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.

PERJETA (BLA-125409)

(PERTUZUMAB)

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

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04/23/2026 (SUPPL-141)

Approved Drug Label (PDF)

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Encourage women who are exposed to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception to report their pregnancy to Genentech [see Use in Speci?ic Populations (8.1)].

…

06/27/2025 (SUPPL-139)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Left Ventricular Dysfunction

Additions and/or revisions underlined:

…

In patients receiving PERJETA as a neoadjuvant treatment in combination with trastuzumab and docetaxel in NeoSphere, LVEF decline >10% and a drop to < 50% occurred in 8% of patients and left ventricular dysfunction occurred in 3% of patients. LVEF recovered to ? 50% in all these patients.

…

12/18/2018 (SUPPL-123)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions are underlined)

Pregnancy Pharmacovigilance Program

There is a pregnancy pharmacovigilance program for PERJETA.

09/20/2018 (SUPPL-121)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Infusion-Related Reactions

(Additions and/or revisions are underlined)

PERJETA has been associated with infusion reactions, including fatal events.

5.4 Hypersensitivity Reactions/Anaphylaxis

(Additions and/or revisions are underlined)

Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis and fatal events, have been observed in patients treated with PERJETA. Angioedema has been described in post-marketing reports. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.

6 Adverse Reactions

6.3 Post-Marketing Experience

(Newly Added Subsection)

The following adverse reactions have been identified during post-approval use of PERJETA. 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.

Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated with PERJETA. Patients with significant tumor burden (e.g., bulky metastases) may be at a higher risk. Patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS. Providers should consider additional monitoring and/or treatment as clinically indicated.

12/20/2017 (SUPPL-113)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Left Ventricular Dysfunction

(extensive additions and revisions, please refer to label)

5.3 Infusion-Related Reaction

(additions underlined)

PERJETA has been associated with infusion reactions. An infusion reaction was defined in CLEOPATRA as any event described as hypersensitivity, anaphylactic reaction, acute infusion reaction, or cytokine release syndrome occurring during an infusion or on the same day as the infusion.

…

In NeoSphere, TRYPHAENA, and APHINITY, PERJETA was administered on the same day as the other study treatment drugs. For APHINITY, infusion-related reactions occurred in 21% of patients on the first day of PERJETA administration (in combination with trastuzumab and chemotherapy) and in 18% of patients in the placebo arm.

…

5.4 Hypersensitivity Reactions/Anaphylaxis

(addition and revisions underlined)

In CLEOPATRA, the overall frequency of hypersensitivity/anaphylaxis reactions was 11% in the PERJETA-treated group and 9% in the placebo-treated group. The incidence of Grade 3 – 4 hypersensitivity/anaphylaxis reactions was 2% in the PERJETA-treated group and 3% in the placebo-treated group according to NCI - CTCAE v3.0. Overall, 4 patients in the PERJETA- treated group and 2 patients in the placebo-treated group experienced anaphylaxis.

In NeoSphere, TRYPHAENA, BERENICE, and APHINITY, hypersensitivity/anaphylaxis events were consistent with those observed in CLEOPATRA. In NeoSphere, two patients in the PERJETA- and docetaxel-treated group experienced anaphylaxis. In APHINITY, the overall frequency of hypersensitivity/anaphylaxis was 5% in the PERJETA treated group vs. 4% in the placebo-treated group. The incidence was highest in the PERJETA plus TCH treated group (8%) of which 1% were NCI-CTCAE (v4.0) Grade 3 – 4.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive additions and revisions, please refer to label)

6.2 Immunogenicity

(additions and revisions underlined)

As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to pertuzumab in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.

Patients in CLEOPATRA were tested at multiple time-points for antibodies to PERJETA. 3% (13/389) of patients in the PERJETA-treated group and 7% (25/372) of patients in the placebo- treated group tested positive for anti-PERJETA antibodies. Of these 38 patients, none experienced anaphylactic/hypersensitivity reactions that were clearly related to the anti-drug antibodies (ADA). The presence of pertuzumab in patient serum at the levels expected at the time of ADA sampling can interfere with the ability of this assay to detect anti-pertuzumab antibodies. In addition, the assay may be detecting antibodies to trastuzumab. As a result, data may not accurately reflect the true incidence of anti-pertuzumab antibody development.

In the neoadjuvant period of BERENICE, 0.3% (1/383) of patients treated with PERJETA tested positive for anti-PERJETA antibodies. This patient did not experience any anaphylactic/hypersensitivity reactions.

7 Drug Interactions

(additions underlined)

No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel, paclitaxel, or carboplatin.

8 Use in Specific Populations

8.5 Geriatric Use

(additions underlined)

In studies in the indicated populations, CLEOPATRA, NeoSphere, TRYPHAENA, BERENICE, and APHINITY, 464 patients who received PERJETA were greater than or equal to 65 years of age and 47 were greater than or equal to 75 years of age. The most common (greater than or equal to 10%) Grade 3-4 adverse reactions in both age groups were neutropenia (22% greater than or equal to 65 years, 23% greater than or equal to 75 years), febrile neutropenia (12% greater than or equal to 65 years, 13% greater than or equal to 75 years), diarrhea (15% greater than or equal to 65 years, 17% greater than or equal to 75 years) and anemia (15% greater than or equal to 75 years).

The incidence of the following all grade adverse events was at least 5% higher in patients aged greater than or equal to 65 years of age, compared to patients aged < 65 years of age: decreased appetite (13% higher), anemia (7% higher), weight decreased (7% higher), asthenia (7% higher), dysgeusia (7% higher), neuropathy peripheral and hypomagnesemia (both 5% higher).

No overall differences in efficacy of PERJETA were observed in patients aged greater than or equal to 65 and <65 years of age. There are too few patients aged greater than or equal to 75 years to draw conclusions on efficacy in this age group.

Based on a population pharmacokinetic analysis, no significant difference was observed in the pharmacokinetics of pertuzumab between patients < 65 years (n=306) and patients greater than or equal to 65 years (n=175).

12/20/2017 (SUPPL-118)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Left Ventricular Dysfunction

(extensive additions and revisions, please refer to label)

5.3 Infusion-Related Reaction

(additions underlined)

…

5.4 Hypersensitivity Reactions/Anaphylaxis

(addition and revisions underlined)

…

6 Adverse Reactions

6.1 Clinical Trials Experience

(Extensive additions and revisions, please refer to label)

6.2 Immunogenicity

(additions and revisions underlined)

As with all therapeutic proteins, there is the potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.

7 Drug Interactions

(additions underlined)

No drug-drug interactions were observed between pertuzumab and trastuzumab, or between pertuzumab and docetaxel, paclitaxel, or carboplatin.

8 Use in Specific Populations

8.5 Geriatric Use

(additions underlined)