Consumer medicine information

Ozempic 0.25 mg, 0.5 mg

Semaglutide

BRAND INFORMATION

Brand name

Ozempic

Active ingredient

Semaglutide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Ozempic 0.25 mg, 0.5 mg.

What is in this leaflet

What is in this leaflet

What Ozempic® is used for

Before you use Ozempic®

How to use Ozempic®

While you are using Ozempic®

Things to be careful of

Side effects

After using Ozempic®

Product description

Further information

Instructions For Use

This leaflet answers some common questions about Ozempic®.

It does not contain all the available information. It does not take the place of talking to your doctor, diabetes education nurse or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Ozempic® against the benefits they expect it will have for you.

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 Ozempic® is used for

Ozempic® contains the active ingredient semaglutide. This belongs to a group of medicines called ‘GLP-1 receptor agonists’. Ozempic® is an injection that is used once a week.

Ozempic® is used to lower blood sugar (glucose) in adults with type 2 diabetes mellitus.

Diabetes mellitus is a condition where your pancreas does not produce enough insulin to control the level of sugar in your blood or, your body is not able to use the insulin it makes properly.

Ozempic® helps your body to produce more insulin when your blood sugar level is high.

Ozempic® is used on its own if your blood sugar is not properly controlled by diet and exercise alone. Ozempic® is also able to be used with other medicines for diabetes when they are not enough to control your blood sugar levels. These medicines may include oral antidiabetics (such as metformin, thiazolidinedione medicines (TZD’s), sulfonylurea medicines ) or insulin.

It is important that you keep following any diet and lifestyle advice from your doctor, diabetes education nurse or pharmacist while using Ozempic®.

Ozempic® has not been studied in children and should not be used in children or adolescents under 18 years.

Ozempic® is not addictive.

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

Ask your doctor, diabetes education nurse or pharmacist if you have any questions about why Ozempic® has been prescribed for you.

Before you use Ozempic®

When you must not use it

Do not use Ozempic® if you are allergic (hypersensitive) to semaglutide or to any of the ingredients listed in the “Ingredients” section 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.

If you are not sure whether you should start using this medicine, talk to your doctor.

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 are also taking a sulfonylurea (such as glimepiride or glibenclamide) or insulin. Your doctor may tell you to test your blood sugar levels. This will help your doctor to decide if the dose of the sulfonylurea or insulin needs to be changed to avoid you getting hypoglycaemia (low blood sugar).
  • you have a history of diabetic retinopathy.
  • you have a history of gallstones.

Drink plenty of fluids to avoid dehydration if you experience vomiting or diarrhoea when beginning treatment with Ozemic®. Dehydration can lead to kidney problems, particularly in patients who have pre-existing kidney disease.

If you notice your urine changes appearance or you produce urine less frequently, see your doctor. Contact your doctor if you have any questions or concerns.

Ozempic® should not be used if you have type 1 diabetes or diabetic ketoacidosis (a complication of diabetes that happens when the body is not able to break don glucose because there is not enough insulin). Ozempic® is not an insulin.

If you experience symptoms of acute pancreatitis, like persistent, severe abdominal pain, you should consult your doctor.

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. Ozempic® should not be used during pregnancy and for at least two months before a planned pregnancy because Ozempic® may harm your unborn child. If you could become pregnant while using Ozempic®, it is recommended to use contraception.

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

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

Taking other medicines

Tell your doctor, pharmacist or diabetes education nurse 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 if you are using medicines containing any of the following active ingredients:

  • A sulfonylurea (such as glimepiride or glibenclamide), and/or insulin. This is because using Ozempic® at the same time may cause your blood sugar level to become too low (hypoglycaemia or a “hypo”).
    - When you first start using these medicines together, your doctor may tell you to lower the dose of the sulfonylurea or insulin.
    - If you are also taking a sulfonylurea and/or insulin together with Ozempic®, your doctor may ask you to test your blood sugar levels to begin with. This will help your doctor to decide if the dose of the sulfonylurea and/or insulin needs to be changed.

Tell your doctor about any other medicines that you are taking. This is very important. Your doctor will advise you if it is all right 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 this medicine.

How to use Ozempic®

Your doctor, diabetes education nurse 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, diabetes education nurse or pharmacist for help.

Ozempic® is supplied as a pre-filled pens containing 1.5 mL or 3 mL of semaglutide solution. The Ozempic® pen containing 1.5 mL can deliver doses of 0.25 mg or 0.5 mg. The Ozempic® pen containing 3 mL delivers doses of 1 mg.

How much to use

Your doctor or diabetes education nurse will tell you how much of this medicine you need to use.

  • When you first start using Ozempic®, the starting dose is 0.25 mg once a week for four weeks.
  • After four weeks you should increase your dose to 0.5 mg once a week. Talk to your doctor before increasing your dose.
  • Your doctor may increase your dose to 1 mg if your blood sugar is not controlled well enough with a dose of 0.5 mg once a week.
  • Do not change your dose unless your doctor has told you to. Any change in dose should be made cautiously and only under medical supervision.

When to use it

You should use Ozempic® once a week on the same day each week if possible.

You can give yourself the injection at any time of the day – regardless of meals.

To help you remember to inject Ozempic® once a week only, it is recommended to note the chosen weekday (e.g. Wednesday) on the carton. You can also write the date on the carton every time you have injected Ozempic®.

If necessary you can change the day of your weekly injection of Ozempic® as long as it has been at least 3 days since your last injection of Ozempic®.

How to use it

  • Inject Ozempic® under the skin (subcutaneous injection) as shown to you by your doctor or diabetes education nurse. Never inject Ozempic® into a vein or muscle.
  • Ozempic® may be injected into the front of your waist (abdomen), the front of your thigh, or your upper arm.
  • Before you use the pen for the first time, your doctor or diabetes education nurse will show you how to use it.

Checking your Ozempic® pen:

Ozempic® should be clear and colourless, or almost colourless.

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

Ozempic® should not be used if it has been frozen.

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

How long to use it

Do not stop using Ozempic® unless your doctor tells you to. If you stop using it, your blood sugar levels may increase.

If you use too much (overdose)

If you use more Ozempic® than you should, talk to your doctor straight away. You may get side effects such a feeling sick (nausea) or being sick (vomiting), or diarrhoea. You may need medical treatment.

If you forget to use it

If you forget a dose and:

  • it is 5 days or less since you should have used Ozempic®, use it as soon as you remember. Then inject your next dose as usual on your schedule day.
  • it is more than 5 days since you should have used Ozempic®, skip the missed dose. Then inject your next dose as usual on your scheduled day.

Do not take an extra dose or increase the dose to make up for a missed dose.

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

While you are using Ozempic®

Things you must do

Make sure all your friends, relatives, workmates or carers know that you have diabetes.

Tell your doctor if you often have hypos (low blood sugar levels).

