Consumer medicine information

Mounjaro

Tirzepatide

BRAND INFORMATION

Brand name

Mounjaro

Active ingredient

Tirzepatide

Schedule

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. 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, dentist, pharmacist, or diabetes nurse educator you visit that you are using MOUNJARO. 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. 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 diabetes nurse educator 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', which are used to help treat 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.

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 while you are using MOUNJARO.
- 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.
- 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 your 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 your 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 diabetes nurse educator if you are unsure.

How to use MOUNJARO

Follow all directions given to you by your doctor, nurse, or pharmacist 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, nurse, or pharmacist 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.
Wash your hands.
Place all the items you will need on a clean surface where you will not be disturbed. These should include:
- syringe with needle attached (or as recommended by your healthcare provider).
- A sharps container
Pull off the protective cap from the vial, but do not remove the rubber stopper.
Remove the needle shield/cap.

Draw Up

Push the needle through the rubber stopper of the vial.
Turn the vial and syringe 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, dentist, pharmacist or diabetes nurse educator you visit that you are using MOUNJARO.

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
Tell your doctor, pharmacist, or diabetes nurse educator 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 diabetes nurse educator can provide you with some helpful information.

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)

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 diabetes nurse educator 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 diabetes nurse educator 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 diabetes nurse educator if you have any further questions about side effects.

Less serious side effects

Less serious side effects

What 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
farting (flatulence)
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 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:

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.
changes to how foods or drinks taste.

Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effects

What 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.

Tell your doctor, pharmacist or diabetes nurse educator 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 allergens	none

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 January 2024.

(vA2.0)

Published by MIMS February 2024

BRAND INFORMATION

Brand name

Mounjaro

Active ingredient

Tirzepatide

Schedule

1 Name of Medicine

Tirzepatide.

2 Qualitative and Quantitative Composition

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

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 [autoinjector].

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 [autoinjector].

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 [autoinjector].

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 [autoinjector].

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 [autoinjector].

Each vial and pre-filled pen contains tirzepatide 15 mg in 0.5 mL solution.
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, preservative-free, sterile solution for subcutaneous administration.

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.

4.2 Dose and Method of Administration

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.)
Self-monitoring of blood glucose is not needed in order 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, thigh or upper arm.
Product is for single use in one patient only. Discard any residue.
It is recommended to rotate injection sites with each dose.

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.

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.

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.

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 C_max and a delayed t_max, 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 C_max by 55 to 66%, with a 16 to 23% reduction in area under the curve (AUC) and a delay in t_max 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.

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), and vomiting (common). 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 of an altered pharmacokinetic profile or an impact on efficacy and safety associated with the development of anti-drug antibodies (ADAs).
Consistent with the potentially immunogenic properties of protein and peptide medicinal products, patients may develop antibodies following treatment with tirzepatide.
Across seven Phase 3 clinical studies, 2,570 (51.1%) tirzepatide-treated patients developed ADAs. Of the overall tirzepatide-treated patients, 1.9% and 2.1% had neutralising antibodies against tirzepatide activity on the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, respectively. 0.9% and 0.4% had neutralising antibodies against native GIP and GLP-1, respectively.

Heart rate.

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 arrythmia 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).

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.

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.

Postmarketing data.

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

Immune system disorders.

Anaphylactic reaction and angioedema.

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: not yet assigned.

Mechanism of action.

Tirzepatide is a long-acting dual GIP and GLP-1 receptor agonist. It is a 39-amino acid peptide 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.

Clinical trials - clinical efficacy and safety.

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 3 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 4 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 5 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 6 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 7 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.

Special populations.

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.

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. 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 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.