This information is not for clinical use. These highlights do not include all the information needed to use Saxenda safely and effectively. Before taking Saxenda please consult with your doctor. See full prescribing information for Saxenda.
BOXED 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)]. 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).
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. 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).
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Dosage And Administration
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Dosage Forms And Strengths
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). •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).
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)]. •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).
Warning and Cautions
•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 post-marketing, 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: Post-marketing 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). 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 post-marketing 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 post-marketing 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. 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 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.
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)] •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. 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%). 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 % Saxenda N = 3384 % Gastrointestinal Disorders Nausea 13.8 39.3 Diarrhea 9.9 20.9 Constipation 8.5 19.4 Vomiting 3.9 15.7 Dyspepsia 2.7 9.6 Abdominal Pain 3.1 5.4 Upper Abdominal Pain 2.7 5.1 Gastroesophageal Reflux Disease 1.7 4.7 Abdominal Distension 3.0 4.5 Eructation 0.2 4.5 Flatulence 2.5 4.0 Dry Mouth 1.0 2.3 Metabolism and Nutrition Disorders Hypoglycemia in T2DM1 12.7 23.0 Decreased Appetite 2.3 10.0 Nervous System Disorders Headache 12.6 13.6 Dizziness 5.0 6.9 General Disorders and Administration Site Conditions Fatigue 4.6 7.5 Injection Site Erythema 0.2 2.5 Injection Site Reaction 0.6 2.5 Asthenia 0.8 2.1 Infections and Infestations Gastroenteritis 3.2 4.7 Urinary Tract Infection 3.1 4.3 Viral Gastroenteritis 1.6 2.8 Investigations Increased Lipase 2.2 5.3 Psychiatric Disorders Insomnia 1.7 2.4 Anxiety 1.6 2.0 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 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, 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 hypotension, circulatory collapse, and decreased blood pressure) were reported more frequently with Saxenda (1.1%) compared with placebo (0.5%) in Saxenda clinical trials. Systolic blood pressure decreases to less than 80 mmHg were observed in 4 (0.1%) Saxenda-treated patients compared with no placebo-treated patients. One of the Saxenda-treated patients had hypotension associated with gastrointestinal adverse reactions and renal failure [see Warnings and Precautions (5.6)]. Laboratory Abnormalities Liver Enzymes Increases in alanine aminotransferase (ALT) greater than or equal to 10 times the upper limit of normal were observed in 5 (0.15%) Saxenda-treated patients (two of whom had ALT greater than 20 and 40 times the upper limit of normal) compared with 1 (0.05%) placebo-treated patient during the Saxenda clinical trials. Because clinical evaluation to exclude alternative causes of ALT and aspartate aminotransferase (AST) increases was not done in most cases, the relationship to Saxenda is uncertain. Some increases in ALT and AST were associated with other confounding factors (such as gallstones). Serum Calcitonin Calcitonin, a biological marker of MTC, was measured throughout the clinical development program [see Warnings and Precautions (5.1)]. More patients treated with Saxenda in the clinical trials were observed to have high calcitonin values during treatment, compared with placebo. The proportion of patients with calcitonin greater than or equal to 2 times the upper limit of normal at the end of the trial was 1.2% in Saxenda-treated patients and 0.6% in placebo-treated patients. Calcitonin values greater than 20 ng/L at the end of the trial occurred in 0.5% of Saxenda-treated patients and 0.2% of placebo-treated patients; among patients with pre-treatment serum calcitonin less than 20 ng/L, none had calcitonin elevations to greater than 50 ng/L at the end of the trial. Serum Lipase and Amylase Serum lipase and amylase were routinely measured in the Saxenda clinical trials. Among Saxenda-treated patients, 2.1% had a lipase value at anytime during treatment of greater than or equal to 3 times the upper limit of normal compared with 1.0% of placebo-treated patients. 0.1% of Saxenda-treated patients had an amylase value at anytime in the trial of greater than or equal to 3 times the upper limit of normal versus 0.1% of placebo-treated patients. The clinical significance of elevations in lipase or amylase with Saxenda is unknown in the absence of other signs and symptoms of pancreatitis [see Warnings and Precautions (5.2)]. 6.2 Post-Marketing Experience The following adverse reactions have been reported during post-approval use of liraglutide, the active ingredient of Saxenda. 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. Neoplasms Medullary thyroid carcinoma [see Warnings and Precautions (5.1)] Gastrointestinal Disorders Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death [see Warnings and Precautions (5.2)] Metabolism and Nutrition Disorders Dehydration resulting from nausea, vomiting and diarrhea [see Adverse Reactions (6.1)] Renal and Urinary Disorders Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis [see Warnings and Precautions (5.6)] General Disorders and Administration Site Conditions Allergic reactions: rash and pruritus [see Adverse Reactions (6.1)] Immune System Disorders Angioedema and anaphylactic reactions [see Warnings and Precautions (5.7)] Hepatobiliary Disorders Elevations of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis [see Adverse Reactions (6.1)]
•Saxenda delays gastric emptying. May impact absorption of concomitantly administered oral medications. Use with caution (7). 7.1 Oral Medications Saxenda causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, liraglutide did not affect the absorption of the tested orally administered medications to any clinically relevant degree. Nonetheless, monitor for potential consequences of delayed absorption of oral medications concomitantly administered with Saxenda.
