PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

wegovy® 2.4 mg

NDC 0169-4524-14 List 452414

2.4 mg

wegovy**®**

(semaglutide) injection

2.4 mg/0.75 mL

Use Wegovy 1 time a week

4 Single-Dose Prefilled Pens

Each pen delivers a single dose of 2.4 mg semaglutide

For subcutaneous use only

Single-Dose only

Rx only

Contains: 4 Wegovy pens, Product Literature.

Dispense the enclosed Medication Guide to each patient.

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Indications and Usage (1)………………………………….03/2024

Dosing and Administration (2.2)…………………………. 07/2023

Warnings and Precautions, Hypoglycemia (5.4)…………..03/2024

DESCRIPTION SECTION

11 DESCRIPTION

WEGOVY (semaglutide) injection, for subcutaneous use, contains semaglutide, a human GLP-1 receptor agonist (or GLP-1 analog). The peptide backbone is produced by yeast fermentation. The main protraction mechanism of semaglutide is albumin binding, facilitated by modification of position 26 lysine with a hydrophilic spacer and a C18 fatty di-acid. Furthermore, semaglutide is modified in position 8 to provide stabilization against degradation by the enzyme dipeptidyl-peptidase 4 (DPP-4). A minor modification was made in position 34 to ensure the attachment of only one fatty di-acid. The molecular formula is C187H291N45O59 and the molecular weight is 4113.58 g/mol.

**Figure 1. Structural Formula of semaglutide**

WEGOVY is a sterile, aqueous, clear, colorless solution. Each 0.5 mL single- dose pen contains a solution of WEGOVY containing 0.25 mg, 0.5 mg or 1 mg of semaglutide; and each 0.75 mL single-dose pen contains a solution of WEGOVY containing 1.7 or 2.4 mg of semaglutide. Each 1 mL of WEGOVY contains the following inactive ingredients: disodium phosphate dihydrate, 1.42 mg; sodium chloride, 8.25 mg; and water for injection. WEGOVY has a pH of approximately 7.4. Hydrochloric acid or sodium hydroxide may be added to adjust pH.

CLINICAL PHARMACOLOGY SECTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1.

GLP-1 is a physiological regulator of appetite and caloric intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. Animal studies show that semaglutide distributed to and activated neurons in brain regions involved in regulation of food intake.

The exact mechanism of cardiovascular risk reduction has not been established.

12.2 Pharmacodynamics

Semaglutide lowers body weight with greater fat mass loss than lean mass loss. Semaglutide decreases calorie intake. The effects are likely mediated by affecting appetite.

Semaglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner. These effects can lead to a reduction of blood glucose.

Gastric Emptying

Semaglutide delays gastric emptying.

Cardiac Electrophysiology (QTc)

The effect of semaglutide on cardiac repolarization was tested in a thorough QTc trial. Semaglutide did not prolong QTc intervals at doses up to 1.5 mg at steady state.

12.3 Pharmacokinetics

Absorption

Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached 1 to 3 days post dose.

Similar exposure was achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm.

The average semaglutide steady state concentration following subcutaneous administration of WEGOVY was approximately 75 nmol/L in patients with either obesity (BMI greater than or equal to 30 kg/m2) or overweight (BMI greater than or equal to 27 kg/m2). The steady state exposure of WEGOVY increased proportionally with doses up to 2.4 mg once weekly.

Distribution

The mean volume of distribution of semaglutide following subcutaneous administration in patients with obesity or overweight is approximately 12.5 L. Semaglutide is extensively bound to plasma albumin (greater than 99%) which results in decreased renal clearance and protection from degradation.

Elimination

The apparent clearance of semaglutide in patients with obesity or overweight is approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 to 7 weeks after the last dose of 2.4 mg.

Metabolism

The primary route of elimination for semaglutide is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.

Excretion

The primary excretion routes of semaglutide-related material are via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide.

Specific Populations

The effects of intrinsic factors on the pharmacokinetics of semaglutide are shown in Figure 2.

**Figure 2. Impact of intrinsic factors on semaglutide exposure**

Data are steady-state dose-normalized average semaglutide exposures relative to a reference subject profile (non-Hispanic or Latino ethnicity, white female aged 18 to less than 65 years, with a body weight of 110 kg and normal renal function, who injected in the abdomen). Body weight categories (74 and 143 kg) represent the 5% and 95% percentiles in the dataset.

