Consumer medicine information

Mounjaro Vial

Tirzepatide

BRAND INFORMATION

Brand name

Mounjaro

Active ingredient

Tirzepatide

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mounjaro Vial.

SUMMARY CMI

MOUNJARO® vial

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

▼ This medicine is new or being used differently. Please report side effects. See the full CMI for further details.

1. Why am I using MOUNJARO?

MOUNJARO contains the active ingredient tirzepatide. In adults with type 2 diabetes, MOUNJARO is used to improve blood sugar control. In adults who are overweight or have obesity, MOUNJARO is used for weight management.

For more information, see Section 1. Why am I using MOUNJARO? in the full CMI.

2. What should I know before I use MOUNJARO?

Do not use if you have ever had an allergic reaction to tirzepatide or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use MOUNJARO? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with MOUNJARO and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use MOUNJARO?

  • MOUNJARO is supplied as a single-use vial that is used once a week, on the same day each week if you can.
  • When you first start using MOUNJARO, the starting dose is 2.5 mg once a week for 4 weeks. After 4 weeks your dose will be increased to 5 mg once a week.
  • Your doctor may choose to increase your dose by 2.5 mg every 4 weeks to achieve a dose of 7.5 mg, 10 mg, 12.5 mg or 15 mg once a week if needed. The maximum dose is 15 mg once weekly.

More instructions can be found in Section 4. How do I use MOUNJARO? in the full CMI.

5. What should I know while using MOUNJARO?

Things you should do
  • Remind any doctor, surgeon, anaesthetist, pharmacist, or nurse you visit that you are using MOUNJARO.
  • If you have diabetes, always carry glucose or sugary foods with you. Tell your doctor if you experience low blood sugar, called hypoglycaemia and this occurs often.
Things you should not do
  • Do not stop using this medicine suddenly and without consulting your Doctor/Healthcare provider.
  • Do not use this medicine if you think it has been frozen or exposed to excessive heat.
Driving or using machines
  • Be careful before you drive or use machines or tools until you know how MOUNJARO affects you.
  • Hypoglycaemia (low blood sugar) may affect your ability to concentrate.
Drinking alcohol
  • Tell your doctor if you drink alcohol. Alcohol may mask the symptoms of hypoglycaemia (low blood sugar) or make it worse.
Looking after your medicine
  • Store MOUNJARO in a refrigerator (2°C - 8°C). Do not freeze.
  • Keep MOUNJARO in the original package in order to protect from light until ready to use.

For more information, see Section 5. What should I know while using MOUNJARO? in the full CMI.

6. Are there any side effects?

The most common side effects are nausea, diarrhoea, vomiting, abdominal (stomach) pain, and decreased appetite. These side effects are usually not severe. Serious side effects which may require urgent medical attention may include inflamed pancreas (acute pancreatitis - sudden severe pain in the stomach and back), gallbladder complaints and allergic reactions. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

▼ This medicine is subject to additional monitoring due to approval of an extension of indications. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. You can report side effects to your doctor, or directly at www.tga.gov.au/reporting-problems.



FULL CMI

MOUNJARO® vial (muhn-JAHR-oh)

Active ingredient: tirzepatide

Consumer Medicine Information (CMI)

This leaflet provides important information about using MOUNJARO. You should also speak to your doctor, pharmacist, or nurse if you would like further information or if you have any concerns or questions about using MOUNJARO.

Where to find information in this leaflet:

1. Why am I using MOUNJARO?
2. What should I know before I use MOUNJARO?
3. What if I am taking other medicines?
4. How do I use MOUNJARO?
5. What should I know while using MOUNJARO?
6. Are there any side effects?
7. Product details

1. Why am I using MOUNJARO?

MOUNJARO contains the active ingredient tirzepatide. MOUNJARO is a type of medicine called 'GIP and GLP-1 receptor agonists'. In adults, this medicine is used to help treat diabetes. In adults who are overweight or have obesity, this medicine is used to reduce weight or maintain weight loss.

Type 2 Diabetes

Diabetes mellitus is a condition in which your pancreas does not produce enough insulin to control your blood sugar (glucose) level.

In adults with type 2 diabetes, MOUNJARO is used to improve blood sugar control.
MOUNJARO may be used alone or in combination with other diabetes medicines to control your blood sugar levels.

Weight Management

In adults who are overweight or have obesity, MOUNJARO is used for weight management, including weight loss and weight maintenance.

2. What should I know before I use MOUNJARO?

Warnings

Do not use MOUNJARO if:

  • you are allergic to tirzepatide, or any of the ingredients listed at the end of this leaflet.
  • Always check the ingredients to make sure you can use this medicine.

Children and adolescents

This medicine should not be given to children and adolescents under 18 years of age because it has not been studied in this age group.

Check with your doctor if you:

  • have any other medical conditions such as:
    - gastrointestinal disease, including severe gastroparesis (also called delayed gastric emptying), a condition affecting your digestive system. Your doctor may need to monitor your condition more closely and in some cases your doctor may need to change your dose or stop MOUNJARO if symptoms are severe.
    - malnutrition (your body does not get enough of the right nutrients to meet your body's needs).
    - inflammation of the pancreas (pancreatitis) - an inflamed pancreas causing severe stomach and back pain which does not go away. MOUNJARO may cause inflammation of the pancreas.
    - problems with your eyes (diabetic retinopathy). Your doctor may need to monitor your condition more closely while you are using MOUNJARO.
    - thoughts of suicide or death.
    - congestive heart failure.
    - kidney impairment (kidneys are not working as well as they should).
    - liver impairment (liver does not work as well as it should).
  • are taking other medicines to treat type 2 diabetes (such as a sulfonylurea or insulin) as this may cause your blood sugar to be too low (hypoglycaemia). Your doctor may tell you to test your blood sugar to decide if any of the medicine/s or doses need to be changed.
  • take any medicines for any other condition.
  • have had an allergic reaction to any medicine which you have used previously to treat type 2 diabetes.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Do not use MOUNJARO if you are pregnant as the effects of this medicine during pregnancy have not been studied.

If you could become pregnant while using MOUNJARO, it is recommended to use contraception.

It is unknown if MOUNJARO passes into breast milk. Talk to your doctor if you are breastfeeding or intend to breastfeed.

Dehydration

  • When starting treatment with MOUNJARO, you may experience dehydration due to vomiting or diarrhoea.
  • Dehydration can lead to kidney problems. It is important to avoid dehydration by drinking plenty of fluids.
  • Symptoms of dehydration include dry mouth, decreased frequency of urination, dark urine, headache, muscle weakness, or dizziness. Check with your doctor if you have any questions or concerns.

3. What if I am taking other medicines?

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

Some medicines may interfere with MOUNJARO and affect how it works.

When MOUNJARO is used with a medicine that contains sulfonylurea or insulin, hypoglycaemia can occur. The dose of your sulfonylurea or insulin may need to be reduced.

Some medicines may be affected by MOUNJARO and affect how they work.

MOUNJARO delays stomach (gastric) emptying. If you take any medicines via mouth (orally), such as slow-release medicines, medicines with quick absorption from the stomach, medicines that have a narrow therapeutic index (e.g., warfarin, digoxin), or an oral contraceptive ('the pill'), MOUNJARO may affect how well these medicines work. Check with your doctor or pharmacist if you are not sure.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect MOUNJARO.

4. How do I use MOUNJARO?

How much to use

  • When you first start using MOUNJARO, the starting dose is 2.5 mg once a week for 4 weeks. After 4 weeks your doctor will increase your dose to 5 mg once a week.
  • Your doctor may increase your dose by 2.5 mg every 4 weeks to achieve a dose of 7.5 mg, 10 mg, 12.5 mg or 15 mg once a week if needed. The maximum dose is 15 mg once weekly.
  • Follow the instructions provided and use MOUNJARO until your doctor tells you to stop. Do not change your dose unless your doctor has told you to do so. If you stop using it, your blood sugar levels may increase.

