Consumer medicine information

Saxenda

Liraglutide

BRAND INFORMATION

Brand name

Saxenda

Active ingredient

Liraglutide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Saxenda.

What is in this leaflet

What Saxenda® is and what it is used for

Before you use Saxenda®

How to use Saxenda®

While you are using Saxenda®

Things to be careful of

Side effects

After using Saxenda®

Product description

Further information

This leaflet answers some common questions about Saxenda®. It does not contain all the available information. It does not take the place of talking to your doctor, nurse or pharmacist.

All medicines have risks and benefits. You should discuss with your doctor the risks of using Saxenda® against the expected benefits.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Saxenda® is and what it is used for

Saxenda® is a weight loss medicine that contains the active ingredient liraglutide. It is similar to a naturally occurring hormone called GLP-1 that is released from the intestine after a meal. Saxenda® is an injection that is used once a day.

Saxenda® is used for weight loss, in addition to diet and exercise, in adults aged 18 years and above who have:

  • a BMI greater than or equal to 30 (obese), or
  • a BMI greater than or equal to 27 and less than 30 (overweight) and weight related health problems (such as diabetes, high blood pressure, abnormal levels of fats in the blood or breathing problems during sleep, called ‘obstructive sleep apnoea’).

You should only continue using Saxenda® if you have lost at least 5% of your initial body weight after 12 weeks on the 3.0 mg/day dose. Consult your doctor before you continue.

Saxenda® should be used with a reduced calorie diet and increased physical activity.

BMI (Body Mass Index) is a simple measure of your weight in relation to your height. It is calculated by dividing your weight in kg by your height in metres squared.

Saxenda® works by acting on receptors in the brain that control your appetite, causing you to feel fuller and less hungry. This may help you eat less food and reduce your body weight.

Weight loss normally starts within 2 weeks and continues for 9 to 12 months on Saxenda® treatment. Saxenda® will then help you to maintain this new lower weight and help to prevent weight being regained.

Saxenda® should not be used in children and adolescents under 18 years. This is because the effects of this medicine have not been studied in this age group.

Saxenda® is not addictive.

Saxenda® is available only with a doctor’s prescription.

Ask your doctor if you have any questions about why Saxenda® has been prescribed for you.

Before you use Saxenda®

When you must not use it

Do not use Saxenda® if you are allergic to liraglutide or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • redness, swelling, rash and itching at the injection site
  • rash, itching or hives on the skin
  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

Before you start to use it

Tell your doctor if:

  • you have palpitations (you feel aware of your heartbeat) or if you have feelings of a racing heartbeat while at rest during Saxenda® treatment.
  • you have diabetes. Do not use Saxenda® as a replacement for insulin. Saxenda® and insulin should not be used together.
  • you have heart failure (disease of the heart with shortness of breath, and swelling of the feet or legs due to fluid build-up). The use of Saxenda® is not recommended if you have severe heart failure.
  • you are taking any other weight loss medications, including prescription, over the counter or herbal medicines.
  • you have inflammatory bowel disease, such as Crohn's disease.
  • you have gastroparesis (a condition in which your stomach has difficulty in emptying food properly).
  • you currently have or have had thyroid disease, including thyroid nodules and enlargement of the thyroid gland.
  • you have kidney disease or are on dialysis (a treatment where your blood is filtered and purified using a machine).
  • you have liver problems.
  • you have or have had a disease of the pancreas.
  • you have or have had depression, suicidal thoughts or any other major mental illness.
  • you have other medical conditions or have taken other medicines that may have caused you to gain weight.

Drink plenty of fluids to avoid dehydration, particularly if you experience vomiting or diarrhoea when beginning treatment with Saxenda®. Dehydration can cause kidney problems that sometimes require dialysis. Contact your doctor if you have any questions or concerns.

Stop taking Saxenda® and contact a doctor immediately if you experience severe pain in your upper abdomen, usually worse on the right side under the ribs. The pain may be felt through to your back or right shoulder. If you lose substantial weight, you are at risk of gallstones and thereby inflamed gallbladder.

There is little experience with Saxenda® in patients ≥ 75 years old. It is not recommended if you are 75 years or older.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant. Use of this medicine in pregnancy has not been studied. Saxenda® should not be used during pregnancy. It is not known if Saxenda® may harm your unborn child.

Tell your doctor if you are breast-feeding or plan to breast-feed. It is not known if Saxenda® passes into breast milk. Do not use Saxenda® if you are breast-feeding.

If you have not told your doctor about any of the above, tell them before you use Saxenda®.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you buy without a prescription from your pharmacy, supermarket, naturopath or health food shop.

In particular, tell your doctor or pharmacist if you are using medicines:

  • for the treatment of type 2 diabetes, such as a sulfonylurea (including glimepiride or glibenclamide). You may get low blood sugar (hypoglycaemia) when you use these medicines with Saxenda®. Your doctor may adjust the dose of your diabetes medicine to prevent you from getting low blood sugar.
  • to thin your blood (anticoagulants), such as warfarin or other types of medicines called ‘coumarin derivatives’. Your doctor may need to monitor you more closely.
  • for high blood pressure, such as amlodipine, atenolol or bisoprolol or for heart disease, such as digoxin.
  • for HIV, such as atazanavir or ritonavir.

Tell your doctor about any other medicines that you are taking. This is very important. Your doctor will advise you if it is alright to keep taking them or if you should stop taking them.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while using Saxenda®.

How to use Saxenda®

Your doctor or pharmacist will have given you advice on how to use your medicine. Carefully follow all the directions. They may differ from the information contained in this leaflet.

If you do not understand the instructions, ask your doctor, nurse or pharmacist for help.

Your doctor will start you on a diet and exercise programme. Stay on this programme while you are using Saxenda®.

Saxenda® is supplied as a pre-filled pen containing liraglutide. The Saxenda® pen can give doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg.

How much to use

Your doctor will tell you how much of this medicine you need to use each day.

  • The usual starting dose is 0.6 mg once a day.
  • Your doctor will tell you how long to keep taking this dose. It will be for at least one week.
  • Your dose may then be increased by 0.6 mg each week until you reach the recommended dose of 3.0 mg once a day.
  • Your doctor will tell you how much Saxenda® to use each week. Usually, you will be told to follow the table below:

Once you reach the recommended dose of 3.0 mg in Week 5 of treatment, keep using this dose until your treatment period ends. Do not increase your dose further.

Visit your doctor on a regular basis to assess your need for continued treatment with Saxenda®.

Do not change your dose unless your doctor has told you to.

When to use it

You can use Saxenda® at any time of day, with or without food and drinks. It is preferable to use Saxenda® at about the same time each day, at a time that is most convenient for you.

How to use it

Before you use the pen for the first time, your doctor or nurse will show you how to use the pen.

  • Saxenda® pre-filled pen is designed to be used with NovoFine® needles, up to a length of 8 mm. Needles are not included with the pen.
  • Ask your doctor or nurse which needle width (gauge) and length is best for you.
  • Use a new needle for each injection and dispose of it after use.
  • Saxenda® is given as an injection under the skin (subcutaneous injection) as shown to you by your doctor or nurse. Never inject Saxenda® into a vein or muscle.
  • Saxenda® may be injected into the front of your waist (abdomen), the front of your thigh, or your upper arm.

Checking your Saxenda® pen:
Saxenda® should be clear and colourless.

Do not use this medicine if it is thickened, coloured, or has solid bits in it.

Read the instructions printed later in this leaflet carefully in order to prepare and handle your Saxenda® pen correctly.

How long to use it

Only continue using Saxenda® if you have lost at least 5% of yourinitial body weight after 12 weeks on the 3.0 mg/day dose (see ‘How much to use,’ above). Consult your doctor before you continue. Your doctor will assess your treatment on a regular basis.

If you use too much (overdose)

If you use more Saxenda® than you should, talk to your doctor or go to a hospital straight away. Take the medicine pack with you. You may need medical treatment. Using too much Saxenda® may cause nausea (feeling sick), vomiting (being sick), or low blood sugar (hypoglycaemia). see below for the early warning signs of hypos.

If you forget to use it

If you forget a dose and remember it within 12 hours from when you usually take the dose, inject Saxenda® as soon as you remember.

However, if more than 12 hours have passed since you should have used Saxenda®, skip the missed dose and inject your next dose the following day at the usual time.

Do not use an extra dose or increase the dose on the following day to make up for the missed dose.

If you are not sure what to do, talk to your doctor, nurse or pharmacist.

While you are using Saxenda®

Things you must do

Tell your doctor if you have diabetes. They may adjust the dose of your diabetes medicine to prevent you getting ‘hypos’ (low blood sugar levels).