When Ozempic® is used with a sulfonylurea (such as glimepiride or glibenclamide) or with insulin, hypos can occur. The dose of your sulfonylurea or insulin may need to be reduced while you take Ozempic®.

If you experience any of the symptoms of a hypo, immediately eat some sugary food or have a sugary drink, e.g. lollies, biscuits or fruit juice.

Tell your doctor, diabetes education 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 Ozempic® in the country you are visiting.

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

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using Ozempic®.

Things you must not do

Do not stop using your medicine unless your doctor tells you to. If you stop using it, your blood sugar levels may increase.

Do not use this medicine if you think it has been frozen or exposed to excessive heat. It will not work as well.

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 your pen or needles with anyone else.

Things to be careful of

Low blood sugar (hypoglycaemia) may affect your ability to concentrate. Avoid driving or using machines if you get any signs of low blood sugar, including dizziness. Talk to your doctor for further information.

Side effects

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

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, diabetes education nurse or pharmacist to answer any questions you may have.

The most common side effects when using Ozempic® are diarrhoea and nausea. 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:

  • decreased appetite
  • headache
  • vomiting (being sick)
  • indigestion (dyspepsia)
  • burping, wind (flatulence) or constipation
  • heartburn
  • painful or swollen stomach (abdomen)
  • blocked or runny nose, sneezing, cough and/or sore throat (upper respiratory tract infection)
  • injection site reactions (such as bruising, pain, irritation, itching and rash)
  • fast heart beat
  • feeling tired
  • feeling dizzy
  • changes to your vision or eyesight
  • unpleasant, abnormal or altered taste sensation
  • increase in pancreas blood test results
  • low blood sugar (a hypo).

Hypos are more likely to occur if you are also taking a sulfonylurea (such as glimepiride or glibenclamide) or insulin. A hypo may come on suddenly. The warning signs of a hypo can include:

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

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 or insulin, your doctor may reduce the dose of these medicines before you start using Ozempic®.

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

Tell your doctor if you experience:

  • gallstones
  • inflamed gall bladder.

When initiating treatment with Ozempic®, you may in some cases experience dehydration as a result of vomiting, nausea or diarrhoea. It is important to avoid dehydration by drinking plenty of fluids.

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

  • severe and persistent pain in the abdomen (stomach area) which might reach through to your back, as well as nausea and vomiting. These can be symptoms of acute pancreatitis. Pancreatitis can be a serious, potentially life-threatening medical condition.
  • an allergic reaction. Some symptoms may include:
    - skin rashes over a large part of the body
    - shortness of breath, wheezing
    - swelling of the face, lips or tongue
    - fast pulse
    - sweating.

This list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are rare or very rare. Tell your doctor if you notice anything else that is making you feel unwell.

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

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

After using Ozempic®

Storage

Before opening:
Keep your unopened Ozempic® pens in a refrigerator (2°C to 8°C). Keep away from the cooling element. Do not freeze.

During use:
While you are using your Ozempic® pen you can keep it for 6 weeks either at room temperature (not above 30°C), or in a refrigerator (2°C to 8°C), away from the cooling element. Do not freeze.

Discard the Ozempic® pen you are using after 6 weeks even if there is still some medicine left in it.

The medicine in Ozempic® 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 from light. Never use Ozempic® after the expiry date (EXP) printed on the pen label and carton. The expiry date refers to the last day of that month.

Never use Ozempic® if the solution is not clear and colourless, or almost colourless.

Keep out of the reach of children.

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

Ozempic® is supplied as a clear, colourless, or almost colourless solution for injection in a pre-filled pen. Each pen contains 1.5 mL of solution, delivering doses of 0.25 mg or 0.5 mg.

One mL solution for injection contains 1.34 mg semaglutide.

One pre-filled pen contains 2 mg semaglutide.

Ozempic® 0.25 mg, 0.5 mg/dose is available in a pack containing 1 pen and 6 disposable NovoFine® Plus needles.

Ingredients

Ozempic® contains semaglutide (rys) 1.34 mg/mL as the active ingredient. The abbreviation “rys” indicates the method of genetic engineering used to manufacture semaglutide.

Ozempic® also contains the following inactive ingredients:

  • dibasic sodium phosphate dihydrate
  • propylene glycol
  • phenol
  • hydrochloric acid
  • sodium hydroxide
  • water for injections.

Sponsor

Ozempic® is supplied in Australia by:

Novo Nordisk Pharmaceuticals Pty. Ltd.
Level 3
21 Solent Circuit
Baulkham Hills NSW 2153

This leaflet was prepared on 2 June 2020.

Australian Registration Number:
AUST R 308324

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

© 2020
Novo Nordisk A/S

Further information

For further information call the NovoCare® Customer Care Centre on 1800 668 626.

www.novonordisk.com.au

You can also get more information about diabetes from Diabetes Australia:

freecall helpline 1300 136 588

www.diabetesaustralia.com.au

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

www.novonordisk.com.au

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

Ozempic®

semaglutide (rys), 0.25 mg or 0.5 mg/dose solution for injection pre-filled pen

Instructions For Use

Please read these instructions carefully before using your Ozempic® 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 Ozempic® 0.25 mg, 0.5 mg/dose, 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 Ozempic® pre-filled pen.

Your pen is a pre-filled dial-a-dose pen. It contains 2 mg of semaglutide, and you can select doses of 0.25 mg or 0.5 mg. Your pen is designed to be used with NovoFine® disposable needles up to a length of 8 mm.

NovoFine® Plus needles are 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 Ozempic® 0.25 mg, 0.5 mg/dose. This is especially important if you take more than one type of injectable medicine. Using the wrong mediine could be harmful to your health.

A. Pull off the pen cap.

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

C. Take a new needle and tear off the paper tab. If the paper tab is broken, do not use the needle, as sterility is not guaranteed.

D. Push the needle straight onto the pen. Turn until it is on tight.

E. 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.

F. 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 damage the needle.

2. Check the flow

A. Before your first injection with each new pen, check the flow. If your pen is already in use, go to step 3 ‘Select your dose’.

Turn the dose selector until the dose counter shows the flow check symbol ( ).

B. Hold the pen with the needle pointing up. Press and hold 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 Ozempic®.

3. Select your dose

A. Turn the dose selector until the dose counter shows your dose (0.25 mg or 0.5 mg).

If you select the wrong dose, you can turn the dose selector forwards or backwards to the correct dose.

The pen can dial up to a maximum of 0.5 mg.

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 0.5 mg per dose. When your pen contains less than 0.5 mg, the dose counter stops before 0.5 mg is shown.

The dose selector clicks differently when turned forwards, 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.

Only doses of 0.25 mg or 0.5 mg must 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

A. To see how much solution is left, use the dose counter: Turn the dose selector until the dose counter stops.
If it shows 0.5, at least 0.5 mg is left in your pen.
If the dose counter stops before 0.5 mg, there is not enough solution left for a full dose of 0.5 mg.