When to use MOUNJARO

  • MOUNJARO should be used once a week, on the same day each week if you can.
  • You can inject MOUNJARO at any time of the day, with or without meals.
  • To help you remember, you may wish to write the day of the week when you take your first dose of MOUNJARO on a calendar.
  • If necessary, you can change the day of your usual weekly injection of MOUNJARO as long as it has been at least 3 days since your last injection of MOUNJARO. Speak to your doctor, pharmacist or nurse if you are unsure.

How to use MOUNJARO

Follow all directions given to you by your doctor, pharmacist or nurse carefully. They may differ from the information contained in this leaflet.

How to inject MOUNJARO will be explained to you by a healthcare professional. After being trained by your healthcare professional, you can inject MOUNJARO yourself at home.

MOUNJARO must not be injected into a vein or muscle. MOUNJARO is intended for subcutaneous (under the skin) injection.

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

When injecting, it is important to change the injection site to different areas of the body, to help reduce potential pain and irritation.

Areas with a good amount of fat below the skin (upper thigh, upper arm or stomach) are the most suitable areas to inject.

Prepare:

  • Inspect the vial carefully before using. MOUNJARO should be clear and colourless to slightly yellow.
  • Check the name and coloured label to make sure it is the correct medicine 'MOUNJARO' and it is the correct strength prescribed for you.
  • Place all the items you will need on a clean surface where you will not be disturbed. These should include:
    - syringe with needle (as recommended by your healthcare provider).
    - A sharps container
  • Wash your hands.
  • Pull off the protective cap from the vial, but do not remove the rubber stopper.
  • Firmly attach the needle to the top of the syringe. You can omit this step if the needle and syringe are already attached and in one piece.
  • Remove the needle shield/cap.

Draw Up

  • Push the needle through the centre of the rubber stopper of the vial.
  • Leave the needle in the rubber stopper and turn the vial upside down.
  • Slowly pull the plunger down until the plunger tip is past the 0.5 mL line.
  • If there are air bubbles in the syringe, tap the syringe gently a few times to let any air bubbles rise to the top.
  • Slowly push the plunger up until the plunger tip reaches the 0.5 mL line.
  • Pull the syringe out of the rubber stopper of the vial.

Inject

  • You can use MOUNJARO under the skin (subcutaneous) of your stomach (abdomen) or upper leg (thigh) as you have been instructed. If MOUNJARO is given by someone else, they may inject in the back of your upper arm.
  • If you want to do so, you can inject the same area of your body each week. But be sure to choose a different injection site within that area.
  • If using a needle that is 8 mm or longer, pinch up a fold of skin and insert the needle into your skin at a 45 degree angle. For needles less than 8 mm, you can insert the needle into your skin at 90 degree angle, there is no need to pinch up the skin.
  • Push down on the plunger to inject your dose.
  • The plunger tip should be at the bottom of the syringe and the needle should stay in your skin for at least 5 seconds to make sure you have injected all of your medicine.
  • Pull the needle out of your skin and place the needle directly into your sharps container. Do not share or reuse your needle or syringe.
  • Dispose of the used vial (including any residue) in your sharps container.

If you forget to use MOUNJARO

MOUNJARO should be used regularly each week on the same day each week.

If you miss or forget your dose, it should be administered as soon as possible.

If there are fewer than 3 days until your next dose, then skip the missed dose. Inject the next MOUNJARO dose as usual on your regular day.

Do not take a double dose to make up for a forgotten dose.

If you use too much MOUNJARO

If you think that you have used too much MOUNJARO, seek urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

5. What should I know while using MOUNJARO?

Things you should do

Remind any doctor, surgeon, anaesthetist, pharmacist or nurse you visit that you are using MOUNJARO.

Tell your doctor, pharmacist, or nurse if you are planning to travel overseas. You may not be able to get MOUNJARO in the country you are visiting, and you may need to carry a letter explaining why you are taking injecting devices with you. Your doctor, pharmacist or nurse can provide you with some helpful information.

If you have diabetes:

  • Make sure all your family, relatives, friends, workmates, or carers know that you have diabetes and can recognise the symptoms of hypoglycaemia (low blood sugar).
  • Let your doctor know if you start taking/using another medicine to treat type 2 diabetes. This could affect your blood sugar levels. Your doctor may want you to monitor your blood sugar levels more often.
  • Always carry something to show you have diabetes.
  • Always carry glucose or sugary foods with you.
  • Let your doctor know if you plan to have any surgery or need general anaesthesia for any reason

Call your doctor straight away if you:

  • Experience severe low blood sugar, called hypoglycaemia, and this worries you.

Things you should not do

  • Do not stop using this medicine suddenly and without consulting your Doctor/Healthcare provider.
  • Do not use this medicine if you think it has been frozen or exposed to excessive heat, or if it is cloudy or contains particles. Appropriately discard and use a new vial for your injection.
  • Do not use this medicine if the packaging is torn or shows signs of tampering.
  • Do not give your MOUNJARO to anyone else, even if they have the same condition as you. Your doctor has prescribed MOUNJARO only for you.

Hypoglycaemia (low blood sugar) in patients with diabetes

It is important you know and can recognise the symptoms of hypoglycaemia.

Symptoms of mild to moderate hypoglycaemia can include:

  • sweating
  • hunger, headache
  • tremor, unsteady movement
  • light-headedness
  • drowsiness, dizziness
  • depressive mood, anxiety
  • irritability, personality change
  • abnormal behaviour
  • inability to concentrate
  • sleep disturbance
  • blurred vision
  • increased heart rate or irregular heartbeat
  • tingling in the hands/feet/lips or tongue
  • slurred speech

Tell your doctor, pharmacist or nurse if you have trouble recognising the symptoms of hypoglycaemia.

Recognising these mild to moderate hypoglycaemic symptoms early may allow you to take the necessary steps to avoid more serious hypoglycaemia.

Symptoms of severe hypoglycaemia can include:

  • disorientation
  • seizures
  • unconsciousness

If you experience symptoms of hypoglycaemia, eat some sugary food or drink, such as jellybeans, orange juice or glucose tablets.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how MOUNJARO affects you.

Hypoglycaemia (low blood sugar) may affect your ability to concentrate. Avoid driving or using machines if you get any signs of hypoglycaemia.

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may mask the symptoms of hypoglycaemia (low blood sugar) or make it worse.

Looking after your medicine

  • Store MOUNJARO in a refrigerator (2°C - 8°C).
  • When refrigeration is not possible, you can keep your vial at room temperature (below 30°C) for up to a total of 21 days.
  • Do not allow the vial to freeze. DO NOT use if it has been frozen.
  • Keep MOUNJARO in the original package in order to protect from light.
  • Never use MOUNJARO after the expiry date (month, year) stamped or printed on the carton, or on the label.

Keep it where young children cannot reach it.

When to discard your medicine

  • If your doctor tells you to stop taking MOUNJARO, or
  • If the expiry date on the carton or vial has passed.

Empty vials and used syringes and needles, should be disposed of in a yellow plastic sharps container or similar puncture proof container composed of hard plastic or glass. Ask your doctor, pharmacist, or nurse for further information.

