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.

KEYTRUDA QLEX (BLA-761467)

(PEMBROLIZUMAB;BERAHYALURONIDASE ALFA-PMPH)

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

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06/24/2026 (SUPPL-4)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

in combination with belzutifan (reported in 225%): decreased hemoglobin, increased alanine aminotransferase, fatigue, increased aspartate aminotransferase, decreased lymphocytes, and increased alkaline phosphatase.
…

in combination with sacituzumab govitecan-hziy: anemia, neutropenia, diarrhea, nausea, fatigue, alopecia, constipation, rash, vomiting, headache and abdominal pain.

…

Locally Advanced or Metastatic TNBC

The safety of intravenous pembrolizumab in combination with sacituzumab govitecan-hziy was evaluated in KEYNOTE-D19 in 221 patients with unresectable locally advanced or metastatic TNBC who had not been previously treated with systemic therapy for advanced disease and whose tumors express PD-L1, and who had received at least one dose of intravenous pembrolizumab 200 mg every 3 weeks in combination with sacituzmab govitecan-hziy [see Clinical Studies (14.20)]. The median duration of exposure to intravenous pembrolizumab was 8.5 months (range: 1 day to 26.8 months).

Fatal adverse reactions occurred in 3.2% of patients receiving intravenous pembrolizumab in combination with sacituzumab govitecan-hziy, including death due to unknown cause (0.9%), and completed suicide, neutropenic sepsis, sepsis, pneumonia, and pulmonary embolism (0.5% each).

Serious adverse reactions occurred in 38% of patients receiving intravenous pembrolizumab in combination with sacituzumab govitecan-hziy. Serious adverse reactions in 22% of patients were febrile neutropenia (7%), neutropenia (6%), diarrhea (5%), fatigue and pneumonia (2.3% each).

Permanent discontinuation of intravenous pembrolizumab due to an adverse reaction occurred in 9% of patients. The adverse reactions which resulted in permanent discontinuation of intravenous pembrolizumab most commonly (21%) were pneumonitis and rash (1.4% each).

Dosage interruptions of intravenous pembrolizumab due to adverse reactions occurred in 67% of patients. Adverse reactions which required dosage interruption in 22% of patients included neutropenia (36%), diarrhea (7%), upper respiratory tract infection (4.5%), anemia (4.1%), fatigue (4.1%), increased

ALT (3.2%), cough (2.7%), leukopenia (2.7%), nausea (2.7%), pyrexia (2.7%), rash (2.7%), vomiting(2.7%), and COVID-19 (2.3%).

The most common (225%) adverse reactions, including laboratory abnormalities, occurring in patients treated with intravenous pembrolizumab in combination with sacituzumab govitecan-hziy were decreased neutrophil count and decreased hemoglobin (86% each), decreased leukocyte count (84%), diarrhea (72%), nausea (68%), decreased lymphocyte count (61%), fatigue (58%), alopecia (52%) increased alkaline phosphatase and increased glucose (50% each), increased alanine aminotransferase (47%), constipation (41%), increased aspartate aminotransferase (40%), rash (37%), decreased potassium (35%), increased lactate dehydrogenase (34%), vomiting (29%), abdominal pain, headache, and increased eosinophils, (26% each), and decreased albumin (25%).

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

…

Of 221 adult patients with TNBC who were treated with intravenous pembrolizumab in

combination with sacituzumab govitecan-hziy in KEYNOTE-D19, 26% of patients were 65 years

and over and 5% were 75 years and older. No overall differences in effectiveness were observed

between elderly patients and younger patients. There was a higher rate of serious adverse

reactions in patients aged 65 years or older (48%) compared with younger adult patients (34%).

…

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

MEDICATION GUIDE

Additions and/or revisions underlined:

What is KEYTRUDA QLEX?

KEYTRUDA QLEX is a prescription medicine used to treat:

…

a kind of cancer called triple-negative breast cancer (TNBC).

KEYTRUDA QLEX may be used with chemotherapy medicines as treatment before surgery and then continued alone after surgery when you:
- have early-stage breast cancer, and
- are at high risk of your breast cancer coming back.
KEYTRUDA QLEX may be used with the medicine sacituzumab govitecan-hziy in adults as your first treatment when your breast cancer:
- cannot be removed by surgery, has spread to nearby tissues (locally advanced) or other parts of the body (metastatic), and
- tests positive for “PD-L1”.
KEYTRUDA QLEX may be used with chemotherapy medicines when your breast cancer:

has returned to nearby tissues and cannot be removed by surgery or has spread, and
tests positive for “PD-L1”.