  • If there is not enough solution left in your pen for a full dose, do not use it. Use a new Ozempic® pen.

4. Inject your dose

A. 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.

B. 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.

C. 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.

D. 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 that you select the full dose you need.

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

5. After your injection

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

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

C. 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 or pharmacist.

  • 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 immediately 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 the 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

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which may lead to high blood sugar levels or abdominal discomfort such as nausea or vomiting.

Do not leave the pen in a car or another place where it can get too hot or too cold.

Do not inject Ozempic® which has been frozen. If you do that, your blood sugar level may get too high or you might feel abdominal discomfort such as nausea or vomiting.

Do not inject Ozempic® which has been exposed to direct sunlight. If you do that, your blood sugar level may get too high.

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 July 2020

BRAND INFORMATION

Brand name

Ozempic

Active ingredient

Semaglutide

Schedule

S4

 

1 Name of Medicine

Semaglutide (rys).

2 Qualitative and Quantitative Composition

Ozempic 0.25 mg, 0.5 mg/dose.

One mL of solution contains 1.34 mg of semaglutide. One pre-filled pen contains 2 mg semaglutide in 1.5 mL solution.

Ozempic 1 mg/dose.

One mL of solution contains 1.34 mg semaglutide. One pre-filled pen contains 4 mg semaglutide in 3 mL solution.
Semaglutide is a human glucagon-like-peptide-1 (GLP-1) receptor agonist produced in Saccharomyces cerevisiae by recombinant DNA technology followed by protein purification.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Ozempic solution for injection is provided in a pre-filled multidose disposable pen, which contains semaglutide in a 1.5 mL or 3 mL cartridge.
It is a clear and colourless, or almost colourless, isotonic solution with pH = 7.4.

4 Clinical Particulars

4.1 Therapeutic Indications

Ozempic is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise:
as monotherapy when metformin is not tolerated or contraindicated;
in addition to other medicinal products for the treatment of type 2 diabetes.

4.2 Dose and Method of Administration

Dosage.

Ozempic starting dose is 0.25 mg once weekly. After 4 weeks, the dose should be increased to 0.5 mg once weekly. After at least 4 weeks with a dose of 0.5 mg once weekly, the dose can be increased to 1 mg once weekly to further improve glycaemic control.
Ozempic 0.25 mg is not a maintenance dose.
When Ozempic is added to existing metformin and/or thiazolidinedione therapy, the current dose of metformin and/or thiazolidinedione can be continued unchanged.
When Ozempic is added to existing therapy of a sulfonylurea or insulin, a reduction in the dose of sulfonylurea or insulin should be considered to reduce the risk of hypoglycaemia (see Section 4.4 Special Warnings and Precautions for Use).
The use of Ozempic does not require blood glucose self-monitoring. Self-monitoring may be performed when Ozempic is used together with sulfonylurea or insulin in order to allow adjustment of the dose of these medications.

Method of administration.

Ozempic is to be administered once weekly, on the same day each week, at any time of the day, with or without meals.
Ozempic is to be injected subcutaneously in the abdomen, in the thigh or in the upper arm. The injection site can be changed without dose adjustment. Ozempic should not be administered intravenously or intramuscularly. For further information on administration, see Section 6 Pharmaceutical Particulars.
The day of weekly administration can be changed if necessary as long as the time between two doses is at least 3 days (> 72 hours). After selecting a new dosing day, once-weekly dosing should be continued.
If a dose is missed, it should be administered as soon as possible and within 5 days after the missed dose. If more than 5 days have passed, the missed dose should be skipped, and the next dose should be administered on the regularly scheduled day. In each case, patients can then resume their regular once weekly dosing schedule.

Dosage adjustment.

Elderly (≥ 65 years old).

No dose adjustment is required based on age. Therapeutic experience in patients ≥ 75 years of age is limited (see Section 5.2 Pharmacokinetic Properties).

Gender.

No dose adjustment is required based on gender.

Race and ethnicity.

No dose adjustment is required based on race and ethnicity.

Patients with hepatic impairment.

No dose adjustment is required for patients with hepatic impairment (see Section 5.2 Pharmacokinetic Properties). Experience with the use of semaglutide in patients with severe hepatic impairment is limited. Caution should be exercised when treating these patients with semaglutide.

Patients with renal impairment.

No dose adjustment is required for patients with renal impairment. Experience with the use of semaglutide in patients with severe (CrCL < 30 mL/min) renal impairment is limited.
Semaglutide is not recommended for use in patients with end-stage renal disease (see Section 5.2 Pharmacokinetic Properties).

Children and adolescents.

Safety and efficacy of Ozempic in children and adolescents below 18 years have not been studied.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed, see Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Ozempic should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Ozempic is not a substitute for insulin.

Gastrointestinal effects.

Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions. This should be considered when treating patients with impaired renal function as nausea, vomiting, and diarrhoea, may cause dehydration which could cause a deterioration of renal function.

Acute pancreatitis.

Acute pancreatitis has been observed with the use of GLP-1 receptor agonists. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Ozempic should be discontinued; if confirmed, Ozempic should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

Hypoglycaemia.

Patients treated with Ozempic in combination with a sulfonylurea or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia can be lowered by reducing the dose of sulfonylurea or insulin when initiating treatment with Ozempic.

Diabetic retinopathy.

In patients with diabetic retinopathy treated with insulin and semaglutide, an increased risk of developing diabetic retinopathy complications has been observed (see Section 4.8 Adverse Effects (Undesirable Effects)). Caution should be exercised when using semaglutide in patients with diabetic retinopathy treated with insulin. Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Long-term glycaemic control decreases the risk of diabetic retinopathy. Patients with a history of diabetic retinopathy should be monitored for worsening and treated according to clinical guidelines.

Heart failure.

There is no therapeutic experience in patients with congestive heart failure New York Heart Association (NYHA) class IV and therefore use of semaglutide is not recommended in these patients.

Use in hepatic impairment.

Experience with the use of semaglutide in patients with severe hepatic impairment is limited. Caution should be exercised when treating these patients with semaglutide.

Use in renal impairment.

Experience with the use of semaglutide in patients with severe (CrCL < 30 mL/min) renal impairment is limited. Semaglutide is not recommended for use in patients with end-stage renal disease (see Section 5.1 Pharmacodynamic Properties; Section 5.2 Pharmacokinetic Properties).

Use in elderly.

See Section 5.2 Pharmacokinetic Properties.

Paediatric use.

The safety and efficacy of semaglutide in children and adolescents aged below 18 years has not been studied.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In vitro studies have shown very low potential for semaglutide to inhibit or induce CYP enzymes, and to inhibit drug transporters.
The delay of gastric emptying with semaglutide may influence the absorption of concomitantly administered oral medicinal products, therefore semaglutide should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption. The potential effect of semaglutide on the absorption of co-administered oral medications was studied in trials at semaglutide 1 mg steady state exposure.
No clinically relevant drug-drug interaction with semaglutide (Figure 1) was observed based on the evaluated medications. Therefore, no dose adjustment is required when co-administered with semaglutide.