Getting rid of any unwanted medicine

If you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor, pharmacist, or nurse if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Stomach related:
  • feeling sick (nausea)
  • diarrhoea (also refer to Serious Side Effects)
  • vomiting - this usually goes away over time (also refer to Serious Side Effects)
  • abdominal (stomach) pain (also refer to Serious Side Effects)
  • heartburn (typically a burning sensation that begins just below the breastbone and moves up towards the throat)
  • indigestion (dyspepsia) - discomfort in the upper stomach
  • swelling or bloating of the stomach which may be painful (abdominal distension)
  • constipation
  • burping or belching
  • farting (flatulence)
  • bloating and/or difficulty passing wind (farting)
  • feeling less hungry (decreased appetite)
General disorders and injection site related:
  • general feeling of tiredness
  • injection site reaction such as: redness, swelling or itching at the injection site.
Hypoglycaemia (low blood sugar):
When MOUNJARO is used to treat diabetes together with:
  • a sulfonylurea (such as gliclazide, glibenclamide, glipizide) or insulin,
  • metformin and an SGLT-2i (such as metformin and dapagliflozin, or metformin and empagliflozin, or metformin and ertugliflozin)
Refer to Section 5 for signs and symptoms of hypoglycaemia.
Other effects:
  • dizziness
  • dehydration.
    When initiating treatment with MOUNJARO, 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.
  • hair loss
  • low blood pressure (hypotension)
  • changes to how foods or drinks taste.
  • changes to sensation or unusual feelings of the skin
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Acute pancreatitis:
Symptoms of Inflamed pancreas (acute pancreatitis) may include:
  • severe pain in the stomach and back which does not go away;
    and
  • vomiting and/or diarrhoea
Allergic reactions:
Symptoms of an allergic reaction may include:
  • rashes
  • itching and rapid swelling of the tissues of the neck, face, mouth and/or throat
  • hives (urticaria)
  • problems breathing or swallowing
Gallbladder complaints:
  • Gallstones or an inflamed gallbladder (symptoms may include sudden, severe pain in your upper stomach (abdomen), fever, yellowing of skin or eyes (jaundice), clay-coloured stools)
Call your doctor straight away or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Slowing down or blockage of intestinal function:
Causing symptoms that may include:
  • severe pain in the stomach/abdomen
  • bloating and/or difficulty passing wind (farting)
  • feeling sick (nausea), vomiting and/or diarrhoea
  • constipation/bowel urges with no resulting movement
Tell your doctor as soon as possible.

Tell your doctor, pharmacist or nurse if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What MOUNJARO contains

Active ingredient
(main ingredient)		tirzepatide
Other ingredients
(inactive ingredients)		dibasic sodium phosphate heptahydrate
sodium chloride
hydrochloric acid
sodium hydroxide
water for injections
Potential allergensnone

Do not take this medicine if you are allergic to any of these ingredients.

MOUNJARO vials are for single-use and do not contain any preservative. Discard after use.

What MOUNJARO looks like

MOUNJARO is a clear, colourless to slightly yellow solution available as a single-use vial.

MOUNJARO vials are available in the following strengths:

  • 2.5 mg/0.5 mL (AUST R 407055)
  • 5.0 mg/0.5 mL (AUST R 407050)
  • 7.5 mg/0.5 mL (AUST R 407051)
  • 10 mg/0.5 mL (AUST R 407053)
  • 12.5 mg/0.5 mL (AUST R 407052)
  • 15 mg/0.5 mL (AUST R 407054)

Who distributes MOUNJARO

Australia:

Eli Lilly Australia Pty Ltd
Level 9, 60 Margaret Street,
Sydney, NSW 2000

Further Information

If you have any questions about MOUNJARO, contact Lilly at 1800 454 559 or your healthcare professional for assistance.

To check for CMI updates and obtain the latest version, visit www.ebs.tga.gov.au

® = Registered Trademark

This leaflet was prepared in September 2024.

(vA4.0)

Published by MIMS October 2024

BRAND INFORMATION

Brand name

Mounjaro

Active ingredient

Tirzepatide

Schedule

S4

 

1 Name of Medicine

Tirzepatide.

2 Qualitative and Quantitative Composition

Single-dose vial and pre-filled pen (autoinjector).

Mounjaro tirzepatide 2.5 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 2.5 mg in 0.5 mL solution.

Mounjaro tirzepatide 5 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 5 mg in 0.5 mL solution.

Mounjaro tirzepatide 7.5 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 7.5 mg in 0.5 mL solution.

Mounjaro tirzepatide 10 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 10 mg in 0.5 mL solution.

Mounjaro tirzepatide 12.5 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 12.5 mg in 0.5 mL solution.

Mounjaro tirzepatide 15 mg/0.5 mL solution for injection vial and pre-filled pen.

Each vial and pre-filled pen contains tirzepatide 15 mg in 0.5 mL solution.

Multiple-dose pre-filled pen (KwikPen).

Mounjaro KwikPen tirzepatide 4.17 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 2.5 mg tirzepatide.

Mounjaro KwikPen tirzepatide 8.33 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 5 mg tirzepatide.

Mounjaro KwikPen tirzepatide 12.5 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 7.5 mg tirzepatide.

Mounjaro KwikPen tirzepatide 16.67 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 10 mg tirzepatide.

Mounjaro KwikPen tirzepatide 20.83 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 12.5 mg tirzepatide.

Mounjaro KwikPen tirzepatide 25 mg/mL solution for injection multiple-dose pre-filled pen.

Each multiple-dose pre-filled pen delivers four 0.6 mL doses containing 15 mg tirzepatide.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection.
Mounjaro is a clear, colourless to slightly yellow, sterile solution for subcutaneous administration. The single dose vial and pre-filled pen are preservative-free. The multiple-dose pre-filled pen contains preservatives.

4 Clinical Particulars

4.1 Therapeutic Indications

Type 2 diabetes mellitus.

Mounjaro 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.

Chronic weight management.

Mounjaro is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management, including weight loss and weight maintenance, in adults with an initial body mass index (BMI) of:
≥ 30 kg/m2 (obesity) or
≥ 27 kg/m2 to < 30 kg/m2 (overweight) in the presence of at least one weight-related comorbid condition (e.g. hypertension, dyslipidaemia, obstructive sleep apnoea, cardiovascular disease, prediabetes or type 2 diabetes mellitus).

4.2 Dose and Method of Administration

Type 2 diabetes mellitus and chronic weight management.

Use in adults (≥ 18 years).
The starting dose of tirzepatide is 2.5 mg once weekly.
After 4 weeks, increase the dose to 5 mg once weekly.
If needed, dose increases can be made in 2.5 mg increments after a minimum of 4 weeks on the current dose.
The recommended doses are 5 mg, 10 mg and 15 mg.
The 2.5 mg, 7.5 mg and 12.5 mg are not maintenance doses.
The maximum dose of tirzepatide is 15 mg once weekly.
Available doses are 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg. (See Section 2 Qualitative and Quantitative Composition.)
The Mounjaro KwikPen is a variable dosing device and there is potential for underdosing in patients if used incorrectly. Please refer to the Instructions for Use leaflet in the carton and ensure the dose knob on the Mounjaro KwikPen device is turned to the '1' icon to inject a full dose.
Self-monitoring of blood glucose is not needed to adjust the dose of tirzepatide.
When tirzepatide is added to existing metformin and/or sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy, the current dose of metformin and/or SGLT2i can be continued.
When tirzepatide is added to existing therapy of a sulfonylurea and/or insulin, a reduction in the dose of sulfonylurea or insulin may be considered to reduce the risk of hypoglycaemia. Blood glucose self-monitoring is necessary to adjust the dose of sulfonylurea and insulin. A stepwise approach to insulin reduction is recommended. (See Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

Missed dose.

If a dose is missed, it should be administered as soon as possible.
If there are fewer than 3 days until the next regularly scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day. Patients can then resume their regular once weekly dosing schedule.

Changing the weekly dosing schedule.

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).

Special population.

Use in the elderly (≥ 65 years).

