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.

EPKINLY (BLA-761324)

(EPCORITAMAB-BYSP)

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

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06/17/2026 (SUPPL-11)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Infections

Additions and/or revisions underlined:

…

Consider monitoring immunoglobulin levels during treatment and administration of immunoglobulin treatment as appropriate.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Other Clinical Trials Experience

The following adverse reactions have been reported following administration of epcoritamab-bysp: hypogammaglobulinemia.

03/27/2026 (SUPPL-10)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Cytokine Release Syndrome

Additions and/or revisions underlined:

EPKINLY can cause CRS, including serious or fatal reactions [see Adverse Reactions (6.1)]. Relapsed or Refractory Large B-cell Lymphoma

CRS occurred in 51% (80/157) of patients with LBCL receiving EPKINLY at the recommended dosage schedule in EPCORE NHL-1, with Grade 1 CRS occurring in 37%, Grade 2 in 17%, and Grade 3 in 2.5% of patients. Recurrent CRS occurred in 31% of these patients. Most CRS events (92%) occurred during Cycle 1. In Cycle 1, CRS events occurred in 6% of patients after the 0.16 mg dose, 12% after the 0.8 mg dose, 43% after the first 48 mg dose, and 5% after the next 48 mg dose. The median time to onset of CRS from the most recent EPKINLY dose was 24 hours (range: 0 to 10 days). The median time to onset after the first 48 mg dose was 21 hours (range: 0 to 7 days).

For patients with LBCL, assess whether hospitalization or outpatient monitoring for the first 48 mg dose (Cycle 1 Day 15) is appropriate based on comorbidities or other situational factors [see Dosage and Administration (2.1)]. During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.

Relapsed or Refractory Follicular Lymphoma

…

For patients with FL, assess whether hospitalization or outpatient monitoring for the first 48 mg dose (Cycle 1 Day 22) is appropriate based on comorbidities or other situational factors [see Dosage and Administration (2.1)]. During outpatient monitoring after the first 48 mg dose, patients should remain in proximity to a healthcare facility that can assess and manage CRS.

…

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

People with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma may be hospitalized after receiving their first full dose of EPKINLY on Day 15 of Cycle 1 due to the risk of CRS and neurologic problems.

People with follicular lymphoma (FL) may be hospitalized after receiving their first full dose of EPKINLY on Day 22 of Cycle 1 due to the risk of CRS and neurologic problems.

…

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Cytokine Release Syndrome (CRS)

Inform patients of the risk of CRS, and to immediately contact their healthcare provider should signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, tachycardia, headache, and dyspnea) occur at any time. Advise patients with DLBCL or high-grade B-cell lymphoma that they may be hospitalized after administration of the Cycle 1 Day 15 dosage of 48 mg and patients with FL after administration of the Cycle 1 Day 22 dosage of 48 mg. Patients who receive Cycle 1 Day 15 and patients who receive Cycle 1 Day 22 first full dosage of 48 mg at an outpatient facility should remain in proximity of a healthcare facility that can assess and manage CRS afterwards. Advise all patients who experience symptoms that impair consciousness not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve [see Warnings and Precautions (5.1)].

…

11/18/2025 (SUPPL-9)

Approved Drug Label (PDF)

Boxed Warning

WARNING: CYTOKINE RELEASE SYNDROME AND IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including serious or fatal reactions, can occur in patients receiving EPKINLY. Initiate treatment with the EPKINLY step-up dosage schedule to reduce the incidence and severity of CRS. Withhold EPKINLY until CRS resolves or permanently discontinue based on severity [see Dosage and Administration (2.1, 2.2, 2.6) and Warnings and Precautions (5.1)].

. . .

5 Warnings and Precautions

Extensive changes; please refer to label for complete information.

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:

. . .

In patients with relapsed or refractory FL who received EPKINLY in combination with lenalidomide and rituximab in EPCORE FL-1, 88 (36%) were 65 years of age or older and 20 (8%) were 75 years of age or older. No clinically meaningful differences in safety or efficacy were observed between patients who were 65 years of age and older compared with younger patients.

. . .

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

MEDICATION GUIDE

Additions and/or revisions underlined:

What is the most important information I should know about EPKINLY? EPKINLY can cause serious side effects, including:

Cytokine Release Syndrome (CRS). CRS is common during treatment with EPKINLY and can also be serious or lead to death.

. . .

People with follicular lymphoma (FL) may need to be hospitalized after receiving their first full dose of EPKINLY on Day 22 of Cycle 1 due to the risk of CRS.

