL/min) or end-stage renal disease undergoing hemodialysis on the pharmacokinetics of niraparib is unknown.

Patients With Hepatic Impairment

Balmy hepatic impairment (total bilirubin <1.5 x ULN and any AST level or bilirubin ≤ ULN and AST > ULN) had no clinically significant effect on the pharmacokinetics of niraparib.

In a trial of patients with moderate hepatic impairment (full bilirubin ≥1.5 x ULN to 3.0 x ULN and any AST level) (north = viii), niraparib AUCinf was ane.56 (90% CI: one.06 to 2.30) times higher compared with patients with normal hepatic office (n = nine) following administration of a single 300-mg dose. Niraparib dosage reduction is recommended for patients with moderate hepatic harm [see DOSAGE AND Assistants]. Moderate hepatic impairment did not have an upshot on niraparib Cmax or on niraparib protein binding.

The effect of severe hepatic harm (total bilirubin >3.0 x ULN and any AST level) on the pharmacokinetics of niraparib is unknown.

Drug Interaction Studies

No clinical drug interaction studies accept been performed with ZEJULA.

In Vitro Studies

Inhibition of Cytochrome P450 (CYP) Enzymes

Neither niraparib nor the major chief metabolite M1 is an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4.

Induction Of CYP Enzymes

Neither niraparib nor M1 is a CYP3A4 inducer. Niraparib weakly induces CYP1A2 in vitro.

Substrate Of CYP Enzymes

Niraparib is a substrate of CEs and the resulting M1 is further metabolized through the formation of glucuronides in vivo.

Inhibition Of Uridine v'-Diphospho-Glucuronosyltransferases (UGTs)

Niraparib did not showroom inhibitory effect against the UGT isoforms (UGT1A1, UGT1A4, UGT1A9, and UGT2B7) upward to 200 microM in vitro. Therefore, the potential for a clinically relevant inhibition of UGTs by niraparib is minimal.

Inhibition Of Transporter Systems

Niraparib is a weak inhibitor of breast cancer resistance poly peptide (BCRP), simply does not inhibit P-glycoprotein (P-gp), bile salt export pump (BSEP), or multidrug resistance-associated poly peptide two (MRP2).

Niraparib is an inhibitor of multidrug and toxin extrusion (MATE) 1 and 2 with IC50 of 0.18 microM and ≤0.14 microM, respectively. Increased plasma concentrations of coadministered drugs that are substrates of these transporters (e.thou., metformin) cannot exist excluded.

The M1 metabolite is not an inhibitor of P-gp, BCRP, BSEP, MRP2, or MATE1 or 2. Neither niraparib nor M1 is an inhibitor of organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT1)1, organic anion transporter (OAT)1, OAT3, or OCT2.

Substrate Of Transporter Systems

Niraparib is a substrate of P-gp and BCRP. Niraparib is not a substrate of BSEP, MRP2, or MATE1 or ii. The M1 metabolite is non a substrate of P-gp, BCRP, BSEP, or MRP2. Yet, M1 is a substrate of MATE1 and 2. Neither niraparib nor M1 is a substrate of OATP1B1, OATP1B3, OCT1, OAT1, OAT3, or OCT2.

Animal Toxicology And/Or Pharmacology

In vitro, niraparib leap to DAT, Internet, and SERT and inhibited uptake of norepinephrine and dopamine in cells with IC50 values that were lower than the Cmin at steady-country in patients receiving the recommended dose. Niraparib has the potential to cause effects in patients related to inhibition of these transporters (e.g., cardiovascular, fundamental nervous system).

Intravenous administration of niraparib to vagotomized dogs over 30 minutes at one, three, and 10 mg/kg resulted in an increased range of arterial pressures of 13% to xx%, xviii% to 27%, and 19% to 25%, respectively, and increased range of eye rates of 2% to xi%, 4% to 17%, and 12% to 21%, respectively, above pre-dose levels. The unbound plasma concentrations of niraparib in dogs at these dose levels were approximately 0.five, 1.5, and 5.8 times the unbound Cmax at steady-land in patients receiving the recommended dose.

In addition, niraparib crossed the blood-brain barrier in rats and monkeys following oral administration. The cerebrospinal fluid:plasma Cmax ratios of niraparib administered at 10 mg/kg orally to 2 rhesus monkeys were 0.10 and 0.52.

Clinical Studies

First-Line Maintenance Treatment Of Advanced Ovarian Cancer

PRIMA (NCT02655016) was a double-blind, placebo-controlled trial in which patients (Due north = 733) in complete or partial response to kickoff-line platinum-based chemotherapy were randomized ii:1 to ZEJULA or matched placebo. Initially, the patients received a starting dosage of 300 mg once daily regardless of body weight or platelet count. The study was amended to include a starting dose of 200 mg for patients weighing <77 kg (<170 lbs) OR with a platelet count of <150,000/mcL or 300 mg for patients weighing ≥77 kg (≥170 lbs) AND who had a platelet count ≥150,000/mcL.