No dose adjustment is needed based on age.

Gender and body weight.

No dose adjustment is needed based on gender or body weight.

Race and ethnicity.

No dose adjustment is needed based on race and ethnicity.

Renal impairment.

No dose adjustment is needed in patients with renal impairment (including end-stage renal disease). Experience with the use of tirzepatide in patients with severe renal impairment and ESRD is limited. Caution should be exercised when treating these patients with tirzepatide.

Hepatic impairment.

No dose adjustment is needed in patients with hepatic impairment. Experience with the use of tirzepatide in patients with severe hepatic impairment is limited. Caution should be exercised when treating these patients with tirzepatide.

Paediatric population.

The safety and efficacy of tirzepatide in children aged less than 18 years have not yet been established. No data are available.

Method of administration.

Mounjaro can be injected at any time of the day, with or without meals.
Inject tirzepatide subcutaneously in the abdomen or thigh.
It is recommended to rotate injection sites with each dose.

Single-dose vial and pre-filled pen.

Preservative-free, for single use in one patient only.
Discard any residue.

Multiple-dose pre-filled pen.

For single-patient use only.

4.3 Contraindications

Mounjaro is contraindicated in patients with known hypersensitivity to tirzepatide or any of the excipients listed in Section 6.1 List of Excipients.

4.4 Special Warnings and Precautions for Use

Mounjaro should not be used in patients with Type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Acute pancreatitis.

Tirzepatide has not been studied in patients with a history of pancreatitis and should be used in caution with these patients.
Acute pancreatitis has been reported in patients treated with tirzepatide.
Patients should be informed of the symptoms of acute pancreatitis. If pancreatitis is suspected, tirzepatide should be discontinued. If the diagnosis of pancreatitis is confirmed, tirzepatide should not be restarted. In the absence of other signs and symptoms of pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.

Hypoglycaemia in patients with type 2 diabetes mellitus.

Patients receiving tirzepatide in combination with an insulin secretagogue (for example, a sulfonylurea) or insulin may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of the insulin secretagogue or insulin (see Section 4.2 Dose and Method of Administration; Section 4.8 Adverse Effects (Undesirable Effects)).

Gastrointestinal effects.

Tirzepatide has been associated with gastrointestinal adverse reactions, which include nausea, vomiting, and diarrhoea (see Section 4.8 Adverse Effects (Undesirable Effects)). These events may lead to dehydration, which could cause a deterioration in renal function, including acute renal failure.
Patients treated with tirzepatide should be advised of the potential risk of dehydration, particularly in relation to gastrointestinal adverse reactions and take precautions to avoid fluid depletion. Monitor renal function when initiating or escalating doses of Mounjaro in patients with renal impairment reporting severe gastrointestinal adverse reactions.

Severe gastrointestinal disease.

Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, and should be used with caution in these patients. Events related to impaired gastric emptying, including severe gastroparesis, have been reported. Monitor and consider dose modification or discontinuation in patients who develop severe gastrointestinal symptoms while on treatment.
Events related to malnutrition have been reported, including severe, in patients receiving tirzepatide. Risks associated with malnutrition include, but are not limited to, vitamin and mineral deficiency, protein deficiency, and low body weight. Balanced nutritional support should be considered. Discontinuation should be considered for severe or persistent cases.

Diabetic retinopathy.

Rapid improvement in glucose control has been associated with a temporary worsening of diabetic retinopathy. Tirzepatide has not been studied in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy or diabetic macular oedema, and should be used with caution in these patients with appropriate monitoring.

Pulmonary aspiration.

Tirzepatide delays gastric emptying. Pulmonary aspiration has been reported in patients receiving long acting GLP-1 receptor agonists undergoing general anaesthesia or deep sedation. This should be considered prior to such procedures.

Psychiatric disorders.

Suicidal behaviour and ideation have been reported with products which induce weight loss. Monitor patients for the emergence or worsening of depression, suicidal thoughts or behaviours, and/or any unusual changes in mood or behaviour. Consider the benefits and risks for individual patients prior to initiating or continuing therapy in patients with suicidal thoughts or behaviours or have a history of suicidal attempts.

Congestive heart failure.

There is limited therapeutic experience in patients with congestive heart failure.

Use in hepatic impairment.

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

Use in renal impairment.

No dose adjustment is needed in patients with renal impairment (including end-stage renal disease) (see Section 5.2 Pharmacokinetic Properties). Experience with the use of tirzepatide in patients with severe renal impairment and ESRD is limited. Caution should be exercised when treating these patients with tirzepatide.

Use in the elderly.

No dose adjustment is required based on age. Only very limited data are available from patients aged ≥ 85 years.

Paediatric use.

The safety and efficacy of tirzepatide in children aged less than 18 years have not yet been established. No data are available.

Effects on laboratory tests.

No information on the effect of tirzepatide on laboratory tests is available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Tirzepatide delays gastric emptying and has the potential to affect the rate of absorption of concomitantly administered oral medications. This effect, resulting in decreased Cmax and a delayed tmax, is most pronounced at the time of tirzepatide treatment initiation.
Based on the results from a study with paracetamol, which was used as a model medicinal product to evaluate the effect of tirzepatide on gastric emptying, it is not anticipated that tirzepatide treatment will result in a clinically meaningful impact on orally administered drugs that do not have a narrow therapeutic index. However, it is recommended to monitor patients on oral medicinal products with a narrow therapeutic index (e.g. warfarin, digoxin), especially during the early phase of treatment with tirzepatide and following any dose increase. The risk of delayed effect should also be considered for any oral medicinal product for which a rapid onset of effect is important.

Oral contraceptives.

Administration of a combination oral contraceptive (0.035 mg ethinylestradiol plus 0.25 mg norgestimate) in the presence of a single dose of tirzepatide (5 mg) resulted in a reduction of oral contraceptive Cmax by 55 to 66%, with a 16 to 23% reduction in area under the curve (AUC) and a delay in tmax of 2.5 to 4.5 hours. This reduction in exposure after a single 5 mg dose of tirzepatide is not considered clinically relevant. Doses other than a single 5 mg dose of tirzepatide were not investigated in this interaction study.
The reduction in exposure described above may be significant in a setting with concomitant administration of medicines also affecting those exposures. Appropriate contraception methods (including non-oral contraceptives) should be discussed with the patient based on the patient's individual circumstances prior to commencing tirzepatide.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

The effect of tirzepatide on fertility in humans is unknown.
Tirzepatide did not affect fertility in male rats at doses up to 3 mg/kg/day, resulting in exposures 2 times the clinical AUC at the maximum recommended human dose (MRHD). In female rats, prolonged oestrus cycling and decreases in the mean numbers of corpora lutea, implantation sites, and viable embryos per litter was observed at subclinical exposures based on AUC at the MRHD.
(Category D)
There are no adequate and well-controlled studies of tirzepatide in pregnant women. Tirzepatide should not be used during pregnancy. Women of childbearing potential are advised to use contraception during treatment with tirzepatide (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). If a patient wishes to become pregnant or becomes pregnant, treatment with tirzepatide should be discontinued.
Studies in animals have shown reproductive toxicity when tirzepatide was administered during organogenesis. In pregnant rats, embryofetal toxicity (increased post-implantation loss, impaired growth and an increased incidence of fetal abnormalities) was observed at subclinical plasma exposures. All developmental effects occurred at maternally toxic doses. Exposures at the No Observed Adverse Effects Level (NOAEL) were subclinical and a direct effect of tirzepatide on the fetus cannot be excluded.
 It is unknown whether tirzepatide is excreted in human milk. Administer tirzepatide to nursing women only if the potential benefit to the mother justifies the potential risk to the infant. A risk to the newborns/ infants cannot be excluded.

