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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.
TRODELVY (BLA-761115)
(SACITUZUMAB GOVITECAN-HZIY)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
03/26/2025 (SUPPL-59)
5 Warnings and Precautions
WARNINGS AND PRECAUTIONS
5.1 Neutropenia
Additions and/or revisions underlined:
TRODELVY can cause severe, life-threatening, or fatal neutropenia as early as the first cycle of treatment. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days (range: 1 to 435 days). Neutropenia occurred earlier in patients with reduced UGT1A1 activity [see Warnings and Precautions (5.5)]. Neutropenic colitis occurred in 1.4% of patients.
Primary prophylaxis with G-CSF is recommended starting in the first cycle of treatment in all patients at increased risk of febrile neutropenia, including older patients, patients with previous neutropenia, poor performance status, organ dysfunction, or multiple comorbidities.
Monitor absolute neutrophil count (ANC) during treatment. Withhold TRODELVY for ANC below 1500/mm3 on Day 1 of any cycle or below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Treat neutropenia with G-CSF and administer prophylaxis in subsequent cycles as clinically indicated or indicated in Table 2 [see Dosage and Administration (2.3)].
5.4 Nausea and Vomiting
Additions and/or revisions underlined:
TRODELVY is emetogenic and can cause severe nausea and vomiting. Nausea occurred in 64% of all patients treated with TRODELVY. Grade 3-4 nausea occurred in 3% of patients.
. . .
8 Use in Specific Populations
8.5 Geriatric Use
Additions and/or revisions underlined:
Of the 366 patients with TNBC who were treated with TRODELVY, 19% of patients were 65 years and 3% were 75 years and older. Patients 65 and older had an increased incidence of neutropenia, including fatal outcomes. No other differences in safety and effectiveness were observed between patients greater than or equal to 65 years of age and younger patients.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
What is the most important information I should know about TRODELVY? TRODELVY can cause serious side effects, including:
Low white blood cell count (neutropenia). Low white blood cell counts are common with TRODELVY and can sometimes be severe and lead to infections that can be life-threatening or cause death as early as the first cycle of treatment. Your healthcare provider should check your blood cell counts during treatment with TRODELVY and may give a medicine to help prevent low blood cell count starting in the first cycle of treatment if you have an increased risk for developing low white blood cell count with a fever (febrile neutropenia). If your white blood cell count is too low, your healthcare provider may need to delay treatment or lower your dose of TRODELVY, give you a medicine to treat low blood cell count, or in some cases may permanently stop TRODELVY. Your healthcare provider may need to give you antibiotic medicines if you develop fever while your white blood cell count is low.
. . .
Severe diarrhea. Diarrhea is common with TRODELVY and can also be severe. Severe diarrhea can lead to loss of too much body fluid (dehydration) and kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control your diarrhea. If you lose too much body fluid, your healthcare provider may need to give you fluids and electrolytes to replace body salts. If you develop diarrhea during treatment with TRODELVY, your healthcare provider should check to see if diarrhea may be caused by an infection. Your healthcare provider may decrease your dose, delay treatment, or permanently stop TRODELVY if your diarrhea is severe and cannot be controlled with anti-diarrheal medicines.
. . .
- Nausea and vomiting. Nausea and vomiting are common with TRODELVY and can sometimes be severe. Before each dose of TRODELVY, you will receive medicines to help prevent nausea and vomiting. You should be given medicines to take home with you, along with instructions about how to take them to help prevent and treat any nausea and vomiting after you receive TRODELVY. Call your healthcare provider right away if you have nausea or vomiting that is not controlled with the medicines prescribed for you. Your healthcare provider may decide to decrease your dose, delay treatment, or permanently stop TRODELVY if your nausea and vomiting is severe and cannot be controlled with anti-nausea medicines.
. . .
11/22/2024 (SUPPL-58)
6 Adverse Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY in 1063 patients, which included 366 patients with mTNBC and 322 patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer from IMMU-132-01, ASCENT, and TROPiCS-02; and 375 patients with other tumor types. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 1063 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 63 months). In this pooled safety population, the most common (> 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%).