Patients were randomized post-completion of first-line platinum-based chemotherapy plus surgery. Randomization was stratified past all-time response during the front-line platinum regimen (complete response vs. partial response), neoadjuvant chemotherapy (NACT) (yes vs. no), and HRD condition (positive vs. negative or not determined). HRD condition was determined using the FDA-approved Myriad myChoice CDx assay. HRD positive status included either tumor BRCA mutant (tBRCAm) or a genomic instability score (GIS) ≥42.

The major efficacy effect measure out, progression-free survival (PFS), was adamant past blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.one. In some cases, criteria other than RECIST, such every bit clinical signs and symptoms and increasing CA-125, were besides applied. Overall survival was an additional efficacy outcome measure. PFS testing was performed hierarchically: first in the homologous recombination (HR)-deficient (HRD positive) population, then in the overall population. The median age of 62 ranged from 32 to 85 years among patients randomized with ZEJULA and 33 to 88 years among patients randomized with placebo. Eighty-ix per centum of all patients were White. Sixty-nine percent of patients randomized with ZEJULA and 71% of patients randomized with placebo had an Eastern Cooperative Oncology Group Functioning Status (ECOG PS) of 0 at written report baseline. Approximately 45% of patients were enrolled in the U.S. or Canada. In the overall population, 65% of patients had stage 3 affliction and 35% had stage Iv disease. Sixty-seven percent of the patients received NACT. Sixty-9 percentage of the patients had a complete response to the get-go-line platinum-based chemotherapy. Approximately 35% (n = 258) of patients received a starting dose of 200 or 300 mg depending on baseline torso weight and platelet count. Amongst those patients, 186 patients received a starting dose of 200 mg.

PRIMA demonstrated a statistically pregnant improvement in PFS for patients randomized to ZEJULA as compared with placebo in the 60 minutes-deficient and overall population (Tabular array 10, Figure one, and Figure ii).

Table 10. Efficacy Results – PRIMA (determined by BICR^a)

	60 minutes-Deficient Population		Overall Population
	ZEJULA (n = 247)	Placebo (n = 126)	ZEJULA (n = 487)	Placebo (northward = 246)
Progression-complimentary	81 (33)	73 (58)	232 (48)	155 (63)
Progression-free survival median in months (95% CI)	21.9 (19.3, NE)	10.4 (8.one, 12.1)	13.8 (11.v, fourteen.9)	8.2 (7.three, eight.five)
Hazard ratiob (95% CI)	0.43 (0.31, 0.59)		0.62 (0.fifty, 0.76)
P valuec	<0.0001		<0.0001
60 minutes = Homologous Recombination, NE = not estimable. a Efficacy analysis was based on blinded independent fundamental review. b Based on a stratified Cox proportional hazards model. c Based on a stratified log-rank exam.

In exploratory subgroup analyses of patients who were administered a starting dose of ZEJULA or matched placebo based on baseline weight or platelet count, the gamble ratio for PFS was 0.39 (95% CI: 0.22, 0.72) in the 60 minutes-scarce subgroup (n = 130) and 0.68 (95% CI: 0.48, 0.97) in the overall population (n = 258).

Figure i. Progression-Free Survival – PRIMA Patients with HR-Scarce Tumors (Intent-to-Treat Population, Due north = 373)

Effigy 2. Progression-Costless Survival – PRIMA Overall Population (Intent-to-Treat Population, N = 733)

At the time of the PFS analysis, overall survival data were young, with 11% deaths in the overall population.

Maintenance Treatment Of Recurrent Germline BRCA-Mutated Ovarian Cancer

NOVA (NCT01847274) was a double-blind, placebo-controlled trial in which patients (N = 553) with platinum-sensitive recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer were randomized 2:ane to ZEJULA 300 mg orally daily or matched placebo within 8 weeks of the final therapy. Handling was continued until disease progression or unacceptable toxicity. All patients had received at least 2 prior platinum-containing regimens and were in response (complete or partial) to their most recent platinum-based regimen.

Randomization was stratified by time to progression after the penultimate platinum therapy (six to <12 months and ≥12 months), use of bevacizumab in conjunction with the penultimate or last platinum regimen (yeah/no), and best response during the most recent platinum regimen (complete response and partial response). Eligible patients were assigned to one of two cohorts based on the results of germline BRCA testing. Patients with deleterious or suspected deleterious germline BRCA mutations (kBRCAmut) were assigned to the germline BRCA-mutated (gBRCAmut) accomplice (n = 203), and those without germline BRCA mutations were assigned to the non-thouBRCAmut cohort (n = 350). The efficacy results are based on the grandBRCAmut cohort only.