Patients with Renal Impairment

Renal impairment did not impact the exposure of semaglutide in a clinically relevant manner. The pharmacokinetics of semaglutide were evaluated following a single dose of 0.5 mg semaglutide in a study of patients with different degrees of renal impairment (mild, moderate, severe, or ESRD) compared with subjects with normal renal function. The pharmacokinetics were also assessed in subjects with overweight (BMI 27-29.9 kg/m2) or obesity (BMI greater than or equal to 30 kg/m2) and mild to moderate renal impairment, based on data from clinical trials.

Patients with Hepatic Impairment

Hepatic impairment did not impact the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated following a single dose of 0.5 mg semaglutide in a study of patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function.

Drug Interactions Studies

In vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes, or to inhibit drug transporters.

The delay of gastric emptying with semaglutide may influence the absorption of concomitantly administered oral medications [see Drug Interactions (7.2)]. The potential effect of semaglutide on the absorption of co-administered oral medications was studied in trials at semaglutide 1 mg steady-state exposure. No clinically relevant drug-drug interactions with semaglutide (Figure 3) were observed based on the evaluated medications. In a separate study, no apparent effect on the rate of gastric emptying was observed with semaglutide 2.4 mg.

**Figure 3. Impact of semaglutide 1 mg on the pharmacokinetics of co-administered medications**

Relative exposure in terms of AUC and Cmax for each medication when given with semaglutide compared to without semaglutide. Metformin and oral contraceptive drug (ethinylestradiol/levonorgestrel) were assessed at steady state. Warfarin (S-warfarin/R-warfarin), digoxin and atorvastatin were assessed after a single dose.

Abbreviations: AUC: area under the curve, Cmax: maximum concentration, CI: confidence interval.

12.6 Immunogenicity

The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of semaglutide or of other semaglutide products.

During the 68-week treatment periods in Studies 2 and 3 [see Clinical Studies (14.2)], 50/1709 (3%) of WEGOVY-treated patients developed anti-semaglutide antibodies. Of these 50 WEGOVY-treated patients, 28 patients (2% of the total WEGOVY-treated study population) developed antibodies that cross-reacted with native GLP-1. No identified clinically significant effect of anti-semaglutide antibodies on pharmacokinetics for WEGOVY was observed. There is insufficient evidence to characterize the effects of anti-semaglutide antibodies on pharmacodynamics or effectiveness of semaglutide.

INDICATIONS & USAGE SECTION

Highlight: WEGOVY is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated in combination with a reduced calorie diet and increased physical activity:

•

to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight (1).

•

to reduce excess body weight and maintain weight reduction long term in: 

o

Adults and pediatric patients aged 12 years and older with obesity

o

Adults with overweight in the presence of at least one weight-related comorbid condition (1).

Limitations of Use:

•

Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended (1).

1 INDICATIONS AND USAGE

WEGOVY is indicated in combination with a reduced calorie diet and increased physical activity:

•

 to reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight. 

•

 to reduce excess body weight and maintain weight reduction long term in: 

o

 Adults and pediatric patients aged 12 years and older with obesity

o

 Adults with overweight in the presence of at least one weight-related comorbid condition.

Limitations of Use

•

WEGOVY contains semaglutide. Coadministration with other semaglutide-containing products or with any other GLP-1 receptor agonist is not recommended.

DOSAGE & ADMINISTRATION SECTION

Highlight: •

Administer WEGOVY once weekly as an adjunct to diet and increased physical activity, on the same day each week, at any time of day, with or without meals (2.1).

•

Inject subcutaneously in the abdomen, thigh or upper arm (2.1).

•

In patients with type 2 diabetes, monitor blood glucose prior to starting and during WEGOVY treatment (2.1).

•

Initiate at 0.25 mg once weekly for 4 weeks. Then follow the dosage escalation schedule, titrating every 4 weeks to achieve the maintenance dosage (2.2, 2.3).

•

The maintenance dosage of WEGOVY in adults is either 2.4 mg (recommended) or 1.7 mg once weekly (2.2). 

•

The maintenance dosage of WEGOVY in pediatric patients aged 12 years and older is 2.4 mg once weekly (2.3).

2 DOSAGE AND ADMINISTRATION

2.1 Important Monitoring and Administration Instructions

•

In patients with type 2 diabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment [see Warnings and Precautions (5.4)].

•

Prior to initiation of WEGOVY, train patients on proper injection technique. Refer to the accompanying Instructions for Use for complete administration instructions with illustrations.

•

Inspect WEGOVY visually prior to each injection. Only use if solution is clear, colorless, and contains no particles.

•

Administer WEGOVY in combination with a reduced-calorie diet and increased physical activity. 