Oral contraceptives.

Semaglutide is not anticipated to decrease the effectiveness of oral contraceptives as semaglutide did not change the overall exposure of ethinylestradiol and levonorgestrel to a clinically relevant degree when an oral contraceptive combination medicinal product (0.03 mg ethinylestradiol/0.15 mg levonorgestrel) was co-administered with semaglutide. Exposure of ethinylestradiol was not affected; an increase of 20% was observed for levonorgestrel exposure at steady state. Cmax was not affected for any of the compounds.

Atorvastatin.

Semaglutide did not change the overall exposure of atorvastatin following a single dose administration of atorvastatin (40 mg). Atorvastatin Cmax was decreased by 38%. This was assessed not to be clinically relevant.

Digoxin.

Semaglutide did not change the overall exposure or Cmax of digoxin following a single dose of digoxin (0.5 mg).

Metformin.

Semaglutide did not change the overall exposure or Cmax of metformin following dosing of 500 mg twice daily over 3.5 days.

Warfarin.

Semaglutide did not change overall exposure or Cmax of R- and S-warfarin following a single dose of warfarin (25 mg), and the pharmacodynamic effects of warfarin as measured by the international normalised ratio were not affected in a clinically relevant manner.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of semaglutide on fertility in humans is unknown. Semaglutide did not affect male fertility in rats at daily SC doses of 828 microgram/kg, resulting in exposures approximately 13 times the clinical AUC. In female rats, an increase in oestrous length and a small reduction in number of ovulations were observed at doses associated with maternal body weight loss (≥ 30 microgram/kg/day SC, resulting in subclinical exposures).
(Category D)
Semaglutide should not be used during pregnancy. Women of childbearing potential are recommended to use contraception when treated with semaglutide. If a patient wishes to become pregnant, or pregnancy occurs, semaglutide should be discontinued. Semaglutide should be discontinued at least 2 months before a planned pregnancy due to the long half-life (see Section 5.1 Pharmacodynamic Properties).
Studies in animals have shown reproductive toxicity when semaglutide was administered during organogenesis. In pregnant rats, embryofetal toxicity (lethality, impaired growth and an increased incidence of fetal abnormalities) was observed at subclinical plasma exposures. Mechanistic studies suggest a direct GLP-1 receptor mediated role of semaglutide on some of the effects in rats (species specific). In pregnant rabbits, pharmacologically mediated reductions in maternal body weight gain and food consumption were observed at all dose levels. Early pregnancy losses and increased incidences of minor visceral (kidney, liver) and skeletal (sternebra) fetal abnormalities were observed at ≥ 0.0025 mg/kg/day, at clinically relevant exposures. In pregnant cynomolgus monkeys, pharmacologically mediated, marked initial maternal body weight loss and reductions in body weight gain and food consumption coincided with the occurrence of sporadic abnormalities (vertebra, sternebra, ribs) and with an increase in early pregnancy losses at ≥ 0.075 mg/kg twice weekly (> 2.7 fold clinical exposure at 1 mg/week). Exposures at the NOAEL in all species were subclinical and a direct effect of semaglutide on the fetus cannot be excluded.
In lactating rats, semaglutide was excreted in milk. A risk to a breast-fed child cannot be excluded. Semaglutide should not be used during breast-feeding.

4.7 Effects on Ability to Drive and Use Machines

Ozempic has no or negligible influence on the ability to drive or use machines. When it is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.
Adverse effects of Ozempic include dizziness which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

In 8 phase 3a trials, 4,792 patients were exposed to Ozempic alone or in combination with other glucose lowering medicinal products. The duration of the treatment ranged from 30 weeks to 2 years.
The most frequently reported adverse reactions in clinical trials were gastrointestinal disorders, including nausea, diarrhoea and vomiting. In general, these reactions were mild or moderate in severity and of short duration.

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 www.tga.gov.au/reporting-problems.

Tabulated list of adverse events.

See Table 1.

Adverse reactions.

Table 2 lists adverse reactions identified in phase 3a trials in patients with type 2 diabetes (further described, see Section 5.1 Pharmacodynamic Properties). The frequencies of the adverse reactions are based on a pool of the phase 3a trials excluding the cardiovascular outcomes trial.
The reactions are listed in Table 2 by system organ class and absolute frequency. Frequencies are defined as: very common: (≥ 1/10); common: (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare: (≥ 1/10,000 to < 1/1,000); and very rare: (< 1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

2-year cardiovascular outcomes and safety trial.

In a high cardiovascular risk population the adverse reaction profile was similar to that seen in the other phase 3a trials (see Section 5.1 Pharmacodynamic Properties).

Description of selected adverse reactions.

Hypoglycaemia.

No episodes of severe hypoglycaemia were observed when Ozempic was used as monotherapy. Severe hypoglycaemia was primarily observed when Ozempic was used with a sulfonylurea (1.2% of subjects, 0.03 events/patient year) or insulin (1.5% of subjects, 0.02 events/patient year). Few severe episodes (0.1% of subjects, 0.001 events/patient year) were observed with Ozempic in combination with oral antidiabetics other than sulfonylureas.

Gastrointestinal adverse reactions.

Nausea occurred in 17.0% and 19.9% patients when treated with Ozempic 0.5 mg and 1 mg respectively, diarrhoea in 12.2% and 13.3% and vomiting in 6.4% and 8.4%. Most events were mild to moderate in severity and of short duration. The events led to treatment discontinuation in 3.9% and 5.9% of subjects. The events were most frequently reported during the first months on treatment. Patients with low body weight may experience more gastrointestinal side effects when treated with semaglutide.

Diabetic retinopathy complications.

In a 2-year clinical trial involving 3,297 patients with type 2 diabetes and high cardiovascular risk, long duration of diabetes and poorly controlled blood glucose, adjudicated events of diabetic retinopathy complications occurred in more patients treated with Ozempic (3.0%) compared to placebo (1.8%). The treatment difference appeared early and persisted throughout the trial. The absolute risk increase for diabetic retinopathy complications was larger among patients with a history of diabetic retinopathy treated with insulin at baseline. In the patients that did not have a documented history of diabetic retinopathy the number of events were similar for Ozempic and placebo.
In other clinical trials up to 1 year involving 4,807 patients with type 2 diabetes patients, adverse events related to diabetic retinopathy were reported in similar proportions of subjects treated with Ozempic (1.7%) and comparators (2.0%).

Discontinuation due to an adverse event.

The incidence of discontinuation of treatment due to adverse events was 6.1% and 8.7% for patients treated with semaglutide 0.5 mg and 1 mg respectively, versus 1.5% for placebo. The most frequent adverse events leading to discontinuation were gastrointestinal.

