`
`
`
`
`
`
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE FORMS AND STRENGTHS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`Injection, pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg,
`•
`1.8 mg, 2.4 mg or 3 mg (6 mg/mL, 3 mL) (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 product components (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).
`• Serious Hypoglycemia: Can occur when Saxenda is used with an insulin
`secretagogue (e.g. a sulfonylurea). Consider lowering the dose of anti-
`diabetic drugs to reduce the risk 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, hypoglycemia, diarrhea, constipation, vomiting, headache,
`decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, and
`increased lipase (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).
`
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙USE IN SPECIFIC POPULATIONS∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• Pediatric Use: Safety and effectiveness not established and use not
`recommended (8.4).
`
`See 17 for PATIENT COUNSELING INFORMATION and
`Medication Guide.
` Revised:10/2018
`
`
`
`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∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`
`Indications and Usage, Limitations of Use (1)……………………10/2018
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙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) (1) 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).
`Limitations of Use:
`• Saxenda is not indicated for the treatment of type 2 diabetes (1).
`• Saxenda should not be used in combination with any other GLP-1
`receptor agonist (1).
`• Saxenda should not be used with insulin (1, 5.4).
`• The safety and efficacy of coadministration with other products for
`weight loss have not been established (1).
`
`∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙DOSAGE AND ADMINISTRATION∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙
`• Recommended dose of Saxenda is 3 mg daily. Administer at any
`time of day, without regard to the timing of meals (2).
`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).
`Inject subcutaneously in the abdomen, thigh or upper arm (2).
`•
`• The injection site and timing can be changed without dose
`adjustment (2).
`
`•
`
`Reference ID: 4337722
`
`

`

`8
`
`10
`11
`12
`
`
`
`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
`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.
`
`13
`
`14
`16
`
`17
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`BOXED WARNING: RISK OF THYROID C-CELL TUMORS
`
`
`
` 1
`
`
`2
`3
`4
`5
`
`INDICATIONS AND USAGE
`DOSAGE AND ADMINISTRATION
`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 Risk for Hypoglycemia with Concomitant Use of
` Anti-Diabetic Therapy
` 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 Postmarketing Experience
`DRUG INTERACTIONS
` Oral Medications
`7.1
`
`7
`
`
`
`
`
`
`
`Reference ID: 4337722
`
`

`

`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
`
`
`• 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)
`
`
`Limitations of Use
` Saxenda is not indicated for the treatment of type 2 diabetes mellitus.
`
` Saxenda and Victoza® both contain the same active ingredient, liraglutide, and therefore should not be used
`together. Saxenda should not be used in combination with any other GLP-1 receptor agonist.
`
` Saxenda has not been studied in patients taking insulin. Saxenda and insulin should not be used together [see
`Warnings and Precautions (5.4)].
`
` 
`
` 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 ADMINISTRATION
`
`The recommended dosage of Saxenda is 3 mg daily. The dose escalation schedule in Table 1 should be used to
`reduce the likelihood of gastrointestinal symptoms. If patients do not tolerate an increased dose during dose
`escalation, consider delaying dose escalation for approximately one additional week. Saxenda should be
`discontinued, however, if a patient cannot tolerate the 3 mg dose, as efficacy has not been established at lower
`doses (0.6, 1.2, 1.8, and 2.4 mg).
`
`Table 1.
`
`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
`
`
`
`Reference ID: 4337722
`
`