  • Do not mix Saxenda® with other medicines that you inject (e.g. insulins).
  • Do not use Saxenda® in combination with other medicines that contain GLP-1 receptor agonists (e.g. exenatide or lixisenatide).

Tell your doctor, nurse or pharmacist if you are travelling. Ask them for a letter explaining why you are taking injecting devices with you. Each country you visit will need to see this letter, so you should take several copies.

You may not be able to get Saxenda® in the country you are visiting.

Your doctor, nurse or pharmacist can provide you with some helpful information.

Things you must not do

Do not stop using your medicine unless your doctor tells you to.

Do not use this medicine if you think it has been frozen or exposed to excessive heat.

Do not use this medicine to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not share needles or pens.

Things to be careful of

Be careful driving or operating machinery until you know how Saxenda® affects you. For further information talk to your doctor or pharmacist.

Side effects

Tell your doctor, nurse or pharmacist as soon as possible if you do not feel well while you are using Saxenda®.

All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor, nurse or pharmacist to answer any questions you may have.

The most common side effects when using Saxenda® are:

  • feeling sick (nausea)
  • being sick (vomiting)
  • diarrhoea
  • constipation
  • headache.

These side effects are usually mild and normally decrease with continued use.

Tell your doctor if you notice any of the following and they worry you:

  • changed sense of taste
  • dizziness
  • indigestion (dyspepsia)
  • feeling bloated, burping, wind (flatulence), or dry mouth
  • heartburn
  • painful or swollen abdomen
  • low blood sugar (a ‘hypo’)
  • injection site reactions (such as bruising, pain, irritation, itching and rash)
  • fast heartbeat
  • feeling weak or tired
  • difficulty sleeping (insomnia).
    This usually occurs during the first 3 months of treatment
  • increase of pancreatic enzymes (such as lipase and amylase).

The above list includes the more common side effects of your medicine. They are usually mild and short-lived.

Other, less common side effects include:

  • feeling generally unwell.
  • urticaria (a type of skin rash).
  • loss of fluids (dehydration). This is more likely to occur at the start of treatment and may be due to you being sick (vomiting), feeling sick (nausea), and diarrhoea.

Hypos are more likely to occur if you have diabetes and are also taking a sulfonylurea. A hypo may come on suddenly. The warning signs of a hypo can include:

  • cold sweat, cool pale skin
  • headache
  • fast heartbeat
  • feeling sick
  • feeling very hungry
  • changes in vision
  • feeling sleepy
  • feeling weak, nervous, anxious, or confused
  • difficulty concentrating
  • shaking (tremor)

Your doctor can provide you with further information about how to treat low blood sugar levels and what to do if you notice these warning signs. If you are already taking a sulfonylurea when you start using Saxenda® your doctor may tell you to reduce the dose of the sulfonylurea.

Tell your doctor immediately if you:

  • experience severe and persistent pain in the abdomen (stomach area) which might reach through to your back, as well as nausea and vomiting. This could be a sign of an inflamed pancreas (pancreatitis). Pancreatitis is a serious, potentially life-threatening medical condition. Stop taking Saxenda® if you experience this.
  • get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath.
  • experience the signs of reduced kidney function, which may include reduction in urine volume, a metallic taste in your mouth and bruising easily.
  • experience upper right side abdominal pain, yellowing of the skin and eyes or clay coloured stools, which may be signs of gallbladder problems.
  • experience depression or have any mental changes (especially sudden changes in mood, behaviours, thoughts or feelings) that are new, worse or worry you.

Tell your doctor if you notice anything else that is making you feel unwell.

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • skin rashes over a large part of the body
  • shortness of breath, wheezing
  • swelling of the face, lips or tongue
  • fast heartbeat
  • sweating.

This list includes very serious side effects that could be signs of a severe allergic reaction. You may need urgent medical attention or hospitalisation. These side effects are rare.

Other side effects not listed above may also occur in some people.

Ask your doctor, nurse or pharmacist to answer any questions you have.

After using Saxenda®

Storage

Store Saxenda® pens that are not being used between 2°C and 8°C in a refrigerator (not in or too near the freezer section or cooling element). Do not freeze. When Saxenda® is being used, you can keep the pen for 1 month either at room temperature (below 30˚C) or in a refrigerator (2˚C to 8˚C), away from the cooling element. Store the pen without a needle attached.

Discard Saxenda® after 1 month even if there is still some medicine left in it.

The medicine in Saxenda® must not be frozen, or exposed to heat or direct sunlight.

When you are not using the pen, keep the pen cap on in order to protect it from light.

Do not use Saxenda® after the expiry date printed on the pen label and carton. The expiry date refers to the last day of that month.

Do not use Saxenda® if the solution is not clear and colourless.

Keep it where children cannot reach it.

Disposal

Dispose of used needles safely into a yellow plastic sharps container.

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Saxenda® is supplied as a clear and colourless solution for injection in a pre-filled pen. Each pen contains 3 mL of solution, and is able to deliver doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3.0 mg.

Saxenda® is available in packs containing 1, 3 or 5 pens. Not all pack sizes may be marketed.

Needles are not included.

Ingredients

Saxenda® contains liraglutide (rys) 6 mg/mL as the active ingredient. The abbreviation ‘rys’ indicates the method of genetic engineering used to manufacture the liraglutide.

Saxenda® also contains the following inactive ingredients: dibasic sodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid, sodium hydroxide and water for injections.

Supplier/Sponsor

Saxenda® is supplied in Australia by:

Novo Nordisk Pharmaceuticals Pty. Ltd.
Level 10
118 Mount Street
North Sydney NSW 2160

Saxenda® is supplied in New Zealand by:

Novo Nordisk Pharmaceuticals Ltd.
58 Richard Pearse Drive
Airport Oaks
Mangere

This leaflet was prepared on 21 June 2021.

Australian Registration Number:
AUST R 225804

Saxenda®, NovoFine® and NovoCare® are trademarks owned by Novo Nordisk A/S.

© 2021
Novo Nordisk A/S

Further information

The Australian ‘Product Information’ document is available from the following websites:

www.novonordisk.com.au
https://www.ebs.tga.gov.au/

For further information call the NovoCare® Customer Care Centre on 1800 668 626 or 0800 733 737 (NZ)..

www.novonordisk.com.au
www.novonordisk.co.nz

For further dietary advice, refer to the dietary guidelines on the NH&MRC website at www.nhmrc.gov.au (Australia), or the current food and nutrition guidelines on the Ministry of Health website at www.health.govt.nz (New Zealand).

Instructions on how to use Saxenda® 6 mg/mL solution for injection in pre-filled pen

Please read these instructions carefully before using your Saxenda® pre-filled pen.

Do not use the pen without proper training from your doctor or nurse. Start by checking your pen to make sure that it contains Saxenda® 6 mg/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the Saxenda® pre-filled pen.

Your pen is a pre-filled dial-a-dose pen. It contains 18 mg of liraglutide, and delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg. Your pen is designed to be used with NovoFine® disposable needles up to a length of 8 mm.
Needles are not included in the pack.

Important information

Pay special attention to these notes as they are important for safe use of the pen.

1 Prepare your pen with a new needle

  • Check the name and coloured label of your pen, to make sure that it contains Saxenda®. This is especially important if you take more than one type of injectable medicine. Using the wrong medicine could be harmful to your health.
  • Pull off the pen cap.

  • Check that the solution in your pen is clear and colourless. Look through the pen window. If the solution looks cloudy, do not use the pen.

  • Take a new NovoFine® needle and tear off the paper tab.

  • Push the needle straight onto the pen. Screw the needle so that it is on tight and secure.

  • Pull off the outer needle cap and keep it for later. You will need it after the injection, to safely remove the needle from the pen.

  • Pull off the inner needle cap and throw it away. If you try to put it back on, you may accidentally stick yourself with the needle.
    A drop of solution may appear at the needle tip. This is normal, but you must still check the flow, if you use a new pen for the first time.
    Do not attach a new needle to your pen until you are ready to take your injection.

Always use a new needle for each injection.
This may prevent blocked needles, contamination, infection and inaccurate dosing.

Never use a bent or damaged needle.

2 Check the flow

  • Before your first injection with each new pen check the flow. If your pen is already in use, go to 3 ‘Select your dose’.
  • Turn the dose selector until the dose counter shows the flow check symbol ).
 

  • Hold the pen with the needle pointing up.
    Press and hold in the dose button until the dose counter returns to 0.
    The 0 must line up with the dose pointer.
    A drop of solution should appear at the needle tip.
    A small drop may remain at the needle tip, but it will not be injected.
    If no drop appears, repeat step 2 ‘Check the flow’ up to 6 times. If there is still no drop, change the needle and repeat step 2 ‘Check the flow’ once more.
    If a drop still does not appear, dispose of the pen and use a new one.