•

Administer WEGOVY once weekly, on the same day each week, at any time of day, with or without meals. 

•

Inject WEGOVY subcutaneously in the abdomen, thigh, or upper arm. The time of day and the injection site can be changed without dose adjustment.

2.2 Recommended Dosage in Adults

Dosage Initiation and Escalation

•

Initiate WEGOVY with a dosage of 0.25 mg injected subcutaneously once weekly. Then follow the dose escalation schedule presented in Table 1 to minimize gastrointestinal adverse reactions [see Adverse Reactions (6.1)].

•

If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks.

Table 1. Recommended Dosage Regimen for Adults

Maintenance Dosage

•

 The maintenance dosage of WEGOVY in adults is either 2.4 mg (recommended) or 1.7 mg once weekly. Consider treatment response and tolerability when selecting the maintenance dosage [see Clinical Studies (14.2)].

2.3 Recommended Dosage in Pediatric Patients Aged 12 Years and Older

Dosage Initiation and Escalation

•

 Initiate WEGOVY according to the dosage escalation schedule in Table 2 to minimize gastrointestinal adverse reactions [see Adverse Reactions (6.1)].

•

 If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks.

•

 The 0.25 mg, 0.5 mg, and 1 mg once-weekly dosages are initiation and escalation dosages and are not approved as maintenance dosages.

Table 2. Recommended Dosage Regimen for Pediatric Patients Aged 12 Years and Older

aNot approved as maintenance dosages
bSee Dosage Modifications for Adverse Reactions

Maintenance Dosage

•

The maintenance dosage of WEGOVY in pediatric patients aged 12 years and older is 2.4 mg once weekly.

Dosage Modifications for Adverse Reactions

•

If patients do not tolerate the 2.4 mg once weekly maintenance dosage, the maintenance dosage may be reduced to 1.7 mg once weekly.

•

Discontinue WEGOVY if the patient cannot tolerate the 1.7 mg once-weekly dosage.

2.4 Recommendations Regarding Missed Dose

•

If one dose is missed and the next scheduled dose is more than 2 days away (48 hours), administer WEGOVY as soon as possible. If one dose is missed and the next scheduled dose is less than 2 days away (48 hours), do not administer the dose. Resume dosing on the regularly scheduled day of the week.

•

If 2 or more consecutive doses are missed, resume dosing as scheduled or, if needed, reinitiate WEGOVY and follow the dose escalation schedule, which may reduce the occurrence of gastrointestinal symptoms associated with reinitiation of treatment.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Injection: pre-filled, single-dose pen that delivers doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg or 2.4 mg (3).

3 DOSAGE FORMS AND STRENGTHS

Injection: clear, colorless solution available in 5 pre-filled, disposable, single-dose pens:

•

0.25 mg/0.5 mL

•

0.5 mg/0.5 mL

•

1 mg/0.5 mL

•

1.7 mg/0.75 mL

•

2.4 mg/0.75 mL

CONTRAINDICATIONS SECTION

Highlight: •

Personal or family history of MTC or in patients with MEN 2 (4).

•

Known hypersensitivity to semaglutide or any of the excipients in WEGOVY (4).

4 CONTRAINDICATIONS

WEGOVY is contraindicated in the following conditions:

•

A personal or family history of MTC or in patients with MEN 2 [see Warnings and Precautions (5.1)].

•

A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY. Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with WEGOVY [see Warnings and Precautions (5.6)].

Boxed Warning section

WARNING: RISK OF THYROID C-CELL TUMORS

See full prescribing information for complete boxed warning.

•

**In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether WEGOVY causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined (****5.1****,****13.1****).**

•

**WEGOVY is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors (****4****,****5.1****).**

ADVERSE REACTIONS SECTION

Highlight: Most common adverse reactions (incidence ≥ 5%) in adults or pediatric patients aged 12 years and older are: nausea, diarrhea, vomiting, constipation, abdominal pain, headache, fatigue, dyspepsia, dizziness, abdominal distension, eructation, hypoglycemia in patients with type 2 diabetes, flatulence, gastroenteritis, gastroesophageal reflux disease, and nasopharyngitis (6.1).

**To report SUSPECTED ADVERSE REACTIONS, contactNovo Nordisk Inc., at 1-833-934-6891 or FDA at 1-800-FDA-1088 or **www.fda.gov/medwatch.

