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.

ZIEXTENZO (BLA-761045)

(PEGFILGRASTIM-BMEZ)

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

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05/12/2026 (SUPPL-17)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.7 Thrombocytopenia

Additions and/or revisions underlined:

Pegfilgrastim products can cause thrombocytopenia. Monitor platelet counts during ZIEXTENZO therapy.

5.12 Nuclear Imaging

Additions and/or revisions underlined:

Increased hematopoietic activity of the bone marrow in response to growth factor therapy, including pegfilgrastim products, has been associated with transient positive bone imaging changes. This should be considered when interpreting bone imaging results.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

The safety and effectiveness of ZIEXTENZO for chemotherapy-induced neutropenia and hematopoietic subsyndrome of acute radiation syndrome have been established in pediatric patients aged newborn and older.

Use of ZIEXTENZO in pediatric patients for chemotherapy-induced neutropenia is based on adequate and well-controlled studies of pegfilgrastim in adults with additional pharmacokinetic and safety data of pegfilgrastim in pediatric patients aged 8 months and older with sarcoma [see Clinical Pharmacology (12.3) and Clinical Studies (14.1)].

. . .

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

PATIENT INFORMATION

Additions and/or revisions underlined:

What is ZIEXTENZO?

ZIEXTENZO is a prescription medicine that is used:

in adults and children aged newborn and older to help reduce the chance of infection due to a low white blood cell count, in people with certain types of cancer (non-myeloid), who receive anti-cancer medicines (chemotherapy) that can cause fever and low blood cell count.
in adults and children aged newborn and older for acute radiation syndrome. The effectiveness of pegfilgrastim for this use was only studied in animals, because it could not be studied in people.

. . .

You should not inject a dose of ZIEXTENZO to children weighing less than 99 pounds (45 kg) from a ZIEXTENZO prefilled syringe.

. . .

If you inject too much ZIEXTENZO, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.

. . .

02/28/2024 (SUPPL-14)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Immunogenicity

Additions and/or revisions underlined:

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of pegfilgrastim or of other pegfilgrastim products.

Binding antibodies to pegfilgrastim were detected using a BIAcore assay. The approximate limit of detection for this assay is 500 ng/mL. Pre-existing binding antibodies were detected in approximately 6% (51/849) of patients with metastatic breast cancer. Four of 521 pegfilgrastim-treated subjects who were negative at baseline developed binding antibodies to pegfilgrastim following treatment. None of these 4 patients had evidence of neutralizing antibodies detected using a cell-based bioassay.

8 Use in Specific Populations

8.4 Pediatric Use

Additions and/or revisions underlined:

…

The use of ZIEXTENZO to increase survival in pediatric patients acutely exposed to myelosuppressive doses of radiation is based on ZIEXTENZO’s approval as a biosimilar to pegfilgrastim and evidence from efficacy studies of pegfilgrastim conducted in animals and clinical data supporting the use of pegfilgrastim in patients with cancer receiving myelosuppressive chemotherapy. Efficacy studies of pegfilgrastim products could not be conducted in humans with acute radiation syndrome for ethical and feasibility reasons. Results from population modeling and simulation indicate that two doses of pegfilgrastim (Table 1), administered one week apart provide pediatric patients with exposures comparable to that in adults receiving two 6 mg doses one week apart [see Dosage and Administration (2.3), Clinical Pharmacology (12.3) and Clinical Studies (14.2)].

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Advise patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome) that efficacy studies of pegfilgrastim products for this indication could not be conducted in humans for ethical and feasibility reasons and that, therefore, approval of this use was based on efficacy studies conducted in animals [see Clinical Studies (14.2)].

…

PATIENT INFORMATION

Additions and/or revisions underlined:

What is ZIEXTENZO?

ZIEXTENZO is a man-made form of granulocyte colony-stimulating factor (G-CSF). G-CSF is a substance produced by the body. It stimulates the growth of neutrophils, a type of white blood cell important in the body’s fight against infection.

Acute Radiation Syndrome: The effectiveness of pegfilgrastim for this use was only studied in animals, because it could not be studied in people.

…

03/12/2021 (SUPPL-6)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer

New subsection added

MDS and AML have been associated with the use of pegfilgrastim products in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for signs and symptoms of MDS/AML in these settings.

5.7 Thrombocytopenia

New subsection added

Thrombocytopenia has been reported in patients receiving pegfilgrastim. Monitor platelet counts.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Thrombocytopenia [see Warnings and Precautions (5.7)]
Myelodysplastic syndrome [see Warnings and Precautions (5.10)]
Acute myeloid leukemia [see Warnings and Precautions (5.10)]
6.3 Postmarketing Experience
Addition of the following to the bulleted line listing:

Thrombocytopenia [see Warnings and Precautions (5.7)]
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions (5.10)]

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

PATIENT COUNSELING INFORMATION

Addition of the following to the bulleted line listing:

Increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with breast and lung cancer who receive ZIEXTENZO in conjunction with chemotherapy and/or radiation therapy

PATIENT INFORMATION

Additions underlined

…

What are possible side effects of ZIEXTENZO?

…

Decreased platelet count (thrombocytopenia). Your healthcare provider will check your blood during treatment with ZIEXTENZO. Tell your healthcare provider if you have unusual bleeding or bruising during treatment with ZIEXTENZO. This could be a sign of decreased platelet counts, which may reduce the ability of your blood to clot.

…

Myelodysplastic syndrome and acute myeloid leukemia. If you have breast cancer or lung cancer, when ZIEXTENZO is used with chemotherapy and radiation therapy, or with radiation therapy alone, you may have an increased risk of developing a precancerous blood condition called myelodysplastic syndrome (MDS) or a blood cancer called acute myeloid leukemia (AML). Symptoms may include tiredness, fever, and easy bruising or bleeding. Call your healthcare provider if you develop these symptoms during treatment with ZIEXTENZO.

…

How should I store ZIEXTENZO?

…

Throw away (dispose of) any ZIEXTENZO that has been left at room temperature, 68°F to 95°F (20°C to 35°C), for more than 120 hours.
…