Always make sure that a drop appears at the needle tip before you use a new pen for the first time. This makes sure that the solution flows. If no drop appears, you will not inject any medicine, even though the dose counter may move. This may indicate a blocked or damaged needle.

If you do not check the flow before your first injection with each new pen, you may not get the prescribed dose and the intended effect of Saxenda®.

3 Select your dose

  • Turn the dose selector until the dose counter shows your dose (0.6mg, 1.2mg, 1.8mg, 2.4mg or 3.0mg).
    If you select the wrong dose, you can turn the dose selector forward or backwards to the correct dose.
    The pen can dial up to a maximum of 3.0mg.
    The dose selector changes the dose. Only the dose counter and dose pointer will show how many mg you select per dose.
    You can select up to 3.0mg per dose. When your pen contains less than 3.0mg the dose counter stops before 3.0 is shown.
    The dose selector clicks differently when turned forward, backwards or past the number of mg left. Do not count the pen clicks.

Always use the dose counter and the dose pointer to see how many mg you have selected before injecting this medicine.
Do not count the pen clicks.
Do not use the pen scale. It only shows approximately how much solution is left in your pen.

Only doses of 0.6mg, 1.2mg, 1.8mg, 2.4mg or 3.0mg can be selected with the dose selector. The selected dose must line up precisely with the dose pointer to ensure that you get a correct dose.

How much solution is left?

  • The pen scale shows you approximately how much solution is left in your pen.

  • To see precisely how much solution is left, use the dose counter: Turn the dose selector until the dose counter stops. If it shows 3.0, at least 3.0mg are left in your pen. If the dose counter stops before 3.0mg, there is not enough solution left for a full dose of 3.0mg.

If you need more medicine than what is left in your pen

Only if trained or advised by your doctor or nurse, you may split your dose between your current pen and a new pen. Use a calculator to plan the doses as instructed by your doctor or nurse.

Be very careful to calculate correctly.
If you are not sure how to split your dose using two pens, then select and inject the dose you need with a new pen.

4 Inject your dose

  • Insert the needle into your skin as your doctor or nurse has shown you.
  • Make sure you can see the dose counter. Do not cover it with your fingers. This could interrupt the injection.

  • Press and hold down the dose button until the dose counter shows 0. The 0 must line up with the dose pointer. You may then hear or feel a click.

  • Keep the needle in your skin after the dose counter has returned to 0 and count slowly to 6.
  • If the needle is removed earlier, you may see a stream of solution coming from the needle tip. If so, the full dose will not be delivered.

  • Remove the needle from your skin.
    If blood appears at the injection site, press lightly. Do not rub the area.
    You may see a drop of solution at the needle tip after injecting. This is normal and does not affect your dose.

Always watch the dose counter to know how many mg you inject.
Hold the dose button down until the dose counter shows 0.

How to identify a blocked or damaged needle?

  • If 0 does not appear in the dose counter after continuously pressing the dose button, you may have used a blocked or damaged needle.
  • In this case - you have not received any medicine - even though the dose counter has moved from the original dose that you have set.

How to handle a blocked needle?

Change the needle as described in step 5 ‘After your injection’, and repeat all steps starting with step 1‘Prepare your pen with a new needle’. Make sure you select the full dose you need.

Never touch the dose counter when you inject. This can interrupt the injection.

5 After your injection

  • Lead the needle tip into the outer needle cap on a flat surface without touching the needle or the outer needle cap.

  • Once the needle is covered, carefully push the outer needle cap completely on.
  • Unscrew the needle and dispose of it carefully.

  • Put the pen cap on your pen after each use to protect the solution from light.

Always dispose of the needle after each injection to ensure convenient injections and prevent blocked needles. If the needle is blocked, you will not inject any medicine.

When the pen is empty, throw it away without a needle on as instructed by your doctor, nurse, pharmacist or local authorities.

Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.

Always remove the needle from your pen after each injection.
This may prevent blocked needles, contamination, infection, leakage of solution and inaccurate dosing.

Further important information

  • Always keep your pen and needles out of sight and reach of others, especially children.
  • Never share your pen or your needles with other people.
  • Caregivers must be very careful when handling used needles - to prevent needle injury and cross-infection.

Caring for your pen

  • Do not leave the pen in a car or other place where it can get too hot or too cold.
  • Do not inject Saxenda® which has been frozen. If you do that, you may not get the intended effect of this medicine.
  • Do not expose your pen to dust, dirt or liquid.
  • Do not wash, soak or lubricate your pen. If necessary, clean it with a mild detergent on a moistened cloth.
  • Do not drop your pen or knock it against hard surfaces. If you drop it or suspect a problem, attach a new needle and check the flow before you inject.
  • Do not try to refill your pen. Once empty, it must be disposed of.
  • Do not try to repair your pen or pull it apart.

Published by MIMS August 2021

BRAND INFORMATION

Brand name

Saxenda

Active ingredient

Liraglutide

Schedule

S4

 

1 Name of Medicine

Liraglutide (rys).

2 Qualitative and Quantitative Composition

Saxenda contains liraglutide, a human glucagon-like peptide-1 (GLP-1) analogue that binds to and activates the GLP-1 receptor (GLP-1R). Liraglutide is produced by recombinant DNA technology using Saccharomyces cerevisiae.
Saxenda is a solution for injection in a pre-filled pen. One mL contains 6 mg salt-free anhydrous liraglutide. One pre-filled pen contains 18 mg liraglutide in 3 mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Saxenda is a solution for injection. It is a sterile, clear, colourless, isotonic solution, pH = 8.15.

4 Clinical Particulars

4.1 Therapeutic Indications

Saxenda is indicated as an adjunct to a reduced calorie diet and increased physical activity for weight management in adult patients with an initial Body Mass Index (BMI) of ≥ 30 kg/m2 (obese) or ≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight related comorbidity, such as dysglycaemia (pre-diabetes and type 2 diabetes mellitus), hypertension, dyslipidaemia, or obstructive sleep apnoea.
Treatment with Saxenda should be discontinued after 12 weeks on the 3.0 mg/day dose if a patient has not lost at least 5% of their initial body weight.

4.2 Dose and Method of Administration

Saxenda has not been studied in patients taking insulin. Saxenda and insulin should not be used together [see Section 4.4 Special Warnings and Precautions for Use].
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.

Dosage.

The starting dose is 0.6 mg once daily. The dose should be increased to 3.0 mg daily in increments of 0.6 mg with at least one week intervals to improve gastro-intestinal tolerability (see Table 1). If escalation to the next dose step is not tolerated for two consecutive weeks, consider discontinuing treatment. Daily doses higher than 3.0 mg are not recommended.
The need for continued treatment should be re-evaluated whenever a new prescription is written and at least annually.

Method of administration.

Saxenda is for subcutaneous use only. It must not be administered intravenously or intramuscularly.
Saxenda is administered once daily at any time, independent of meals. Saxenda pen is for use by one person only. It should be injected in the abdomen, thigh or upper arm. The injection site and timing can be changed without dose adjustment. However, it is preferable that Saxenda is injected around the same time of the day, when the most convenient time of the day has been chosen.
If a dose is missed within 12 hours from when it is usually taken, the patient should take the dose as soon as possible. If there is less than 12 hours to the next dose, the patient should not take the missed dose and resume the once-daily regimen with the next scheduled dose. An extra dose or increase in dose should not be taken to make up for the missed dose.
Saxenda should not be mixed with other injectable medicinal products (e.g. infusion fluids [see Section 4.4 Special Warnings and Precautions for Use]).

Dosage adjustment.

Patients with type 2 diabetes.

When initiating Saxenda, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (such as sulfonylureas) to reduce the risk of hypoglycaemia [see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)].
Saxenda is not a substitute for insulin.

Specific patient groups.

Elderly (> 65 years old).

No dose adjustment is required based on age. Therapeutic experience with patients ≥ 75 years of age is limited and use in these patients is not recommended. Saxenda should be used with caution in patients aged 65-74 years. [See Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties].

Patients with hepatic impairment.

Saxenda is not recommended in patients with hepatic impairment [see Section 4.4 Special Warnings and Precautions for Use].

Patients with renal impairment.

No dose adjustment is required for patients with mild or moderate renal impairment (creatinine clearance ≥ 30 mL/min). There is limited experience in patients with severe renal impairment (creatinine clearance < 30 mL/min). Saxenda is currently not recommended for use in patients with severe renal impairment including patients with end-stage renal disease [see Section 4.4 Special Warnings and Precautions for Use; Section 5.2 Pharmacokinetic Properties].

Children and adolescents.

The safety and efficacy of Saxenda in children and adolescents below 18 years of age have not been established [see Section 5.1 Pharmacodynamic Properties]. No data are available. Saxenda is not indicated for use in paediatric patients.