6 ADVERSE REACTIONS

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)]

•

Acute Pancreatitis [see Warnings and Precautions (5.2)]

•

Acute Gallbladder Disease [see Warnings and Precautions (5.3)]

•

Hypoglycemia [see Warnings and Precautions (5.4)]

•

Acute Kidney Injury [see Warnings and Precautions (5.5)]

•

Hypersensitivity Reactions [see Warnings and Precautions (5.6)]

•

Diabetic Retinopathy Complications in Patients with Type 2 Diabetes [see Warnings and Precautions (5.7)]

•

Heart Rate Increase [see Warnings and Precautions (5.8)]

•

Suicidal Behavior and Ideation [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adverse Reactions in Clinical Trials in Adults with Obesity or Overweight

WEGOVY 2.4 mg Subcutaneous Weekly Dosage

WEGOVY was evaluated for safety in 3 randomized, double-blind, placebo- controlled trials that included 2,116 adult patients with obesity or overweight treated with 2.4 mg WEGOVY for up to 68 weeks and a 7 week off-drug follow-up period [see Clinical Studies (14.2)]. Baseline characteristics included a mean age of 48 years, 71% female, 72% White, 14% Asian, 9% Black or African American, and 5% reported as other or unknown; and 85% were not Hispanic or Latino ethnicity, 13% were Hispanic or Latino ethnicity, and 2% reported as unknown. The baseline characteristics were 42% with hypertension, 19% with type 2 diabetes, 43% with dyslipidemia, 28% with a BMI greater than 40 kg/m2, and 4% with cardiovascular disease.

In these clinical trials, 6.8% of patients treated with 2.4 mg WEGOVY and 3.2% of patients treated with placebo permanently discontinued treatment as a result of adverse reactions. The most common adverse reactions leading to discontinuation were nausea (1.8% versus 0.2%), vomiting (1.2% versus 0%), and diarrhea (0.7% versus 0.1%) for WEGOVY and placebo, respectively.

Adverse reactions reported in clinical trials in adults and greater than or equal to 2% of WEGOVY-treated patients and more frequently than in placebo- treated patients are shown in Table 3.

Table 3. Adverse Reactions (≥2% and Greater Than Placebo) in WEGOVY-treated Adults with Obesity or Overweight

aIncludes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort

bIncludes fatigue and asthenia

cDefined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia or severe hypoglycemia (requiring the assistance of another person) in patients with type 2 diabetes not on concomitant insulin (Study 3, WEGOVY N=403, Placebo N=402). See text below for further information regarding hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus

dIncludes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis
eIncludes paresthesia, hyperesthesia, burning sensation, allodynia, dysesthesia, skin burning sensation, pain of skin, and sensitive skin

In a cardiovascular outcomes trial, 8,803 patients were exposed to WEGOVY for a median of 37.3 months and 8,801 patients were exposed to placebo for a median of 38.6 months [see Clinical Studies (14.1)]. Safety data collection was limited to serious adverse events (including death), adverse events leading to discontinuation, and adverse events of special interest. Sixteen percent (16%) of WEGOVY-treated patients and 8% of placebo-treated patients, respectively, discontinued study drug due to an adverse event. Additional information from this trial is included in subsequent sections below when relevant.

Adverse Reactions in a Clinical Trial of Pediatric Patients Aged 12 Years and Older with Obesity

WEGOVY was evaluated in a 68-week, double-blind, randomized, parallel group, placebo-controlled, multi-center trial in 201 pediatric patients aged 12 years and older with obesity [see Clinical Studies (14.3)]. Baseline characteristics included a mean age of 15.4 years; 38% of patients were male; 79% were White, 8% were Black or African American, 2% were Asian, and 11% were of other or unknown race; and 11% were of Hispanic or Latino ethnicity. The mean baseline body weight was 107.5 kg, and mean BMI was 37 kg/m2.

Table 4 shows adverse reactions reported in greater than or equal to 3% of WEGOVY-treated pediatric patients and more frequently than in the placebo group from a study in pediatric patients aged 12 years and older.

Table 4. Adverse Reactions (≥3% and Greater than Placebo) in WEGOVY-Treated Pediatric Patients Aged 12 Years and Older with Obesity

**Other Adverse Reactions in Adults and/or Pediatric Patients**

Acute Pancreatitis

In WEGOVY clinical trials in adults, acute pancreatitis was confirmed by adjudication in 4 WEGOVY-treated patients (0.2 cases per 100 patient years) versus 1 in placebo-treated patients (less than 0.1 cases per 100 patient years). One additional case of acute pancreatitis was confirmed in a patient treated with WEGOVY in another clinical trial.