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. When tirzepatide is used in combination with a sulfonylurea or insulin, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines (see Section 4.4 Special Warnings and Precautions for Use).

4.8 Adverse Effects (Undesirable Effects)

Summary of safety profile.

Type 2 diabetes mellitus.

In 7 completed phase 3 studies, 5,119 patients were exposed to tirzepatide alone or in combination with other glucose lowering medicinal products. The most frequently reported adverse reactions in clinical studies were gastrointestinal disorders, including nausea (very common), diarrhoea (very common), constipation (common) and vomiting (common), see Table 2. In general, these reactions were mostly mild or moderate in severity and occurred more often during dose escalation and decreased over time. (See Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use.)

Chronic weight management.

In 2 completed phase 3 studies, 2519 patients were exposed to tirzepatide. The most frequently reported adverse reactions were gastrointestinal disorders, including nausea (very common), diarrhoea (very common), constipation (very common), and vomiting (very common), see Table 3. In general, these reactions were mostly mild or moderate in severity and occurred more often during dose escalation and decreased over time (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

Tabulated list of adverse reactions.

The following related adverse reactions have been identified and are listed in Table 1 as MedDRA preferred term by system organ class and in order of decreasing incidence (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; very rare: < 1/10,000) and not known (cannot be estimated from the available data). Within each incidence grouping, adverse reactions are presented in order of decreasing frequency. See Table 2.

Description of selected adverse reactions.

Gastrointestinal adverse reactions. In the placebo-controlled phase 3 studies, gastrointestinal disorders were dose-dependently increased for tirzepatide 5 mg (37.1%), 10 mg (39.6%) and 15 mg (43.6%) compared with placebo (20.4%). Nausea occurred in 12.2%, 15.4% and 18.3% versus 4.3% and diarrhoea in 11.8%, 13.3% and 16.2% versus 8.9% for tirzepatide 5 mg, 10 mg and 15 mg versus placebo. Gastrointestinal adverse reactions were mostly mild (74%) or moderate (23.3%) in severity. The incidence of nausea, vomiting, and diarrhoea was higher during the dose escalation period and decreased over time.
More subjects in the tirzepatide 5 mg (3.0%), 10 mg (5.4%) and 15 mg (6.6%) groups compared to the placebo group (0.4%) discontinued permanently due to the gastrointestinal event.
Hypoglycaemia. The risk of severe hypoglycaemia with tirzepatide is low. In clinical studies, 10 (0.20%) patients reported 12 episodes of severe hypoglycaemia. Of these 10 patients, 5 (0.10%) were on a background of insulin glargine or sulfonylurea who reported 1 episode each.
Clinically significant hypoglycaemia occurred in 10 to 14% (0.14 to 0.16 events/patient year) of patients when tirzepatide was added to sulfonylurea and in 14 to 19% (0.43 to 0.64 events/patient year) of patients when tirzepatide was added to basal insulin.
The rate of clinically significant hypoglycaemia when tirzepatide was used as monotherapy or when added to other oral antidiabetic medication was up to 0.03 events/patient year (see Table 1; see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use; Section 5.1 Pharmacodynamic Properties).
Hypersensitivity reactions. Hypersensitivity reactions have been reported with tirzepatide in the pool of placebo-controlled trials, sometimes severe (e.g. urticaria and eczema); hypersensitivity reactions were reported in 3.2% of tirzepatide-treated patients compared to 1.7% of placebo-treated patients.
Immunogenicity. There was no evidence that the pharmacokinetic profile and efficacy were impacted by the development of anti-drug antibodies (ADAs). More tirzepatide-treated patients who developed anti-tirzepatide antibodies experienced hypersensitivity reactions or injection site reactions than those who did not develop these antibodies.
Consistent with the potentially immunogenic properties of protein and peptide medicinal products, patients may develop antibodies following treatment with tirzepatide.
In the Phase 3 clinical studies, approximately 51 - 65% of tirzepatide-treated patients developed ADAs.
Of the overall tirzepatide-treated patients, 1.9 - 2.8% and 2.1 - 2.7% had neutralising antibodies against tirzepatide activity on the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, respectively.
0.8 - 0.9% and 0.1 - 0.4% had neutralising antibodies against native GIP and GLP-1, respectively.
Heart rate.

Type 2 diabetes mellitus.

In the placebo-controlled phase 3 studies, treatment with tirzepatide resulted in a maximum mean increase in heart rate of 3 to 5 beats per minute. The maximum mean increase in heart rate in placebo-treated patients was 1 beat per minute.
The incidence of patients who had a change of baseline heart rate of > 20 bpm for 2 or more consecutive visits was 2.1%, 3.8% and 2.9%, for tirzepatide 5 mg, 10 mg and 15 mg, respectively, compared with 2.1% for placebo.
Small mean increases in PR interval were observed with tirzepatide when compared to placebo (mean increase of 1.4 to 3.2 msec and mean decrease of 1.4 msec respectively). No difference in arrhythmia and cardiac conduction disorder treatment emergent events were observed between tirzepatide 5 mg, 10 mg, 15 mg and placebo (3.8%, 2.1%, 3.7% and 3% respectively).

Chronic weight management.

Treatment with tirzepatide resulted in a mean increase in heart rate of 1 to 3 beats per minute. There was a mean increase in heart rate of 0 beats per minute in placebo-treated patients.
Injection site reactions. In the placebo-controlled phase 3 studies, injection site reactions were increased for tirzepatide (3.2%) compared with placebo (0.4%).
Overall, in the phase 3 studies, the most common signs and symptoms of injection site reactions were erythema and pruritus. The maximum severity of injection site reactions for patients was mild (90%) or moderate (10%). No injection site reactions were serious.
Pancreatic enzymes.

Type 2 diabetes mellitus.

In the placebo-controlled phase 3 studies, treatment with tirzepatide resulted in mean increases from baseline in pancreatic amylase of 33% to 38% and lipase of 31% to 42%. Placebo treated patients had an increase from baseline in amylase of 4% and no changes were observed in lipase.

Chronic weight management.

In the placebo-controlled phase 3 studies, treatment with tirzepatide resulted in mean increases from baseline in pancreatic amylase of 20% to 25% and lipase of 28% to 35%.

Postmarketing data.

The following adverse drug reactions are based on post marketing reports of tirzepatide:

Immune system disorders.

Anaphylactic reaction and angioedema.

Gastrointestinal disorders.

Intestinal obstruction including ileus.

Nervous system disorders.

Dysaesthesia: uncommon (≥ 0.1% - < 1%).

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

In the event of overdose, appropriate supportive treatments should be initiated according to the patient's clinical signs and symptoms. A period of observation and treatment of these symptoms may be necessary, taking into account the half-life of tirzepatide (approximately 5 days).
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, blood glucose lowering drugs, excl. insulins.
ATC code: A10BX16.

Mechanism of action.

Tirzepatide is a long-acting GIP and GLP-1 receptor agonist. It is an amino acid sequence with a C20 fatty diacid moiety that enables albumin binding and prolongs half-life. Both receptors are present on the pancreatic α and β endocrine cells, brain, heart, vasculature, immune cells (leukocytes), gut and kidney. GIP receptors are also present on adipocytes.
Tirzepatide is selective to human GIP and GLP-1 receptors. Tirzepatide has high affinity to both the GIP and GLP-1 receptors. The activity of tirzepatide on the GIP receptor is similar to native GIP hormone. The activity of tirzepatide on the GLP-1 receptor is lower compared to native GLP-1 hormone. Tirzepatide is a biased agonist at the GLP-1 receptor with preferential signaling towards the activation of adenylyl cyclase as opposed to the recruitment of β-arrestin.

Pharmacodynamic effects.

Glycaemic control.