Special precautions for disposal and other handling.

Saxenda should not be used if it does not appear clear and colourless or almost colourless.
Saxenda should not be used if it has been frozen.
The pen is designed to be used with NovoFine disposable needles up to a length of 8 mm. Injection needles are not included.
The patient should be advised to discard the injection needle after each injection and store the pen without a needle attached. This may prevent blocked needles, contamination, infection, leakage of solution and inaccurate dosing.

4.3 Contraindications

Saxenda is not to be used in patients with hypersensitivity to liraglutide or any of its excipients.

4.4 Special Warnings and Precautions for Use

General.

Saxenda must not be used as a substitute for insulin in patients with diabetes mellitus.
Saxenda and insulin should not be used together. Saxenda has not been studied in patients taking insulin.
Saxenda is not indicated for the treatment of type 2 diabetes mellitus.
Saxenda is not indicated in patients with obesity secondary to endocrinological or eating disorders or to treatment with medicinal products that may cause weight gain.
Saxenda is not recommended in combination with other medicinal products intended for weight loss, including prescription medicines, over-the-counter medicines, and complementary medicines/herbal preparations. Efficacy and safety have not been established.

Cardiovascular events.

Increase in heart rate.

An increase in heart rate with Saxenda was observed in clinical trials [see Section 4.8 Adverse Effects (Undesirable Effects)].
Heart rate should be monitored at regular intervals consistent with good clinical practice. Patients should be informed of the symptoms of increased heart rate (palpitations or feelings of a racing heartbeat while at rest). For patients who experience a sustained increase in resting heart rate, Saxenda should be discontinued.
The effect on the heart rate of co-administration of Saxenda with other medicines that increase heart rate (e.g. sympathomimetic drugs) has not been evaluated. Consequently, co-administration of Saxenda with these medicines should be undertaken with caution.

Dehydration, renal impairment and acute renal failure.

Patients treated with Saxenda should be advised of the potential risk of dehydration in relation to gastrointestinal side effects and take precautions to avoid fluid depletion.
In patients treated with GLP-1 receptor agonists, including liraglutide, there have been reports of acute renal injury/failure and worsening of chronic renal failure, sometimes requiring haemodialysis [see Section 4.8 Adverse Effects (Undesirable Effects)]. 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, and diarrhoea leading to volume depletion. Some of the reported events occurred in patients receiving one or more medications known to affect renal function and 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.

Use in hepatic impairment.

The safety and efficacy of Saxenda in patients with hepatic insufficiency has not been studied. Saxenda is not recommended in patients with hepatic insufficiency.

Use in renal impairment.

The safety and efficacy of Saxenda in patients with severe renal impairment have not been established. Saxenda is not recommended for use in patients with severe renal impairment, including end-stage renal disease.

Use in the elderly.

In 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. Patients ≥ 65 years may experience more gastrointestinal adverse reactions with Saxenda than younger patients [see Section 4.4 Special Warnings and Precautions for Use, Dehydration, renal impairment and acute renal failure]. No overall differences in safety or effectiveness were observed between these patients and younger patients. Use caution in patients aged 65-74 years. Saxenda is not recommended in patients 75 years or older.

Paediatric use.

The efficacy and safety of Saxenda have not been studied in paediatric patients. Saxenda is not indicated for use in paediatric patients.

Pancreatitis.

Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. After initiation of Saxenda, observe patients carefully for signs and symptoms of pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Saxenda should be discontinued and appropriate management initiated. If acute pancreatitis is confirmed, Saxenda should not be restarted.
In Saxenda clinical trials, acute pancreatitis was confirmed by adjudication more commonly in Saxenda-treated patients versus placebo-treated patients [see Section 4.8 Adverse Effects (Undesirable Effects)].
It is unknown whether patients with a history of pancreatitis are at increased risk for pancreatitis while using Saxenda, since these patients were excluded from clinical trials.
Saxenda is not recommended for use in patients with a history of pancreatitis.
In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.

Cholelithiasis and cholecystitis.

In the Saxenda clinical trials, cholelithiasis or cholecystitis was reported more commonly in Saxenda-treated patients than in placebo-treated patients [see Section 4.8 Adverse Effects (Undesirable Effects)]. The majority of Saxenda-treated patients with cholelithiasis or cholecystitis required cholecystectomy. Substantial or rapid weight loss can increase the risk of acute gallbladder disease; however, the incidence was greater in Saxenda-treated patients versus placebo-treated patients even after accounting for weight loss. Patients should be informed of the characteristic symptoms of cholelithiasis and cholecystitis.

Inflammatory bowel disease and diabetic gastroparesis.

There is limited experience in patients with inflammatory bowel disease and diabetic gastroparesis. Saxenda is not recommended in these patients because it is associated with gastrointestinal adverse reactions, including nausea, vomiting and diarrhoea.

Hypoglycaemia with concomitant use of anti-diabetic therapy.

The risk of serious hypoglycaemia is increased when Saxenda is used in combination with insulin secretagogues (e.g. sulfonylureas) in patients with type 2 diabetes [see Section 4.8 Adverse Effects (Undesirable Effects), Table 2]. The risk of hypoglycaemia can be lowered by a reduction in the dose of sulfonylurea.
The addition of Saxenda in patients treated with insulin has not been evaluated. The SCALE-Diabetes trial excluded patients on insulin [see Section 5.1 Pharmacodynamic Properties, Clinical trials]. Saxenda and insulin should not be used together.
Saxenda can lower blood glucose. Monitor blood glucose parameters before starting Saxenda and during Saxenda treatment in patients with type 2 diabetes. If needed, adjust co-administered anti-diabetic medicines based on glucose monitoring and risk of hypoglycaemia.

Malignancies.

In the clinical development program for weight loss, there was no imbalance for all neoplasms, combined. However, when subgroup analyses were done by individual types of cancer, imbalances were identified, including, invasive breast cancer in women and colorectal neoplasms (mainly adenomas) [see Section 4.8 Adverse Effects (Undesirable Effects)].

Thyroid C-cell tumours.

Liraglutide caused thyroid C-cell adenomas and carcinomas in two-year studies in mice and rats. Such medullary thyroid cancers are extremely rare cancers in humans. C-cell neoplasia was observed in mice at subcutaneous doses ≥ 1 mg/kg/day (relative exposure based on plasma AUC, ≥ 8) and in rats at all doses tested (≥ 0.075 mg/kg/day subcutaneously; relative exposure, ≥ 0.5). No tumours or other C-cell proliferative changes were seen in monkeys treated with liraglutide for 20 months (≤ 5 mg/kg/day subcutaneously; relative exposure, ≤ 70). The findings in mice and rats are mediated by a specific GLP-1 receptor-mediated mechanism to which rodents are particularly sensitive. The relevance for humans is likely to be low but cannot presently be completely excluded.

Thyroid disease.

In clinical trials in type 2 diabetes, thyroid adverse events such as goitre have been reported, in particular, in patients with pre-existing thyroid disease. Cases of increased blood calcitonin were also observed in the weight management clinical trials. Saxenda should be used with caution in patients with thyroid disease.

Hypersensitivity reactions.

There have been reports of serious hypersensitivity reactions (e.g. anaphylactic reactions and angioedema) in patients treated with liraglutide. If a hypersensitivity reaction occurs, then the patient should discontinue Saxenda and other suspect medicines and promptly seek medical advice.
Angioedema has been reported with other GLP-1 receptor agonists. Do not use Saxenda in patients with a history of angioedema with another GLP-1 receptor agonist because such patients may be predisposed to angioedema with Saxenda.

Suicide behaviour and ideation.

Patients treated with Saxenda should be monitored for the emergence of depression, suicide thoughts or behaviour, or any unusual changes in mood or behaviour. Discontinue Saxenda in patients who experience suicidal thoughts or behaviours or who develop other symptoms of depression [see Section 4.8 Adverse Effects (Undesirable Effects)].
Patients with a history of major depressive disorder or other major psychiatric disorder were excluded from the Saxenda clinical trials. Because of the lack of data on efficacy and safety in patients with a history of major depressive disorder or other major psychiatric disorder, Saxenda is not recommended in these patients.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No clinically significant drug interactions have been demonstrated with Saxenda.

In vitro assessment of drug-drug interaction.

Liraglutide has very low potential for pharmacokinetic drug-drug interactions related to cytochrome P450 (CYP) and plasma protein binding.

In vivo assessment of drug-drug interaction.

The drug-drug interaction studies were performed at steady state with liraglutide 1.8 mg/day. The effect on rate of gastric emptying (paracetamol AUC0-5h) was equivalent between liraglutide 1.8 mg and 3.0 mg [see Section 5.1 Pharmacodynamic Properties]. Administration of the interacting drugs was timed so that Cmax of liraglutide (8-12 h) would coincide with the absorption peak of the co-administered drugs.