Acute Gallbladder Disease

In WEGOVY clinical trials in adults, cholelithiasis was reported by 1.6% of WEGOVY-treated patients and 0.7% of placebo-treated patients. Cholecystitis was reported by 0.6% of WEGOVY-treated adult patients and 0.2% of placebo- treated patients. In a clinical trial in pediatric patients aged 12 years and older [see Clinical Studies (14.3)], cholelithiasis was reported by 3.8% of WEGOVY-treated patients and 0% placebo-treated patients. Cholecystitis was reported by 0.8% of WEGOVY-treated pediatric patients and 0% placebo-treated patients.

Hypoglycemia

Patients with Type 2 Diabetes

In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m2, clinically significant hypoglycemia (defined as a plasma glucose less than 54 mg/dL) was reported in 6.2% of WEGOVY-treated patients versus 2.5% of placebo-treated patients. A higher rate of clinically significant hypoglycemic episodes was reported with WEGOVY (semaglutide 2.4 mg) versus semaglutide 1 mg (10.7 vs. 7.2 episodes per 100 patient years of exposure, respectively); the rate in the placebo-treated group was 3.2 episodes per 100 patient years of exposure. In addition, one episode of severe hypoglycemia requiring intravenous glucose was reported in a WEGOVY-treated patient versus none in placebo-treated patients. The risk of hypoglycemia was increased when WEGOVY was used with a sulfonylurea.

Patients without Type 2 Diabetes

Episodes of hypoglycemia have been reported with GLP-1 receptor agonists in adult patients without type 2 diabetes mellitus. In WEGOVY clinical trials in adult patients without type 2 diabetes mellitus, there was no systematic capturing or reporting of hypoglycemia.

In a cardiovascular outcomes trial in adult patients without type 2 diabetes, 3 episodes of serious hypoglycemia were reported in WEGOVY-treated patients versus 1 episode in placebo. Patients with a history of bariatric surgery (a risk factor for hypoglycemia) had more events of serious hypoglycemia while taking WEGOVY (2.3%, 2/87) than placebo (0%, 0/97).

Acute Kidney Injury

Acute kidney injury occurred in clinical trials in 7 adult patients (0.4 cases per 100 patient years) receiving WEGOVY versus 4 patients (0.2 cases per 100 patient years of exposure) receiving placebo. Some of these adverse reactions occurred in association with gastrointestinal adverse reactions or dehydration. In addition, 2 patients treated with WEGOVY had acute kidney injury with dehydration in other clinical trials. The risk of renal adverse reactions with WEGOVY was increased in adult patients with a history of renal impairment (trials included 65 patients with a history of moderate or severe renal impairment at baseline), and occurred more frequently during dose titration.

Retinal Disorders in Patients with Type 2 Diabetes

In a trial of adult patients with type 2 diabetes and BMI greater than or equal to 27 kg/m2, retinal disorders were reported by 6.9% of patients treated with WEGOVY (semaglutide 2.4 mg), 6.2% of patients treated with semaglutide 1 mg, and 4.2% of patients treated with placebo. The majority of events were reported as diabetic retinopathy (4.0%, 2.7%, and 2.7%, respectively) and non- proliferative retinopathy (0.7%, 0%, and 0%, respectively).

Increase in Heart Rate

Mean increases in resting heart rate of 1 to 4 beats per minute (bpm) were observed with routine clinical monitoring in WEGOVY-treated adult patients compared to placebo in clinical trials. In trials in which adult patients were randomized prior to dose-escalation, more patients treated with WEGOVY, compared with placebo, had maximum changes from baseline at any visit of 10 to 19 bpm (41% versus 34%, respectively) and 20 bpm or more (26% versus 16%, respectively). In a clinical trial in pediatric patients aged 12 years and older with normal baseline heart rate, more patients treated with WEGOVY compared to placebo had maximum changes in heart rate of 20 bpm or more (54% versus 39%).

Hypotension and Syncope

Adverse reactions related to hypotension (hypotension, orthostatic hypotension, and decreased blood pressure) were reported in 1.3% of WEGOVY- treated adult patients versus 0.4% of placebo-treated patients and syncope was reported in 0.8% of WEGOVY-treated patients versus 0.2% of placebo-treated patients. Some reactions were related to gastrointestinal adverse reactions and volume loss associated with WEGOVY. Hypotension and orthostatic hypotension were more frequently seen in patients on concomitant antihypertensive therapy. In a clinical trial in pediatric patients aged 12 years and older, hypotension was reported in 2.3% of WEGOVY-treated patients versus 0% in placebo-treated patients.