Tirzepatide improves glycaemic control by lowering fasting and postprandial glucose concentrations in patients with type 2 diabetes through several mechanisms.

Insulin secretion.

Tirzepatide increases β-cell glucose sensitivity. In a hyperglycaemic clamp study in patients with type 2 diabetes, tirzepatide was compared to placebo and the selective GLP-1 receptor agonist semaglutide 1 mg for insulin secretion. Tirzepatide 15 mg enhanced the first- and second-phase insulin secretion rate by 466% and 302% from baseline, respectively, in a glucose dependent manner. There was no change in first- and second-phase insulin secretion rate for placebo and the rates increased for semaglutide 1 mg by 298% and 223%, respectively.

Insulin sensitivity.

Tirzepatide 15 mg improved whole body insulin sensitivity by 63%, as measured by M-value, a measure of glucose tissue uptake using hyperinsulinemic euglycaemic clamp. The M-value was unchanged for placebo and increased in semaglutide 1 mg by 35%.
Tirzepatide lowers body weight in patients with type 2 diabetes, which may contribute to improvement in insulin sensitivity. Reduced food intake with tirzepatide contributes to body weight loss. Body weight reduction is mostly due to reduced fat mass.

Glucagon concentration.

Tirzepatide reduced the fasting and postprandial glucagon concentrations. Tirzepatide 15 mg reduced fasting glucagon concentration by 28% and glucagon AUC after a mixed meal by 43%, compared with no change for placebo, and decreases for semaglutide 1 mg in fasting glucagon by 22% and in glucagon AUC by 29%.

Gastric emptying.

Tirzepatide delays gastric emptying, with largest delay after the first dose and this effect diminishes over time. Slowing post-meal glucose absorption and can lead to a beneficial effect on postprandial glycaemia.

Energy intake.

In patients with type 2 diabetes, tirzepatide reduced food intake contributing to body weight loss. In pre-clinical rodent studies tirzepatide induced a preference to lower fat food.

Appetite regulation.

Tirzepatide regulates appetite and decreases food intake. Both the GIP and GLP-1 receptors are found in areas of the brain that are important for appetite regulation.

Body weight.

Tirzepatide reduces and controls body weight. Studies in diet-induced obese mice have shown that tirzepatide modulates fat utilisation.

Clinical trials - clinical efficacy and safety.

Type 2 diabetes mellitus.

Glycaemic control and body weight.

The safety and efficacy of tirzepatide were evaluated in five (5) global randomised, controlled, phase 3 studies (SURPASS 1 to 5) assessing glycaemic efficacy as the primary objective involving 6,263 treated patients with type 2 diabetes (4,199 treated with tirzepatide). The secondary objectives included body weight, fasting serum glucose (FSG) and proportion of patients reaching target HbA1c. All five phase 3 studies assessed tirzepatide 5 mg, 10 mg and 15 mg. All patients treated with tirzepatide started with 2.5 mg for 4 weeks. Then the dose of tirzepatide was increased by 2.5 mg every 4 weeks until they reached their assigned dose.
Across all studies, treatment with tirzepatide demonstrated sustained, statistically significant and clinically meaningful reductions from baseline in HbA1c and body weight compared to either placebo or active control treatment (semaglutide, insulin degludec and insulin glargine) for up to 1 year. In 1 study these effects were sustained for up to 2 years. Results from the phase 3 studies are presented below based on the modified intent-to-treat (mITT) population consisting of all randomly assigned patients who were exposed to at least 1 dose of study treatment, excluding patients discontinuing study treatment due to inadvertent enrolment. The analysis aligned to the efficacy estimand for a longitudinal continuous variable employed a mixed model for repeated measurements.
SURPASS 1 - monotherapy. In a 40-week double blind placebo-controlled study (GPGK), 478 patients with inadequate glycaemic control with diet and exercise, were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or placebo. Patients had a mean age of 54 years and 52% were men. At baseline the patients had a mean duration of diabetes of 5 years and the mean BMI was 32 kg/m2. See Table 4 and Figure 1.
SURPASS 2 - combination therapy with metformin. In a 40-week (GPGL) active-controlled open-label study, (double-blind with respect to tirzepatide dose assignment) 1,879 patients were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or semaglutide 1 mg once weekly, all in combination with metformin. Patients had a mean age of 57 years and 47% were men. At baseline the patients had a mean duration of diabetes of 9 years and the mean BMI was 34 kg/m2. See Table 5 and Figure 2.
SURPASS 3 - combination therapy with metformin, with or without SGLT2i. In a 52-week active-controlled open-label study (GPGH), 1,444 patients were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or insulin degludec, all in combination with metformin and with or without a sodium-glucose co-transporter 2 inhibitor (SGLT2i). 32% of patients were using SGLT2i at baseline. At baseline the patients had a mean duration of diabetes of 8 years, a mean BMI of 34 kg/m2, a mean age of 57 years and 56% were men.
Patients treated with insulin degludec started at a dose of 10 U/day which was adjusted using an algorithm for a target fasting blood glucose of < 5 mmol/L. The mean dose of insulin degludec at week 52 was 49 units/day. See Table 6 and Figure 3.

Continuous glucose monitoring (CGM).

A subset of patients (N = 243) participated in an evaluation of the 24-hour glucose profiles captured with blinded CGM. At 52-weeks, patients treated with tirzepatide (10 mg and 15 mg pooled) spent significantly more time with glucose values in the euglycaemic range defined as 3.9 to 7.8 mmol/L compared to patients treated with insulin degludec, with 73% and 48% of the 24-hour period in range, respectively.
At 52-weeks patients in all 3 tirzepatide dose groups spent a greater proportion of the 24 hour period with blood glucose in the range of 3.9 to 10.0 mmol/L than patients treated with insulin degludec: tirzepatide (range), 84.9% to 91.2%; insulin degludec, 75.0%.

Liver fat content (LFC) and adipose tissue.

A subset of patients (N = 296) participated in an evaluation of LFC, visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (ASAT) assessed through magnetic resonance imaging. At 52-weeks, patients treated with tirzepatide (10 mg and 15 mg pooled) demonstrated statistically significantly greater mean reductions in LFC compared to insulin degludec, -8.09% versus -3.38% respectively, from baselines of 15.67% and 16.58%. Patients treated with tirzepatide 5 mg, 10 mg and 15 mg had significantly greater reductions in volume of VAT (-1.10, -1.53 and -1.65 L respectively) and ASAT (-1.40, -2.25 and -2.05 L respectively) from overall baselines of 6.6 L and 10.4 L respectively at 52 weeks compared with an increase in the insulin degludec group (0.38 and 0.63 L).
SURPASS 4 - combination therapy with 1-3 oral antidiabetic medicinal products: metformin, sulfonylureas or SGLT2i. In an active-controlled open-label study of up to 104 weeks (primary endpoint at 52 weeks) (GPGM), 2,002 patients with type 2 diabetes and increased cardiovascular risk were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or insulin glargine once daily on a background of metformin (95%) and/or sulfonylureas (54%) and/or SGLT‑2i (25%). At baseline the patients had a mean duration of diabetes of 12 years, a mean BMI of 33 kg/m2, a mean age of 64 years and 63% were men. Patients treated with insulin glargine started at a dose of 10 U/day which was adjusted using an algorithm with a fasting blood glucose target of < 5.6 mmol/L. The mean dose of insulin glargine at week 52 was 44 units/day. See Table 7 and Figure 4.
SURPASS 5 - combination therapy with titrated basal insulin, with or without metformin. In a 40-week double-blind placebo-controlled study (GPGI), 475 patients with inadequate glycaemic control using insulin glargine with or without metformin were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or placebo. Insulin glargine doses were adjusted utilising an algorithm with a fasting blood glucose target of < 5.6 mmol/L. At baseline the patients had a mean duration of diabetes of 13 years, a mean BMI of 33 kg/m2, a mean age of 61 years and 56% were men. The overall estimated median dose of insulin glargine at baseline was 34 units/day. The median dose of insulin glargine at week 40 was 38, 36, 29 and 59 units/day for tirzepatide 5 mg, 10 mg, 15 mg and placebo respectively. See Table 8 and Figure 5.

