Drug Safety-related Labeling Changes (SrLC)

Get Email Alerts | 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.

ZEPBOUND (NDA-217806)

(TIRZEPATIDE)

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

Download Data

Expand all

12/20/2024 (SUPPL-13)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Severe Gastrointestinal Adverse Reactions

Additions and/or revisions underlined:

… Similar rates of severe gastrointestinal adverse reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND clinical trials for OSA.

…

5.4 Acute Gallbladder Disease

Additions and/or revisions underlined:

…

In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), cholelithiasis was reported in 1.1% of ZEPBOUND-treated patients and 1% of placebo-treated patients, cholecystitis was reported in 0.7% of ZEPBOUND- treated patients and 0.2% of placebo-treated patients, and cholecystectomy was reported in 0.2% of ZEPBOUND-treated patients and no placebo-treated patients. Acute gallbladder events were associated with weight reduction. Similar rates of cholelithiasis were reported in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA. If cholecystitis is suspected, gallbladder diagnostic studies and appropriate clinical follow-up are indicated.

5.5 Acute Pancreatitis

Additions and/or revisions underlined:

… In a pool of two ZEPBOUND clinical trials for weight reduction (Studies 1 and 2), 0.2% of ZEPBOUND-treated patients had acute pancreatitis confirmed by adjudication (0.14 patients per 100 years of exposure) versus 0.2% of placebo-treated patients (0.15 patients per 100 years of exposure). The exposure-adjusted incidence rate for treatment-emergent adjudication-confirmed pancreatitis in the pooled clinical studies for OSA (Studies 5 and 6) was 0.84 patients per 100 years for ZEPBOUND and 0 for placebo-treated patients.

After initiation of ZEPBOUND, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue ZEPBOUND and initiate appropriate management. Continuation of ZEPBOUND after a confirmed diagnosis of pancreatitis should be individually determined in the clinical judgment of a patient’s health care provider.

5.6 Hypersensitivity Reactions

Additions and/or revisions underlined:

… In a pool of two ZEPBOUND clinical studies for weight reduction (Studies 1 and 2), 0.1% of ZEPBOUND-treated patients had severe hypersensitivity reactions compared to no placebo-treated patients. Similar rates of severe hypersensitivity reactions were observed in ZEPBOUND clinical trials for weight reduction and in ZEPBOUND trials for OSA.

…

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

…

Adverse Reactions in Patients with Obstructive Sleep Apnea

ZEPBOUND was evaluated in 2 randomized, double-blind, placebo-controlled trials (Study 5 and Study 6) that included a total of 467 adult patients with moderate to severe OSA and obesity [see Clinical Studies (14.2)]. Study 5 enrolled 234 patients who were unable or unwilling to use Positive Airway Pressure (PAP) therapy and Study 6 enrolled 235 patients who were on PAP therapy. The adverse reactions observed with ZEPBOUND 10 mg or 15 mg administered subcutaneously once weekly were similar to those reported in the two pooled placebo controlled clinical trials for weight reduction (Study 1 and Study 2).

8 Use in Specific Populations

8.5 Geriatric Use

Additions and/or revisions underlined:

…

In a pool of two fixed dose ZEPBOUND clinical studies for weight reduction (Study 1 and Study 2), 226 (9%) ZEPBOUND- treated patients were 65 years of age or older, and 13 (0.5%) ZEPBOUND-treated patients were 75 years of age or older at baseline.

…

ZEPBOUND clinical studies in OSA (Study 5 and Study 6) did not include sufficient numbers of patients age 65 years or older to determine whether they respond differently from younger adult patients. Other reported clinical experience with tirzepatide has not identified differences in responses between the elderly and younger patients.

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

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is ZEPBOUND?

ZEPBOUND is an injectable prescription medicine that may help adults with:
- obesity, or some adults with overweight who also have weight-related medical problems, to lose excess body weight and keep the weight off.
- moderate to severe obstructive sleep apnea (OSA) and obesity to improve their OSA.
  …

10/18/2024 (SUPPL-15)

Approved Drug Label (PDF)

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

Medication Guide

Additions and revisions underlined:

. . .