Injection site reactions.

Injection site reactions (e.g. injection site rash, erythema) have been reported by 0.6% and 0.5% of patients receiving semaglutide 0.5 mg and 1 mg respectively. A similar rate of injection site reactions was experienced by patients receiving placebo. These reactions have usually been mild.

Immunogenicity.

Consistent with the potentially immunogenic properties of medicinal products containing proteins or peptides, patients may develop antibodies following treatment with semaglutide. The proportion of patients tested positive for anti-semaglutide antibodies at any time point post-baseline was low (1-2%) and no patients had anti-semaglutide neutralising antibodies or anti-semaglutide antibodies with endogenous GLP-1 neutralising effect at end-of-trial.

Heart rate increase.

Increased heart rate has been observed with GLP-1 receptor agonists. In the phase 3a trials, mean increases of 1 to 6 beats per minute (bpm) from a baseline of 72 to 76 bpm were observed in subjects treated with semaglutide. In a long-term trial in subjects with cardiovascular risk factors, 16% of semaglutide-treated subjects had an increase in heart rate of > 10 bpm compared to 11% of subjects on placebo after 2 years of treatment.

Increases in amylase and lipase.

In placebo-controlled trials, patients exposed to semaglutide had a mean increase from baseline in amylase of 13% and lipase of 22%. These changes were not observed in placebo-treated patients. In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.

Cholelithiasis.

In placebo-controlled trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with semaglutide 0.5 mg and 1 mg respectively. Cholelithiasis was not reported in placebo-treated patients.

Fatigue, dysgeusia and dizziness.

Other adverse reactions with a frequency of > 0.4% associated with semaglutide include fatigue, dysgeusia and dizziness.

4.9 Overdose

Overdoses of up to 4 mg in a single dose, and up to 4 mg in a week have been reported in clinical trials. The most commonly reported adverse event was nausea. All patients recovered without complications.
There is no specific antidote for overdose with Ozempic. In the event of overdose, appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms. A prolonged period of observation and treatment for these symptoms may be necessary, taking into account the long half-life of Ozempic of approximately 1 week (see Section 5.2 Pharmacokinetic Properties).
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Drugs used in diabetes, Glucagon-like peptide-1 (GLP-1) analogues, ATC code: A10BJ06.

Mechanism of action.

Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that binds to and activates the GLP-1 receptor, the target for native GLP-1.
GLP-1 is a physiological hormone that has multiple actions in glucose and appetite regulation, and in the cardiovascular system. The glucose and appetite effects are specifically mediated via GLP-1 receptors in the pancreas and the brain. GLP-1 receptors are also expressed in the heart, vasculature and immune system and kidney from where it may mediate cardiovascular and microvascular effects.
Compared to native GLP-1, semaglutide has a prolonged half-life of around 1 week making it suitable for once weekly s.c. administration. The principal mechanism of protraction is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilised against degradation by the DPP-4 enzyme.
Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. During hypoglycaemia semaglutide diminishes insulin secretion and does not impair glucagon secretion.
Semaglutide reduces body weight and body fat mass through lowered energy intake, involving an overall reduced appetite, which includes increased satiety and reduced hunger, as well as improved control of eating and decreased food cravings. Insulin resistance is also reduced, probably through reduction in body weight. In addition, semaglutide reduces the preference for high fat foods. Semaglutide had a beneficial effect on plasma lipids, lowered systolic blood pressure and reduced inflammation in clinical studies.
In animal studies, semaglutide attenuates the development of atherosclerosis by preventing aortic plaque progression and reducing inflammation in the plaque.

Pharmacodynamic effects.

All pharmacodyamic evaluations were performed after 12 weeks of treatment (including dose escalation) at steady state with semaglutide 1 mg once weekly.

Fasting and postprandial glucose.

Semaglutide reduces fasting and postprandial glucose concentrations. In patients with type 2 diabetes, treatment with semaglutide 1 mg resulted in reductions in glucose in terms of absolute change from baseline (mmol/L/ mg/dL) and relative reduction compared to placebo (%) for fasting glucose (1.6 mmol/L/ 29 mg/dL; 22%), 2 hour postprandial glucose (4.1 mmol/L/ 74 mg/dL; 37%), mean 24 hour glucose concentration (1.7 mmol/L/ 30 mg/dL; 22% reduction) and postprandial glucose excursions over 3 meals (0.6-1.1 mmol/L/ 11-20 mg/dL) compared to placebo (see Figure 2).
Semaglutide lowered fasting glucose after the first dose.

Beta-cell function and insulin secretion.

Semaglutide improves beta-cell function. Semaglutide, compared to placebo, improved first- and second-phase insulin response, with a 3- and 2-fold increase, respectively, following an intravenous bolus of glucose, and increased maximal beta-cell secretory capacity after an arginine stimulation test in patients with type 2 diabetes. In addition, semaglutide treatment increased fasting insulin concentrations compared to placebo.

Glucagon secretion.

Semaglutide lowers the fasting and postprandial glucagon concentrations. In patients with type 2 diabetes, semaglutide resulted in the following relative reductions in glucagon compared to placebo: fasting glucagon (8-21%), postprandial glucagon response (14-15%) and mean 24 hour glucagon concentration (12%).

Glucose dependent insulin and glucagon secretion.

Semaglutide lowered high blood glucose concentrations by stimulating insulin secretion and lowering glucagon secretion in a glucose dependent manner. With semaglutide, the insulin secretion rate in patients with type 2 diabetes was comparable to that of healthy subjects (see Figure 3).
During induced hypoglycaemia, semaglutide compared to placebo did not alter the counter regulatory responses of increased glucagon, and did not impair the decrease of C-peptide in patients with type 2 diabetes.

Gastric emptying.

Semaglutide caused a minor delay of early postprandial gastric emptying, thereby reducing the rate at which glucose appears in the circulation postprandially.

Body weight and body composition.

A greater reduction in body weight was observed with semaglutide compared to studied comparators (placebo, sitagliptin, exenatide ER and insulin glargine) (see Section 5.1 Pharmacodynamic Properties). The body weight loss with semaglutide was predominantly from fat tissue with loss of fat mass being 3-fold larger than loss of lean mass.

Appetite, energy intake and food choice.

Semaglutide compared to placebo lowered the energy intake of 3 consecutive ad libitum meals by 18-35%. This was supported by a semaglutide-induced suppression of appetite in the fasting state as well as postprandially, improved control of eating, less food cravings and a relative lower preference for high fat food.

Fasting and postprandial lipids.

Semaglutide compared to placebo lowered fasting triglyceride and VLDL cholesterol concentrations by 12% and 21%, respectively. The postprandial triglyceride and VLDL cholesterol response to a high fat meal was reduced by > 40%.

Cardiac electrophysiology (QTc).