Appendicitis

Appendicitis (including perforated appendicitis) occurred in 10 (0.5%) WEGOVY- treated adult patients and 2 (0.2%) patients receiving placebo.

Gastrointestinal Adverse Reactions

In clinical trials in adults, 73% of WEGOVY-treated patients and 47% of patients receiving placebo reported gastrointestinal adverse reactions, including severe reactions that were reported more frequently among patients receiving WEGOVY (4.1%) than placebo (0.9%). The most frequently reported reactions were nausea (44% vs. 16%), vomiting (25% vs. 6%), and diarrhea (30% vs. 16%). Other reactions that occurred at a higher incidence among WEGOVY- treated adult patients included dyspepsia, abdominal pain, abdominal distension, eructation, flatulence, gastroesophageal reflux disease, gastritis, hemorrhoids, and hiccups. These reactions increased during dose escalation.

In the pediatric clinical trial, 62% of WEGOVY-treated patients and 42% of placebo-treated patients reported gastrointestinal disorders. The most frequently reported reactions were nausea (42% vs. 18%), vomiting (36% vs. 10%), and diarrhea (22% vs. 19%). Other gastrointestinal-related reactions that occurred at a higher incidence than placebo among WEGOVY-treated pediatric patients included abdominal pain, constipation, eructation, gastroesophageal reflux disease, dyspepsia, and flatulence.

Permanent discontinuation of treatment as a result of a gastrointestinal adverse reaction occurred in 4.3% of WEGOVY-treated adult patients versus 0.7% of placebo-treated patients. In a pediatric clinical trial, 2.3% of patients treated with WEGOVY versus 1.5% of patients who received placebo discontinued treatment as a result of gastrointestinal adverse reactions.

Injection Site Reactions

In clinical trials in adults, 1.4% of WEGOVY-treated patients and 1.0% of patients receiving placebo experienced injection site reactions (including injection site pruritus, erythema, inflammation, induration, and irritation).

Hypersensitivity Reactions

Serious hypersensitivity reactions (e.g., anaphylaxis, angioedema) have been reported with WEGOVY.

In a pediatric clinical trial, rash was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients, and urticaria was reported in 3% of WEGOVY-treated patients and 0% of placebo-treated patients.

In adult clinical trials, allergic reactions occurred in 16% (8/50) of WEGOVY- treated patients with anti-semaglutide antibodies and in 7% (114/1659) of WEGOVY-treated patients who did not develop anti-semaglutide antibodies [see Clinical Pharmacology (12.6)].

Fractures

In the cardiovascular outcomes trial in adults, more fractures of the hip and pelvis were reported on WEGOVY than on placebo in female patients: 1.0% (24/2448) vs. 0.2% (5/2424), and in patients ages 75 years and older: 2.4% (17/703) vs. 0.6% (4/663), respectively.

Urolithiasis

In a cardiovascular outcomes trial, 1.2% of WEGOVY-treated patients and 0.8% of patients receiving placebo reported urolithiasis, including serious reactions that were reported more frequently among patients receiving WEGOVY (0.6%) than placebo (0.4%).

Dysgeusia

In clinical trials in adults, 1.7% of WEGOVY-treated patients and 0.5% of placebo-treated patients reported dysgeusia.

Laboratory Abnormalities

Amylase and Lipase

Adult and pediatric patients treated with WEGOVY had a mean increase from baseline in amylase of 15-16% and lipase of 39%. These changes were not observed in the placebo group. The clinical significance of elevations in lipase or amylase with WEGOVY is unknown in the absence of other signs and symptoms of pancreatitis.

Liver Enzymes

In a pediatric clinical trial, increases in alanine aminotransferase (ALT) greater than or equal to 5 times the upper limit of normal were observed in 4 (3%) WEGOVY-treated patients compared with 0% of placebo-treated patients. In some patients, increases in ALT and AST were associated with other confounding factors (such as gallstones). In the cardiovascular outcomes trial in adults, increases in total bilirubin greater than or equal to 3 times the upper limit of normal were observed in 0.3% (30/8585) of WEGOVY-treated patients versus 0.2% (14/8579) of placebo-treated patients.

6.2 Postmarketing Experience

The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of WEGOVY. 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: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death; ileus

Hypersensitivity: anaphylaxis, angioedema, rash, urticaria

Renal and Urinary Disorders: acute kidney injury

OVERDOSAGE SECTION

10 OVERDOSAGE

Overdoses have been reported with other GLP-1 receptor agonists. Effects have included severe nausea, severe vomiting, and severe hypoglycemia. In the event of overdose, appropriate supportive treatment should be initiated according to the patient’s clinical signs and symptoms. In the event of an overdose of WEGOVY, consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of WEGOVY of approximately 1 week.