Cardiovascular evaluation.

Cardiovascular (CV) risk was assessed via a meta-analysis of patients with at least one adjudication confirmed major adverse cardiac event (MACE). The composite endpoint of MACE-4 included CV death, nonfatal myocardial infarction, non-fatal stroke, or hospitalisation for unstable angina.
In a primary meta-analysis of phase 2 and 3 registration studies, a total of 116 patients (tirzepatide: 60 [n = 4410]; all comparators: 56 [n = 2169]) experienced at least one adjudication confirmed MACE-4: The results showed that tirzepatide was not associated with excess risk for CV events compared with pooled comparators (HR: 0.81; CI: 0.52 to 1.26).
An additional analysis was conducted specifically for the SURPASS-4 study that enrolled patients with established CV disease. A total of 109 patients (tirzepatide: 47 [n=995]; insulin glargine: 62 [n=1000]) experienced at least one adjudication confirmed MACE-4: The results showed that tirzepatide was not associated with excess risk for CV events compared with insulin glargine (HR: 0.74; CI:0.51 to 1.08).

Blood pressure.

Treatment with tirzepatide resulted in a mean decrease in systolic and diastolic blood pressure of 6 to 9 mmHg and 3 to 4 mmHg, respectively. There was a mean decrease in systolic and diastolic blood pressure of 2 mmHg each in placebo-treated patients.

Other information.

Fasting serum glucose.

Treatment with tirzepatide resulted in significant reductions from baseline in FSG (changes from baseline to primary end point were -2.4 mmol/L to -3.8 mmol/L). Significant reductions from baseline in FSG could be observed as early as 2 weeks. The improvement in FSG was sustained through the longest study duration of 104 weeks.

Postprandial glucose.

Treatment with tirzepatide resulted in significant reductions in mean 2-hour post prandial glucose (mean of 3 main meals of the day) from baseline (changes from baseline to primary end point were -3.35 mmol/L to -4.85 mmol/L).

Pancreatic enzymes.

Treatment with tirzepatide resulted in an increase from baseline in pancreatic amylase of 33% to 38% and lipase of 31% to 42%. Placebo-treated patients had an increase from baseline in amylase of 4% and no changes were observed in lipase. In the absence of other signs and symptoms of acute pancreatitis, elevations in pancreatic enzymes alone are not predictive of acute pancreatitis.

Triglycerides.

Across SURPASS 1-5 trials, tirzepatide 5 mg, 10 mg and 15 mg resulted in reduction in serum triglyceride of 15 - 19%, 18 - 27% and 21 - 25% respectively.
In the 40-week trial versus semaglutide 1 mg, tirzepatide 5 mg, 10 mg and 15 mg resulted in 19%, 24% and 25% reduction in serum triglycerides levels respectively compared to 12% reduction with semaglutide 1 mg.

Proportion of patients reaching HbA1c < 5.7% without clinically significant hypoglycaemia.

In the 4 studies where tirzepatide was not combined with basal insulin, 93.6% to 100% of patients who achieved a normal glycaemia of HbA1c < 5.7%, at the primary endpoint visit with tirzepatide treatment did so without clinically significant hypoglycaemia. In Study SURPASS-5, 85.9% patients treated with tirzepatide who reached HbA1c < 5.7% did so without clinically significant hypoglycaemia.

Chronic weight management.

The safety and efficacy of tirzepatide for chronic weight management (weight reduction and maintenance) in combination with a reduced calorie intake and increased physical activity were evaluated in two randomised double-blinded, placebo-controlled phase 3 studies in patients without diabetes mellitus (SURMOUNT-1) and with diabetes mellitus (SURMOUNT2). SURMOUNT-1 included a total of 2539 patients (1896 randomised to treatment with tirzepatide), while a total of 938 patients (623 randomised to treatment with tirzepatide) were included in SURMOUNT-2.
All patients treated with tirzepatide started with 2.5 mg for 4 weeks. Then the dose of tirzepatide was increased by 2.5 mg every 4 weeks until they reached their assigned dose.
In SURMOUNT-1, the dose of tirzepatide or matching placebo was escalated to 5 mg, 10 mg, or 15 mg subcutaneously once weekly during a 20-week period followed by the maintenance period.
In SURMOUNT-2, the dose of tirzepatide or matching placebo was escalated to 10 mg or 15 mg subcutaneously once weekly during a 20-week period followed by the maintenance period.
SURMOUNT-1. In a 72-week double blind placebo-controlled study, 2539 adult patients with obesity (BMI ≥ 30 kg/m2), or with overweight (BMI ≥ 27 kg/m2 to < 30 kg/m2) and at least one weight related comorbid condition, such as treated or untreated dyslipidaemia, hypertension, obstructive sleep apnoea, or cardiovascular disease, were randomised to tirzepatide 5 mg, 10 mg or 15 mg once weekly or placebo. Patients with type 2 diabetes mellitus were excluded. Patients had a mean age of 45 years and 67.5% were women. At baseline 40.6% of patients had prediabetes. Mean baseline body weight was 104.8 kg and mean BMI was 38 kg/m2. See Table 9.
In SURMOUNT-1, pooled doses of tirzepatide 5 mg, 10 mg and 15 mg led to a significant improvement compared to placebo in systolic blood pressure (-8.1 mmHg vs. -1.3 mmHg), diastolic blood pressure (-5.3 mmHg vs -1.0 mmHg), total cholesterol (-6.1% vs -1.2%), triglycerides (-27.6% vs. -6.3%), non-HDL (-11.4% vs. -1.8%), LDL (-6.8% vs -0.9%), HDL (7.9% vs. 0.2%), and HbA1c (-0.5% vs. -0.1% or -5.1 mmol/mol vs -0.8 mmol/mol). See Figure 6.
Among the patients in SURMOUNT-1 with prediabetes at baseline (N = 1032), 95.3% patients treated with tirzepatide reverted to normoglycaemia at week 72, as compared with 61.9% of patients in the placebo group.
SURMOUNT-2. In a 72-week double blind placebo-controlled study, 938 adult patients with BMI ≥ 27 kg/m2 and type 2 diabetes mellitus, were randomised to tirzepatide 10 mg or 15 mg once weekly or placebo. Patients had a mean age of 54 years and 50.7% were women. Mean baseline body weight was 100.7 kg and mean BMI was 36.1 kg/m2. See Table 10.
In SURMOUNT-2, pooled doses of tirzepatide 10 mg and 15 mg led to a significant improvement compared to placebo in systolic blood pressure (-7.2 mmHg vs. -1.0 mmHg), diastolic blood pressure (-2.6 mmHg vs -0.2 mmHg), total cholesterol (-2.6% vs 2.1%), triglycerides (-28.7% vs. -5.8%), non-HDL (-6.7% vs. 2.3%), LDL (2.8% vs 6.3%), HDL (8.3% vs. 1.1%), and HbA1c (-2.2% vs. -0.2% or -23.9 mmol/mol vs -1.8 mmol/mol).
During the trial, treatment was permanently discontinued by 9.3% and 13.8% of patients randomised to tirzepatide 10 mg and 15 mg respectively compared to 14.9% randomised to placebo. See Figure 7.

Cardiovascular evaluation.