…
02/03/2023 (SUPPL-35)
5 Warnings and Precautions
5.1 NeutropeniaAdditions and/or revisions underlined:
Severe, life-threatening, or fatal neutropenia can occur in patients treated with TRODELVY. Neutropenia occurred in 64% of patients treated with TRODELVY. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6% of patients. The median time to first onset of neutropenia (including febrile neutropenia) was 16 days and has occurred earlier in some patient populations [see Warnings and Precautions (5.5)]. Neutropenic colitis occurred in 1.4% of patients.
Withhold TRODELVY for absolute neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil count below 1000/mm3 on Day 8 of any cycle. Withhold TRODELVY for neutropenic fever. Dose modifications may be required due to neutropenia. Administer G-CSF as clinically indicated or indicated in Table 1 [see Dosage and Administration (2.3)].
Additions and/or revisions underlined:
TRODELVY can cause severe diarrhea. Diarrhea
occurred in 64% of all patients
treated with TRODELVY. Grade 3-4 diarrhea
occurred in 11% of all patients treated with TRODELVY. One patient had
intestinal perforation following diarrhea. Diarrhea that led to dehydration
and subsequent acute kidney injury occurred in 0.7% of all patients.
…
Additions and/or
revisions underlined:
…
Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 2% of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.2%. The incidence of anaphylactic reactions was 0.2%.
…
Additions and/or revisions underlined:
TRODELVY is emetogenic. Nausea
occurred in 64% of all patients
treated with TRODELVY. Grade 3-4 nausea
occurred in 3% of patients.
Vomiting occurred in 35% of all patients
treated with TRODELVY.
Grade 3-4 vomiting
occurred in 2%
of these patients.
…
Additions and/or revisions underlined:
Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele
are at increased risk for
neutropenia, febrile neutropenia, and anemia; and may be at increased risk for
other adverse reactions when treated with TRODELVY.
The incidence of neutropenia and
anemia was analyzed in 948 patients who received TRODELVY and had UGT1A1
genotype results. In patients homozygous for the UGT1A1
*28 allele (n=112), the incidence of Grade 3-4 neutropenia was 58%. In patients heterozygous
for the UGT1A1*28 allele (n=420), the incidence of Grade 3-4 neutropenia
was 49%. In patients homozygous for the wild-type allele (n=416),
the incidence of Grade 3-4 neutropenia was 43% [see Clinical Pharmacology (12.5)]. In patients homozygous for the
UGT1A1 *28 allele, the incidence of Grade 3-4 anemia was 21%. In patients
heterozygous for the UGT1A1*28 allele,
the incidence of Grade 3-4 anemia was 10%. In patients homozygous for the wild-type allele, the
incidence of Grade 3-4 anemia was 9%.
The median time to first neutropenia including febrile neutropenia was 9 days in patients homozygous for the UGT1A1*28 allele, 15 days in patients heterozygous for the UGT1A1*28 allele, and 20 days in patients homozygous for the wild-type allele. The median time to first anemia was 21 days in patients homozygous for the UGT1A1*28 allele, 25 days in patients heterozygous for the UGT1A1*28 allele, and 28 days in patients homozygous for the wild-type allele.
Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 enzyme activity [see Dosage and Administration (2.3)].
6 Adverse Reactions
6.1 Clinical Trials ExperienceExtensive changes; please refer to label for complete information
8 Use in Specific Populations
8.5 Geriatric UseAdditions and/or revisions underlined:
Of the 366 patients with TNBC who were treated with TRODELVY, 19% of patients were 65 years and 3% were 75 years and older. No overall differences in safety and effectiveness were observed between patients greater than or equal to 65 years of age and younger patients.
Of the 322 patients with HR+/HER2- breast cancer who were treated with TRODELVY, 26% of patients were 65 years and older and 6% were 75 years and older. No overall differences in effectiveness were observed between patients greater than or equal to 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (3%).