Oral medications.

The delay of gastric emptying caused by liraglutide may impact absorption of concomitantly administered oral medicinal products. Interaction studies did not show any clinically relevant delay of absorption of the compounds that were studied, however, clinically relevant interactions with other compounds where the effect is dependent on Cmax and Tmax, drugs with narrow therapeutic index, or medications associated with local gastrointestinal irritation (e.g. bisphosphonates, potassium chloride) cannot be excluded.
Few patients treated with liraglutide reported at least one episode of severe diarrhoea. Diarrhoea may affect the absorption of concomitant oral medicinal products.

Paracetamol.

Liraglutide did not change the overall exposure (AUC) of paracetamol following a single dose of paracetamol 1000 mg, administered 8 hours after the dose of liraglutide at steady state. Paracetamol Cmax was decreased by 31% and median Tmax was delayed up to 15 min. No dose adjustment for concomitant use of paracetamol is required.

Atorvastatin.

Liraglutide did not change the overall exposure (AUC) of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after the dose of liraglutide at steady state. Atorvastatin Cmax was decreased by 38% and median Tmax was delayed from 1 hour to 3 hours with liraglutide. Therefore, no dose adjustment of atorvastatin is required when given with liraglutide.

Griseofulvin.

Liraglutide did not change the overall exposure (AUC) of griseofulvin following co-administration of a single dose of griseofulvin 500 mg with liraglutide at steady state. Griseofulvin Cmax increased by 37% while median Tmax did not change. Dose adjustments of griseofulvin and other compounds with low solubility and high permeability are not required.

Digoxin.

A single dose administration of digoxin 1 mg was administered 7 hours after the dose of liraglutide at steady state. The concomitant administration with liraglutide resulted in a reduction of digoxin AUC by 16%; Cmax decreased by 31%. Digoxin median time to maximum concentration (Tmax) was delayed from 1 hour to 1.5 hours. No dose adjustment of digoxin is required based on these results.

Lisinopril.

A single dose administration of lisinopril 20 mg was administered 5 minutes after the dose of liraglutide at steady state. The co-administration with liraglutide resulted in a reduction of lisinopril AUC by 15%; Cmax decreased by 27%. Lisinopril median Tmax was delayed from 6 hours to 8 hours with liraglutide. No dose adjustment of lisinopril is required based on these results.

Oral contraceptives.

A single dose of an oral contraceptive combination product containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel was administered under fed conditions and 7 hours after the dose of liraglutide at steady state. Liraglutide lowered ethinylestradiol and levonorgestrel Cmax by 12 and 13%, respectively. Tmax was delayed by 1.5 hours with liraglutide for both compounds. There was no clinically relevant effect on the overall exposure (AUC) of ethinylestradiol. Liraglutide increased the levonorgestrel AUC0-∞ by 18%. The contraceptive effect is therefore anticipated to be unaffected when co-administered with liraglutide.

Warfarin and other coumarin derivatives.

No interaction study has been performed. A clinically relevant interaction with active substances with poor solubility or narrow therapeutic index such as warfarin cannot be excluded. Upon initiation of Saxenda treatment in patients on warfarin or other coumarin derivatives, more frequent monitoring of INR (International Normalised Ratio) is recommended.

Insulin.

No pharmacokinetic interaction was observed between liraglutide and insulin detemir when separate subcutaneous injections of insulin detemir 0.5 units/kg (single-dose) and liraglutide 1.8 mg (steady state) were administered in patients with type 2 diabetes.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No adverse effects on fertility were observed in male and female rats given subcutaneous doses of liraglutide at ≤ 1 mg/kg/day, yielding exposure to liraglutide (plasma AUC) 12-14 times higher than that of patients at the maximum recommended human dose.
(Category B3)
Increased embryofetal death and minor fetal skeletal abnormalities (kinked ribs) were observed in rats given liraglutide at 1 mg/kg/day by subcutaneous injection (yielding 12-times the plasma AUC in humans at the maximum recommended clinical dose). In rabbits treated at doses ≥ 0.01 mg/kg/day (relative exposure, ≥ 0.2), there was retardation of fetal growth and an increased incidence of several minor skeletal and visceral abnormalities. Postnatal body weight gain was reduced in the offspring of rats treated with liraglutide during gestation and lactation. These findings may have occurred secondary to reduced maternal food consumption. Placental transfer of liraglutide and/or its metabolites was demonstrated in the animal species.
There are limited data from the use of Saxenda in pregnant women. Saxenda should not be used during pregnancy. If a patient wishes to become pregnant, or pregnancy occurs, treatment with Saxenda should be discontinued.
It is not known whether liraglutide is excreted in human milk. Studies in lactating rats have shown that the transfer of liraglutide and metabolites of close structural relationship into milk is low. Non-clinical studies have shown a treatment related reduction of neonatal growth in suckling rat pups. Due to lack of experience, Saxenda must not be used during breast-feeding.

4.7 Effects on Ability to Drive and Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Patients with type 2 diabetes should be advised to take precautions to avoid hypoglycaemia while driving and using machines, in particular, when Saxenda is used in combination with a sulfonylurea.

4.8 Adverse Effects (Undesirable Effects)

Summary of safety profile.

Overall, gastrointestinal reactions were the most frequently reported adverse reactions during treatment with Saxenda: nausea, vomiting, diarrhoea and constipation reported by > 10% of subjects, see section 'Description of selected adverse reactions' below.

Tabulated summary of adverse reactions.

The data in Table 2 reflect exposure to Saxenda in four randomised, double-blind, placebo controlled, multicentre Phase 3 clinical trials, one of 32-weeks duration and three of 56-weeks duration, and one Phase 2 supportive trial in 469 adult patients.
In clinical trials, 9.8% of patients treated with Saxenda prematurely discontinued treatment due to adverse reactions, compared with 4.3% of placebo-treated patients. Adverse reactions reported in greater than or equal to 1% of Saxenda-treated patients and more frequently than in placebo patients are shown in Table 2.

Nervous system disorders.

Very common (≥ 1/10) - headache.

Less common AE's in clinical trials (< 1%).

Adverse reactions are listed by system organ class using the frequency categories uncommon (≥ 1/1,000 to < 1/100) and rare (≥ 1/10,000 to < 1/1,000).

Gastrointestinal disorders.

Uncommon: pancreatitis.

Metabolism and nutrition disorders.

Uncommon: dehydration.

General disorders and administration site conditions.

Uncommon: malaise.

Hepatobiliary disorders.

Uncommon: cholecystitis.

Immune system disorders.

Rare: anaphylactic reaction.

Cardiac disorders.

Uncommon: tachycardia.

Skin and subcutaneous tissue disorders.

Uncommon: urticaria.

Renal and urinary disorders.

Rare: acute renal failure, renal impairment.

Description of selected adverse reactions.

Cardiovascular events.

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%); and 20 bpm (5% versus 2%). 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 [see Section 4.4 Special Warnings and Precautions for Use].
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.

Major adverse cardiovascular events.

Major adverse cardiovascular events (MACE) were adjudicated by an external independent group of experts and defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. From the 5 double-blind controlled phase 2 and phase 3 clinical trials there were 6 (0.1%) confirmed MACE for Saxenda-treated patients and 10 (0.5%) for placebo-treated patients. The hazard ratio and 95% CI was 0.33 [0.12; 0.90] for Saxenda versus placebo. Favourable trends for cardiovascular disease in pre-market trials (that were not powered for this endpoint and who enrolled low-risk patients) did not necessarily provide reassurance of cardiovascular safety.
The Liraglutide Effect and Action in Diabetes Evaluation of Cardiovascular Outcomes Results (LEADER) study provides some supportive evidence for the use of liraglutide in cardiovascular disease. Extrapolation of the results of LEADER to Saxenda is to be performed with caution given that the maintenance dose of Saxenda is 3.0 mg per day (versus 1.8 mg per day in the LEADER trial), and that the patient population treated in LEADER all had type 2 diabetes mellitus, were of a high CV risk, and were significantly older than Saxenda patients on average. The duration of exposure to liraglutide was between 3.5 and 5 years. The mean age was 64 years and the mean BMI was 32.5 kg/m2. Mean baseline HbA1c was 8.7%. Liraglutide significantly reduced the rate of major adverse cardiovascular events (primary endpoint events, MACE) vs. placebo (3.41 vs. 3.90 per 100 patient years' of observation in the liraglutide and placebo groups, respectively) with a risk reduction of 13%.

Cardiac conduction disorders and PR interval prolongation.

