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.

OZEMPIC (NDA-209637)

(SEMAGLUTIDE)

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

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01/28/2025 (SUPPL-25)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.7 Severe Gastrointestinal Adverse Reactions

Newly added subsection:

Use of OZEMPIC has been associated with gastrointestinal adverse reactions, sometimes severe [see Adverse Reactions (6.1)]. In OZEMPIC clinical trials, severe gastrointestinal adverse reactions were reported more frequently among patients receiving OZEMPIC (0.5 mg 0.4%, 1 mg 0.8%) than placebo (0%).

OZEMPIC is not recommended in patients with severe gastroparesis.

Additions and/or revisions underlined:

5.2 Acute Pancreatitis

Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including semaglutide [see Adverse Reactions (6.1)].

After initiation of OZEMPIC, observe patients carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue OZEMPIC and initiate appropriate management.

Additions and/or revisions underlined:

5.6 Acute Kidney Injury Due to Volume Depletion

There have been postmarketing reports of acute kidney injury, in some cases requiring hemodialysis, in patients treated with semaglutide. The majority of the reported events occurred in patients who experienced gastrointestinal reactions leading to dehydration such as nausea, vomiting, or diarrhea [see Adverse Reactions(6.1)]. Monitor renal function in patients reporting adverse reactions to OZEMPIC that could lead to volume depletion, especially during dosage initiation and escalation of OZEMPIC.

6 Adverse Reactions

Additions and/or revisions underlined:

…

Acute Pancreatitis [see Warnings and Precautions (5.2)]
…
Acute Kidney Injury Due to Volume Depletion [see Warnings and Precautions (5.6)]
Severe Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.7)]
…
6.1 Clinical Trials Experience
Additions and/or revisions underlined:
…
In the FLOW trial [see Clinical Studies 14.3] in patients with type 2 diabetes mellitus and chronic kidney disease, safety data collection was limited to serious adverse events and selected predefined categories of adverse events regardless of seriousness. There were no new serious or severe adverse reactions identified in this trial.
…
Acute Pancreatitis
In glycemic control trials, acute pancreatitis was confirmed by adjudication in 7 OZEMPIC-treated patients (0.3 cases per 100 patient years) versus 3 in comparator-treated patients (0.2 cases per 100 patient years).
…
6.2 Postmarketing Experience
Additions and/or revisions underlined:
…
Hepatobiliary: cholecystitis, cholecystectomy
Neurologic: dysesthesia
…
Skin and Subcutaneous Tissue: alopecia.

8 Use in Specific Populations

8.6 Renal Impairment

No dose adjustment of OZEMPIC is recommended for patients with renal impairment. In subjects with renal impairment including kidney failure, no clinically relevant change in semaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)].

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

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

…

Acute Pancreatitis

Inform patients of the potential risk for acute pancreatitis and its symptoms: severe abdominal pain that may radiate to the back, and which may or may not be accompanied by vomiting. Instruct patients to discontinue OZEMPIC promptly and contact their physician if pancreatitis is suspected [see Warnings and Precautions (5.2)].

…

Acute Kidney Injury Due to Volume Depletion

Inform patients of the potential risk of acute kidney injury due to dehydration associated with gastrointestinal adverse reactions. Advise patients to take precautions to avoid fluid depletion. Inform patients of the signs and symptoms of acute kidney injury and instruct them to promptly report any of these signs or symptoms or persistent (or extended) nausea, vomiting, and diarrhea to their healthcare provider [see Warnings and Precautions (5.6)].

Severe Gastrointestinal Adverse Reactions

Inform patients of the potential risk of severe gastrointestinal adverse reactions. Instruct patients to contact their healthcare provider if they have severe or persistent gastrointestinal symptoms [see Warnings and Precautions (5.7)]

…

MEDICATION GUIDE

Additions and/or revisions underlined:

…

What is OZEMPIC?

OZEMPIC is an injectable prescription medicine used:

…

to reduce the risk of kidney disease worsening, kidney failure (end-stage kidney disease), and death due to cardiovascular disease in adults with type 2 diabetes mellitus and chronic kidney disease.
…
Before using OZEMPIC, tell your healthcare provider if you have any other medical conditions, including if you:

have or have had problems with your pancreas.
have a history of diabetic retinopathy.
have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).
are pregnant or plan to become pregnant. It is not known if OZEMPIC will harm your unborn baby. You should stop using OZEMPIC at least 2 months before you plan to become pregnant. Talk to your healthcare provider about the best way to control your blood sugar if you plan to become pregnant or while you are pregnant.
…
How should I use OZEMPIC?
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If you take too much OZEMPIC, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away.
…
What are the possible side effects of OZEMPIC?
OZEMPIC may cause serious side effects, including:
…

Dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away.
Severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use OZEMPIC. Tell your healthcare provider if you have stomach problems that are severe or will not go away.
…
What are the ingredients in OZEMPIC?
Active Ingredient: semaglutide
Inactive Ingredients: disodium phosphate dihydrate, propylene glycol, phenol and water for injection. Hydrochloric acid or sodium hydroxide may be added to adjust pH.

