Drug Safety-related Labeling Changes (SrLC)

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Drug Safety-related Labeling Changes (SrLC) Database

ANDA	Abbreviated New Drug Application
BLA	Biologics License Application
CDER	Center for Drug Evaluation and Research
MG	Medication Guide
NDA	New Drug Application
PCI	Patient Counseling Information
PI	Patient Information
PLR	Physician Labeling Rule
PLLR	Pregnancy and Lactation Labeling Rule
Italics	For the most part, italics indicate an FDA comment such as: Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section.
Underlines	Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text.

Sections

BW	Box Warning
WP	Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format)
AR	Adverse Reactions (in pre-PLR format, this may be a subheading under precautions).
DI	Drug Interactions (in pre-PLR format, this may be a subheading under precautions).
USP	Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format.
PCI/PI/MG	Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events.

Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.

Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.

ZEJULA (NDA-214876)

(NIRAPARIB TOSYLATE)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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06/18/2025 (SUPPL-3)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Myelodysplastic Syndrome/Acute Myeloid Leukemia

Additions and/or revisions underlined:

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

In PRIMA, of patients within the HRD-positive population, MDS/AML occurred in 8 out of 245 (3.3%) patients treated with ZEJULA and in 3 out of 125 (2.4%) patients treated with placebo with a follow-up of 6.1 years [see Adverse Reactions (6.1)]. The duration of therapy with ZEJULA in patients who developed secondary MDS/cancer-therapy–related AML varied from 5.5 months to 5 years.

. . .

6 Adverse Reactions

6.1 Clinical Trials Experience

. . .

Subsection title revised:

First-Line Maintenance Treatment of HRD-Positive Advanced Ovarian Cancer

Additions and/or revisions underlined:

The safety of ZEJULA for the treatment of patients with advanced ovarian cancer following first-line treatment with platinum-based chemotherapy was studied in the PRIMA trial, a placebo-controlled, double-blind study in which 484 patients received ZEJULA. Among this population, 245 patients were HRD-positive and their median duration of treatment was 13 months (range: 3 days to 29 months).

HRD-Positive Patients Receiving ZEJULA in PRIMA: Serious adverse reactions occurred in 30% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were thrombocytopenia (11%) and anemia (5%). Fatal adverse reactions occurred in 1.6% of patients, including AML (0.4%), cardiac arrest (0.4%), intestinal perforation (0.4%), and sudden death (0.4%).

Permanent discontinuation due to adverse reactions occurred in 11% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >1% of patients who received ZEJULA included thrombocytopenia (3.7%), nausea (1.6%), and anemia (1.2%).

Adverse reactions led to dose reduction or interruption in 79% of patients, most frequently (>10%) from thrombocytopenia (53%), anemia (32%), and neutropenia (19%).

Tables 4 and 5 summarize the common adverse reactions and abnormal laboratory findings observed in the PRIMA trial.

Table 4. Adverse Reactions Reported in Greater Than or equal to 10% of HRD-Positive Patients Receiving ZEJULA in PRIMA

Extensive changes to table; please refer to label for complete information.

Table 5. Abnormal Laboratory Findings in Greater Than or Equal to 25% of HRD-Positive Patients Receiving ZEJULA in PRIMA

Extensive changes to table; please refer to label for complete information.

HRD-Positive 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 (n = 86), the median duration of treatment was 12 months (range: 4 days to 16 months).

Serious adverse reactions occurred in 24% of patients receiving ZEJULA. Serious adverse reactions in >2% of patients were anemia (9%) and thrombocytopenia (2%).

Permanent discontinuation due to adverse reactions occurred in 11% of patients who received ZEJULA. Adverse reactions resulting in permanent discontinuation in >2% of patients who received ZEJULA included nausea (3.5%).

Adverse reactions led to dose reduction or interruption in 72% of patients, most frequently (>10%) from thrombocytopenia (35%), anemia (22%), and neutropenia (17%).

Tables 6 and 7 summarize adverse reactions and abnormal laboratory findings observed in this group.

Table 6. Adverse Reactions Reported in Greater Than or Equal to 10% of HRD-Positive Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMA

Extensive changes to table; please refer to label for complete information.

Table 7. Abnormal Laboratory Findings in Greater Than or Equal to 25% of HRD-Positive Patients Receiving ZEJULA Based on Baseline Weight or Platelet Count in PRIMA

Extensive changes to table; please refer to label for complete information.

. . .

8 Use in Specific Populations

8.6 Hepatic Impairment

Additions and/or revisions underlined:

For patients with moderate hepatic impairment, the recommended dosage of ZEJULA is 200 mg once daily, regardless of body weight or platelet count. Monitor patients for hematologic toxicity and reduce the dose, if needed [see Dosage and Administration (2.3, 2.4)]. Niraparib exposure increased in patients with moderate hepatic impairment (total bilirubin greater than or equal to 1.5 to 3 x ULN and any AST level).

For patients with mild hepatic impairment (total bilirubin <1.5 x ULN and any AST level or bilirubin less than or equal to ULN and AST >ULN), no dosage modification is recommended.

The effect of severe hepatic impairment (total bilirubin >3 x ULN and any AST level) on niraparib pharmacokinetics is unknown.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Additions and/or revisions underlined:

. . .

What is ZEJULA?

ZEJULA is a prescription medicine used to treat adults for:

maintenance treatment of advanced ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with a certain type of abnormal BRCA gene or a positive laboratory tumor test for genomic instability called homologous recombination deficiency (HRD). ZEJULA is used after the cancer has responded (complete or partial response) to treatment with first-line platinum-based chemotherapy.

. . .