The effect of semaglutide on cardiac repolarization was tested in a thorough QTc trial. Semaglutide did not prolong QTc intervals at supra-therapeutic dose levels (up to 1.5 mg at steady state).

Clinical trials.

Both improvement of glycaemic control and reduction of cardiovascular morbidity and mortality are an integral part of the treatment of type 2 diabetes.
The efficacy and safety of Ozempic 0.5 mg and 1 mg once weekly were evaluated in six randomised controlled phase 3a trials. Of these, five trials (SUSTAIN 1-5) had glycaemic efficacy assessment as the primary objective, while one trial (SUSTAIN 6) had cardiovascular outcome as the primary objective. Additionally, two phase 3 trials were conducted with Ozempic in Japanese patients with safety as the primary objective and efficacy the secondary objective.
The trials included in total 8,124 randomised patients with type 2 diabetes (4,792 treated with semaglutide).
An additional trial including 1,201 patients was conducted to compare the efficacy and safety of Ozempic 0.5 mg and 1 mg once weekly versus dulaglutide 0.75 mg and 1.5 mg once weekly, respectively.
Treatment with Ozempic demonstrated statistically significant and clinically meaningful reductions in HbA1c (see Figure 4) and body weight maintained for up to 2 years compared to placebo and active control treatment (sitagliptin, insulin glargine, exenatide ER and dulaglutide).
The efficacy of Ozempic was not impacted by age, gender, race, ethnicity, BMI at baseline, body weight (kg) at baseline, diabetes duration and level of renal function impairment.

SUSTAIN 1 - monotherapy.

In a 30-week double-blind trial, 388 patients inadequately controlled with diet and exercise were randomised to Ozempic 0.5 mg or Ozempic 1 mg once weekly or placebo.
Patients had a mean age of 54 years and a mean duration of type 2 diabetes of 4.2 years. There were 64% White patients, 8% were Black or African Americans and 21% were Asian. For ethnicity, 30% of patients (n=115) were Hispanic or Latino. The mean BMI was 33 kg/m2. See Table 3.

SUSTAIN 2 - Ozempic vs. sitagliptin both in combination with 1-2 antidiabetic drugs (metformin and/or thiazolidinediones).

In a 56-week double-blind trial, 1,231 patients were randomised to Ozempic 0.5 mg once weekly, Ozempic 1 mg once weekly or sitagliptin 100 mg once daily, all in combination with metformin (94%) and/or thiazolidinediones (6%). Patients had a mean age of 55 years and a mean duration of type 2 diabetes of 6.6 years. There were 68% White patients, 5% were Black or African-American and 25% were Asian. For ethnicity, 17% of patients (n=209) were Hispanic or Latino. Mean BMI was 32 kg/m2. See Table 4 and Figure 5.

SUSTAIN 7 - Ozempic vs. dulaglutide both in combination with metformin.

In a 40-week open-label trial, 1,201 patients on metformin were randomised to either Ozempic 0.5 mg or 1 mg once weekly or dulaglutide 0.75 mg or 1.5 mg once weekly. The trial compared 0.5 mg of semaglutide to 0.75 mg of dulaglutide and 1 mg of semaglutide to 1.5 mg of dulaglutide. Patients had a mean age of 56 years and a mean duration of type 2 diabetes of 7.4 years. There were 77% White patients, 6% were Black or African-American and 16% were Asian. For ethnicity, 11% of patients (n=138) were Hispanic or Latino. Mean BMI was 33.5 kg/m2. See Table 5 and Figure 6.

SUSTAIN 3 - Ozempic vs. exenatide ER both in combination with metformin or metformin with sulfonylurea.

In a 56-week open-label trial, 813 patients on metformin alone (49%), metformin with sulfonylurea (45%) or other (6%) were randomised to Ozempic 1 mg or exenatide ER 2.0 mg each administered once-weekly. Patients had a mean age of 57 years and a mean duration of type 2 diabetes of 9 years. There were 84% White patients, 7% were Black or African-American and 2% were Asian. For ethnicity, 24% of patients (n=197) were Hispanic or Latino. Mean BMI was 34 kg/m2. See Table 6.

SUSTAIN 4 - Ozempic vs. insulin glargine both in combination with 1-2 oral antidiabetic drugs (metformin monotherapy or metformin and sulfonylurea).

In a 30-week open-label trial, 1,089 patients were randomised to Ozempic 0.5 mg once weekly, Ozempic 1 mg once weekly, or insulin glargine once daily on a background of metformin (48%) or metformin and sulfonylurea (51%).
Patients on insulin glargine started on 10 U injected once daily. The mean daily insulin dose at the end of the trial was 29 U per day.
Patients had a mean age of 57 years and a mean duration of type 2 diabetes of 8.6 years. 77% were White, 9% were Black or African-Americans and 11% were Asian. For ethnicity, 20% of patients (n=213) were Hispanic or Latino. Mean BMI was 33 kg/m2.
The proportion of patients reporting severe or blood glucose confirmed (< 3.1 mmol/L) hypoglycaemic episodes were lower with Ozempic 0.5 mg (4.4%), and Ozempic 1 mg (5.6%) compared to insulin glargine (10.6%).
More patients on Ozempic 0.5 mg (47%) and Ozempic 1 mg (64%) achieved HbA1c < 7% without severe or blood glucose confirmed symptomatic hypoglycaemia and without weight gain compared to insulin glargine (16%). See Table 7.

SUSTAIN 5 - Ozempic vs. placebo in combination with basal insulin.

In a 30-week double-blind trial, 397 patients inadequately controlled with basal insulin with or without metformin were randomised to Ozempic 0.5 mg once weekly, Ozempic 1 mg once weekly or placebo. Patients with HbA1c ≤ 8.0% at screening reduced the insulin dose by 20% at the beginning of trial to reduce the risk of hypoglycaemia.
Patients had a mean age of 59 years and a mean duration of type 2 diabetes of 13 years, 78% were White, 5% were Black or African-American and 17% were Asian. For ethnicity, 12% of patients (n=46) were Hispanic or Latino. Mean BMI was 32 kg/m2.
Severe or blood glucose (BG)-confirmed symptomatic episodes of hypoglycaemia were not significantly different between Ozempic and placebo. The proportion of patients reporting severe or confirmed (< 3.1 mmol) hypoglycaemic symptomatic episodes was higher with Ozempic compared to placebo with screening HbA1c ≤ 8%, and comparable for patients with screening HbA1c > 8%. See Table 8.

Combination with sulfonylurea monotherapy.

In SUSTAIN 6 (see Section 5.1 Pharmacodynamic Properties, Clinical trials), a subgroup on sulfonylurea monotherapy was evaluated at week 30. There were 123 patients on sulfonylurea monotherapy at baseline. HbA1c at baseline was 8.2%, 8.4% and 8.4% for Ozempic 0.5 mg, Ozempic 1 mg, and placebo, respectively. At week 30, the change in HbA1c was -1.6%, -1.5% and 0.1% for Ozempic 0.5 mg, Ozempic 1 mg, and placebo, respectively.

Combination with premix insulin ± 1-2 OADs.

In SUSTAIN 6 (see Section 5.1 Pharmacodynamic Properties, Clinical trials), a subgroup on premix insulin (with or without 2 OADs) was evaluated at week 30. There were 867 patients on premix insulin at baseline. HbA1c at baseline was 8.8%, 8.9% and 8.9% for Ozempic 0.5 mg, Ozempic 1 mg, and placebo, respectively. At week 30, the change in HbA1c was -1.3%, -1.8% and -0.4% for Ozempic 0.5 mg, Ozempic 1 mg, and placebo, respectively.

Body weight.

Ozempic 1 mg used as monotherapy or in combination with 1-2 medicinal products resulted in statistically superior reductions in body weight up to 6.5 kg, compared to patients receiving placebo, sitagliptin, exenatide ER, insulin glargine or dulaglutide (Table 3 to 7). The reduction in body weight was sustained for up to 2 years (Figure 7).

Fasting plasma glucose and postprandial increments.

Ozempic 0.5 mg and 1 mg showed significant reductions in fasting plasma glucose levels of up to 2.8 mmol/L and reductions in postprandial increments across all three daily meals (difference between pre-meal and post-meal values from three meals) of up to 1.2 mmol/L (in addition see Section 5.1 Pharmacodynamic Properties).

Beta-cell function and insulin resistance.

Beta-cell function measured by homeostasis model assessment for beta-cell function (HOMA-B) and insulin resistance measured by homeostasis model assessment for insulin resistance (HOMA-IR) overall improved with Ozempic 0.5 mg and 1 mg (in addition see Section 5.1 Pharmacodynamic Properties).

Lipids.

Overall, improvements in the fasting blood lipid profile were seen with Ozempic treatment across trials, mostly for the 1 mg group (in addition see Section 5.1 Pharmacodynamic Properties).

Prevention of cardiovascular disease.

In a 104-week double-blind trial (SUSTAIN 6), 3,297 patients with type 2 diabetes at high cardiovascular risk were randomised to Ozempic 0.5 mg or 1 mg once weekly or placebo 0.5 mg or placebo 1 mg in addition to standard-of-care hereafter followed for 2 years. In total 98.0% of the patients completed the trial and the vital status was known at the end of the trial for 99.6% of the patients.
The trial population was distributed by age as: 1,598 patients (48.5%) ≥ 65 years, 321 (9.7%) ≥ 75 years and 20 (0.6%) ≥ 85 years. There were 2,358 patients with normal or mild renal impairment, 832 with moderate and 107 with severe or end stage renal impairment. There were 61% males, the mean age was 65 years and mean BMI was 33 kg/m2. The mean duration of diabetes was 13.9 years.
The primary endpoint was the time from randomisation to first occurrence of a major adverse cardiovascular event (MACE): cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. The secondary endpoint was time from randomisation to first occurrence of an expanded composite cardiovascular outcome, defined as MACE, revascularisation (coronary and peripheral), unstable angina requiring hospitalisation or hospitalisation for heart failure. The total number of primary component MACE endpoints was 254, including 108 (6.6%) with Ozempic and 146 (8.9%) with placebo.
Treatment with Ozempic resulted in a 26% risk reduction in the primary composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or non-fatal stroke. This was mainly driven by 39% decrease in the rate of non-fatal stroke and a 26% decrease in non-fatal myocardial infarction with no difference in cardiovascular death (see Figure 8 and Figure 9).
Microvascular outcome comprised 158 new or worsening of nephropathy events. The hazard ratio for time to nephropathy (new onset of persistent macroalbuminuria, persistent doubling of serum creatinine, need for continuous renal replacement therapy and death due to renal disease) was 0.64 [0.46; 0.88] driven by new onset of persistent macroalbuminuria.
A significant and sustained reduction in HbA1c from baseline to week 104 was observed with Ozempic 0.5 mg and 1 mg vs placebo 0.5 mg and 1 mg, in addition to standard-of-care (-1.1 and -1.4 vs -0.4 and -0.4, respectively).

Blood pressure.

Significant reductions in mean systolic blood pressure were observed when Ozempic 0.5 mg (3.5-5.1 mmHg) and Ozempic 1 mg (5.4-7.3 mmHg) were used in combination with oral antidiabetic medicinal products or basal insulin. For diastolic blood pressure, there were no significant differences between Ozempic and comparators.

Patient reported outcomes.

Patient reported outcomes were assessed by the Diabetes Treatment Satisfaction Questionnaire status version (DTSQs): Ozempic significantly improved total treatment satisfaction and reduced perceived frequency of hyperglycaemia compared to exenatide once weekly, insulin glargine and placebo.
General health status was assessed by the Short Form health survey (SF-36 v2): Ozempic 1 mg once weekly demonstrated significantly greater improvement from baseline in a long-term cardiovascular safety study compared to placebo (SUSTAIN 6) in both mental component summary (MCS) and physical component summary (PCS) scores of the SF-36 v2.

Other clinical trials.

In an open label monotherapy trial comparing the safety (primary objective) and efficacy (secondary objective) of Ozempic 0.5 mg and 1 mg once weekly with sitagliptin 100 mg once daily in 308 Japanese patients, a significant greater reduction of HbA1c levels from baseline after 30 weeks of treatment were achieved with Ozempic 0.5 mg and 1 mg compared to sitagliptin (-1.9%, -2.2% vs -0.7%).
Significantly more patients achieved an HbA1c level of 7% with Ozempic 0.5 mg (84%) and 1 mg (95%) compared to sitagliptin (35%). Patients treated with Ozempic 0.5 mg and 1 mg had a significant decrease in body weight compared to that of patients treated with sitagliptin (-2.2 kg and -3.9 kg vs 0.0 kg). The most frequently reported adverse reactions (ARs) in this trial were gastrointestinal disorders. Greater proportions of patients treated with Ozempic 0.5 mg and 1 mg experienced gastrointestinal disorders vs patients treated with sitagliptin (38% and 41% for Ozempic 0.5 mg and 1 mg vs 17% with sitagliptin).
In an open label trial comparing the safety (primary objective) and efficacy (secondary objective) of Ozempic 0.5 mg and 1 mg once weekly with 1-2 OADs in 601 Japanese patients on monotherapy or 1 OAD, a higher reduction in HbA1c was seen with Ozempic 0.5 mg (-1.7%) and 1 mg (-2.0%) compared to additional OAD (-0.7%). Patients treated with Ozempic 0.5 mg and 1 mg had a significant decrease in body weight compared to that of patients treated with additional OAD (-1.4 kg and -3.2 kg vs +0.4 kg). The most frequently reported ARs in this trial were gastrointestinal disorders. Greater proportion of patients treated with Ozempic 0.5 mg and 1 mg experienced gastrointestinal disorders vs patients treated with additional OAD (54% and 54% vs 20%).

5.2 Pharmacokinetic Properties

Semaglutide has pharmacokinetic properties compatible with once weekly administration, with an elimination half-life of approximately 1 week.

Absorption.

Maximum concentration was reached 1 to 3 days post dose.
Steady-state exposure was achieved following 4-5 weeks of once weekly administration. In patients with type 2 diabetes, the mean steady state concentrations following s.c. administration of 0.5 mg and 1 mg semaglutide were approximately 16 nanomol/L and 30 nanomol/L, respectively.
Semaglutide exposure increased in a dose proportional manner for doses of 0.5 mg and 1 mg.
Similar exposure was achieved with s.c. administration of semaglutide in the abdomen, thigh, or upper arm.
Absolute bioavailability of s.c. semaglutide was 89%.

Distribution.

The mean volume of distribution of semaglutide following s.c. administration in patients with type 2 diabetes was approximately 12.5 L. Semaglutide was extensively bound to plasma albumin (> 99%).

Metabolism.

Semaglutide is metabolised through proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.

Excretion.

The primary excretion routes of semaglutide related material were via the urine and faeces. Approximately 3% of the dose was excreted as intact semaglutide via urine.
Clearance of semaglutide in patients with type 2 diabetes was approximately 0.05 L/h. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose.

Special populations.

No dose adjustment of semaglutide is needed based on age, gender, race, ethnicity, body weight, or renal or hepatic impairment. The effects of intrinsic factors on the pharmacokinetics of semaglutide are shown in Figure 10.

Age.

Age had no effect on the pharmacokinetics of semaglutide based on data from phase 3a studies including patients of 20-86 years of age.

Gender.

Gender had no effect on the pharmacokinetics of semaglutide.

Race.

Race (White, Black or African-American, Asian) had no effect on the pharmacokinetics of semaglutide.

Ethnicity.

Ethnicity (Hispanic or Latino) had no effect on the pharmacokinetics of semaglutide.

Body weight.

Body weight had an effect on the exposure of semaglutide. Higher body weight results in lower exposure. Semaglutide doses of 0.5 mg and 1 mg provide adequate systemic exposure over a body weight range of 40-198 kg.

Renal impairment.

Renal impairment did not impact the pharmacokinetics of semaglutide in a clinically relevant manner. This was shown with a single dose of 0.5 mg semaglutide for patients with different degrees of renal impairment (mild, moderate, severe or patients in dialysis) compared with subjects with normal renal function. This was also shown for subjects with type 2 diabetes and renal impairment based on data from phase 3a studies (Figure 10), although the experience in patients with end-stage renal disease was limited.

Hepatic impairment.

Hepatic impairment did not have any impact on the exposure of semaglutide. The pharmacokinetics of semaglutide were evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function in a study with a single-dose of 0.5 mg semaglutide.

Paediatrics.

Semaglutide has not been studied in paediatric patients.

5.3 Preclinical Safety Data

Genotoxicity.

Semaglutide was not mutagenic in the bacterial reverse mutation assay, and was not clastogenic in vitro (cytogenetic assay in human lymphocytes), or in vivo (rat bone marrow micronucleus test).

Carcinogenicity.

Non-lethal thyroid C-cell tumours observed in rodents are a class effect for GLP-1 receptor agonists. In 2-year carcinogenicity studies in rats and mice, semaglutide caused thyroid C-cell tumours at clinically relevant exposures (at ≥ 4x the clinical AUC in mice [based on the plasma AUC at the maximum recommended human dose of 1 mg/week] and subclinical exposures in rats; a no effect level was not established in either species). No other treatment-related tumours were observed. The rodent C-cell tumours are caused by a non-genotoxic, specific GLP-1 receptor mediated mechanism to which rodents are particularly sensitive. The relevance for humans is considered to be low, but cannot be completely excluded.

Juvenile toxicity.

In juvenile rats, semaglutide caused delayed sexual maturation in both males and females. These delays had no impact upon fertility and reproductive capacity of either sex, or on the ability of the females to maintain pregnancy.

6 Pharmaceutical Particulars

6.1 List of Excipients

Dibasic sodium phosphate dihydrate, propylene glycol, phenol, hydrochloric acid, sodium hydroxide, water for injections.

6.2 Incompatibilities

Substances added to Ozempic may cause degradation of semaglutide. Ozempic 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.
Shelf-life for pen in use: 42 days (6 weeks).

6.4 Special Precautions for Storage

Before use.

Store in a refrigerator (2°C to 8°C). Keep away from the cooling element. Protect from light.
Do not freeze Ozempic and do not use Ozempic if it has been frozen.

After first use.

Store below 30°C or in a refrigerator (2°C to 8°C). Do not freeze Ozempic and do not use Ozempic if it has been frozen. Keep the pen cap on when the Ozempic pen is not in use in order to protect from light.
Ozempic should be protected from excessive heat and light.
The Ozempic pen is for use by one person only.
Ozempic should not be used if it does not appear clear and colourless, or almost colourless.
Always remove the injection needle immediately after each injection and store the Ozempic pen without a needle attached. This may prevent blocked needles, contamination, infection, leakage of solution and inaccurate dosing.

6.5 Nature and Contents of Container

The primary packaging is a 1.5 mL or 3 mL glass cartridge (Type I glass) closed at one end with a rubber plunger (Type I/chlorobutyl) and at the other end with an aluminium cap with a rubber disc (Type I/bromobutyl/polyisoprene) inserted. The cartridge is assembled into a pre-filled multidose disposable pen made of polypropylene, polyoxymethylene polycarbonate and acrylonitrile butadiene styrene.
There are two variants of the pre-filled pen for Ozempic:
Ozempic 0.25 mg, 0.5 mg/dose solution for injection in pre-filled pen is able to deliver doses of 0.25 mg or 0.5 mg. This pen is intended to be used for dose escalation and maintenance treatment at the 0.5 mg dose. The pen contains 1.5 mL solution.
Ozempic 1 mg/dose for injection in pre-filled pen is only able to deliver doses of 1 mg. This pen is to be used for maintenance treatment at the 1 mg dose only. The pen contains 3 mL solution.
Ozempic can be administered with needles up to a length of 8 mm. The pen is designed to be used with NovoFine disposable needles. NovoFine Plus needles are included in the Ozempic package.
Pack sizes of:

Ozempic 0.25 mg, 0.5 mg/dose.

1 pre-filled pen including 6 disposable NovoFine Plus needles.

Ozempic 1 mg/dose.

1 pre-filled pen including 4 disposable NovoFine Plus needles.

6.6 Special Precautions for Disposal

The patient should be advised to discard the injection needle after each injection in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.

Molecular formula: C187H291N45O59.
Molecular weight: 4113.6 daltons.

CAS number.

RN910463-68-2.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes