Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | Guide

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.

NEULASTA (BLA-125031)

(PEGFILGRASTIM)

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

Download Data

Expand all

02/02/2021 (SUPPL-203)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(Additions and/or revisions underlined)

The following adverse reactions have been identified during post approval use of Neulasta. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Alveolar hemorrhage

01/05/2021 (SUPPL-202)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Thrombocytopenia

(Newly Added Section)

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

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

(Newly Added Section)

MDS and AML have been associated with the use of Neulasta 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.

6 Adverse Reactions

(Additions and/or revisions underlined)

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:

Splenic Rupture [see Warnings and Precautions (5.1)]
Acute Respiratory Distress Syndrome [see Warnings and Precautions (5.2)]
Serious Allergic Reactions [see Warnings and Precautions (5.3)]
Allergies to Acrylics [see Warnings and Precautions (5.4)]
Use in Patients with Sickle Cell Disorders [see Warnings and Precautions (5.5)]
Glomerulonephritis [see Warnings and Precautions (5.6)]
Leukocytosis [see Warnings and Precautions (5.7)]
Thrombocytopenia [see Warnings and Precautions (5.8)]
Capillary Leak Syndrome [see Warnings and Precautions (5.9)]
Potential for Tumor Growth Stimulatory Effects on Malignant Cells [see Warnings and Precautions (5.10)]
Myelodysplastic syndrome [see Warnings and Precautions (5.11)]
Acute myeloid leukemia [see Warnings and Precautions (5.11)]
Aortitis [see Warnings and Precautions (5.13)]

6.3 Postmarketing Experience

(Additions and/or revisions underlined)

Splenic rupture and splenomegaly (enlarged spleen) [see Warnings and Precautions (5.1)]
Acute respiratory distress syndrome (ARDS) [see Warnings and Precautions (5.2)]
Allergic reactions/hypersensitivity, including anaphylaxis, skin rash, urticaria, generalized erythema, and flushing [see Warnings and Precautions (5.3)]
Sickle cell crisis [see Warnings and Precautions (5.5)]
Glomerulonephritis [see Warnings and Precautions (5.6)]
Leukocytosis [see Warnings and Precautions (5.7)]

Thrombocytopenia [see Warnings and Precautions (5.8)]
Capillary Leak Syndrome [see Warnings and Precautions (5.9)]
Injection site reactions
Sweet’s syndrome (acute febrile neutrophilic dermatosis), cutaneous vasculitis
Application site reactions (including events such as application site hemorrhage, application site pain, application site discomfort, application site bruise, and application site erythema) have been reported with the use of the on-body injector for Neulasta.

Contact dermatitis and local skin reactions such as rash, pruritus, and urticaria have been reported with the use of the on-body injector for Neulasta, possibly indicating a hypersensitivity reaction to the adhesive.
Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with breast and lung cancer receiving chemotherapy and/or radiotherapy [see Warnings and Precautions (5.11)]
Aortitis [see Warnings and Precautions (5.13)]

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

17 PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Advise patients of the following risks and potential risks with Neulasta:

Splenic rupture and splenomegaly
Acute Respiratory Distress Syndrome
Serious allergic reactions
Sickle cell crisis
Glomerulonephritis
Increased risk of Myelodysplastic Syndrome and/or Acute Myeloid Leukemia in patients with congenital neutropenia who receive Neulasta and in patients with breast and lung cancer who receive Neulasta in conjunction with chemotherapy and/or radiation therapy
Capillary Leak Syndrome
Aortitis

01/06/2020 (SUPPL-199)

Approved Drug Label (PDF)

6 Adverse Reactions

‘clinically significant’ replaces ‘serious’ in first sentence.

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient:
- do not use other materials to hold the on-body injector in place that could cover audio/visual indicators or compress the on-body injector against the patient’s skin, as this could dislodge the cannula and lead to a missed dose or incomplete dose of Neulasta.
Advise the patient to avoid:
- use of lotions, creams, or oils on their arms and abdomen prior to their next scheduled OBI for Neulasta dose (to help with device adherence to the skin).

PATIENT INFORMATION

Additions and/or revisions underlined:

What is the most important information I need to know about receiving Neulasta with the on?body injector for Neulasta?

Before your next scheduled Neulasta dose, avoid use of lotions, creams, or oils on your arms and stomach area (abdomen) to help keep the device on your skin.

Other

Healthcare Provider Instructions for Use

Additions and/or revisions underlined:

Important

READ THE FOLLOWING INSTRUCTIONS BEFORE USING NEULASTA ONPRO KIT

Warning: Do not use Neulasta Onpro kit to deliver any other drug product.

Do not use other materials to hold it in place that could cover audio/visual indicators or compress the on-body injector against the patient’s skin, as this could dislodge the cannula and lead to a missed or incomplete dose of Neulasta.
STEP 1: Prepare

Clean an area on the injection site larger than the on-body injector adhesive backing.

Thoroughly clean the site with alcohol to enhance on-body injector adherence to the skin. Only use alcohol to clean the skin.
STEP 3: Apply

Before the cannula deploys, securely apply the on?body injector so it is visible and can be monitored by the patient or caregiver.
You now have time to carefully apply the on?body injector without folding or wrinkling the adhesive.