…

The most common side effects seen with pembrolizumab given into the vein (intravenous pembrolizumab), which may happen with KEYTRUDA QLEX, are shown below:

…

when used with sacituzumab govitecan-hziy include: low red blood cell count, low white blood count, diarrhea, nausea, feeling tired or weak, hair loss, constipation, rash, vomiting, headache, and abdominal pain.

…

06/12/2026 (SUPPL-9)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label for complete information

05/12/2026 (SUPPL-7)

Approved Drug Label (PDF)

5 Warnings and Precautions

WARNINGS AND PRECAUTIONS

5.1 Severe and Fatal Immune-Mediated Adverse Reactions

Additions and/or revisions underlined:

. . .

Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reporting as the co-occurrence of either two or all three adverse reactions.

02/10/2026 (SUPPL-2)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

The most common adverse reactions (greater than or equal to 20%) in patients who received intravenous pembrolizumab were:

…

in combination with chemotherapy and bevacizumab: peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, decreased appetite pyrexia, epistaxis, decreased white blood cell count, and stomatitis.
…
Ovarian Cancer
The safety of intravenous pembrolizumab in combination with paclitaxel with or without bevacizumab was evaluated in 463 patients with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS greater than or equal to1) enrolled in KEYNOTE-B96 [see Clinical Studies (14.20)]. Among patients who received intravenous pembrolizumab, the median duration of exposure was 7.4 months (range: 1 day to 35.9 months).
Serious adverse reactions occurred in 54% of patients receiving intravenous pembrolizumab and paclitaxel with or without bevacizumab. Serious adverse reactions in greater than or equal to 2% of patients were pneumonia (4.3%), urinary tract infection (3.9%), adrenal insufficiency (3%), hyponatremia (3%), COVID-19 (2.6%),decreased neutrophil count (2.6%), pulmonary embolism (2.6%), abdominal pain (2.1%), anemia (2.1%), colitis (2.1%), diarrhea (2.1%), febrile neutropenia (2.1%), pyrexia (2.1%) and vomiting (2.1%).
Fatal adverse reactions occurred in 3.9% of patients receiving intravenous pembrolizumab and paclitaxel with or without bevacizumab, including assisted suicide (0.9%), death (0.4%), intestinal perforation (0.4%), sepsis (0.4%), COVID-19 (0.4%), cardio-respiratory arrest (0.4%), colitis (0.4%), and embolic
stroke (0.4%).
Intravenous pembrolizumab was permanently discontinued for adverse reactions in 16% of patients. The most common adverse reactions resulting in permanent discontinuation of intravenous pembrolizumab (?1%) were colitis (1.3%) and increased alanine aminotransferase (1.3%). Adverse reactions leading to the interruption of intravenous pembrolizumab occurred in 44% of patients. The most common adverse reactions leading to interruption of intravenous pembrolizumab in greater than or equal to 2% were urinary tract infection (3.9%), adrenal insufficiency (2.6%), pyrexia (2.6%), pneumonitis (2.6%), upper respiratory tract infection (2.6%),
neutropenia (2.1%), diarrhea (2.1%) and COVID-19 (2.1%).
The most common (greater than or equal to 20%) adverse reactions for patients treated with intravenous pembrolizumab in combination with paclitaxel with or without bevacizumab were: diarrhea (45%), fatigue (43%), nausea (41%), alopecia (38%), peripheral neuropathy (38%), epistaxis (31%), urinary tract infection (27%),
constipation (25%), abdominal pain (24%), decreased appetite (24%), vomiting (24%), hypothyroidism
(21%), cough (20%), hypertension (20%), and rash (20%). The most common (greater than or equal to 20%) laboratory abnormalities worsening from baseline were: anemia (85%), leukopenia (82%), decreased neutrophil count (71%), lymphopenia (60%), hypoalbuminemia (50%), hyponatremia (53%), hypomagnesemia
(45%), increased aspartate aminotransferase (43%), increased alanine aminotransferase (40%), hypocalcemia(40%), increased alkaline phosphatase (31%), increased creatinine (29%), hypokalemia (27%) and neutropenia (21%).
For patients treated with intravenous pembrolizumab in combination with paclitaxel and bevacizumab (N=169), decreased white blood cell count (27%), stomatitis (22%) and pyrexia (21%) were also reported as adverse reactions.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

…

Of 643 adult patients with ovarian cancer who were treated with intravenous pembrolizumab in combination with paclitaxel with or without bevacizumab in KEYNOTE-B96, 236 (37%) were 65 years and over and 58 (9%) were 75 years and over.
…

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is KEYTRUDA QLEX?

