`
`
`
`
`
`
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE FORMS AND STRENGTHS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`Injection: 6 mg/mL solution in a 3 mL pre-filled, single-patient-use pen that
`•
`delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg (3).
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙CONTRAINDICATIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• Personal or family history of medullary thyroid carcinoma or Multiple
`Endocrine Neoplasia syndrome type 2 (4, 5.1).
`• Hypersensitivity to liraglutide or any excipients in SAXENDA (4, 5.7).
`• Pregnancy (4, 8.1).
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙WARNINGS AND PRECAUTIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• Thyroid C-cell Tumors: See Boxed Warning (5.1).
`• Acute Pancreatitis: Discontinue promptly if pancreatitis is suspected. Do
`not restart if pancreatitis is confirmed (5.2).
`• Acute Gallbladder Disease: If cholelithiasis or cholecystitis are suspected,
`gallbladder studies are indicated (5.3).
`• Hypoglycemia: Can occur in adults when SAXENDA is used with an
`insulin secretagogue (e.g. a sulfonylurea) or insulin. The risk may be
`lowered by a reduction in the dose of concomitantly administered insulin
`secretagogues or insulin. In the pediatric clinical trial, patients did not have
`type 2 diabetes. Hypoglycemia occurred in SAXENDA-treated pediatric
`patients. Inform all patients of the risk of hypoglycemia and educate them
`on the signs and symptoms of hypoglycemia (2, 5.4).
`• Heart Rate Increase: Monitor heart rate at regular intervals (5.5).
`• Renal Impairment: Has been reported postmarketing, usually in association
`with nausea, vomiting, diarrhea, or dehydration which may sometimes
`require hemodialysis. Use caution when initiating or escalating doses of
`SAXENDA in patients with renal impairment (5.6).
`• Hypersensitivity Reactions: Postmarketing reports of serious
`hypersensitivity reactions (e.g., anaphylactic reactions and angioedema).
`Discontinue SAXENDA and other suspect medications and promptly seek
`medical advice (5.7).
`• Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts.
`Discontinue SAXENDA if symptoms develop (5.8).
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ADVERSE REACTIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• Most common adverse reactions, reported in greater than or equal to 5%
`are: nausea, diarrhea, constipation, vomiting, injection site reactions,
`headache, hypoglycemia, dyspepsia, fatigue, dizziness, abdominal pain,
`increased lipase, upper abdominal pain, pyrexia, and gastroenteritis (6.1).
`
`
`To report SUSPECTED ADVERSE REACTIONS, contact Novo Nordisk
`Inc. at 1-844-363-4448 or FDA at 1-800-FDA-1088 or
`www.fda.gov/medwatch.
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DRUG INTERACTIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• SAXENDA delays gastric emptying. May impact absorption of
`concomitantly administered oral medications. Use with caution (7).
`
`
`
`See 17 for PATIENT COUNSELING INFORMATION and
`Medication Guide.
` Revised: 06/2022
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`SAXENDA® safely and effectively. See full prescribing information
`for SAXENDA.
`
`SAXENDA (liraglutide) injection, for subcutaneous use
`Initial U.S. Approval: 2010
`WARNING: RISK OF THYROID C-CELL TUMORS
`See full prescribing information for complete boxed warning.
`Liraglutide causes thyroid C-cell tumors at clinically relevant
`exposures in both genders of rats and mice. It is unknown
`whether SAXENDA causes thyroid C-cell tumors, including
`medullary thyroid carcinoma (MTC), in humans, as the human
`relevance of liraglutide-induced rodent thyroid C-cell tumors
`has not been determined (5.1).
`SAXENDA 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 the symptoms of
`thyroid tumors (4, 5.1, 13.1).
`
`•
`
`•
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙RECENT MAJOR CHANGES∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`Dosage and Administration (2.2)………………………………...06/2022
`Contraindications (4)…………………………………………….06/2022
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙INDICATIONS AND USAGE∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`SAXENDA is a glucagon like peptide 1 (GLP-1) receptor agonist
`indicated as an adjunct to a reduced-calorie diet and increased physical
`activity for chronic weight management in:
`Adult patients with an initial body mass index (BMI) of
`30 kg/m2 or greater (obese), or
`•
`27 kg/m2 or greater (overweight) in the presence of at least
`•
`one weight-related comorbid condition (e.g. hypertension,
`type 2 diabetes mellitus, or dyslipidemia) (1).
`Pediatric patients aged 12 years and older with:
`body weight above 60 kg and
`•
`•
`an initial BMI corresponding to 30 kg/m2 for adults (obese) by
`international cut-offs (1).
`
`Limitations of Use:
`• SAXENDA contains liraglutide and should not be coadministered
`with other liraglutide-containing products or with any other GLP-1
`receptor agonist (1).
`• The safety and effectiveness of SAXENDA in pediatric patients with
`type 2 diabetes have not been established (1).
`• The safety and efficacy of SAXENDA in combination with other
`products intended for weight loss have not been established (1).
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE AND ADMINISTRATION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`Inject SAXENDA subcutaneously in the abdomen, thigh, or upper
`•
`arm once daily at any time of day, without regard to the timing of
`meals (2.2).
`• The recommended dose of SAXENDA is 3 mg daily (2.3).
`Initiate at 0.6 mg per day for one week. In weekly intervals, increase
`•
`the dose until a dose of 3 mg is reached (2.3).
`If pediatric patients do not tolerate an increased dose during dose
`escalation, the dose may also be lowered to the previous level. Dose
`escalation for pediatric patients may take up to 8 weeks (2.3).
`• Pediatric patients who do not tolerate 3 mg daily may have their
`dose reduced to 2.4 mg daily (2.3).
`• Adult patients with type 2 diabetes should monitor blood glucose
`prior to starting SAXENDA and during SAXENDA treatment (2.3).
`
`•
`
`Reference ID: 4999640
`
`

`

`8
`
`
`
`USE IN SPECIFIC POPULATIONS
`8.1
` Pregnancy
`8.2
` Lactation
`8.4
` Pediatric Use
`8.5
` Geriatric Use
`8.6 Renal Impairment
`8.7 Hepatic Impairment
`8.8 Gastroparesis
`OVERDOSAGE
`DESCRIPTION
`CLINICAL PHARMACOLOGY
`12.1 Mechanism of Action
`12.2 Pharmacodynamics
`12.3 Pharmacokinetics
`NONCLINICAL TOXICOLOGY
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`CLINICAL STUDIES
`14.1 Weight Management Trials in Adults with Overweight or
` Obesity
`14.2 Weight Management Trial in Pediatric Patients Ages 12 and
` Older with Obesity
`14.3 Cardiovascular Outcomes Trial of Liraglutide 1.8 mg in Adult
` Patients with Type 2 Diabetes and Cardiovascular Disease
`HOW SUPPLIED/STORAGE AND HANDLING
`16.1 How Supplied
`16.2 Recommended Storage
`PATIENT COUNSELING INFORMATION
`
`*Sections or subsections omitted from the full prescribing information are not
`listed.
`
`10
`11
`12
`
`13
`
`14
`
`16
`
`17
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`BOXED WARNING: RISK OF THYROID C-CELL TUMORS
`
`
`
` 1
`
`
`2
`
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`2.1 Patient Selection
`2.2 Important Administration Instructions
`2.3 Dosage in Adults and Pediatric Patients Aged 12 Years
` and Older
`DOSAGE FORMS AND STRENGTHS
`CONTRAINDICATIONS
`WARNINGS AND PRECAUTIONS
`5.1 Risk of Thyroid C-cell Tumors
` 5.2 Acute Pancreatitis
` 5.3 Acute Gallbladder Disease
`5.4 Hypoglycemia
`5.5 Heart Rate Increase
` 5.6 Renal Impairment
` 5.7 Hypersensitivity Reactions
` 5.8 Suicidal Behavior and Ideation
`6
`ADVERSE REACTIONS
`6.1 Clinical Trials Experience
`6.2 Post-Marketing Experience
`DRUG INTERACTIONS
` Oral Medications
`7.1
`
`3
`4
`5
`
`7
`
`
`
`
`
`
`
`Reference ID: 4999640
`
`

`

`FULL PRESCRIBING INFORMATION
`
`WARNING: RISK OF THYROID C-CELL TUMORS
`• Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at
`clinically relevant exposures in both genders of rats and mice. It is unknown whether
`SAXENDA causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in
`humans, as the human relevance of liraglutide-induced rodent thyroid C-cell tumors has not
`been determined [see Warnings and Precautions (5.1) and Nonclinical Toxicology (13.1)].
`• SAXENDA is contraindicated in patients with a personal or family history of MTC and in
`patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients
`regarding the potential risk of MTC with use of SAXENDA and inform them of symptoms of
`thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine
`monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early
`detection of MTC in patients treated with SAXENDA [see Contraindications (4), Warnings and
`Precautions (5.1)].
`
` 1
`
`INDICATIONS AND USAGE
`
`SAXENDA is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic
`weight management in:
`
` •
`
` Adult patients with an initial body mass index (BMI) of [see Dosage and Administration (2.1)]:
` 30 kg/m2 or greater (obese), or
` 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid
`condition (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia)
`
`
`• Pediatric patients aged 12 years and older with:
` body weight above 60 kg and
` an initial BMI corresponding to 30 kg/m2 or greater for adults (obese) by international cut-offs
`(Cole Criteria, Table 2) [see Dosage and Administration (2.1)]
`
`
`Limitations of Use
` SAXENDA contains liraglutide and should not be coadministered with other liraglutide-containing products
`or with any other GLP-1 receptor agonist.
` The safety and effectiveness of SAXENDA in pediatric patients with type 2 diabetes have not been
`established.
` The safety and effectiveness of SAXENDA in combination with other products intended for weight loss,
`including prescription drugs, over-the-counter drugs, and herbal preparations, have not been established.
`
` 2
`
`DOSAGE AND ADMINISTRATIONPatient Selection
`
`Select patients for SAXENDA treatment as an adjunct to a reduced-calorie diet and increased physical activity
`for chronic weight management based on the BMI values provided in Tables 1 and 2.
`
`Adult and Pediatric Patients
`BMI is calculated by dividing weight in (kilograms) by height (in meters) squared. A chart for determining BMI
`based on height and weight is provided in Table 1.
`
`
`Reference ID: 4999640
`
`

`

` Table 1: BMI Conversion Chart
`
`
`
`Age (years)
`
`
`Pediatric Patients Aged 12 Years and Older
`BMI cut-offs for obesity in pediatric patients aged 12 years and older are presented in Table 2.
`
`Table 2: International Obesity Task Force BMI Cut-offs for Obesity by Sex and Age for Pediatric
`Patients Aged 12 Years and Older (Cole Criteria)
`Body mass index
`30 kg/m2
`Males
`Females
`26.02
`26.67
`26.43
`27.24
`26.84
`27.76
`27.25
`28.20
`27.63
`28.57
`27.98
`28.87
`28.30
`29.11
`28.60
`29.29
`28.88
`29.43
`29.14
`29.56
`29.41
`29.69
`29.70
`29.84
`
`12
`12.5
`13
`13.5
`14
`14.5
`15
`15.5
`16
`16.5
`17
`17.5
`
`
`Important Administration Instructions
`2.2
`• Prior to initiation of SAXENDA, train patients on proper injection technique. Refer to the accompanying
`Instructions for Use for complete administration instructions with illustrations.
`Inspect SAXENDA visually prior to each injection. Only use if solution is clear, colorless, and contains no
`particles.
`Inject SAXENDA subcutaneously once daily at any time of day, without regard to the timing of meals.
`Inject SAXENDA subcutaneously in the abdomen, thigh, or upper arm. No dose adjustment is needed if
`changing the injection site and/or timing.
`
`•
`
`•
`•
`
`Reference ID: 4999640
`
`

`

`•
`
`•
`
`• Rotate injection sites within the same region in order to reduce the risk of cutaneous amyloidosis [see
`Adverse Reactions (6.2)].
`If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not
`administer an extra dose or increase the dose to make up for the missed dose.
`If more than 3 days have elapsed since the last SAXENDA dose, reinitiate SAXENDA at 0.6 mg daily and
`follow the dose escalation schedule in Table 3, to reduce the occurrence of gastrointestinal adverse reactions
`associated with reinitiation of treatment.
`
`
`2.3 Dosage in Adults and Pediatric Patients Aged 12 Years and Older
`Initiate SAXENDA with a dose of 0.6 mg daily for one week. Then follow the dose escalation schedule in
`•
`Table 3 to minimize gastrointestinal adverse reactions [see Adverse Reactions (6.1)].
`
`
`Table 3: Dose Escalation Schedule
`Week
`1
`2
`3
`4
`5 and onward
`
`Daily Dose
`0.6 mg
`1.2 mg
`1.8 mg
`2.4 mg
`3 mg
`
`
`Adult Patients
`• For adults, the recommended dosage of SAXENDA is 3 mg daily, lower doses are for titration only.
`• Discontinue SAXENDA if the patient cannot tolerate the 3 mg dose.
`If patients do not tolerate an increased dose during dose escalation, consider delaying dose escalation for
`•
`approximately one additional week.
`• Evaluate the change in body weight 16 weeks after initiating SAXENDA and discontinue SAXENDA if the
`patient has not lost at least 4% of baseline body weight, since it is unlikely that the patient will achieve and
`sustain clinically meaningful weight loss with continued treatment.
`In adult patients with type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during
`SAXENDA treatment.
`
`Pediatric Patients
`• For pediatric patients, the recommended maintenance dosage of SAXENDA is 3 mg daily. Pediatric patients
`who do not tolerate 3 mg daily may have their maintenance dose reduced to 2.4 mg daily. Discontinue
`SAXENDA if the patient cannot tolerate the 2.4 mg dose.
`If pediatric patients do not tolerate an increased dose during dose escalation, the dose may also be lowered
`to the previous level. Dose escalation for pediatric patients may take up to 8 weeks.
`• Evaluate the change in BMI after 12 weeks on the maintenance dose and discontinue SAXENDA if the
`patient has not had a reduction in BMI of at least 1% from baseline, since it is unlikely that the patient will
`achieve and sustain clinically meaningful weight loss with continued treatment.
`
`•
`
`•
`
`
`
` 3
`
`DOSAGE FORMS AND STRENGTHS
`
`Injection: 6 mg/mL clear, colorless solution in a 3 mL pre-filled, single-patient-use pen that delivers doses of
`0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg.
`
` 4
`
`CONTRAINDICATIONS
`
`SAXENDA is contraindicated in:
`• Patients with a personal or family history of medullary thyroid carcinoma (MTC) or patients with
`Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) [see Warnings and Precautions (5.1)].
`
`Reference ID: 4999640
`
`

`

`• Patients with a serious hypersensitivity reaction to liraglutide or to any of the excipients in SAXENDA.
`Serious hypersensitivity reactions including anaphylactic reactions and angioedema have been reported
`with SAXENDA [see Warnings and Precautions (5.7)].
`• Pregnancy [see Use in Specific Populations (8.1)].
`
` 5
`
`WARNINGS AND PRECAUTIONS
`
`Risk of Thyroid C-cell Tumors
`5.1
`Liraglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors (adenomas
`and/or carcinomas) at clinically relevant exposures in both genders of rats and mice [see Nonclinical
`Toxicology (13.1)]. Malignant thyroid C-cell carcinomas were detected in rats and mice. It is unknown whether
`SAXENDA will cause thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as the
`human relevance of liraglutide-induced rodent thyroid C-cell tumors has not been determined.
`
`Cases of MTC in patients treated with liraglutide have been reported in the postmarketing period; the data in
`these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in
`humans.
`
`SAXENDA is contraindicated in patients with a personal or family history of MTC or in patients with MEN 2.
`Counsel patients regarding the potential risk for MTC with the use of SAXENDA and inform them of
`symptoms of thyroid tumors (e.g., a mass in the neck, dysphagia, dyspnea, persistent hoarseness).
`
`Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of
`MTC in patients treated with SAXENDA. Such monitoring may increase the risk of unnecessary procedures,
`due to low test specificity for serum calcitonin and a high background incidence of thyroid disease.
`Significantly elevated serum calcitonin may indicate MTC, and patients with MTC usually have calcitonin
`values greater than 50 ng/L. If serum calcitonin is measured and found to be elevated, the patient should be
`further evaluated. Patients with thyroid nodules noted on physical examination or neck imaging should also be
`further evaluated.
`
`Acute Pancreatitis
`5.2
`Based on spontaneous postmarketing reports, acute pancreatitis, including fatal and non-fatal hemorrhagic or
`necrotizing pancreatitis, has been observed in patients treated with liraglutide. After initiation of SAXENDA,
`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, SAXENDA should promptly be discontinued and appropriate management should be initiated. If
`pancreatitis is confirmed, SAXENDA should not be restarted.
`
`In SAXENDA clinical trials in adults, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291
`SAXENDA-treated patients and 2 (0.1%) of 1843 placebo-treated patients. In addition, there were 2 cases of
`acute pancreatitis in SAXENDA-treated patients who prematurely withdrew from these clinical trials, occurring
`74 and 124 days after the last dose. There were 2 additional cases in SAXENDA-treated patients, 1 during an
`off-treatment follow-up period within 2 weeks of discontinuing SAXENDA, and 1 that occurred in a patient
`who completed treatment and was off-treatment for 106 days.
`
`In a SAXENDA pediatric clinical trial, pancreatitis was not independently adjudicated. Pancreatitis was
`reported in 1 (0.8%) SAXENDA-treated patient and resulted in treatment discontinuation.
`
`Liraglutide has been studied in a limited number of adult patients with a history of pancreatitis. It is unknown if
`patients with a history of pancreatitis are at higher risk for development of pancreatitis on SAXENDA.
`
`5.3
`
`Acute Gallbladder Disease
`
`Reference ID: 4999640
`
`

`

`In SAXENDA clinical trials in adults, 2.2% of SAXENDA-treated patients reported adverse events of
`cholelithiasis versus 0.8% of placebo-treated patients. The incidence of cholecystitis was 0.8% in SAXENDA-
`treated patients versus 0.4% in placebo-treated patients. The majority of SAXENDA-treated patients with
`adverse events of cholelithiasis and cholecystitis required cholecystectomy. Substantial or rapid weight loss can
`increase the risk of cholelithiasis; however, the incidence of acute gallbladder disease was greater in
`SAXENDA-treated patients than in placebo-treated patients even after accounting for the degree of weight loss.
`If cholelithiasis is suspected, gallbladder studies and appropriate clinical follow-up are indicated.
`
`5.4 Hypoglycemia
`Adult patients with type 2 diabetes mellitus on an insulin secretagogue (e.g., sulfonylurea) or insulin may have
`an increased risk of hypoglycemia with use of SAXENDA, including severe hypoglycemia. In patients with
`type 2 diabetes, monitor blood glucose prior to starting SAXENDA and during SAXENDA treatment [see
`Dosage and Administration (2) and Adverse Reactions (6.1)].
`
`The risk of hypoglycemia may be lowered by a reduction in the dose of sulfonylurea (or other concomitantly
`administered insulin secretagogues) or insulin. Inform patients using these concomitant medications of the risk
`of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
`
`In the pediatric clinical trial, patients did not have type 2 diabetes but were provided with blood glucose meters.
`Clinically significant hypoglycemia, defined as blood glucose <54 mg/dL, occurred in 1.6% of the SAXENDA-
`treated patients compared to 0.8% of placebo-treated patients [see Adverse Reactions (6.1)]. Inform all pediatric
`patients of the risk of hypoglycemia and educate them on the signs and symptoms of hypoglycemia.
`
`5.5 Heart Rate Increase
`Mean increases in resting heart rate of 2 to 3 beats per minute (bpm) were observed with routine clinical
`monitoring in SAXENDA-treated adult patients compared to placebo in clinical trials. More patients treated
`with SAXENDA, compared with placebo, had changes from baseline at two consecutive visits of more than 10
`bpm (34% versus 19%, respectively) and 20 bpm (5% versus 2%, respectively). At least one resting heart rate
`exceeding 100 bpm was recorded for 6% of SAXENDA-treated patients compared with 4% of placebo-treated
`patients, with this occurring at two consecutive study visits for 0.9% and 0.3%, respectively. Tachycardia was
`reported as an adverse reaction in 0.6% of SAXENDA-treated patients and in 0.1% of placebo-treated patients.
`
`In a clinical pharmacology trial that monitored heart rate continuously for 24 hours, SAXENDA treatment was
`associated with a heart rate that was 4 to 9 bpm higher than that observed with placebo.
`
`In a pediatric clinical trial, mean increases from baseline in resting heart rate of 3 to 7 bpm were observed with
`SAXENDA treatment.
`
`Heart rate should be monitored at regular intervals consistent with usual clinical practice. Patients should inform
`health care providers of palpitations or feelings of a racing heartbeat while at rest during SAXENDA treatment.
`For patients who experience a sustained increase in resting heart rate while taking SAXENDA, SAXENDA
`should be discontinued.
`
`Renal Impairment
`5.6
`In patients treated with GLP-1 receptor agonists, including SAXENDA, there have been reports of acute renal
`failure and worsening of chronic renal failure, sometimes requiring hemodialysis [see Adverse Reactions (6.2)].
`Some of these events were reported in patients without known underlying renal disease. A majority of the
`reported events occurred in patients who had experienced nausea, vomiting, or diarrhea leading to volume
`depletion. Some of the reported events occurred in patients receiving one or more medications known to affect
`renal function or volume status. Altered renal function has been reversed in many of the reported cases with
`supportive treatment and discontinuation of potentially causative agents, including liraglutide. Use caution
`
`Reference ID: 4999640
`
`

`

`when initiating or escalating doses of SAXENDA in patients with renal impairment [see Use in Specific
`Populations (8.6)].
`
`5.7 Hypersensitivity Reactions
`There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in
`patients treated with SAXENDA [see Contraindications (4) and Adverse Reactions (6.1, 6.2)]. If a
`hypersensitivity reaction occurs, the patient should discontinue SAXENDA and other suspect medications and
`promptly seek medical advice.
`
`Anaphylaxis and angioedema have been reported with other GLP-1 receptor agonists. Use caution in a patient
`with a history of anaphylaxis or angioedema with another GLP-1 receptor agonist because it is unknown
`whether such patients will be predisposed to these reactions with SAXENDA.
`
`5.8 Suicidal Behavior and Ideation
`In SAXENDA adult clinical trials, 9 (0.3%) of 3384 SAXENDA-treated patients and 2 (0.1%) of the 1941
`placebo-treated patients reported suicidal ideation; one of these SAXENDA-treated patients attempted suicide.
`
`In a SAXENDA pediatric clinical trial, 1 (0.8%) of the 125 SAXENDA-treated patients died by suicide. There
`was insufficient information to establish a causal relationship to SAXENDA.
`
`Patients treated with SAXENDA should be monitored for the emergence or worsening of depression, suicidal
`thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue SAXENDA in patients who
`experience suicidal thoughts or behaviors. Avoid SAXENDA in patients with a history of suicidal attempts or
`active suicidal ideation.
`
` 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)]
`• Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy [see Warnings and Precautions
`(5.4)]
`• Heart Rate Increase [see Warnings and Precautions (5.5)]
`• Renal Impairment [see Warnings and Precautions (5.6)]
`• Hypersensitivity Reactions [see Warnings and Precautions (5.7)]
`• Suicidal Behavior and Ideation [see Warnings and Precautions (5.8)]
`
`
`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.
`
`SAXENDA was evaluated for safety in 5 double-blind, placebo controlled trials that included 3384 overweight
`or obese adult patients treated with SAXENDA for a treatment period up to 56 weeks (3 trials), 52 weeks (1
`trial), and 32 weeks (1 trial) and one trial of 56 weeks in 125 pediatric patients with obesity aged 12 years and
`older [see Clinical Studies (14.1, 14.2)]. All patients received study drug in addition to a reduced-calorie diet
`and increased physical activity counseling. In the adult trials, patients received SAXENDA for a mean
`treatment duration of 46 weeks (median, 56 weeks). Baseline characteristics included a mean age of 47 years,
`71% women, 85% white, 39% with hypertension, 15% with type 2 diabetes, 34% with dyslipidemia, 29% with
`a BMI greater than 40 kg/m2, and 9% with cardiovascular disease. In one of the 56-week trials, a subset of
`patients (with abnormal glucose measurements at randomization) [see Clinical Studies (14.1)] were enrolled for
`
`Reference ID: 4999640
`
`

`

`a placebo-controlled 160-week period instead, followed by a 12-week off-treatment follow-up. For those
`participating in this 160-week period, patients received SAXENDA for a mean treatment duration of 110 weeks
`(median, 159 weeks). For all trials, dosing was initiated and increased weekly to reach the 3 mg dose.
`
`In adult clinical trials, 9.8% of patients treated with SAXENDA and 4.3% of patients treated with placebo
`prematurely discontinued treatment as a result of adverse reactions. The most common adverse reactions
`leading to discontinuation were nausea (2.9% versus 0.2% for SAXENDA and placebo, respectively), vomiting
`(1.7% versus less than 0.1%), and diarrhea (1.4% versus 0%).
`
`Adverse reactions reported in greater than or equal to 2% of SAXENDA-treated adult patients and more
`frequently than in placebo-treated patients are shown in Table 4. Adverse reactions reported in greater than or
`equal to 3% of SAXENDA-treated pediatric patients and more frequently than in placebo-treated patients are
`shown in Table 5.
`
`Table 4. Adverse Reactions Occurring in > 2% of SAXENDA-treated Adult Patients and More
`Frequently than Placebo
`
`
`
`
`SAXENDA
`Placebo
`N = 3384
`N = 1941
`%
`%
` Nausea
`39.3
`13.8
` Diarrhea
`20.9
`9.9
` Constipation
`19.4
`8.5
` Vomiting
`15.7
`3.9
` Injection Site Reaction1
`13.9
`10.5
` Headache
`13.6
`12.6
` Hypoglycemia in T2DM2
`12.6
`6.6
` Dyspepsia
`9.6
`2.7
`7.5
`4.6
` Fatigue
` Dizziness
`6.9
`5.0
`5.4
`3.1
` Abdominal Pain
`5.3
`2.2
` Increased Lipase
` Upper Abdominal Pain
`5.1
`2.7
`4.7
`3.2
` Gastroenteritis
` Gastroesophageal Reflux Disease
`4.7
`1.7
` Abdominal Distension
`4.5
`3.0
` Eructation
`4.5
`0.2
`4.3
`3.1
` Urinary Tract Infection
` Flatulence
`4.0
`2.5
`2.8
`1.6
` Viral Gastroenteritis
`2.4
`1.7
` Insomnia
` Dry Mouth
`2.3
`1.0
` Asthenia
`2.1
`0.8
`2.0
`1.6
` Anxiety
`1 The most common reactions, each reported by 1% to 2.5% of SAXENDA-treated patients and more commonly than by placebo-
`treated patients, included erythema, pruritus, and rash at the injection site.
`2 Defined as blood glucose <54 mg/dL with or without symptoms of hypoglycemia in patients with type 2 diabetes
`not on concomitant insulin (Study 2, SAXENDA N=423, Placebo N=212). See text below for further information regarding
`hypoglycemia in patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus
`
`
`
`
`Reference ID: 4999640
`
`

`

`Table 5. Adverse Reactions Occurring in > 3% of SAXENDA-treated Pediatric Patients and More
`Frequently than Placebo in a 56 Week Clinical Trial
`
`
`
`SAXENDA
`Placebo
`N = 125
`N = 126
`%
`%
` Nausea
`42.4
`14.3
` Vomiting
`34.4
`4.0
` Diarrhea
`22.4
`14.3
` Hypoglycemia1
`15.2
`4.0
` Gastroenteritis
`12.8
`4.8
` Dizziness
`10.4
`3.2
`8.0
`7.1
` Pyrexia
`4.8
`0.8
` Abdominal discomfort
` Constipation
`4.8
`2.4
`4.8
`3.2
` Dyslipidemia
`4.8
`3.2
` Fatigue
`4.0
`3.2
` Cough
`4.0
`2.4
` Depression
` Dyspepsia
`4.0
`2.4
`4.0
`2.4
` Pain in extremity
` Injection site pain
`3.2
`3.2
` Flatulence
`3.2
`0
` Increased Blood Creatine Kinase
`3.2
`2.4
`3.2
`0.8
` Increased Lipase
`3.2
`0
` Rash
`1 Defined as blood glucose <70 mg/dL with symptoms of hypoglycemia. Pediatric patients did not have type 2 diabetes mellitus. See
`text below for more detailed hypoglycemia information.
`
`Hypoglycemia
`
`Adult Patients with Type 2 Diabetes
`In a clinical trial in adult patients with type 2 diabetes mellitus and overweight (excess weight) or obesity,
`severe hypoglycemia (defined as requiring the assistance of another person) occurred in 3 (0.7%) of 422
`SAXENDA-treated patients (all taking a sulfonylurea) and in none of the 212 placebo-treated patients. In this
`trial, among patients taking a sulfonylurea, hypoglycemia defined as a plasma glucose less than 54 mg/dL with
`or without symptoms occurred in 31 (28.2%) of 110 SAXENDA-treated patients and 7 (12.7%) of 55 placebo-
`treated patients. The doses of sulfonylureas were reduced by 50% at the beginning of the trial per protocol.
`Among patients not taking a sulfonylurea, blood glucose less than 54 mg/dL with or without symptoms
`occurred in 22 (7.1%) of 312 SAXENDA-treated patients and 7 (4.5%) of 157 placebo-treated patients.
`
`In a SAXENDA clinical trial in adult patients with overweight (excess weight) or obesity with type 2 diabetes
`mellitus treated with basal insulin and SAXENDA in combination with a reduced-calorie diet and increased
`physical activity and up to 2 oral anti-diabetes medications, severe hypoglycemia was reported by 3 (1.5%) of
`195 SAXENDA-treated patients and 2 (1.0%) of 197 placebo-treated patients. No meaningful difference in
`hypoglycemia, defined as blood glucose less than 54 mg/dL with or without symptoms, was reported between
`groups.
`
`Adult Patients without Type 2 Diabetes
`In SAXENDA clinical trials in adult patients without type 2 diabetes mellitus, there was no systematic
`capturing or reporting of hypoglycemia; patients were not provided with blood glucose meters or hypoglycemia
`diaries. Spontaneously reported symptomatic episodes of unconfirmed hypoglycemia were reported by 46
`
`Reference ID: 4999640
`
`

`

`(1.6%) of 2962 SAXENDA-treated patients and 19 (1.1%) of 1729 placebo-treated patients. Fasting plasma
`glucose values obtained at routine clinic visits less than 54 mg/dL, irrespective of hypoglycemic symptoms,
`occurred in 2 (0.1%) SAXENDA-treated patients and 1 (0.1%) placebo-treated patients.
`
`
`Pediatric Patients without Type 2 Diabetes
`In a 56-week placebo-controlled clinical trial of pediatric patients without type 2 diabetes mellitus in which
`blood glucose meters were provided, 19 (15.2%) of SAXENDA-treated patients had hypoglycemia with a