`

`Saxenda should be taken once daily at any time of day, without regard to the timing of meals. Saxenda can be
`injected subcutaneously in the abdomen, thigh, or upper arm. The injection site and timing can be changed
`without dose adjustment. Saxenda must not be administered intravenously or intramuscularly.
`
`When initiating Saxenda in patients taking insulin secretagogues (such as sulfonylureas), consider reducing the
`dose of the insulin secretagogue (for example, by one-half) to reduce the risk for hypoglycemia, and monitor
`blood glucose. Saxenda and insulin should not be used together [see Warnings and Precautions (5.4) and
`Adverse Reactions (6.1)]. Conversely, if discontinuing Saxenda in patients with type 2 diabetes, monitor for an
`increase in blood glucose.
`
`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.
`
`If a dose is missed, the once-daily regimen should be resumed as prescribed with the next scheduled dose. An
`extra dose or increase in dose should not be taken to make up for the missed dose. If more than 3 days have
`elapsed since the last Saxenda dose, patients should reinitiate Saxenda at 0.6 mg daily and follow the dose
`escalation schedule in Table 1, which may reduce the occurrence of gastrointestinal symptoms associated with
`reinitiation of treatment.
`
`Prior to initiation of Saxenda, patients should be trained by their healthcare professional on proper injection
`technique. Training reduces the risk of administration errors such as needle sticks and incomplete dosing. Refer
`to the accompanying Instructions for Use for complete administration instructions with illustrations.
`
`Saxenda solution should be inspected prior to each injection, and the solution should be used only if it is clear,
`colorless, and contains no particles.
`
`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 2.
`
` Table 2.
`
`BMI Conversion Chart
`
`
`
`Reference ID: 4337722
`
`
`
`

`

`DOSAGE FORMS AND STRENGTHS
`3
`Solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4
`mg, or 3 mg (6 mg/mL, 3 mL).
`
`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)].
`• Patients with a prior serious hypersensitivity reaction to liraglutide or to any of the product components
`[see Warnings and Precautions (5.7)].
`• Pregnancy [see Use in Specific Populations (8.1)].
`
` 4
`
` 5
`
`WARNINGS AND PRECAUTIONS
`
`5.1 Risk of Thyroid C-cell Tumors
`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.
`
`5.2 Acute Pancreatitis
`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, 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.
`
`
`Reference ID: 4337722
`
`

`

`Liraglutide has been studied in a limited number of 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
`In Saxenda clinical trials, 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 Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy
`The risk for serious hypoglycemia is increased when Saxenda is used in combination with insulin secretagogues
`(for example, sulfonylureas) in patients with type 2 diabetes mellitus. Therefore, patients may require a lower
`dose of sulfonylurea (or other concomitantly administered insulin secretagogues) in this setting [see Dosage
`and Administration (2) and Adverse Reactions (6.1)]. Saxenda should not be used in patients taking insulin.
`
`Saxenda can lower blood glucose [see Clinical Pharmacology (12.2)]. Monitor blood glucose parameters prior
`to starting Saxenda and during Saxenda treatment in patients with type 2 diabetes. If needed, adjust co-
`administered anti-diabetic drugs based on glucose monitoring results and risk 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 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.
`
`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.
`
`5.6 Renal Impairment
`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
`when initiating or escalating doses of Saxenda in patients with renal impairment [see Use in Specific
`Populations (8.6)].
`
`5.7 Hypersensitivity Reactions
`
`Reference ID: 4337722
`
`

`

`There have been reports of serious hypersensitivity reactions (e.g., anaphylactic reactions and angioedema) in
`patients treated with liraglutide [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 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. 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 patients treated with Saxenda for a treatment period up to 56 weeks (3 trials), 52 weeks (1 trial), and 32
`weeks (1 trial). All patients received study drug in addition to diet and exercise counseling. In these 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)] were enrolled for 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 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%).
`
`
`Reference ID: 4337722
`
`