11/01/2024 (SUPPL-32)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.9 Pulmonary Aspiration During General Anesthesia or Deep Sedation

Newly added subsection:

OZEMPIC 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 OZEMPIC, including whether modifying preoperative fasting recommendations or temporarily discontinuing OZEMPIC 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 OZEMPIC.

6 Adverse Reactions

Additions and revisions underlined:

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

. . .

Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
Acute Gallbladder Disease [see Warnings and Precautions (5.8)]
Pulmonary Aspiration During General Anesthesia or Deep Sedation [see Warnings and Precautions (5.9)]

6.3 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)

Medication Guide

Additions and revisions underlined:

Before using OZEMPIC, tell your healthcare provider if you have any other medical conditions, including if you:

have or have had problems with your pancreas or kidneys.
have a history of diabetic retinopathy.
are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation).

. . .

OZEMPIC may cause serious side effects, including:

food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep

sleepiness (deep sedation). OZEMPIC may increase the chance of food getting into your lungs during surgery or

other procedures. Tell all your healthcare providers that you are taking OZEMPIC before you are scheduled to have

surgery or other procedures.

Patient Counseling Information

Newly added information:

Pulmonary Aspiration During General Anesthesia or Deep Sedation

Inform patients that OZEMPIC 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 OZEMPIC [see Warnings and Precautions (5.9)].

09/22/2023 (SUPPL-20)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

Additions and/or revisions underlined:

The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of OZEMPIC. 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.

Gastrointestinal Disorders: Ileus

Hypersensitivity: anaphylaxis, angioedema, rash, urticaria.

Hepatobiliary: cholecystitis, cholecystectomy

7 Drug Interactions

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin

Additions and/or revisions underlined:

OZEMPIC stimulates insulin release in the presence of elevated blood glucose concentrations. Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia. When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.5) and Adverse Reactions (6)].

09/22/2023 (SUPPL-21)

Approved Drug Label (PDF)

6 Adverse Reactions

6.3 Postmarketing Experience

Additions and/or revisions underlined:

7 Drug Interactions

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin

Additions and/or revisions underlined:

10/06/2022 (SUPPL-12)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

Risk Summary

Additions and/or revisions underlined:

There are limited data with semaglutide use in pregnant women to inform a drug-associated risk for adverse developmental outcomes. There are clinical considerations regarding the risks of poorly controlled diabetes in pregnancy (see Clinical Considerations). Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy. OZEMPIC should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

were observed at clinical exposure (rabbit) and ?2-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see Data).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The estimated background risk of major birth defects is 6 to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20 to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/fetal Risk

Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes during pregnancy increases the maternal risk for diabetic ketoacidosis, pre- eclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

03/28/2022 (SUPPL-9)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.8 Acute Gallbladder Disease

New subsection added

Acute events of gallbladder disease such as cholelithiasis or cholecystitis have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with OZEMPIC 0.5 mg and 1 mg, respectively. Cholelithiasis was not reported in placebo- treated patients. If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.

6 Adverse Reactions

Addition of the following to the bulleted line listing:

Acute Gallbladder Disease [see Warnings and Precautions (5.8)]
6.1 Clinical Trials Experience
Additions underlined
…
In a clinical trial with 959 patients treated with OZEMPIC 1 mg or OZEMPIC 2 mg once weekly as add-on to metformin with or without sulfonylurea treatment for 40 weeks, no new safety signals were identified.
…
In the trial with OZEMPIC 1 mg and 2 mg, gastrointestinal adverse reactions occurred more frequently among patients receiving OZEMPIC 2 mg (34.0%) vs OZEMPIC 1 mg (30.8%).
…
6.3 Postmarketing Experience
Additions underlined
…
Hepatobiliary: cholecystitis, cholecystectom

8 Use in Specific Populations

8.1 Pregnancy

Additions and/or revisions underlined

Risk Summary

…

In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal clinical exposure based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses or structural abnormalitieswere observed at clinical exposure (rabbit) and ?2-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see Data).

…

Data

Animal Data

In a combined fertility and embryofetal development study in rats, subcutaneous doses of 0.01, 0.03 and 0.09 mg/kg/day (0.06-, 0.2-, and 0.6-fold the MRHD) were administered to males for 4 weeks prior to and throughout mating and to females for 2 weeks prior to mating, and throughout organogenesis to Gestation Day 17.

…

In an embryofetal development study in pregnant rabbits, subcutaneous doses of 0.0010, 0.0025 or 0.0075 mg/kg/day (0.02-, 0.2-, and 1.2-fold the MRHD) were administered throughout organogenesis from Gestation Day 6 to 19. Pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at greater than or equal to 0.0025 mg/kg/day, at clinically relevant exposures.

In an embryofetal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.5-, 3-, and 8-fold the MRHD) were administered throughout organogenesis, from Gestation Day 16 to 50. Pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) at greater than or equal to 0.075 mg/kg twice weekly (greater than or equal to 3X human exposure).

In a pre- and postnatal development study in pregnant cynomolgus monkeys, subcutaneous doses of 0.015, 0.075, and 0.15 mg/kg twice weekly (0.3-, 2-, and 4-fold the MRHD) were administered from Gestation Day 16 to 140. Pharmacologically mediated marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with an increase in early pregnancy losses and led to delivery of slightly smaller offspring at greater than or equal to 0.075 mg/kg twice weekly (greater than or equal to 2X human exposure).

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

MEDICATION GUIDE

Additions underlined

…

Your dose of OZEMPIC and other diabetes medicines may need to change because of:

change in level of physical activity or exercise, weight gain or loss, increased stress, illness, change in diet, fever, trauma, infection, surgery or because of other medicines you take.
If you take too much OZEMPIC, call your healthcare provider or go to the nearest hospital emergency room right away.

…

What are the possible side effects of OZEMPIC?

OZEMPIC may cause serious side effects, including:

…

gallbladder problems. Gallbladder problems have happened in some people who take OZEMPIC. Tell your healthcare provider right away if you get symptoms of gallbladder problems which may include:

pain in your upper stomach (abdomen)
fever
yellowing of skin or eyes (jaundice)
clay-colored stools

…

PATIENT COUNSELING INFORMATION

Additions underlined

…

Acute Gallbladder Disease

Inform patients of the potential risk for cholelithiasis or cholecystitis. Instruct patients to contact their physician if cholelithiasis or cholecystitis is suspected for appropriate clinical follow-up [see Warnings and Precautions (5.8)].

04/12/2021 (SUPPL-8)

Approved Drug Label (PDF)

4 Contraindications

Additions underlined

…

A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in OZEMPIC. Serious hypersensitivity reactions including anaphylaxis and angioedema have been reported with OZEMPIC [see Warnings and Precautions (5.7)].

5 Warnings and Precautions

5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

Additions underlined

Patients receiving OZEMPIC in combination with an insulin secretagogue (e.g., sulfonylurea) or insulin may have an increased risk of hypoglycemia, including severe hypoglycemia [see Adverse Reactions (6.1) and Drug Interactions (7)].

The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly administered insulin secretagogue) or insulin. Inform patients using these concomitant medications of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

6 Adverse Reactions

6.3 Postmarketing Experience

New subsection added

Hypersensitivity:anaphylaxis, angioedema, rash, urticaria.

7 Drug Interactions

7.1 Concomitant Use with an Insulin Secretagogue (e.g., Sulfonylurea) or with Insulin

Additions underlined

When initiating OZEMPIC, consider reducing the dose of concomitantly administered insulin secretagogue (such as sufonylureas) or insulin to reduce the risk of hypoglycemia [see Warnings and Precautions (5.5) and Adverse Reactions (6)].

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

MEDICATION GUIDE

Additions underlined

…

What is OZEMPIC?

…

OZEMPIC is not for use in people with type 1 diabetes.

…

Do not use OZEMPIC if:

you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
you have had a serious allergic reaction to semaglutide or any of the ingredients in OZEMPIC. See the end of this Medication Guide for a complete list of ingredients in OZEMPIC. Symptoms of a serious allergic reaction include:

swelling of your face, lips, tongue or throat
problems breathing or swallowing
severe rash or itching
fainting or feeling dizzy

…

What are the possible side effects of OZEMPIC?

OZEMPIC may cause serious side effects, including:

…

serious allergic reactions. Stop using OZEMPIC and get medical help right away, if you have any symptoms of a serious allergic reaction including:
- swelling of your face, lips, tongue or throat
- problems breathing or swallowing
- severe rash or itching
- fainting or feeling dizzy
- very rapid heartbeat.
  …

PATIENT COUNSELING INFORMATION

Additions underlined

…

Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin

Inform patients that the risk of hypoglycemia is increased when OZEMPIC is used with an insulin secretagogue (such as a sulfonylurea) or insulin. Educate patients on the signs and symptoms of hypoglycemia [see Warnings and Precautions (5.5)].

…

Hypersensitivity Reactions

Inform patients that serious hypersensitivity reactions have been reported during postmarketing use of OZEMPIC. Advise patients on the symptoms of hypersensitivity reactions and instruct them to stop taking OZEMPIC and seek medical advice promptly if such symptoms occur [see Warnings and Precautions (5.7)].

…

01/16/2020 (SUPPL-3)

Approved Drug Label (PDF)

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

MEDICATION GUIDE

(additions underlined)

…

What is OZEMPIC?

OZEMPIC is an injectable prescription medicine used:

…

to reduce the risk of major cardiovascular events such as heart attack, stroke or death in adults with type 2 diabetes mellitus with known heart disease.

…