SPL MEDGUIDE SECTION

Medication Guide

**Possible thyroid tumors, including cancer**. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, WEGOVY and medicines that work like WEGOVY caused thyroid tumors, including thyroid cancer. It is not known if WEGOVY will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people.

Do not use WEGOVY 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).

WEGOVY is an injectable prescription medicine used with a reduced calorie diet and increased physical activity: 

to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and with either obesity or overweight.

that may help adults and children aged 12 years and older with obesity, or some adults with overweight who also have weight-related medical problems, to help them lose excess body weight and keep the weight off.

WEGOVY contains semaglutide and should not be used with other semaglutide-containing products or other GLP-1 receptor agonist medicines.

It is not known if WEGOVY is safe and effective for use in children under 12 years of age.

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 WEGOVY. See the end of this Medication Guide for a complete list of ingredients in WEGOVY. Symptoms of a serious allergic reaction include:

swelling of your face, lips, tongue or throat

fainting or feeling dizzy

problems breathing or swallowing

very rapid heartbeat

severe rash or itching

have or have had problems with your pancreas or kidneys.

have type 2 diabetes and a history of diabetic retinopathy.

have or have had depression or suicidal thoughts, or mental health issues.

are pregnant or plan to become pregnant. WEGOVY may harm your unborn baby. You should stop using WEGOVY 2 months before you plan to become pregnant.

**Pregnancy Exposure Registry:** There is a pregnancy exposure registry for women who use WEGOVY during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry or you may contact Novo Nordisk at 1-877-390-2760.

are breastfeeding or plan to breastfeed. It is not known if WEGOVY passes into your breast milk. You should talk with your healthcare provider about the best way to feed your baby while using WEGOVY.
**Tell your healthcare provider about all the medicines you take,** including prescription and over-the-counter medicines, vitamins, and herbal supplements. WEGOVY may affect the way some medicines work and some medicines may affect the way WEGOVY works. Tell your healthcare provider if you are taking other medicines to treat diabetes, including sulfonylureas or insulin. WEGOVY slows stomach emptying and can affect medicines that need to pass through the stomach quickly.

Read the**Instructions for Use** that comes with WEGOVY.

Use WEGOVY exactly as your healthcare provider tells you to.

**Your healthcare provider should show you how to use WEGOVY before you use it for the first time.**

WEGOVY is injected under the skin (subcutaneously) of your stomach (abdomen), thigh, or upper arm.**Do not** inject WEGOVY into a muscle (intramuscularly) or vein (intravenously).

Change (rotate) your injection site with each injection.**Do not** use the same site for each injection.

**Use WEGOVY 1 time each week, on the same day each week, at any time of the day.**

Start WEGOVY with 0.25 mg per week in your first month. In your second month, increase your weekly dose to 0.5 mg. In the third month, increase your weekly dose to 1 mg. In the fourth month, increase your weekly dose to 1.7 mg. In the fifth month onwards, your healthcare provider may either maintain your dose at 1.7 mg weekly or increase your weekly dose to 2.4 mg.

If you need to change the day of the week, you may do so as long as your last dose of WEGOVY was given**2** or more days before.

If you miss a dose of WEGOVY and the next scheduled dose is more than 2 days away (48 hours), take the missed dose as soon as possible. If you miss a dose of WEGOVY and the next schedule dose is less than 2 days away (48 hours), do not administer the dose. Take your next dose on the regularly scheduled day.

If you miss doses of WEGOVY for more than 2 weeks, take your next dose on the regularly scheduled day or call your healthcare provider to talk about how to restart your treatment.

You can take WEGOVY with or without food.

If you take too much WEGOVY, you may have severe nausea, severe vomiting and severe low blood sugar. Call your healthcare provider or go to the nearest hospital emergency room right away if you experience any of these symptoms.

**See “What is the most important information I should know about WEGOVY?”**

**inflammation of your pancreas****(pancreatitis).**Stop using WEGOVY and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your abdomen to your back.

**gallbladder problems.**WEGOVY may cause gallbladder problems including gallstones. Some gallbladder problems need surgery. Call your healthcare provider if you have any of the following symptoms:

pain in your upper stomach (abdomen)

yellowing of skin or eyes (jaundice)

fever

clay-colored stools

**increased risk of low blood sugar (hypoglycemia), especially those who also take medicines to treat diabetes mellitus such as insulin or sulfonylureas.** Low blood sugar in patients with diabetes who receive WEGOVY can be a serious side effect. Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking WEGOVY and while you take WEGOVY. Signs and symptoms of low blood sugar may include:

dizziness or light-headedness

sweating

shakiness

blurred vision

slurred speech

weakness

anxiety

hunger

headache

irritability or mood changes

confusion or drowsiness

fast heartbeat

feeling jitteryt

**kidney problems (kidney failure).** In people who have kidney problems, diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration) which may cause kidney problems to get worse. It is important for you to drink fluids to help reduce your chance of dehydration.

**serious****allergic reactions.** Stop using WEGOVY 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

severe rash or itching

very rapid heartbeat

problems breathing or swallowing

fainting or feeling dizzy

**change in vision in people with type 2 diabetes.**Tell your healthcare provider if you have changes in vision during treatment with WEGOVY.

**increased heart rate.**WEGOVY can increase your heart rate while you are at rest. Your healthcare provider should check your heart rate while you take WEGOVY. Tell your healthcare provider if you feel your heart racing or pounding in your chest and it lasts for several minutes.

**depression or thoughts of suicide.** You should pay attention to any mental changes, especially sudden changes in your mood, behaviors, thoughts, or feelings. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.

nausea

stomach (abdomen) pain

dizziness

gas

diarrhea

headache

feeling bloated

stomach flu

vomiting

tiredness (fatigue)

belching

heartburn

constipation

upset stomach

low blood sugar in people with type 2 diabetes

runny nose or sore throat

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised 03/2024

HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

WEGOVY injection is a clear, colorless solution in a pre-filled, disposable, single-dose pen-injector with an integrated needle. It is supplied in cartons containing 4 pen-injectors in the following packaging configurations:

Recommended Storage

Store the WEGOVY single-dose pen in the refrigerator from 2°C to 8°C (36°F to 46°F). If needed, prior to cap removal, the pen can be kept from 8°C to 30°C (46°F to 86°F) up to 28 days. Do not freeze. Protect WEGOVY from light. WEGOVY must be kept in the original carton until time of administration. Discard the WEGOVY pen after use.

INSTRUCTIONS FOR USE SECTION

Instructions for Use

the pen is removed too early**or**

you have not pressed the pen firmly against the skin for the entire injection.

**Supplies you will need to give your WEGOVY injection:**

WEGOVY pen

1 alcohol swab or soap and water

1 gauze pad or cotton ball

1 sharps disposable container for used WEGOVY pens

**Wash your hands.**

**Check your WEGOVY pen.**

Do not use your WEGOVY pen if:

The pen appears to have been used or any part of the pen appears broken, for example if it has been dropped.

The WEGOVY medicine is not clear and colorless through the pen window.

The expiration date (EXP) has passed.

You may inject into your upper leg (front of the thighs), lower stomach (keep 2 inches away from your belly button) or upper arm.

**You will hear 2 clicks during the injection.**

Click 1: the injection has started.

Click 2: the injection is ongoing.

**If you have problems with the injection, refer to the “Troubleshooting” section.**

**If you have problems injecting, change to a more firm injection site, such as upper leg, or upper arm or consider standing up while injecting into the lower stomach.**

**If medicine appears on the skin or squirts from the needle, make sure the next time you inject to keep applying pressure until the yellow bar has stopped moving. Then you can lift the pen slowly from your skin.**
 ![troubleshooting-2](https://medical-cdn.nocode.com/data-engine/drug_fda/ee06186f-2aa3-4990-a760-757579d8f77b/image_23_jpg/98c78cf53acedcc893cac983f6a5157a.jpg)

· made of a heavy-duty plastic,
· able to be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
· upright and stable during use,
· leak-resistant, and
· properly labeled to warn of hazardous waste inside the container.

· Do not reuse the pen.
· Do not recycle the pen or sharps disposal container, or throw them into household trash.

· Do not drop your pen or knock it against hard surfaces.
· Do not expose your pen to any liquids.
· If you think that your pen may be damaged, do not try to fix it. Use a new one.
· Keep the pen cap on until you are ready to inject. Your pen will no longer be sterile if you store an unused pen without the cap, if you pull the pen cap off and put it on again, or if the pen cap is missing. This could lead to an infection.
 ![contact](https://medical-cdn.nocode.com/data-engine/drug_fda/ee06186f-2aa3-4990-a760-757579d8f77b/image_16_jpg/8cfe8d71bf726da9f74a9f1cb84d898c.jpg) If you have any questions about WEGOVY, go to startWegovy.com or call Novo Nordisk Inc. at 1-833-Wegovy-1