KEYTRUDA QLEX is a prescription medicine used to treat:

…

a kind of cancer called ovarian cancer.
- KEYTRUDA QLEX may be used in adults with the chemotherapy medicine paclitaxel, with or without the medicine bevacizumab, when your ovarian fallopian tube, or primary peritoneal cancer:
  - is resistant to chemotherapy that contains platinum and
  - tests positive for “PD-L1”, and
  - you have received 1or 2 types of treatment.
    
    …

11/21/2025 (SUPPL-1)

Approved Drug Label (PDF)

6 Adverse Reactions

Extensive changes; please refer to label for complete information.

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

Of the 251 patients treated with KEYTRUDA QLEX in combination with platinum doublet chemotherapy in Study MK-3745A-D77, 53% were 65 years and older and 16% were 75 years and older. No overall differences in safety or effectiveness of KEYTRUDA QLEX have been observed between patients aged 65 years or older and younger adult patients.

The safety of KEYTRUDA QLEX as monotherapy or in combination with other antineoplastic drugs for its approved indications [see Indications and Usage (1)] has been established in adequate and well- controlled studies of intravenous pembrolizumab as a single agent and in combination with other antineoplastic drugs. Below is a description of geriatric use information from the intravenous pembrolizumab studies.

. . .

Of the 167 patients with MIBC treated with intravenous pembrolizumab in combination with enfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years or older. Patients 75 years of age or older treated with intravenous pembrolizumab in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 12% in patients 75 years or older.

. . .

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

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

What is KEYTRUDA QLEX?

KEYTRUDA QLEX is a prescription medicine used to treat:

. . .

a kind of cancer called head and neck squamous cell cancer (HNSCC).

KEYTRUDA QLEX may be used alone in adults with HNSCC before surgery:

when your cancer can be removed by surgery, has spread to nearby tissues, and your tumor tests positive for “PD-L1”, and
then continued in combination with radiation with or without cisplatin after surgery, and
then continued alone to help prevent your head and neck cancer from coming back.

. . .

a kind of bladder and urinary tract cancer called urothelial cancer.

KEYTRUDA QLEX may be used with the medicine enfortumab vedotin in adults when your bladder or urinary tract cancer has spread or cannot be removed by surgery (locally advanced or metastatic urothelial cancer).
KEYTRUDA QLEX may be used alone when your bladder or urinary tract cancer:

has spread or cannot be removed by surgery (locally advanced or metastatic urothelial cancer), and
you are not able to receive chemotherapy that contains platinum (medicines called either cisplatin or carboplatin), or
you have received chemotherapy that contains platinum, and it did not work or is no longer working.

KEYTRUDA QLEX may be used with the medicine enfortumab vedotin in adults before and after the surgical removal of your bladder when:

your bladder cancer has spread into the muscle layer of the bladder (muscle invasive bladder cancer [MIBC]) but not to other parts of the body, and
you are not able to receive chemotherapy that contains cisplatin.

. . .

What are the possible side effects of KEYTRUDA QLEX?

KEYTRUDA QLEX can cause serious side effects. See “What is the most important information I should know about KEYTRUDA QLEX?”

. . .

when used with certain chemotherapy or chemotherapy with radiation therapy medicines include: feeling tired or weak, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, trouble breathing, fever, hair loss, inflammation of the nerves that may cause pain, weakness, and paralysis in the arms and legs, swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, mouth sores, headache, weight loss, stomach-area (abdominal) pain, joint and muscle pain, trouble sleeping, blisters or rash on the palms of your hands and soles of your feet, urinary tract infection, low levels of thyroid hormone, skin irritation in the radiation area, trouble swallowing, and dry mouth.

. . .