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.

BRENZAVVY (NDA-214373)

(BEXAGLIFLOZIN)

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

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06/03/2026 (SUPPL-2)

Approved Drug Label (PDF)

5 Warnings and Precautions

Additions and/or revisions underlined:

5.2 Lower Limb Amputation

Additions and/or revisions underlined:

. . .

Counsel patients about the importance of routine preventative foot care. Monitor patients receiving BRENZAVVY for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.

5.4 Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections

Additions and/or revisions underlined:

BRENZAVVY increases urinary glucose excretion [see Clinical Pharmacology (12.2)] and increases the risk of genitourinary infections including urinary tract infections and genital mycotic infections in both male and female patients [see Adverse Reactions (6.1)].

Serious genitourinary infections, including urosepsis, pyelonephritis, and necrotizing fasciitis of the perineum (Fournier’s gangrene, a rare life-threatening infection requiring urgent surgical intervention), have occurred in patients receiving SGLT2 inhibitors. Cases have required hospitalization. In patients with Fournier’s gangrene, serious outcomes have included multiple surgeries and death.

Patients with a history of genitourinary infections are more likely to develop genitourinary infections when using BRENZAVVY. Monitor patients for signs and symptoms of genitourinary infections and treat promptly, if indicated.

Immediately evaluate patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, for necrotizing fasciitis. If suspected, discontinue BRENZAVVY and promptly institute appropriate medical and /or surgical intervention.

6 Adverse Reactions

Additions and/or revisions underlined:

The following important adverse reactions are described below and elsewhere in the labeling:

. . .

Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections [see Warnings and Precautions (5.4)]

. . .

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 BRENZAVVY?

BRENZAVVY can cause serious side effects, including:

. . .

Genital and urinary tract infections. BRENZAVVY can cause serious infections in your genital area or urinary tract that could require hospitalization. A rare but serious bacterial infection called necrotizing fasciitis can cause damage to the tissue under the skin in the area between and around the anus and genitals (perineum). This infection may require hospitalization, multiple surgeries, and could lead to death. Seek medical attention immediately if you have a fever or you are feeling very weak, tired or uncomfortable (malaise), and you develop any of the following symptoms in the area between and around your anus and genitals:

pain or tenderness
swelling
redness of skin (erythema)

Also tell your healthcare provider if you have any of these signs or symptoms of urinary tract infections or yeast infections:

Urinary tract infection:

burning feeling when you urinate
need to urinate often or right away
pain in the lower part of your stomach (pelvis)
blood in your urine

You may also have a fever, back pain, nausea, or vomiting.

Vaginal yeast infection:

vaginal odor
white or yellowish vaginal discharge (may be lumpy or look like cottage cheese)
vaginal itching

Yeast infection of the skin around the penis (balanitis or balanoposthitis); If you are uncircumcised, swelling may make it difficult to pull back the skin around the tip of your penis. Other symptoms include:

redness, itching, or swelling of the penis
rash on the penis
bad smelling discharge from the penis
pain in the skin around the penis

Talk to your healthcare provider about what to do if you get symptoms of a yeast infection. They may suggest you use an over-the-counter antifungal medicine. Contact your healthcare provider right away if your symptoms do not improve after using an over-the-counter antifungal medicine.

. . .

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

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

. . .

Genitourinary Infections, including Urosepsis, Pyelonephritis, Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene), and Genital Mycotic Infections

Counsel patients that genitourinary infections may occur when taking BRENZAVVY and may become serious. Educate patients on the symptoms and advise them to seek medical advice if symptoms occur. Specifically, advise patients to promptly seek medical attention if they develop pain or tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever above 100.4°F or malaise. [see Warnings and Precautions (5.4)].

. . .

09/12/2023 (SUPPL-1)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.1 Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Subsection title revised

Additions and revisions underlined:

In patients with type 1 diabetes mellitus, BRENZAVVY significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond background rate. In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium glucose transporter 2 (SGLT2) inhibitors compared to patients who received placebo. BRENZAVVY is not indicated for glycemic control in patients with type 1 diabetes mellitus.

Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors.

Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.

Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing BRENZAVVY [see Clinical Pharmacology (12.2)]; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.

Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation. Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. If ketoacidosis is suspected, discontinue BRENZAVVY, promptly evaluate, and treat ketoacidosis, if confirmed. Monitor patients for resolution of ketoacidosis before restarting BRENZAVVY.

Withhold BRENZAVVY, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. Resume BRENZAVVY when the patient is clinically stable and has resumed oral intake [see Dosage and Administration (2.3)].

Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue BRENZAVVY and seek medical attention immediately if signs and symptoms occur.

6 Adverse Reactions

Additions and revisions underlined:

The following important adverse reactions are described below and elsewhere in the labeling:

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions (5.1)]

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

Medication Guide

Extensive changes; please refer to label

PATIENT COUNSELING INFORMATION

Additions and revisions underlined:

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

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Inform patients that BRENZAVVY can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are risk factors.

Educate all patients on precipitating factors (such as insulin dose reduction or missed insulin doses, infection, reduced caloric intake, ketogenic diet, surgery, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis.

Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue BRENZAVVY and seek medical attention immediately [see Warnings and Precautions (5.1)].

Educate patients or caregivers on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.5)].