The major efficacy consequence measure, PFS, was determined primarily by central independent assessment per RECIST version i.1. In some cases, criteria other than RECIST, such as clinical signs and symptoms and increasing CA-125, were as well applied. Overall survival (Bone) was an additional outcome measure.

For the grandBRCAmut cohort, the median age of patients was 57 years among patients treated with ZEJULA and 58 years among patients treated with placebo. Eighty-8 per centum of all patients were White. 60-6 percent of patients receiving ZEJULA and 74% of patients receiving placebo had an ECOG PS of 0 at study baseline. Approximately xl% of patients were enrolled in the U.South. or Canada, and 51% of all patients were in complete response to most recent platinum-based regimen, with 39% on both artillery with an interval of half dozen to 12 months since the penultimate platinum regimen. Xx-four percent of those treated with ZEJULA and 26% treated with placebo had received prior bevacizumab therapy. Approximately 50% of patients had 3 or more lines of treatment.

The trial demonstrated a statistically significant improvement in PFS for patients randomized to ZEJULA as compared with placebo in the mBRCAmut accomplice (Table xi and Figure 3).

Table xi. Efficacy Results – NOVA gBRCAmut Cohort (IRC Assessment^a)

	ZEJULA (n = 138)	Placebo (n = 65)
Progression-free survival median in months (95% CI)	21.0 (12.9, NR)	5.5 (three.8, 7.two)
Take a chance ratiob (95% CI)	0.26 (0.17, 0.41)
P valuec	<0.0001
IRC = Contained Review Commission, gBRCAmut = germline BRCA-mutated, NR = not reached. a Efficacy analysis was based on blinded central contained radiologic and clinical oncology review committee. b Based on a stratified Cox proportional hazards model. c Based on a stratified log-rank test.

Figure iii. Progression-Free Survival – NOVA gBRCAmut Accomplice Based on IRC Cess (Due north = 203)

gBRCAmut = germline BRCA-mutated, IRC = Contained Review Committee.

A concluding OS analysis was conducted after 154 events were observed. Exploratory Os results showed a HR of 0.85 (95% CI: 0.61, one.20) in the mBRCAmut cohort with a median OS of 40.9 months (95% CI: 34.9, 52.ix) for patients treated with ZEJULA and 38.1 months (95% CI: 27.6, 47.3) for patients on placebo.

PATIENT Information

ZEJULA
(zuh-JOO-luh)
(niraparib) capsules

What is the almost important information I should know nearly ZEJULA?

ZEJULA may cause serious side effects including:

• Os marrow problems called myelodysplastic syndrome (MDS) or a type of cancer of the blood called astute myeloid leukemia (AML). Some people who have ovarian cancer and who take received previous handling with chemotherapy or certain other medicines for their cancer take developed MDS or AML during treatment with ZEJULA. MDS or AML may lead to death. If yous develop MDS or AML, your healthcare provider will stop treatment with ZEJULA.

  Symptoms of low claret prison cell counts (low red blood cells, low white claret cells, and low platelets) are common during handling with ZEJULA, but tin can be a sign of serious bone marrow issues, including MDS or AML. Symptoms may include:

  • weakness
  • fever
  • feeling tired
  • shortness of breath
  • weight loss
  • blood in urine or stool
  • frequent infections
  • bruising or bleeding more easily

  Your healthcare provider volition do blood tests to check your blood cell counts:

  • before treatment with ZEJULA.
  • weekly for the showtime month of handling with ZEJULA.
  • every month for the side by side xi months, then as needed during treatment with ZEJULA.
• High claret force per unit area. Loftier blood pressure is common during treatment with ZEJULA and can become serious. Your healthcare provider will check your claret force per unit area and middle rate at to the lowest degree weekly for the first ii months, and then monthly for the start yr and as needed thereafter during your treatment with ZEJULA.
• Posterior reversible encephalopathy syndrome (PRES). PRES is a status that affects the encephalon and may happen during treatment with ZEJULA. If yous have headache, vision changes, confusion, or seizure with or without high blood pressure, please contact your healthcare provider.

See "What are the possible side furnishings of ZEJULA?" for more information about side effects.

What is ZEJULA?

ZEJULA is a prescription medicine used for the:

• maintenance handling of adults with advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. ZEJULA is used subsequently the cancer has responded (complete or partial response) to treatment with platinum-based chemotherapy.
• maintenance treatment of adults with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of inherited (germline) abnormal BRCA gene that comes back. ZEJULA is used afterward the cancer has responded (consummate or partial response) to treatment with platinum-based chemotherapy. Your healthcare provider will perform a examination to brand certain that ZEJULA is right for you.