Use In Specific Populations
•Pediatric Use: Safety and effectiveness not established and use not recommended (8.4). 8.1 Pregnancy Risk Summary Saxenda is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm [see Clinical Considerations]. There are no available data with liraglutide in pregnant women to inform a drug associated risk for major birth defects and miscarriage. Saxenda should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda should be discontinued. Animal reproduction studies identified increased adverse embryofetal developmental outcomes from exposure during pregnancy. Liraglutide exposure was associated with early embryonic deaths and an imbalance in some fetal abnormalities in pregnant rats administered liraglutide during organogenesis at doses that approximate clinical exposures at the maximum recommended human dose (MRHD) of 3 mg/day. In pregnant rabbits administered liraglutide during organogenesis, decreased fetal weight and an increased incidence of major fetal abnormalities were seen at exposures below the human exposures at the MRHD [see Animal Data]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryofetal risk A minimum weight gain, and no weight loss, is recommended for all pregnant women, including those who are already overweight or obese, due to the necessary weight gain that occurs in maternal tissues during pregnancy. Animal Data Liraglutide has been shown to be teratogenic in rats at or above 0.8-times systemic exposures in obese humans resulting from the maximum recommended human dose (MRHD) of 3 mg/day based on plasma area under the time-concentration curve (AUC) comparison. Liraglutide has been shown to cause reduced growth and increased total major abnormalities in rabbits at systemic exposures below exposure in obese humans at the MRHD based on plasma AUC comparison. Female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide beginning 2 weeks before mating through gestation day 17 had estimated systemic exposures 0.8-, 3-, and 11-times the exposure in obese humans at the MRHD based on plasma AUC comparison. The number of early embryonic deaths in the 1 mg/kg/day group increased slightly. Fetal abnormalities and variations in kidneys and blood vessels, irregular ossification of the skull, and a more complete state of ossification occurred at all doses. Mottled liver and minimally kinked ribs occurred at the highest dose. The incidence of fetal malformations in liraglutide-treated groups exceeding concurrent and historical controls were misshapen oropharynx and/or narrowed opening into larynx at 0.1 mg/kg/day and umbilical hernia at 0.1 and 0.25 mg/kg/day. Pregnant rabbits given subcutaneous doses of 0.01, 0.025 and 0.05 mg/kg/day liraglutide from gestation day 6 through day 18 inclusive, had estimated systemic exposures less than the exposure in obese humans at the MRHD of 3 mg/day at all doses, based on plasma AUC comparison. Liraglutide decreased fetal weight and dose-dependently increased the incidence of total major fetal abnormalities at all doses. The incidence of malformations exceeded concurrent and historical controls at 0.01 mg/kg/day (kidneys, scapula), greater than or equal to 0.01 mg/kg/day (eyes, forelimb), 0.025 mg/kg/day (brain, tail and sacral vertebrae, major blood vessels and heart, umbilicus), greater than or equal to 0.025 mg/kg/day (sternum) and at 0.05 mg/kg/day (parietal bones, major blood vessels). Irregular ossification and/or skeletal abnormalities occurred in the skull and jaw, vertebrae and ribs, sternum, pelvis, tail, and scapula; and dose-dependent minor skeletal variations were observed. Visceral abnormalities occurred in blood vessels, lung, liver, and esophagus. Bilobed or bifurcated gallbladder was seen in all treatment groups, but not in the control group. In pregnant female rats given subcutaneous doses of 0.1, 0.25 and 1 mg/kg/day liraglutide from gestation day 6 through weaning or termination of nursing on lactation day 24, estimated systemic exposures were 0.8-, 3-, and 11-times exposure in obese humans at the MRHD of 3 mg/day, based on plasma AUC comparison. A slight delay in parturition was observed in the majority of treated rats. Group mean body weight of neonatal rats from liraglutide-treated dams was lower than neonatal rats from control group dams. Bloody scabs and agitated behavior occurred in male rats descended from dams treated with 1 mg/kg/day liraglutide. Group mean body weight from birth to postpartum day 14 trended lower in F2 generation rats descended from liraglutide-treated rats compared to F2 generation rats descended from controls, but differences did not reach statistical significance for any group. 8.2 Lactation Risk Summary There are no data on the presence of liraglutide in human milk, the effects on the breastfed infant, or effects on milk production. Liraglutide was present in the milk of lactating rats (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Saxenda and any potential adverse effects on the breastfed infant from Saxenda or from the underlying maternal condition. Data In lactating rats, liraglutide was present unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. 8.4 Pediatric Use Safety and effectiveness of Saxenda have not been established in pediatric patients. Saxenda is not recommended for use in pediatric patients. 8.5 Geriatric Use In the Saxenda clinical trials, 232 (6.9%) of the Saxenda-treated patients were 65 years of age and over, and 17 (0.5%) of the Saxenda-treated patients were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Renal Impairment There is limited experience with Saxenda in patients with mild, moderate, and severe renal impairment, including end‑stage renal disease. However, there have been post-marketing reports of acute renal failure and worsening of chronic renal failure with liraglutide, which may sometimes require hemodialysis [see Warnings and Precautions (5.6) and Adverse Reactions (6.2)]. Saxenda should be used with caution in this patient population [see Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment There is limited experience in patients with mild, moderate, or severe hepatic impairment. Therefore, Saxenda should be used with caution in this patient population [see Clinical Pharmacology (12.3)]. 8.8 Gastroparesis Saxenda slows gastric emptying. Saxenda has not been studied in patients with pre-existing gastroparesis.