Of the 180 patients with UC who were treated with TRODELVY, 59% of patients were 65 years and older and 27% were 75 years and older. No overall differences in effectiveness were observed between patients greater than or equal to 65 years of age and younger patients. There was a higher discontinuation rate due to adverse reactions in patients aged 65 years or older (14%) compared with younger patients (8%).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONAdditions and/or revisions underlined:
…
- Severe diarrhea. Diarrhea is common with TRODELVY and can also be severe. Severe diarrhea can lead to loss of too much body fluid (dehydration) and kidney problems. Your healthcare provider should monitor you for diarrhea and give you medicine as needed to help control your diarrhea. If you lose too much body fluid, your healthcare provider may need to give you fluids and electrolytes to replace body salts. If you develop diarrhea during treatment with TRODELVY, your healthcare provider should check to see if diarrhea may be caused by an infection. Your healthcare provider may decrease your dose or stop TRODELVY if your diarrhea is severe and cannot be controlled with anti-diarrheal medicines.
…
What is TRODELVY?
TRODELVY is a prescription medicine used to treat adults with:
a type of breast cancer called triple-negative breast cancer (TNBC), which is estrogen and progesterone hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative. TRODELVY may be used:
when your breast cancer has spread to other parts of the body (metastatic) or cannot be removed by surgery,
and
if you previously received two or more prior treatments, including at least one treatment for metastatic disease.
a type of breast cancer that is HR-positive and HER2-negative. TRODELVY may be used:
when your breast cancer has spread to other parts of the body or cannot be removed by surgery,
and
if you previously received endocrine therapy and at least two additional treatments for metastatic disease.
…
The most common side effects of TRODELVY include:
decreased white blood cell (leukocyte and lymphocyte) and red blood cell counts
decreased appetite
changes in kidney function test
feeling tired or weak
increased levels of enzyme called alkaline phosphatase in the blood (test for liver or bone problems)
hair loss
constipation
increased sugar levels in the blood
decreased levels of magnesium, potassium, and sodium in the blood
decreased protein levels (albumin) in the blood
06/03/2022 (SUPPL-23)
8 Use in Specific Populations
8.6 Hepatic ImpairmentAdditions and/or revisions underlined:
No adjustment to the starting dosage is required when administering TRODELVY to patients with mild hepatic impairment [see Clinical Pharmacology (12.3)]).
The safety of TRODELVY in patients with moderate (total bilirubin > 1.5 to 3.0 × ULN) or severe (total bilirubin > 3.0 × upper limit of normal [ULN]) hepatic impairment has not been established. TRODELVY has not been tested in patients with AST or ALT > 3 ULN without liver metastases, or AST or ALT > 5 ULN with liver metastases. No recommendations can be made for the starting dosage in these patients.
04/07/2021 (SUPPL-13)
5 Warnings and Precautions
5.1 Neutropenia
Additions and/or revisions underlined:
TRODELVY can cause severe or life-threatening neutropenia that may result in death. Neutropenia occurred in 62% of patients treated with TRODELVY, leading to permanent discontinuation of TRODELVY in 0.5% of patients. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 6% of patients.
Withhold TRODELVY for absolute neutrophil count below 1500/mm3 on Day 1 …
5.2 Diarrhea
Additions and/or revisions underlined:
TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3 diarrhea occurred in 12% of all patients treated with TRODELVY. Neutropenic colitis occurred in 0.5% of patients.
Withhold TRODELVY for Grade 3-4 diarrhea at the time …
Additions and/or revisions underlined:
5.3 Hypersensitivity and Infusion-Related Reactions
Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 1% of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.4%.
Pre-infusion medication for patients receiving TRODELVY is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each TRODELVY infusion …
5.4 Nausea and Vomiting
Additions and/or revisions underlined:
TRODELVY is emetogenic. Nausea occurred in 67% of all patients treated with TRODELVY. Grade 3-4 nausea occurred in 5% of patients.
Vomiting occurred 40% of all patients treated with TRODELVY. Grade 3-4 vomiting occurred in 3% of these patients.
Additions and/or revisions underlined:
5.5 Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity
Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia; and may be at increased risk for other adverse reactions when treated with TRODELVY.
The incidence of neutropenia and anemia was analyzed in 577 patients who received TRODELVY and had UGT1A1 genotype results. In patients homozygous for the UGT1A1 *28 allele (n=70), the incidence of Grade 3-4 neutropenia was 69%. In patients heterozygous for the UGT1A1*28 allele (n=246), the incidence of Grade 3-4 neutropenia was 48%. In patients homozygous for the wild-type allele (n=261), the incidence of Grade 3-4 neutropenia was 46% [see Clinical Pharmacology (12.5)]. In patients homozygous for the UGT1A1 *28 allele (n=70), the incidence of Grade 3-4 anemia was 24%. In patients heterozygous for the UGT1A1*28 allele (n=246), the incidence of Grade 3-4 anemia was 8%. In patients homozygous for the wild-type allele (n=261), the incidence of Grade 3-4 anemia was 10%.
Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on severity of the observed adverse reactions in patients with evidence of acute early- onset or unusually severe adverse reactions, which may indicate UGT1A1 reduced function [see Dosage and Administration (2.3)].
6 Adverse Reactions
Additions and/or revisions to bulleted line listing:
Hypersensitivity and Infusion-Related Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
… The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY as a single agent in 660 patients from two studies, IMMU-132-01 and IMMU-132-05 which included 366 patients with mTNBC who had received prior systemic chemotherapy for advanced disease. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 660 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 51 months). In this pooled safety population, the most common (> 25%) adverse reactions were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite and abdominal pain.
ASCENT Study
The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label trial (ASCENT) in patients with mTNBC who had previously received a taxane and at least two prior therapies. Patients were randomized (1:1) to receive either TRODELVY (n=258) or single agent chemotherapy (n=224) and were treated until disease progression or unacceptable toxicity [see Clinical Studies (14)]. For patients treated with TRODELVY, the median duration of treatment was 4.4 months (range: 0 to 23 months).
Serious adverse reactions occurred in 27% of patients receiving TRODELVY. Serious adverse reactions in > 1% of patients receiving TRODELVY included neutropenia (7%), diarrhea (4%), and pneumonia (3%). Fatal adverse reactions occurred in 1.2% of patients who received TRODELVY, including respiratory failure (0.8%) and pneumonia (0.4%).
TRODELVY was permanently discontinued for adverse reactions in 5% of patients. Adverse reactions leading to permanent discontinuation in greater than or equal to 1 % of patients who received TRODELVY were pneumonia (1%) and fatigue (1%).
Adverse reactions leading to a treatment interruption of TRODELVY occurred in 63% of patients. The most frequent (greater than or equal to 5%) adverse reactions leading to a treatment interruption were neutropenia (47%), diarrhea (5%), respiratory infection (5%), and leukopenia (5%).
Adverse reactions leading to a dose reduction of TRODELVY occurred in 22% of patients. The most frequent (>4%) adverse reactions leading to a dose reduction were neutropenia (11%) and diarrhea (5%).
Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY.
Tables 2 and 3 summarize adverse reactions and select laboratory abnormalities, respectively, in the ASCENT study.
Table 2: Adverse Reactions in greater than or equal to 10% of Patients with mTNBC in ASCENT
Table 3: Select Laboratory Abnormalities in >10% of Patients with mTNBC in ASCENT
Study IMMU-132-01
The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-01) in patients with mTNBC and other malignancies, which included 108 patients with mTNBC who had received at least two prior treatments for metastatic disease [see Clinical Studies (14)]. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses up to 10 mg/kg until disease progression or unacceptable toxicity. The median treatment duration in these 108 patients was 5.1 months (range: 0-51 months).
… Serious adverse reactions occurred in 31% of the patients. Serious adverse reactions in >1% of patients receiving TRODELVY included febrile neutropenia (6%) vomiting (5%), nausea (3%), dyspnea (3%), diarrhea (4%), anemia (2%), pleural effusion, neutropenia, pneumonia, dehydration (each 2%).
TRODELVY was permanently discontinued for adverse reactions in 2% of patients. Adverse reactions leading to permanent discontinuation were anaphylaxis, anorexia/fatigue, headache (each 0.9%). Forty- five percent (45%) of patients experienced an adverse reaction …
8 Use in Specific Populations
8.6 Hepatic ImpairmentAdditions and/or revisions underlined:
… The exposure of TRODELVY in patients with mild hepatic impairment (bilirubin less than or equal to ULN and AST >ULN, or bilirubin >1.0 to 1.5 ULN and AST of any level; n=59 was similar to patients with normal hepatic function (bilirubin or AST<ULN; n=191) …
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONAdditions and/or revisions underlined:
What is TRODELVY?
TRODELVY is a prescription medicine used to treat adults with breast cancer that is:
that has spread to other parts of the body or cannot be removed by surgery, and …
04/07/2021 (SUPPL-5)
5 Warnings and Precautions
5.1 Neutropenia
Additions and/or revisions underlined:
TRODELVY can cause severe or life-threatening neutropenia that may result in death. Neutropenia occurred in 62% of patients treated with TRODELVY, leading to permanent discontinuation of TRODELVY in 0.5% of patients. Grade 3-4 neutropenia occurred in 47% of patients. Febrile neutropenia occurred in 6% of patients.
Withhold TRODELVY for absolute neutrophil count below 1500/mm3 on Day 1 …
5.2 Diarrhea
Additions and/or revisions underlined:
TRODELVY can cause severe diarrhea. Diarrhea occurred in 64% of all patients treated with TRODELVY. Grade 3 diarrhea occurred in 12% of all patients treated with TRODELVY. Neutropenic colitis occurred in 0.5% of patients.
Withhold TRODELVY for Grade 3-4 diarrhea at the time …
Additions and/or revisions underlined:
5.3 Hypersensitivity and Infusion-Related Reactions
Hypersensitivity reactions within 24 hours of dosing occurred in 37% of patients treated with TRODELVY. Grade 3-4 hypersensitivity occurred in 1% of patients treated with TRODELVY. The incidence of hypersensitivity reactions leading to permanent discontinuation of TRODELVY was 0.4%.
Pre-infusion medication for patients receiving TRODELVY is recommended. Observe patients closely for hypersensitivity and infusion-related reactions during each TRODELVY infusion …
5.4 Nausea and Vomiting
Additions and/or revisions underlined:
TRODELVY is emetogenic. Nausea occurred in 67% of all patients treated with TRODELVY. Grade 3-4 nausea occurred in 5% of patients.
Vomiting occurred 40% of all patients treated with TRODELVY. Grade 3-4 vomiting occurred in 3% of these patients.
Additions and/or revisions underlined:
5.5 Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity
Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia; and may be at increased risk for other adverse reactions when treated with TRODELVY.
The incidence of neutropenia and anemia was analyzed in 577 patients who received TRODELVY and had UGT1A1 genotype results. In patients homozygous for the UGT1A1 *28 allele (n=70), the incidence of Grade 3-4 neutropenia was 69%. In patients heterozygous for the UGT1A1*28 allele (n=246), the incidence of Grade 3-4 neutropenia was 48%. In patients homozygous for the wild-type allele (n=261), the incidence of Grade 3-4 neutropenia was 46% [see Clinical Pharmacology (12.5)]. In patients homozygous for the UGT1A1 *28 allele (n=70), the incidence of Grade 3-4 anemia was 24%. In patients heterozygous for the UGT1A1*28 allele (n=246), the incidence of Grade 3-4 anemia was 8%. In patients homozygous for the wild-type allele (n=261), the incidence of Grade 3-4 anemia was 10%.
Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue TRODELVY based on severity of the observed adverse reactions in patients with evidence of acute early- onset or unusually severe adverse reactions, which may indicate UGT1A1 reduced function [see Dosage and Administration (2.3)].