A prolongation of the mean PR interval of up to 10 ms was reported with Saxenda treatment in a clinical trial in healthy volunteers, using lower doses than recommended for weight management.
In Saxenda clinical trials, the incidence of cardiac conduction disorders (e.g. first degree atrioventricular [A-V] block) was higher with Saxenda than placebo; 11 (0.3%) of 3384 Saxenda-treated patients compared with none of the 1941 placebo-treated patients had a cardiac conduction disorder [see Section 4.4 Special Warnings and Precautions for Use, Cardiac conduction disorders].

Hypoglycaemia in patients without type 2 diabetes.

In clinical trials in overweight or obese patients without type 2 diabetes treated with Saxenda in combination with diet and exercise no severe hypoglycaemic events (requiring third party assistance) were reported. Symptoms of hypoglycaemic events were reported by 1.6% of patients treated with Saxenda and 1.1% of patients treated with placebo; however, these events were not confirmed by blood glucose measurements. The majority of events were mild.

Hypoglycaemia in patients with type 2 diabetes.

In a clinical trial in overweight or obese patients with type 2 diabetes treated with Saxenda in combination with diet and exercise, hypoglycaemic events were accompanied by blood glucose measurements and classified accordingly. Severe hypoglycaemia (requiring third party assistance) was reported by 0.7% of patients treated with Saxenda and only in patients concomitantly treated with sulfonylurea. Also, in these patients documented symptomatic hypoglycaemia (defined as plasma glucose ≤ 3.9 mmol/L accompanied by symptoms) was reported by 43.6% of patients treated with Saxenda and in 27.3% of patients treated with placebo. Among patients not concomitantly treated with sulfonylurea, 15.7% of patients treated with Saxenda and 7.6% of patients treated with placebo reported documented symptomatic hypoglycaemic events.

Gastrointestinal adverse reactions.

In Saxenda clinical trials, 68% of Saxenda-treated patients and 39% of placebo-treated patients reported gastrointestinal disorders; the most frequently reported was nausea (39% versus 14%). The percentage of patients reporting nausea declined as treatment continued. Other common adverse reactions that occurred at higher incidence among Saxenda-treated patients included diarrhoea, constipation, vomiting, dyspepsia, abdominal pain, dry mouth, gastritis, gastroesophageal reflux, flatulence, eructation, and abdominal distension. Episodes of gastrointestinal events leading to discontinuation of therapy were: Saxenda 6.2% versus placebo: 0.8% [see Section 4.4 Special Warnings and Precautions for Use].
Most episodes of gastrointestinal events were mild to moderate, transient and the majority did not lead to discontinuation of therapy. The reactions usually occurred during the first weeks of treatment and diminished within a few days or weeks on continued treatment.
Patients older than 65 years of age may experience more gastrointestinal effects when treated with Saxenda [see Section 4.4 Special Warnings and Precautions for Use].
Patients with mild or moderate renal impairment (creatinine clearance ≥ 30 mL/min) may experience more gastrointestinal effects when treated with Saxenda.

Acute renal failure.

In patients treated with GLP-1 receptor agonists, including liraglutide, there have been reports of acute renal injury/failure and worsening chronic renal failure, sometimes requiring haemodialysis. Some of these events were reported in patients without known underlying renal disease. A majority of reported events occurred in patients who had experienced nausea, vomiting, or diarrhoea leading to volume depletion [see Section 4.4 Special Warnings and Precautions for Use]. Some of the reported events occurred in patients receiving one or more medications known to affect renal function and 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.

Malignancy.

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-treated versus 2 placebo-treated women) and ductal carcinoma in situ (4 versus 1). 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.

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 carcinoma were reported in 5 Saxenda-treated patients and 1 in a placebo-treated patient.

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.

Immunogenicity.

Consistent with the potentially immunogenic properties of protein and peptide pharmaceuticals, patients may develop anti-liraglutide antibodies following treatment with Saxenda. In clinical trials, 2.5% of Saxenda-treated patients developed anti-liraglutide antibodies. Antibody formation has not been associated with reduced efficacy of Saxenda.

Injection site reactions.

Injection site reactions have been reported in patients treated with Saxenda. These reactions have usually been mild and transitory and the majority resolved during continued treatment.

Pancreatitis.

Few cases of acute pancreatitis have been reported during long-term clinical trials with liraglutide [see Section 4.4 Special Warnings and Precautions for Use]. In Saxenda clinical trials, acute pancreatitis was confirmed by adjudication in 9 (0.3%) of 3291 Saxenda-treated patients versus 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 the clinical trials, occurring 74 and 124 days after the last dose. There were two additional cases in Saxenda-treated patients, one during an off-treatment follow-up period within 2 weeks of discontinuing Saxenda, and one that occurred in a patient who completed treatment and was off treatment for 106 days.

Allergic reactions.

Few cases of anaphylactic reactions with symptoms such as hypotension, palpitations, dyspnoea or oedema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life threatening.

Suicidal behaviour and ideation.

In the Saxenda clinical trials, 9 (0.3%) of 3384 Saxenda-treated patients and 2 (0.1%) of the 1941 placebo-treated patients reported suicide ideation; one of the Saxenda-treated patients attempted suicide [see Section 4.4 Special Warnings and Precautions for Use].

Hypotension.

Adverse reactions related to hypotension (i.e. 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 Section 4.4 Special Warnings and Precautions for Use].

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 Section 4.4 Special Warnings and Precautions for Use]. 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 nanogram/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 nanogram/L, none had calcitonin elevations to greater than 50 nanogram/L at the end of the trial.

Post-marketing adverse effects.

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.

Gastrointestinal disorders.

Acute pancreatitis, haemorrhagic and necrotising pancreatitis.

General disorders and administration site conditions.

Allergic reactions: urticaria, rash and pruritus. Malaise.

Immune system disorders.

Angioedema and anaphylactic reactions.

Metabolism and nutrition disorders.

Dehydration resulting from nausea, vomiting and diarrhoea.

Renal and urinary disorders.

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

Cardiac disorders.

Increased heart rate.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).
From clinical trials and post-market use of liraglutide, deliberate or accidental administration of doses up to 24 times the recommended maintenance dose (72 mg) have been reported, including one case of a 6-fold overdose (18 mg daily) given for 7 months. These included instances where patients needed hospitalisation either due to severe events of vomiting, nausea and diarrhoea, or as a precaution. In some reports, glucose infusion was administered. Severe hypoglycaemia has also been observed. All patients were reported to have recovered from the events without complications.
In the event of overdosage, appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms. The patient should be observed for clinical signs of dehydration and blood glucose should be monitored.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Liraglutide is an acylated human GLP-1 analogue with 97% amino acid sequence homology to endogenous human GLP-1. Like endogenous GLP-1, liraglutide binds to and activates the GLP-1R. Liraglutide is relatively stable against metabolic degradation and has a plasma half-life of 13 hours after subcutaneous administration.
Unlike native GLP-1, liraglutide has a pharmacokinetic and pharmacodynamic profile in humans suitable for once daily administration. Following subcutaneous administration, the protracted action profile is based on three mechanisms: self-association (which results in slow absorption), binding to albumin and enzymatic stability towards the dipeptidyl peptidase (DPP-IV) and neutral endopeptidase (NEP) enzymes, resulting in a long plasma half-life.
GLP-1 is a physiological regulator of appetite and food intake and GLP-1R is present in several areas of the brain involved in appetite regulation as well as the intestine. In animal studies, peripheral administration of liraglutide led to uptake in specific brain regions including the hypothalamus, where liraglutide, via specific activation of the GLP-1R, increased key satiety and decreased key hunger signals. Transient inhibition of gastric emptying was also observed.
GLP-1 receptors are also expressed in specific locations in the heart, vasculature, immune system, and kidneys. In mouse models of atherosclerosis liraglutide prevented aortic plaque progression and reduced the expression of genes related to inflammation in aortic tissue. In addition, liraglutide had a beneficial effect on plasma lipids, decreasing plasma triglyceride, total cholesterol, LDL and VLDL, and increasing HDL. Liraglutide did not reduce the plaque size of already established plaques.
Liraglutide lowers body weight through decreased food intake and loss of predominantly fat mass. Liraglutide does not increase 24-hour energy expenditure. Liraglutide affects the four main components of appetite. Liraglutide regulates appetite by increasing feelings of fullness and satiety, while lowering feelings of hunger and prospective food consumption.
Liraglutide also has effects on glucose homeostasis, resulting in lowering of fasting and post-prandial glucose. Liraglutide stimulates insulin secretion, lowers inappropriately high glucagon secretion in a glucose-dependent manner and improves beta-cell function. The mechanism of blood glucose lowering also may involve a minor delay in gastric emptying [see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions].

Clinical trials.

The safety and efficacy of Saxenda for weight management in conjunction with reduced caloric intake and increased physical activity were studied in four phase 3 randomised, double-blind, placebo-controlled trials which included a total of 5,358 patients.