`

`Adverse reactions reported in greater than or equal to 2% of Saxenda-treated patients and more frequently than
`in placebo-treated patients are shown in Table 3.
`
`Table 3.
`
`Adverse Reactions Reported in Greater Than or Equal to 2% of Saxenda-treated Patients
`and More Frequently than with Placebo*
`
`Placebo
`N = 1941
`%
`
`13.8
`9.9
`8.5
`3.9
`2.7
`3.1
`2.7
`1.7
`3.0
`0.2
`2.5
`1.0
`
`12.7
`2.3
`
`12.6
`5.0
`
`
`Saxenda
`N = 3384
`%
`
`39.3
`20.9
`19.4
`15.7
`9.6
`5.4
`5.1
`4.7
`4.5
`4.5
`4.0
`2.3
`
`23.0
`10.0
`
`13.6
`6.9
`
`
`
`
`
`Reference ID: 4337722
`
`Gastrointestinal Disorders
` Nausea
` Diarrhea
` Constipation
` Vomiting
` Dyspepsia
` Abdominal Pain
` Upper Abdominal Pain
` Gastroesophageal Reflux Disease
` Abdominal Distension
` Eructation
` Flatulence
` Dry Mouth
`Metabolism and Nutrition Disorders
` Hypoglycemia in T2DM1
` Decreased Appetite
`Nervous System Disorders
` Headache
` Dizziness
`General Disorders and Administration Site
`Conditions
`7.5
`4.6
` Fatigue
` Injection Site Erythema
`2.5
`0.2
`2.5
`0.6
` Injection Site Reaction
` Asthenia
`2.1
`0.8
`Infections and Infestations
`
`
`4.7
`3.2
` Gastroenteritis
`4.3
`3.1
` Urinary Tract Infection
`2.8
`1.6
` Viral Gastroenteritis
`Investigations
`
`
`5.3
`2.2
` Increased Lipase
`Psychiatric Disorders
`
`
`2.4
`1.7
` Insomnia
`2.0
`1.6
` Anxiety
`1 Documented symptomatic (defined as documented symptoms of hypoglycemia in combination with a plasma glucose less than or
`equal to 70 mg/dL) in patients with type 2 diabetes (Study 2). See text below for further information regarding hypoglycemia in
`patients with and without type 2 diabetes. T2DM = type 2 diabetes mellitus
`* Adverse reactions for trials with treatment period up to 56 weeks
`
`Hypoglycemia
`Saxenda can lower blood glucose. In a clinical trial involving patients with type 2 diabetes mellitus and
`overweight or obesity, severe hypoglycemia (defined as requiring the assistance of another person) occurred in
`3 (0.7%) of 422 Saxenda-treated patients and in none of the 212 placebo-treated patients. Each of these 3
`
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`

`Saxenda-treated patients was also taking a sulfonylurea. In the same trial, among patients taking a sulfonylurea,
`documented symptomatic hypoglycemia (defined as documented symptoms of hypoglycemia in combination
`with a plasma glucose less than or equal to 70 mg/dL) occurred in 48 (43.6%) of 110 Saxenda-treated patients
`and 15 (27.3%) of 55 placebo-treated patients. The doses of sulfonylureas were reduced by 50% at the
`beginning of the trial per protocol. The frequency of hypoglycemia may be higher if the dose of sulfonylurea is
`not reduced. Among patients not taking a sulfonylurea, documented symptomatic hypoglycemia occurred in 49
`(15.7%) of 312 Saxenda-treated patients and 12 (7.6%) of 157 placebo-treated patients.
`
`In Saxenda clinical trials involving patients without type 2 diabetes mellitus, there was no systematic capturing
`or reporting of hypoglycemia, as patients were not provided with blood glucose meters or hypoglycemia diaries.
`Spontaneously reported symptomatic episodes of unconfirmed hypoglycemia were reported by 46 (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 or equal to 70 mg/dL, irrespective of hypoglycemic symptoms, were
`reported as “hypoglycemia” in 92 (3.1%) Saxenda-treated patients and 13 (0.8%) placebo-treated patients.
`
`Gastrointestinal Adverse Reactions
`In the clinical trials, approximately 68% of Saxenda-treated patients and 39% of placebo-treated patients
`reported gastrointestinal disorders; the most frequently reported was nausea (39% and 14% of patients treated
`with Saxenda and placebo, respectively). The percentage of patients reporting nausea declined as treatment
`continued. Other common adverse reactions that occurred at a higher incidence among Saxenda-treated patients
`included diarrhea, constipation, vomiting, dyspepsia, abdominal pain, dry mouth, gastritis, gastroesophageal
`reflux disease, flatulence, eructation and abdominal distension. Most episodes of gastrointestinal events were
`mild or moderate and did not lead to discontinuation of therapy (6.2% with Saxenda versus 0.8% with placebo
`discontinued treatment as a result of gastrointestinal adverse reactions). There have been reports of
`gastrointestinal adverse reactions, such as nausea, vomiting, and diarrhea, associated with volume depletion and
`renal impairment [see Warnings and Precautions (5.6)].
`
`Asthenia, Fatigue, Malaise, Dysgeusia and Dizziness
`Events of asthenia, fatigue, malaise, dysgeusia and dizziness were mainly reported within the first 12 weeks of
`treatment with Saxenda and were often co-reported with gastrointestinal events such as nausea, vomiting, and
`diarrhea.
`
`Immunogenicity
`Patients treated with Saxenda may develop anti-liraglutide antibodies. Anti-liraglutide antibodies were detected
`in 42 (2.8%) of 1505 Saxenda-treated patients with a post-baseline assessment. Antibodies that had a
`neutralizing effect on liraglutide in an in vitro assay occurred in 18 (1.2%) of 1505 Saxenda-treated patients.
`Presence of antibodies may be associated with a higher incidence of injection site reactions and reports of low
`blood glucose. In clinical trials, these events were usually classified as mild and resolved while patients
`continued on treatment.
`
`The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
`Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be
`influenced by several factors including assay methodology, sample handling, timing of sample collection,
`concomitant medications, and underlying disease. For these reasons, the incidence of antibodies to Saxenda
`cannot be directly compared with the incidence of antibodies of other products.
`
`Allergic Reactions
`Urticaria was reported in 0.7% of Saxenda-treated patients and 0.5% of placebo-treated patients. Anaphylactic
`reactions, asthma, bronchial hyperreactivity, bronchospasm, oropharyngeal swelling, facial swelling,
`angioedema, pharyngeal edema, type IV hypersensitivity reactions have been reported in patients treated with
`liraglutide in clinical trials. Cases of anaphylactic reactions with additional symptoms such as hypotension,
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`Reference ID: 4337722
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`palpitations, dyspnea, and edema have been reported with marketed use of liraglutide. Anaphylactic reactions
`may potentially be life-threatening.
`
`Injection Site Reactions
`Injection site reactions were reported in approximately 13.9% of Saxenda-treated patients and 10.5% of
`placebo-treated patients. 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.
`0.6% of Saxenda-treated patients and 0.5% of placebo-treated patients discontinued treatment due to injection
`site reactions.
`
`Breast Cancer
`In Saxenda clinical trials, breast cancer confirmed by adjudication was reported in 17 (0.7%) of 2379 Saxenda-
`treated women compared with 3 (0.2%) of 1300 placebo-treated women, including invasive cancer (13
`Saxenda- and 2 placebo-treated women) and ductal carcinoma in situ (4 Saxenda- and 1 placebo-treated
`woman). The majority of cancers were estrogen- and progesterone-receptor positive. There were too few cases
`to determine whether these cases were related to Saxenda. In addition, there are insufficient data to determine
`whether Saxenda has an effect on pre-existing breast neoplasia.
`
`Papillary Thyroid Cancer
`In Saxenda clinical trials, papillary thyroid carcinoma confirmed by adjudication was reported in 8 (0.2%) of
`3291 Saxenda-treated patients compared with no cases among 1843 placebo-treated patients. Four of these
`papillary thyroid carcinomas were less than 1 cm in greatest diameter and 4 were diagnosed in surgical
`pathology specimens after thyroidectomy prompted by findings identified prior to treatment.
`
`Colorectal Neoplasms
`In Saxenda clinical trials, benign colorectal neoplasms (mostly colon adenomas) confirmed by adjudication
`were reported in 20 (0.6%) of 3291 Saxenda-treated patients compared with 7 (0.4%) of 1843 placebo-treated
`patients. Six positively adjudicated cases of malignant colorectal neoplasms were reported in 5 Saxenda-treated
`patients (0.2%, mostly adenocarcinomas) and 1 in a placebo-treated patient (0.1%, neuroendocrine tumor of the
`rectum).
`
`Cardiac Conduction Disorders
`In Saxenda clinical trials, 11 (0.3%) of 3384 Saxenda-treated patients compared with none of the 1941 placebo-
`treated patients had a cardiac conduction disorder, reported as first degree atrioventricular block, right bundle
`branch block, or left bundle branch block.
`
`Hypotension
`Adverse reactions related to hypotension (that is, reports of hypotension, orthostatic