An analysis was conducted for the SURMOUNT-1 study where a total of 14 patients (tirzepatide: 9 (0.47%) out of 1896; placebo: 5 (0.78%) out of 643) experienced at least one adjudication confirmed MACE. Percentages of patients with adjudication confirmed MACE were similar across placebo and tirzepatide groups.
Analysis was conducted for the SURMOUNT-2 study. A total of 11 patients (tirzepatide: 7 (1.12%) out of 623 placebo: 4 (1.27%) out of 315) experienced at least one adjudication confirmed MACE. Percentages of patients with adjudication confirmed MACE were similar across placebo and tirzepatide groups.

Blood pressure.

In SURMOUNT-1 treatment with tirzepatide resulted in a mean decrease in systolic and diastolic blood pressure of 8.1 mmHg and 5.3 mmHg, respectively. There was a mean decrease in systolic and diastolic blood pressure of 1.3 mmHg and 1.0 mmHg respectively in placebo treated patients.
In SURMOUNT-2 treatment with tirzepatide resulted in a mean decrease in systolic and diastolic blood pressure of 7.2 mmHg and 2.6 mmHg, respectively. There was a mean decrease in systolic and diastolic blood pressure of 1.0 mmHg and 0.2 mmHg respectively in placebo treated patients.

Other information.

Changes in body composition.

Changes in body composition were evaluated in a sub-study in SURMOUNT-1 using dual energy X-ray absorptiometry (DEXA). The results of the DEXA assessment showed that treatment with tirzepatide was accompanied by greater reduction in fat mass than in lean body mass leading to an improvement in body composition compared to placebo after 72 weeks. Furthermore, this reduction in total fat mass was accompanied by a reduction in visceral fat. These results suggest that most of the total weight loss was attributable to a reduction in fat tissue, including visceral fat.

Special populations.

In adult patients with type 2 diabetes, the efficacy of tirzepatide was not impacted by age, gender, race, ethnicity, region, or by baseline BMI, HbA1c, diabetes duration and level of renal function impairment.
In adult patients who are overweight or with obesity, treatment with tirzepatide produced a statistically significant reduction from baseline in body weight compared to placebo. A reduction in body weight was observed with tirzepatide irrespective of age, sex, race, ethnicity, baseline BMI, and glycaemic status.

5.2 Pharmacokinetic Properties

Absorption.

Maximum concentration of tirzepatide is reached 8 to 72 hours post dose. Steady state exposure is achieved following 4 weeks of once weekly administration. Tirzepatide exposure increases in a dose proportional manner. Similar exposure was achieved with subcutaneous administration of tirzepatide in the abdomen, thigh, or upper arm. Absolute bioavailability of subcutaneous tirzepatide was 80%.

Distribution.

The mean apparent steady-state volume of distribution of tirzepatide following subcutaneous administration in patients with type 2 diabetes is approximately 10.3 L in patients with type 2 diabetes and 9.7 L in patients with obesity. Tirzepatide is highly bound to plasma albumin (99%).

Metabolism.

Tirzepatide is metabolised by proteolytic cleavage of the peptide backbone, beta-oxidation of the C20 fatty diacid moiety and amide hydrolysis.

Excretion.

The apparent population mean clearance of tirzepatide is approximately 0.06 L/h with an elimination half-life of approximately 5 days, enabling once weekly administration.
Tirzepatide is eliminated by metabolism. The primary excretion routes of tirzepatide metabolites are via urine and faeces. Intact tirzepatide is not observed in urine or faeces.

Special populations.

Age, gender, race, ethnicity, body weight.

Age, gender, race, ethnicity or body weight, do not have a clinically relevant effect on the pharmacokinetics (PK) of tirzepatide.

Renal impairment.

Renal impairment does not impact the PK of tirzepatide. The PK of tirzepatide after a single 5 mg dose was evaluated in patients with different degrees of renal impairment (mild, moderate, severe, ESRD) compared with subjects with normal renal function. This was also shown for patients with both type 2 diabetes mellitus and renal impairment based on data from clinical studies.

Hepatic impairment.

Hepatic impairment does not impact the PK of tirzepatide. The PK of tirzepatide after a single 5 mg dose was evaluated in patients with different degrees of hepatic impairment (mild, moderate, severe) compared with subjects with normal hepatic function.

Paediatric population.

Tirzepatide has not been studied in paediatric patients.

5.3 Preclinical Safety Data

Genotoxicity.

In an in vivo genotoxicity study (bone marrow micronucleus assay) there were no significant increase in micronuclei in polychromatic erythrocytes in bone marrow of male rats after single SC administration of up to 3 mg/kg tirzepatide. Based on the weight of evidence, tirzepatide is not considered genotoxic.

Carcinogenicity.

A 2-year carcinogenicity study was conducted with tirzepatide in male and female rats at doses of 0.15, 0.50, and 1.5 mg/kg (0.12, 0.36, and 1.02-fold the maximum recommended human dose (MRHD) based on area under the curve (AUC)) administered by subcutaneous injection twice weekly. Tirzepatide caused an increase in thyroid C-cell tumours (adenomas and carcinomas) at all doses compared to controls. The human relevance of these findings is currently unknown.
In a 6-month carcinogenicity study in rasH2 transgenic mice, tirzepatide at doses of 1, 3, and 10 mg/kg (up to 11-fold the MRHD based on AUC) administered by subcutaneous injection twice weekly did not produce increased incidences of thyroid C-cell hyperplasia or neoplasia at any dose.

6 Pharmaceutical Particulars

6.1 List of Excipients

Single-dose vial and pre-filled pen (autoinjector).

Sodium chloride, dibasic sodium phosphate heptahydrate, hydrochloric acid, sodium hydroxide, water for injections.

Multiple-dose pre-filled pen (KwikPen).

Dibasic sodium phosphate heptahydrate, benzyl alcohol, glycerol, phenol, sodium chloride, hydrochloric acid, sodium hydroxide, water for injections.

6.2 Incompatibilities

Not applicable for subcutaneous single-dose product.
In the absence of compatibility studies this medicinal product must not be mixed with other medicinal products.

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

Single-dose vial and pre-filled pen (autoinjector).

Mounjaro vials and ready-to-use, single-use, pre-filled pens should be stored at 2°C to 8°C, refrigerated. Do not freeze. Do not shake. Store in original carton to protect from light.

In-use.

Mounjaro may be stored unrefrigerated for up to 21 days at temperatures not above 30°C.

Multiple-dose, pre-filled pen (KwikPen).

Mounjaro ready-to-use, multiple-dose, pre-filled pens should be stored at 2°C to 8°C, refrigerated. Do not freeze. Do not shake. Protect from light.

In-use.

Mounjaro may be stored unrefrigerated for up to 30 days at temperatures not above 30°C.

6.5 Nature and Contents of Container

Mounjaro is available in vials and as ready-to-use pre-filled pens.

Single-use vial.

The product is contained in a clear glass vial (Type I) with a bromobutyl elastomer stopper.
Trade packs of 1 vial and starter packs of 1 vial for the 2.5 mg/0.5 mL presentation.

Multiple-dose, pre-filled pen (KwikPen).

The product is contained in a clear glass cartridge (Type I) encased in a disposable multiple-dose pen.
Trade packs of 1 pre-filled pen and starter packs of 1 pre-filled pen for the 2.5 mg presentation.
No needles are included in the pack.

Single-use prefilled pen (autoinjector).

The product is contained in a glass syringe (Type I) encased in a disposable single-dose pen.
Trade packs of 2 or 4 pre-filled pens, and starter packs of 2 pre-filled pens for the 2.5 mg/0.5 mL presentation.
Not all pack sizes and presentations may be available.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Chemical structure.


Molecular weight: 4,813 daltons.

CAS number.

2023788-19-2.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Medicine.

Summary Table of Changes