Before using ZEPBOUND, tell your healthcare provider about all of your medical conditions, including if you:

have or have had problems with your pancreas or kidneys.
have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
have a history of diabetic retinopathy.
are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).

. . .

How should I use ZEPBOUND?

Read the Instructions for Use that comes with ZEPBOUND.
Use ZEPBOUND exactly as your healthcare provider tells you to. A healthcare provider should show you how to prepare to inject your dose of ZEPBOUND before injecting the first time.
Use ZEPBOUND with a reduced-calorie diet and increased physical activity.

10/18/2024 (SUPPL-19)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.10 Pulmonary Aspiration During General Anesthesia or Deep Sedation

Newly added subsection:

ZEPBOUND delays gastric emptying [see Clinical Pharmacology (12.2)]. There have been rare postmarketing reports of pulmonary aspiration in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation who had residual gastric contents despite reported adherence to preoperative fasting recommendations.

Available data are insufficient to inform recommendations to mitigate the risk of pulmonary aspiration during general anesthesia or deep sedation in patients taking ZEPBOUND, including whether modifying preoperative fasting recommendations or temporarily discontinuing ZEPBOUND could reduce the incidence of retained gastric contents. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking ZEPBOUND.

6 Adverse Reactions

Additions and revisions underlined:

The following serious adverse reactions are described below or elsewhere in the prescribing information:

Risk of Thyroid C-cell Tumors [see Warnings and Precautions (5.1)]
Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.2)]
Acute Kidney Injury [see Warnings and Precautions (5.3)]
Acute Gallbladder Disease [see Warnings and Precautions (5.4)]
Acute Pancreatitis [see Warnings and Precautions (5.5)]
Hypersensitivity Reactions [see Warnings and Precautions (5.6)]
Hypoglycemia [see Warnings and Precautions (5.7)]
Diabetic Retinopathy Complications in Patients with Type 2 Diabetes Mellitus [see Warnings and Precautions (5.8)]
Suicidal Behavior and Ideation [see Warnings and Precautions (5.9)]
Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.10)]

6.2 Postmarketing Experience

Newly added information:

Pulmonary: Pulmonary aspiration has occurred in patients receiving GLP-1 receptor agonists undergoing elective surgeries or procedures requiring general anesthesia or deep sedation.

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

PATIENT COUNSELING INFORMATION

Newly added information:

Pulmonary Aspiration During General Anesthesia or Deep Sedation

Inform patients that ZEPBOUND may cause their stomach to empty more slowly which may lead to complications with anesthesia or deep sedation during planned surgeries or procedures. Instruct patients to inform healthcare providers prior to any planned surgeries or procedures if they are taking ZEPBOUND [see Warnings and Precautions (5.10)].

10/18/2024 (SUPPL-5)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.2 Severe Gastrointestinal Adverse Reactions

Subsection title revised

Additions and revisions underlined:

Use of ZEPBOUND has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6.1)]. In a pool of two ZEPBOUND clinical trials (Studies 1 and 2), severe gastrointestinal adverse reactions were reported more frequently among patients receiving ZEPBOUND (5 mg 1.7%, 10 mg 2.5%, 15 mg 3.1%) than placebo (1%).

ZEPBOUND has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and is therefore not recommended in these patients.

6 Adverse Reactions

6.1 Clinical Trials Experience

Extensive changes; please refer to label

03/28/2024 (SUPPL-3)

Approved Drug Label (PDF)

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underline:

…

Administration

Instruct patients how to prepare and administer the correct dose of ZEPBOUND and assess their ability to inject subcutaneously to ensure the proper administration of ZEPBOUND. Instruct patients using the single-dose vial to use a syringe appropriate for dose administration (e.g., a 1 mL syringe capable of measuring a 0.5 mL dose) [see Dosage and Administration (2.4)].

…