If additional adhesion is deemed appropriate, an adhesive extender that fits around the on-body injector can be obtained by calling 1-844-MYNEULASTA (1-844-696-3852).
Do not use other materials to secure the on?body injector to the patient that could cover audio/visual indicators or compress the on-body injector against the patient’s skin.
STEP 4: FINISH

Fill in the Dose Delivery Information section in the patient instructions.
Be sure to include when the on body injector was applied, when the dose will begin, and your contact information. Review this information with the patient.

Do not use other materials to hold it in place that could cover audio/visual indicators or compress the on-body injector against the patient’s skin, as this could dislodge the cannula and lead to a missed or incomplete dose of Neulasta.

04/16/2019 (SUPPL-198)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

(Additions and/or revisions are underlined)

Alveolar hemorrhage

06/18/2018 (SUPPL-193)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.5 Use in Patients with Sickle Cell Disorders

Severe and sometimes fatal sickle cell crises can occur in patients with sickle cell disorders receiving pegfilgrastim products. Discontinue Neulasta if sickle cell crisis occurs.

Newly created subsections:

5.11 Aortitis

Aortitis has been reported in patients receiving Neulasta. It may occur as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis in patients who develop these signs and symptoms without known etiology. Discontinue Neulasta if aortitis is suspected.

5.12 Nuclear Imaging

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

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Aortitis

6.2 Immunogenicity

Addition of (including neutralizing antibody) following the word antibody throughout section.

7 Drug Interactions

Section only consists of the following newly added language:

Application site reactions (including events such as application site hemorrhage, application site pain, application site discomfort, application site bruise, and application site erythema) have been reported with the use of the on-body injector for Neulasta.
Contact dermatitis and local skin reactions such as rash, pruritus, and urticaria have been reported with the use of the on-body injector for Neulasta, possibly indicating a hypersensitivity reaction to the adhesive.

Aortitis

8 Use in Specific Populations

8.1 Pregnancy

PLLR conversion; additions and/or revisions underlined:

Risk Summary

Although available data with Neulasta use in pregnant women are insufficient to establish whether there is a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, there are available data from published studies in pregnant women exposed to filgrastim products. These studies have not established an association of filgrastim product use during pregnancy with major birth defects, miscarriage, or adverse maternal or fetal outcomes.

In animal studies, no evidence of reproductive/developmental toxicity occurred in the offspring of pregnant rats that received cumulative doses of pegfilgrastim approximately 10 times the recommended human dose (based on body surface area). In pregnant rabbits, increased embryolethality and spontaneous abortions occurred at 4 times the maximum recommended human dose simultaneously with signs of maternal toxicity.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

Pregnant rabbits were dosed with pegfilgrastim subcutaneously every other day during the period of organogenesis. At cumulative doses ranging from the approximate human dose to approximately 4 times the recommended human dose (based on body surface area), the treated rabbits exhibited … and from the first trimester through delivery and lactation.

No evidence of fetal loss or structural malformations was observed in any study. Cumulative doses equivalent to approximately 3 and 10 times the recommended human dose resulted in transient evidence of wavy ribs in fetuses of treated mothers (detected at the end of gestation but no longer present in pups evaluated at the end of lactation).

8.2 Lactation

PLLR conversion; additions and/or revisions underlined:

There are no data on the presence of pegfilgrastim in human milk, the effects on the breastfed child, or the effects on milk production. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not absorbed orally by neonates. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Neulasta and any potential adverse effects on the breastfed child from Neulasta or from the underlying maternal condition.

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

PATIENT COUNSELING INFORMATION

Addition of the following to the bulleting line listing:

Aortitis

Additions and/or revisions underlined:

Advise the patient:

do not reapply the OBI for Neulasta if the OBI for Neulasta comes off before full dose is delivered and instead call their healthcare provider immediately, as they may need a replacement dose.
avoid bumping the OBI for Neulasta or knocking the OBI for Neulasta off the body.
do not use additional materials to hold the on-body injector in place, as this could dislodge the cannula and lead to a missed dose or incomplete dose of Neulasta.

do not expose the OBI for Neulasta to medical imaging studies (e.g., X-ray scan, MRI, CT scan and ultrasound), radiation treatment, and oxygen rich environments …
using bath tubs, hot tubs …

12/09/2017 (SUPPL-191)

Approved Drug Label (PDF)

4 Contraindications

Additions and/or revisions underlined:

Neulasta is contraindicated in patients with a history of serious allergic reactions to pegfilgrastim or filgrastim. Reactions have included anaphylaxis.

5 Warnings and Precautions

5.10 Potential Device Failures

Newly added subsection:

Missed or partial doses have been reported in patients receiving Neulasta via the on-body injector (OBI) due to the device not performing as intended. In the event of a missed or partial dose, patients may be at increased risk of events such as neutropenia, febrile neutropenia and/or infection than if the dose had been correctly delivered. Instruct patients using the OBI to notify their healthcare professional immediately in order to determine the need for a replacement dose of Neulasta if they suspect that the device may not have performed as intended.

6 Adverse Reactions

Additions and/or revisions underlined:

6.1 Clinical Trials Experience

Table 2. Adverse Reactions with greater than or equal to 5% Higher Incidence in Neulasta Patients Compared to Placebo in Study 3

In the table heading, Body System Adverse Reaction replaces System Organ Class Preferred Term.

6.2 Immunogenicity

… For these reasons, comparison of the incidence of antibodies to Neulasta with the incidence of antibodies to other products may be misleading.

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 …