6 Adverse Reactions
Additions and/or revisions to bulleted line listing:
Hypersensitivity and Infusion-Related Reactions
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
… The pooled safety population described in the Warnings and Precautions section reflect exposure to TRODELVY as a single agent in 660 patients from two studies, IMMU-132-01 and IMMU-132-05 which included 366 patients with mTNBC who had received prior systemic chemotherapy for advanced disease. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses of 10 mg/kg until disease progression or unacceptable toxicity. Among the 660 patients treated with TRODELVY, the median duration of treatment was 4.1 months (range: 0 to 51 months). In this pooled safety population, the most common (> 25%) adverse reactions were nausea, neutropenia, diarrhea, fatigue, alopecia, anemia, vomiting, constipation, rash, decreased appetite and abdominal pain.
ASCENT Study
The safety of TRODELVY was evaluated in a randomized, active-controlled, open-label trial (ASCENT) in patients with mTNBC who had previously received a taxane and at least two prior therapies. Patients were randomized (1:1) to receive either TRODELVY (n=258) or single agent chemotherapy (n=224) and were treated until disease progression or unacceptable toxicity [see Clinical Studies (14)]. For patients treated with TRODELVY, the median duration of treatment was 4.4 months (range: 0 to 23 months).
Serious adverse reactions occurred in 27% of patients receiving TRODELVY. Serious adverse reactions in > 1% of patients receiving TRODELVY included neutropenia (7%), diarrhea (4%), and pneumonia (3%). Fatal adverse reactions occurred in 1.2% of patients who received TRODELVY, including respiratory failure (0.8%) and pneumonia (0.4%).
TRODELVY was permanently discontinued for adverse reactions in 5% of patients. Adverse reactions leading to permanent discontinuation in greater than or equal to 1 % of patients who received TRODELVY were pneumonia (1%) and fatigue (1%).
Adverse reactions leading to a treatment interruption of TRODELVY occurred in 63% of patients. The most frequent (greater than or equal to 5%) adverse reactions leading to a treatment interruption were neutropenia (47%), diarrhea (5%), respiratory infection (5%), and leukopenia (5%).
Adverse reactions leading to a dose reduction of TRODELVY occurred in 22% of patients. The most frequent (>4%) adverse reactions leading to a dose reduction were neutropenia (11%) and diarrhea (5%).
Granulocyte-colony stimulating factor (G-CSF) was used in 44% of patients who received TRODELVY.
Tables 2 and 3 summarize adverse reactions and select laboratory abnormalities, respectively, in the ASCENT study.
Table 2: Adverse Reactions in greater than or equal to 10% of Patients with mTNBC in ASCENT
Table 3: Select Laboratory Abnormalities in >10% of Patients with mTNBC in ASCENT
Study IMMU-132-01
The safety of TRODELVY was evaluated in a single-arm, open-label study (IMMU-132-01) in patients with mTNBC and other malignancies, which included 108 patients with mTNBC who had received at least two prior treatments for metastatic disease [see Clinical Studies (14)]. TRODELVY was administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles at doses up to 10 mg/kg until disease progression or unacceptable toxicity. The median treatment duration in these 108 patients was 5.1 months (range: 0-51 months).
… Serious adverse reactions occurred in 31% of the patients. Serious adverse reactions in >1% of patients receiving TRODELVY included febrile neutropenia (6%) vomiting (5%), nausea (3%), dyspnea (3%), diarrhea (4%), anemia (2%), pleural effusion, neutropenia, pneumonia, dehydration (each 2%).
TRODELVY was permanently discontinued for adverse reactions in 2% of patients. Adverse reactions leading to permanent discontinuation were anaphylaxis, anorexia/fatigue, headache (each 0.9%). Forty- five percent (45%) of patients experienced an adverse reaction …
8 Use in Specific Populations
8.6 Hepatic ImpairmentAdditions and/or revisions underlined:
… The exposure of TRODELVY in patients with mild hepatic impairment (bilirubin less than or equal to ULN and AST >ULN, or bilirubin >1.0 to 1.5 ULN and AST of any level; n=59 was similar to patients with normal hepatic function (bilirubin or AST<ULN; n=191) …
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATIONAdditions and/or revisions underlined:
What is TRODELVY?
TRODELVY is a prescription medicine used to treat adults with breast cancer that is:
that has spread to other parts of the body or cannot be removed by surgery, and …