INDICATIONS

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 (obesity), 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.
• 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.

DOSAGE

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).

SIDE EFFECTS

The following serious adverse reactions are described below or elsewhere in the prescribing information:

• Risk of Thyroid C-Cell Tumors
• Acute Pancreatitis
• Acute Gallbladder Disease
• Risk for Hypoglycemia with Concomitant Use of Anti-Diabetic Therapy
• Heart Rate Increase
• Renal Impairment
•  Hypersensitivity Reactions
• Suicidal Behavior and Ideation

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 patients with overweight (excess weight) or obesity 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) 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*

Hypoglycemia

Patients with Type 2 Diabetes

In a clinical trial in 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 Saxendatreated 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. Because Saxenda can lower blood glucose, 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, 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 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.

Patients without Type 2 Diabetes

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 54 mg/dL, irrespective of hypoglycemic symptoms, were reported as “hypoglycemia” in 2 (0.1%) Saxenda-treated patients and 1 (0.1%) 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.

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 Saxendatreated 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 placebotreated 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 Saxendatreated patients had hypotension associated with gastrointestinal adverse reactions and renal failure.

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. 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 pretreatment 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 placebotreated patients. The clinical significance of elevations in lipase or amylase with Saxenda is unknown in the absence of other signs and symptoms of pancreatitis

Postmarketing 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

Gastrointestinal Disorders

Acute pancreatitis, hemorrhagic and necrotizing pancreatitis, sometimes resulting in death

Metabolism And Nutrition Disorders

Dehydration resulting from nausea, vomiting and diarrhea

Renal And Urinary Disorders

Increased serum creatinine, acute renal failure or worsening of chronic renal failure, sometimes requiring hemodialysis

General Disorders And Administration Site Conditions

Allergic reactions: rash and pruritus

Immune System Disorders

Angioedema and anaphylactic reactions

Hepatobiliary Disorders

Elevations of liver enzymes, hyperbilirubinemia, cholestasis and hepatitis.

DRUG INTERACTIONS

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.

PATIENT INFORMATION

SAXENDA
(sax-end-ah)
(liraglutide) injection, for subcutaneous use

Do not share your SAXENDA pen with others even if the needle has been changed. You may give other people a serious infection or get a serious infection from them.

What is the most important information I should know about SAXENDA?

Serious side effects may happen in people who take SAXENDA, including:

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

Do not use SAXENDA if you or any of your family have ever had a type of thyroid cancer called medullary thyroid carcinoma (MTC), or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

What is SAXENDA?

SAXENDA is an injectable prescription medicine used for adults with obesity or overweight (excess weight) who also have weight related medical problems to help them lose weight and keep the weight off.

• SAXENDA should be used with a reduced calorie meal plan and increased physical activity.
• SAXENDA is not for the treatment of type 2 diabetes mellitus.
• SAXENDA and VICTOZA have the same active ingredient, liraglutide, and should not be used together or with other GLP-1 receptor agonist medicines.
• It is not known if SAXENDA is safe and effective when taken with other prescription over-the-counter medicines or herbal weight loss products.
• It is not known if SAXENDA is safe and effective in children under 18 years of age.

Who should not use SAXENDA?

Do not use SAXENDA if:

• you or any of your family have ever had a type of thyroid cancer called medullary thryroid carcinoma (MTC) or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• you are allergic to liraglutide or any of the ingredients in SAXENDA. See the end of this Medication Guide for a complete list of ingredients in SAXENDA.
• you are pregnant or plan to become pregnant. SAXENDA may harm your unborn baby.

Before taking SAXENDA, tell your healthcare provider if you have any other medical conditions, including if you:

• are taking certain medicines called GLP-1 receptor agonists.
• have severe problems with your stomach, such as slowed emptying of your stomach (gastroparesis) or problems with digesting food.
• have or have had problems with your pancreas, kidneys or liver.
• have or have had depression, suicidal thoughts, or mental health issues.
• are breastfeeding or plan to breastfeed. It is not known if SAXENDA passes into your breast milk. You and your healthcare provider should decide if you will take SAXENDA or breastfeed.

Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, and herbal supplements. SAXENDA slows stomach emptying and can affect medicines that need to pass through the stomach quickly. SAXENDA may affect the way some medicines work and some other medicines may affect the way SAXENDA works.

Tell your healthcare provider if you take diabetes medicines, especially insulin and sulfonylurea medicines. Talk with your healthcare provider if you are not sure if you take any of these medicines.

How should I use SAXENDA?

• • Read the Instructions for Use that comes with SAXENDA.
  • Use SAXENDA exactly as prescribed by your healthcare provider.
  • Your healthcare provider should show you how to use SAXENDA before you use it for the first time.
  • Start SAXENDA with 0.6 mg per day in your first week. In your second week, increase your daily dose to 1.2 mg. In the third week, increase your daily dose to 1.8 mg. In the fourth week, increase your daily dose to 2.4 mg and in the fifth week onwards, increase your daily dose to the full dose of 3.0 mg. After that, do not change your dose unless your healthcare provider tells you to.
  • SAXENDA is injected 1 time each day, at any time during the day.
  • Inject your dose of SAXENDA under the skin (subcutaneously) in your stomach area (abdomen), upper leg (thigh), or upper arm, as instructed by your healthcare provider. Do not inject into a vein or muscle.
  • If you take too much SAXENDA, call your healthcare provider right away. Taking too much SAXENDA may cause severe nausea and vomiting.
  • If you miss your daily dose of SAXENDA, take the missed dose as soon as you remember. Take your next daily dose as usual on the following day. Do not take an extra dose of SAXENDA or increase your dose on the following day to make up for your missed dose. If you miss your dose of SAXENDA for 3 days or more, call your healthcare provider to talk about how to restart your treatment.

• You can take SAXENDA with or without food.
• Throw away the used SAXENDA pen after 30 days.

Your healthcare provider should start you on a reduced calorie meal plan and increased physical activity when you start taking SAXENDA. Stay on this program while you are taking SAXENDA.

What are the possible side effects of SAXENDA?

SAXENDA may cause serious side effects, including:

• See “What is the most important information I should know about SAXENDA?”
• inflammation of the pancreas (pancreatitis). Stop using SAXENDA and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without vomiting. You may feel the pain from your stomach area (abdomen) to your back.
• gallbladder problems. SAXENDA may cause gallbladder problems including gallstones. Some gallbladder problems need surgery. Call your healthcare provider if you have any of the following symptoms:
  • pain in your upper stomach (abdomen)
  • fever
  • yellowing of your skin or eyes (jaundice)
  • clay-colored stools
• increased risk of low blood sugar (hypoglycemia) in people with type 2 diabetes mellitus who also take medicines to treat type 2 diabetes mellitus such as sulfonylureas or insulin. Signs and symptoms of low blood sugar may include:
  • shakiness
  • sweating
  • headache
  • drowsiness
  • weakness
  • dizziness
  • confusion
  • irritability
  • hunger
  • fast heartbeat
  • feeling jittery

  Talk to your healthcare provider about how to recognize and treat low blood sugar. You should check your blood sugar before you start taking SAXENDA and while you take SAXENDA.

• increased heart rate. SAXENDA can increase your heart rate while you are at rest. Your healthcare provider should check your heart rate while you take SAXENDA. Tell your healthcare provider if you feel your heart racing or pounding in your chest and it lasts for several minutes.
• kidney problems (kidney failure). SAXENDA may cause nausea, vomiting or diarrhea leading to loss of fluids (dehydration). Dehydration may cause kidney failure which can lead to the need for dialysis. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration. Call your healthcare provider right away if you have nausea, vomiting, or diarrhea that does not go away, or if you cannot drink liquids by mouth.
• serious allergic reactions. Stop using SAXENDA, and get medical help right away if you have any symptoms of a serious allergic reaction including:
  • swelling of your face, lips, tongue, or throat
  • fainting or feeling dizzy
  • very rapid heartbeat
  • problems breathing or swallowing
  • severe rash or itching
• depression or thoughts of suicide. You should pay attention to any mental changes, especially sudden changes, in your mood, behaviors, thoughts, or feelings. Call your healthcare provider right away if you have any mental changes that are new, worse, or worry you.

The most common side effects of SAXENDA include:

• nausea
• low blood sugar (hypoglycemia)
• dizziness
• diarrhea
• headache
• stomach pain
• constipation
• vomiting
• upset stomach (dyspepsia)
• tiredness (fatigue)
• change in enzyme (lipase) levels in your blood

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of SAXENDA. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Keep your SAXENDA pen, pen needles, and all medicines out of the reach of children.

General information about the safe and effective use of SAXENDA.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use SAXENDA for a condition for which it was not prescribed. Do not give SAXENDA to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about SAXENDA that is written for health professionals.

What are the ingredients in SAXENDA?

Active ingredient: liraglutide

Inactive ingredients: disodium phosphate dihydrate, propylene glycol, phenol and water for injection.

This Medication Guide has been approved by the U.S. Food and Drug Administration