Wegovy Drug Information

Important Monitoring and Administration Instructions •

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

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. • If patients do not tolerate a dose during dosage escalation, consider delaying dosage escalation for 4 weeks. Table 1.

Recommended Dosage Regimen for Adults 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.

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. • 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 a Not approved as maintenance dosages b See 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.

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.

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. 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.

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 1 2 a Includes abdominal pain, abdominal pain upper, abdominal pain lower, gastrointestinal pain, abdominal tenderness, abdominal discomfort and epigastric discomfort b Includes fatigue and asthenia c Defined 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 d Includes chronic gastritis, gastritis, gastritis erosive, and reflux gastritis e Includes 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. 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.

The mean baseline body weight was 107.5 kg, and mean BMI was 37 kg/m 2. 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.

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, cholelithiasis was reported by 3.8% of WEGOVY-treated patients and 0% placebo-treated patients. 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.

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.

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 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.

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%). 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. 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.

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: and in patients ages 75 years and older: 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.

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

Concomitant Use with Insulin or an Insulin

Secretagogue (e.g., Sulfonylurea) WEGOVY lowers blood glucose and can cause hypoglycemia. The risk of hypoglycemia is increased when WEGOVY is used in combination with insulin or insulin secretagogues (e.g., sulfonylureas). The addition of WEGOVY in patients treated with insulin has not been evaluated.

When initiating WEGOVY, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia.

Oral Medications

WEGOVY causes a delay of gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials with semaglutide 1 mg, semaglutide did not affect the absorption of orally administered medications. Nonetheless, monitor the effects of oral medications concomitantly administered with WEGOVY.

Pregnancy Pregnancy Exposure Registry There will be a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to semaglutide during pregnancy. Pregnant women exposed to WEGOVY and healthcare providers are encouraged to contact Novo Nordisk at 1-877-390-2760 or www.wegovypregnancyregistry.com. Risk Summary Based on animal reproduction studies, there may be potential risks to the fetus from exposure to semaglutide during pregnancy.

Additionally, weight loss offers no benefit to a pregnant patient and may cause fetal harm. When a pregnancy is recognized, advise the pregnant patient of the risk to a fetus, and discontinue WEGOVY (see Clinical Considerations). Available pharmacovigilance data and data from clinical trials with WEGOVY use in pregnant patients are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

In pregnant rats administered semaglutide during organogenesis, embryofetal mortality, structural abnormalities and alterations to growth occurred at maternal exposures below the maximum recommended human dose (MRHD) based on AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and greater than or equal to 2-fold the MRHD (monkey). These findings coincided with a marked maternal body weight loss in both animal species (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Appropriate weight gain based on pre-pregnancy weight is currently recommended for all pregnant patients, including those who already have overweight or obesity, because of the obligatory weight gain that occurs in maternal tissues during pregnancy.

In parental animals, pharmacologically mediated reductions in body weight gain and food consumption were observed at all dose levels. In the offspring, reduced growth and fetuses with visceral (heart blood vessels) and skeletal (cranial bones, vertebra, ribs) abnormalities were observed at the human exposure. 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.

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 2 times human exposure). 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 1-time human exposure).

Pediatric Use The safety and effectiveness of WEGOVY as an adjunct to a reduced calorie diet and increased physical activity for weight reduction and long-term maintenance have been established in pediatric patients aged 12 years and older with obesity. Use of WEGOVY for this indication is supported by a 68-week, double-blind, placebo-controlled clinical trial in 201 pediatric patients aged 12 years and older with a BMI corresponding to ≥95th percentile for age and sex and from studies in adult patients with obesity. Adverse reactions with WEGOVY treatment in pediatric patients aged 12 years and older were generally similar to those reported in adults.

Pediatric patients aged 12 years and older treated with WEGOVY had greater incidences of cholelithiasis, cholecystitis, hypotension, rash, and urticaria compared to adults treated with WEGOVY. There are insufficient data in pediatric patients with type 2 diabetes treated with WEGOVY for obesity to determine if there is an increased risk of hypoglycemia with WEGOVY treatment similar to that reported in adults. Inform patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.

In pediatric patients aged 12 years and older with type 2 diabetes, monitor blood glucose prior to starting WEGOVY and during WEGOVY treatment. When initiating WEGOVY in pediatric patients aged 12 years and older with type 2 diabetes, consider reducing the dose of concomitantly administered insulin secretagogue (such as sulfonylureas) or insulin to reduce the risk of hypoglycemia. The safety and effectiveness of WEGOVY have not been established in pediatric patients less than 12 years of age.

• WEGOVY is contraindicated in the following conditions:
• A personal or family history of MTC or in patients with MEN 2.
• 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.
• Known hypersensitivity to semaglutide or any of the excipients in WEGOVY.

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.