. . .

What is EPKINLY?

EPKINLY is a prescription medicine used to treat adults with:

certain types of DLBCL or high-grade B-cell lymphoma that has come back (relapsed) or that did not respond (refractory), after 2 or more treatments.
follicular lymphoma that has come back or that did not respond to previous treatment, together with lenalidomide and rituximab
follicular lymphoma that has come back or that did not respond after 2 or more treatments.

It is not known if EPKINLY is safe and effective in children.

. . .

How will I receive EPKINLY?

EPKINLY will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in the lower part of your stomach-area (abdomen) or thigh.
Your EPKINLY treatment schedule is divided into cycles that are usually 28 days (4 weeks) long.
Your healthcare provider will decide how many treatment cycles you will receive and how often you will receive EPKINLY in each cycle.
See “What is the most important information I should know about EPKINLY?” for more information about how you will receive EPKINLY.

. . .

What are the possible side effects of EPKINLY? EPKINLY can cause serious side effects, including:

. . .

Low blood cell counts. EPKINLY can cause low blood cell counts which can be serious or severe. Your healthcare provider will check your blood cell counts during treatment with EPKINLY. EPKINLY may cause the following low blood cell counts:

low white blood cell counts (neutropenia and lymphopenia). Low white blood cells can increase your risk for infection.
low red blood cell counts (anemia). Low red blood cells can cause tiredness and shortness of breath.
low platelet counts (thrombocytopenia). Low platelet counts can cause bruising or bleeding problems.

Your healthcare provider may temporarily stop or completely stop treatment with EPKINLY if you develop certain side effects.

The most common side effects of EPKINLY when used alone in DLBCL or high-grade B-cell lymphoma or FL include:

. . .

The most common severe abnormal laboratory test results with EPKINLY when used alone in DLBCL or high-grade B-cell lymphoma or FL include: decreased white blood cells, decreased red blood cells, and decreased platelets.

The most common side effects of EPKINLY when used together with lenalidomide and rituximab in follicular lymphoma include:

rash
constipation
pneumonia
upper respiratory tract infections
diarrhea
COVID-19
tiredness
CRS
Fever
injection site reactions

The most common severe abnormal laboratory test results with EPKINLY when used together with lenalidomide and rituximab in follicular lymphoma include: decreased white blood cells and decreased platelets.

. . .

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

. . .

Cytokine Release Syndrome (CRS)

Inform patients of the risk of CRS, and to immediately contact their healthcare provider should signs and symptoms associated with CRS (e.g., pyrexia, hypotension, hypoxia, chills, tachycardia, headache, and dyspnea) occur at any time. Advise patients with DLBCL or high-grade B-cell lymphoma that they should be hospitalized for 24 hours after administration of the Cycle 1 Day 15 dosage of 48 mg. Advise patients with FL that they may be hospitalized after administration of the Cycle 1 Day 22 dosage of 48 mg. Patients who receive Cycle 1 Day 22 dosage of 48 mg at an outpatient facility should remain in proximity of a healthcare facility that can assess and manage CRS afterwards. Advise all patients who experience symptoms that impair consciousness not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve [see Warnings and Precautions (5.1)].

. . .

09/11/2025 (SUPPL-8)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.3 Infections

Additions and/or revisions underlined:

. . .

Progressive multifocal leukoencephalopathy (PML), including fatal cases, has occurred in patients treated with EPKINLY. Across a broader clinical trial population, PML was reported in 0.4% (11/3072) of patients, including in the first-line treatment setting. Of the 11 cases of PML, six resulted in fatal outcomes and one was unresolved at the time of death.

. . .

6 Adverse Reactions

Newly added subsection:

6.2 Postmarketing Experience

The following adverse reaction has been identified during post-approval use of EPKINLY. 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.

Immune system disorders: Hemophagocytic Lymphohistiocytosis (HLH)

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

MEDICATION GUIDE

Additions and/or revisions underlined:

. . .

What are the possible side effects of EPKINLY? EPKINLY can cause serious side effects, including:

See “What is the most important information I should know about EPKINLY?”
Infections. EPKINLY can cause serious infections that may lead to death. Your healthcare provider will check you for signs and symptoms of infection before and during treatment with EPKINLY. Your healthcare provider should prescribe medicines before you start treatment to help prevent infection and treat you as needed if you develop an infection during treatment with EPKINLY. Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with EPKINLY, including:

. . .

confusion

. . .