It is not known if ZEJULA is safe and effective in children.

Before taking ZEJULA, tell your healthcare provider about all of your medical atmospheric condition, including if you:

• have centre issues.
• take liver bug.
• have high claret pressure.
• are allergic to FD&C Xanthous No. 5 (tartrazine) or aspirin. ZEJULA capsules comprise FD&C Yellow No. 5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in sure people, particularly people who also accept an allergy to aspirin.
• are meaning or plan to go pregnant. ZEJULA can harm your unborn baby and may cause loss of pregnancy (miscarriage).
  • If you are able to become meaning, your healthcare provider may perform a pregnancy test earlier yous get-go treatment with ZEJULA.
  • Females who are able to become pregnant should use effective birth control (contraception) during handling with ZEJULA and for half dozen months later on the terminal dose of ZEJULA. Talk to your healthcare provider nigh birth command methods that may be right for you.
  • Tell your healthcare provider right away if you get pregnant.
• are breastfeeding or plan to breastfeed. It is not known if ZEJULA passes into your breast milk. Do not breastfeed during treatment with ZEJULA and for 1 month afterward the last dose of ZEJULA. Talk to your healthcare provider about the best way to feed your babe during this time.

Tell your healthcare provider about all the medicines y'all take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How should I accept ZEJULA?

• Have ZEJULA exactly every bit your healthcare provider tells you lot to.
• Take ZEJULA 1 time each day, at the same fourth dimension each solar day.
• ZEJULA may be taken with or without nutrient.
• ZEJULA capsules should be swallowed whole. Do non chew, crush, or split ZEJULA capsules before swallowing.
• Taking ZEJULA at bedtime may help salvage any nausea symptoms you may have.
• Do non end taking ZEJULA without first talking with your healthcare provider.
• If you lot miss a dose of ZEJULA, take your next dose at your scheduled time. Practise not take an extra dose to make up for a missed dose.
• If yous vomit later taking a dose of ZEJULA, do not take an actress dose. Accept your next dose at your scheduled fourth dimension.
• If you have too much ZEJULA, call your healthcare provider or go to the nearest hospital emergency room correct away.

What are the possible side furnishings of ZEJULA?

ZEJULA may cause serious side effects, including:

• See "What is the most important information I should know about ZEJULA?"

The most common side effects of ZEJULA include:

• heart not chirapsia regularly
• nausea
• constipation
• vomiting
• pain in the stomach area
• oral fissure sores
• diarrhea
• indigestion or heartburn
• dry oral fissure
• tiredness
• loss of appetite
• urinary tract infection
• changes in liver function or other blood tests
• pain in your muscles and back
• headache
• dizziness
• modify in the way food tastes
• problem sleeping
• anxiety
• sore throat
• shortness of jiff
• cough
• rash
• changes in the amount or colour of your urine

Your healthcare provider may change your dose, temporarily cease handling, or permanently stop treatment with ZEJULA if yous take certain side effects.

These are non all the possible side effects of ZEJULA.

Phone call your healthcare provider for medical advice about side effects. You lot may report side furnishings to FDA at 1-800-FDA-1088.

How should I store ZEJULA?

Store ZEJULA at room temperature betwixt 68°F to 77°F (twenty°C to 25°C).

Keep ZEJULA and all medicines out of the reach of children.

General information about the safe and constructive utilise of ZEJULA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Data leaflet. Exercise non apply ZEJULA for a condition for which it was not prescribed. Do not give ZEJULA to other people, even if they accept the same symptoms that you have. It may harm them. You tin ask your healthcare provider or pharmacist for information about ZEJULA that is written for health professionals.

What are the ingredients in ZEJULA?

Active ingredient: niraparib.

Inactive ingredients:

Capsule fill: magnesium stearate and lactose monohydrate.

Sheathing vanquish: titanium dioxide and gelatin in the white capsule body and FD&C Bluish No. 1, FD&C Cherry-red No. 3, FD&C Yellow No. 5 (tartrazine), and gelatin in the royal sheathing cap.

The blackness press ink: shellac, dehydrated alcohol, isopropyl booze, butyl booze, propylene glycol, purified water, potent ammonia solution, potassium hydroxide, and black fe oxide.

The white press ink: shellac, dehydrated alcohol, isopropyl alcohol, butyl booze, propylene glycol, sodium hydroxide, povidone, and titanium dioxide.

This Patient Information has been approved past the U.S. Food and Drug Assistants

From

Report Problems to the Food and Drug Administration

You are encouraged to study negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or phone call 1-800-FDA-1088.

Source: https://www.rxlist.com/zejula-drug.htm

Share this post