SCALE-Obesity and pre-diabetes (NN8022-1839).

In this trial, a total of 3,731 patients with obesity (BMI ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with dyslipidaemia and/or hypertension, were stratified according to pre-diabetes status at screening and BMI at baseline (≥ 30 kg/m2 or < 30 kg/m2). All 3,731 patients were randomised to 56 weeks of treatment and the 2,254 patients with pre-diabetes at screening were randomised to 160 weeks of treatment followed by a 12-week off medication/placebo observational follow-up period. Lifestyle intervention in the form of an energy-restricted diet and exercise counselling was background therapy for all patients. The 56 week part of this trial assessed body weight loss in all the 3,731 randomised patients (2,590 completers). The 160 week part of this trial assessed time to onset of type 2 diabetes in the 2,254 randomised patients with pre-diabetes (1,128 completers).

SCALE-Diabetes (NN8022-1922).

A 56-week trial assessing body weight loss in 846 randomised (628 completers) obese and overweight patients with insufficiently controlled type 2 diabetes (HbA1c range 7-10%). The background treatment at trial start was either diet and exercise alone, metformin, a sulfonylurea, a glitazone as single agents or any combination hereof.

SCALE-Sleep apnoea (NN8022-3970).

A 32 week trial assessing sleep apnoea severity and body weight loss in 359 randomised (276 completers) obese patients with moderate or severe obstructive sleep apnoea (OSA).

SCALE-Maintenance (NN8022-1923).

A 56-week trial assessing body weight maintenance and weight loss in 422 randomised (305 completers) obese or overweight patients, with hypertension or dyslipidaemia, after a preceding ≥ 5% weight loss induced by a low caloric diet.
In all studies, patients received one-on-one instruction for a reduced calorie diet (approximately 500 kcal/day (2090 kJ/day) deficit) and exercise counselling (recommended increase in physical activity of minimum 150 mins/week) that began with the first dose of study medication or placebo and continued throughout the trial.

Body weight.

Superior weight loss was achieved with Saxenda compared to placebo in obese/overweight patients in all groups studied including those with and without pre-diabetes, type 2 diabetes and moderate or severe obstructive sleep apnoea. Across the trial populations, greater proportions of the patients achieved ≥ 5% and > 10% weight loss with Saxenda than with placebo (Tables 3-5). A significant body weight reduction was also observed in SCALE-Maintenance, where patients had achieved a mean weight loss of 6.0% on a low calorie diet during a 12 week run-in period prior to treatment with Saxenda. In SCALE-Maintenance, more patients maintained the weight loss achieved prior to treatment initiation with Saxenda than with placebo (81.4% and 48.9%, respectively). Specific data on weight loss responders and time course for all 4 trials are presented in Tables 3-6 and Figures 2-3.
In SCALE-Obesity and Pre-diabetes, patients treated with Saxenda achieved a greater weight loss, as compared to placebo. The weight loss occurred mainly in the first year. The mean percent change in body weight and the proportions of patients achieving greater than or equal to 5% and greater than 10% weight loss from baseline to week 160 were also significant compared to placebo in this trial (Table 3).

Weight loss response after 12 weeks with Saxenda (liraglutide 3.0 mg) treatment.

Early responders were defined as patients who achieved a weight loss of ≥ 5% after 12 weeks on maintenance dose of Saxenda (4 weeks of dose escalation and 12 weeks on maintenance dose). In the 56-week part of SCALE-Obesity and pre-diabetes, 67.5% of the patients achieved ≥ 5% weight loss after 12 weeks. In SCALE-Diabetes, 50.4% of patients achieved ≥ 5% weight loss after 12 weeks. With continued treatment with Saxenda, 86.2% of these early responders achieved a weight loss of ≥ 5% and 51% achieved a weight loss of ≥ 10% after one year of treatment. The mean weight loss in early responders who completed 1 year of treatment was 11.2% of their baseline body weight. For patients who achieved a weight loss of < 5% after 12 weeks on maintenance dose and completed 1 year of treatment, the mean weight loss was 3.8% after 1 year.

Glycaemic control.

Treatment with liraglutide significantly improved glycaemic parameters across sub-populations with normoglycaemia, pre-diabetes and type 2 diabetes.
In the 56-week part of SCALE-Obesity and pre-diabetes, fewer patients treated with Saxenda had developed type 2 diabetes compared to patients treated with placebo (0.2% vs. 1.1%). More patients with pre-diabetes at baseline had reversed their pre-diabetes compared to patients treated with placebo (69.2% vs. 32.7%). In the 160 week part of SCALE-Obesity and Pre-diabetes, the primary efficacy endpoint was the proportion of patients with onset of type 2 diabetes evaluated as time to onset. At week 160, while on treatment, 3% treated with Saxenda and 11% treated with placebo were diagnosed with type 2 diabetes. More patients in the Saxenda 3.0 mg group (65.9%) than the placebo group (36.3%) had regressed their pre-diabetes to normoglycaemia by week 160 (odds ratio 3.6 [95% CI: 3.0 to 4.4], p < 0.001). The estimated time to onset of type 2 diabetes for patients treated with Saxenda 3.0 mg was 2.7 times' longer (with a 95% confidence interval of [1.9, 3.9]), and the hazard ratio for risk of developing type 2 diabetes was 0.2 for Saxenda versus placebo.
During the entire 160 week treatment period, HbA1c was lower in the Saxenda group than in the placebo group with a statistically significant estimated treatment difference of -0.21% [-0.24; -0.18]95% C.I, p < 0.0001 at 160 weeks. After being off treatment for 12 weeks (week 172) a steep increase in HbA1c was observed in the Saxenda group, while a more modest increase was seen in the placebo group. The same pattern was observed with fasting plasma glucose (FPG). During the entire trial FPG was lower with Saxenda than with placebo, and immediately after treatment cessation FPG reversed to baseline level in the Saxenda group, while no change was observed in the placebo group.
In SCALE-Diabetes, 69.2% of obese patients with type 2 diabetes treated with Saxenda achieved an HbA1c < 7% (ADA) target compared to 27.2% for placebo and 56.5% of obese patients with type 2 diabetes treated with Saxenda achieved an HbA1c ≤ 6.5% (IDF) target compared to 15.0% for placebo.

Cardiometabolic risk factors.

Treatment with Saxenda significantly improved systolic blood pressure, waist circumference and fasting lipids compared with placebo (Tables 3 and 4).

Apnoea-hypopnoea index (AHI).

Treatment with Saxenda significantly reduced the severity of obstructive sleep apnoea as assessed by change from baseline in the AHI compared with placebo (Table 5).

SCALE-Obesity and pre-diabetes: weight management in obese and overweight patients with or without pre-diabetes.

See Figure 1 and Table 3.

SCALE-Diabetes: weight management in obese and overweight patients with type 2 diabetes.

See Table 4.

SCALE-Sleep apnoea: weight management in obese patients with moderate or severe obstructive sleep apnoea.

See Table 5.

SCALE-Maintenance: weight loss in obese and overweight patients with at least one comorbid condition after initial ≥ 5% weight loss on low caloric diet.

See Table 6 and Figure 2.

Concomitant medication.

Saxenda was more likely than placebo to reduce the use of antihypertensive and lipid lowering drugs after one year of treatment and in patients with type 2 diabetes, Saxenda was also more likely than placebo to reduce the use of oral anti-diabetic drugs after one year of treatment.

Patient reported outcomes.

Saxenda improved several patient reported outcomes compared to placebo. Significant improvements were seen in the IWQoL-Lite total score (SCALE-Obesity and pre-diabetes and SCALE-Diabetes) and in all domains of the SF-36 (SCALE-Obesity and pre-diabetes), indicating favourable effects on physical function and mental health.

Pharmacodynamics.

In long term clinical trials involving overweight and obese patients Saxenda, in conjunction with reduced calorie intake and increased physical activity, significantly lowered body weight.

Distribution of weight loss.

In a sub-study of obese (BMI 30-40 kg/m2), non-diabetic patients, DEXA analysis and CT scans were performed at baseline and at Week 20 for 15 patients on Saxenda and 14 patients on placebo. In the sub-study, weight loss was predominantly from fat mass rather than from lean body mass for both treatment groups. Mean visceral and subcutaneous adipose tissue area was reduced after 20 weeks of treatment compared to baseline. Moreover, with Saxenda, relative reductions in visceral fat were greater than in subcutaneous fat.

Effects on appetite sensations, calorie intake and energy expenditure, gastric emptying, and fasting and postprandial glycaemia.

A five week clinical pharmacology trial was conducted in 49 obese (BMI 30-40 kg/m2) non-diabetic patients to investigate the pharmacodynamic effects of liraglutide.

Appetite sensations, calorie intake, and energy expenditure.

The weight loss effect of liraglutide is considered to be mediated by regulation of appetite and food intake. Appetite sensations were assessed before and up to five hours after a standardised breakfast meal, and ad libitum food intake was assessed during the subsequent lunch meal. Compared to placebo, Saxenda increased post-prandial satiety and fullness ratings, reduced hunger and prospective food consumption ratings and decreased ad libitum food intake. No treatment related increase in 24-hour energy expenditure was observed as assessed in a respiratory chamber.

Gastric emptying.

Saxenda caused a minor delay in gastric emptying during the first hour after the meal, thereby reducing the rate as well as the total level of postprandial glucose that appeared in the circulation.

Fasting and postprandial glucose, insulin and glucagon.

Fasting and postprandial glucose, insulin and glucagon concentrations were assessed before and up to five hours after a standardised meal test. Compared to placebo, Saxenda reduced fasting glucose and postprandial glucose (AUC0-60 min) in the first hour after the meal, and also reduced 5-hour glucose AUC and incremental glucose (AUC0-300 min). In addition, Saxenda decreased postprandial glucagon (AUC0-300 min) and postprandial insulin (AUC0-60 min) and incremental insulin (iAUC0-60 min) after the meal compared with placebo.
Fasting and incremental glucose and insulin concentrations were also assessed during a 75 g oral glucose tolerance test (OGTT) before and after 56 weeks of treatment in 3,731 overweight and obese patients with and without pre-diabetes [see Section 5.1 Pharmacodynamic Properties, Clinical trials, SCALE-Obesity and pre-diabetes. Compared to placebo, Saxenda reduced fasting and incremental glucose concentrations (Figure 3). The effect was more pronounced in patients with pre-diabetes. In addition, Saxenda reduced fasting insulin and increased incremental insulin concentrations compared to placebo.
Compared to baseline levels, the week 160 post-challenge plasma glucose AUC was reduced with Saxenda, while on treatment, but remained unchanged with placebo. Additionally, post-challenge insulin AUC remained relatively stable with Saxenda during the 160-week treatment period, while declining in the placebo group. The estimated treatment effects were all statistically significant in favour of Saxenda.

Effects on fasting and postprandial glucose increment in overweight and obese patients with type 2 diabetes.

Saxenda reduced fasting glucose and mean postprandial glucose increment (90 minutes after the meal, average over 3 daily meals), compared to placebo.

Beta-cell function.

Clinical studies up to 52 weeks with Saxenda in overweight and obese patients with and without diabetes mellitus have shown a durable secretagogue effect, as well as improvements from baseline in the homeostasis model assessment for beta-cell function (HOMA-B) and the proinsulin to insulin ratio.

Cardiac electrophysiology (QTc).

In a cardiac repolarisation study, liraglutide at steady state concentrations with daily doses up to 1.8 mg did not produce QTc prolongation. The liraglutide exposure for overweight and obese subjects treated with Saxenda is comparable to the exposure evaluated in the liraglutide QTc study.

5.2 Pharmacokinetic Properties

Absorption.

The absorption of liraglutide following subcutaneous administration is slow, reaching maximum concentration approximately 11 hours post dosing. The average steady state concentration of liraglutide (AUCT/24) reached approximately 31 nanomol/L in obese (BMI 30-40 kg/m2) subjects following administration of liraglutide 3.0 mg. Liraglutide exposure increased proportionally with dose in the dose range of 0.6 to 3.0 mg. Saxenda can be administered subcutaneously in the abdomen, thigh, or upper arm.

Distribution.

The mean apparent volume of distribution after subcutaneous administration of a liraglutide 3.0 mg is 20-25 L (for a person weighing approximately 100 kg). The mean volume of distribution after intravenous administration of liraglutide is 0.07 L/kg. Liraglutide is extensively bound to plasma protein (> 98%).

Metabolism/biotransformation.

During the 24 hours following administration of a single [3H]-liraglutide dose to healthy subjects, the major component in plasma was intact liraglutide. Two minor plasma metabolites were detected (≤ 9% and ≤ 5% of total plasma radioactivity exposure).

Excretion.

Liraglutide is endogenously metabolised in a similar manner to large proteins without a specific organ as major route of elimination. Following a [3H]-liraglutide dose, intact liraglutide was not detected in urine or faeces. Only a minor part of the administered radioactivity was excreted as liraglutide-related metabolites in urine or faeces (6% and 5%, respectively). The urine and faeces radioactivity was mainly excreted during the first 6-8 days, and corresponded to three minor metabolites.
The apparent clearance following sub-cutaneous administration of liraglutide 3.0 mg is approximately 0.9-1.4 L/h with an elimination half-life of approximately 13 hours.

Special populations.

Elderly.

No dosage adjustment is required based on age. Age had no clinically relevant effect on the pharmacokinetics of liraglutide 3.0 mg based on a population pharmacokinetic analysis that included overweight and obese subjects (18 to 82 years).

Gender.

Based on results of population pharmacokinetic analyses, females have 24% lower weight adjusted clearance of liraglutide 3.0 mg compared to males. Based on the exposure response data, no dosage adjustment is required based on gender.

Ethnicity.

No dosage adjustment is required based on ethnicity. Ethnicity had no clinically relevant effect on the pharmacokinetics of liraglutide 3.0 mg based on the results of a population pharmacokinetic analysis which included overweight and obese patients.

Body weight.

The exposure of liraglutide decreases with an increase in baseline body weight. The 3.0 mg daily dose of liraglutide provided adequate systemic exposure over the body weight range of 60-234 kg evaluated for exposure response in the clinical trial. Liraglutide exposure was not studied in subjects with body weight > 234 kg.

Hepatic impairment.

The pharmacokinetics of liraglutide were evaluated in subjects with varying degrees of hepatic impairment in a single-dose trial (0.75 mg). Liraglutide exposure was decreased by 23% and 13% in subjects with mild or moderate hepatic impairment respectively, compared to healthy subjects. Exposure was significantly lower (44%) in subjects with severe hepatic impairment (Child Pugh score > 9).

Renal impairment.

Liraglutide exposure was mildly reduced in subjects with renal impairment compared to individuals with normal renal function in a single-dose trial (0.75 mg). Liraglutide exposure was lowered by 33%, 14%, 27% and 26%, in subjects with mild (creatinine clearance, CrCL 50-80 mL/min), moderate (CrCL 30-50 mL/min), and severe (CrCL < 30 mL/min) renal impairment and in end-stage renal disease requiring dialysis, respectively.

Paediatrics.

Saxenda has not been studied in paediatric subjects.

5.3 Preclinical Safety Data

Genotoxicity.

Liraglutide was not mutagenic in the bacterial Ames assay, and not clastogenic in human lymphocytes in vitro, or in rat lymphocytes and bone marrow in vivo.

Carcinogenicity.

See Section 4.4 Special Warnings and Precautions for Use.

6 Pharmaceutical Particulars

6.1 List of Excipients

Each mL of Saxenda contains the following inactive ingredients: 1.42 mg dibasic sodium phosphate dihydrate, 14.0 mg propylene glycol, 5.5 mg phenol, hydrochloric acid q.s., sodium hydroxide q.s. and water for injections to 1 mL.

6.2 Incompatibilities

Substances added to Saxenda may cause degradation of liraglutide. Saxenda must not be mixed with other medicinal products, e.g. infusion fluids.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store in a refrigerator (2°C to 8°C). Keep away from the cooling element. Do not freeze Saxenda and do not use Saxenda if it has been frozen.
After first use of the Saxenda pen, the product can be stored for 1 month at room temperature (below 30°C) or in a refrigerator (2°C to 8°C).
Keep the pen cap on when the Saxenda pen is not in use in order to protect from light.
Saxenda should be protected from excessive heat and sunlight.
Always remove the injection needle after each injection and store the Saxenda pen without an injection needle attached. This may prevent blocked needles, contamination, infection, leakage of solution and inaccurate dosing.

6.5 Nature and Contents of Container

Cartridge (type 1 glass) with a plunger (bromobutyl) and a laminate rubber sheet (bromobutyl/polyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene, polyacetal, polycarbonate and acrylonitrile butadiene styrene.
Each pen contains 3 mL solution and is able to deliver doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg and 3.0 mg.
Pack sizes of 1, 3 or 5 pre-filled pens. Not all pack sizes may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

In liraglutide, the lysine at position 34 has been replaced with arginine, and a palmitic acid has been attached via a glutamoyl spacer to lysine at position 26.

Chemical structure.

Liraglutide (rys) has the molecular formula C172H265N43O51 and a molecular weight of 3751.20 daltons.

CAS number.

204656-20-2.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes