Xultophy® 100 units/mL + 3.6 mg/mL solution for injection – patient leaflet, side effects, dosage

1. What Xultophy® is and what it is used for

Xultophy® with alcohol

If you drink alcohol, your need for Xultophy® may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

What Xultophy® is used for

Xultophy® is used to improve blood glucose (sugar) levels in adult patients with type 2 diabetes mellitus. You have diabetes because your body:

Pregnancy and breast-feeding

Do not use Xultophy® if you are pregnant or plan to become pregnant. Tell your doctor if you are pregnant, think you might be pregnant or are planning to have a baby. It is not known if Xultophy® affects the baby.

• does not make enough insulin to control the level of sugar in your blood or

• is not able to use the insulin properly.

  Do not use Xultophy® if you are breast-feeding. It is not known if Xultophy® passes into breast milk.

How Xultophy® works

Xultophy® contains two active substances that help your body control your blood sugar:

Driving and using machines

Having low or high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is low or high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• insulin degludec – a long-acting basal insulin which lowers your blood sugar levels.

• liraglutide – a ‘GLP-1 analogue’ that helps your body make more insulin during meals and lowers the amount of sugar made by your body.

  • you often get low blood sugar

Xultophy® and oral medicines for diabetes

• you find it hard to recognise low blood sugar.

Xultophy® is used with oral medicines for diabetes (such as metformin, pioglitazone and sulfonylurea medicines). It is prescribed when these medicines (used alone or with GLP-1 treatment or with basal insulin) are not enough to control your blood sugar levels.

Important information about some of the ingredients of Xultophy®

Xultophy® contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

1. 3. How to use Xultophy®

If you use GLP-1 treatment

You should stop your GLP-1 treatment prior to starting on Xultophy®.

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

If you use insulin

You should stop your insulin treatment prior to starting on Xultophy®.

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

2. What you need to know before you use Xultophy®

Your doctor will tell you:

• how much Xultophy® you will need each day

Do not use Xultophy®

• when to check your blood sugar level
• if you are allergic to insulin degludec or liraglutide or any of the other ingredients of this medicine (listed in section 6).
• how to adjust the dose.

Your dose of Xultophy® is administered as ‘dose steps’. The dose counter on the pen shows the number of dose steps.

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Xultophy®.

• If you are also taking a sulfonylurea (such as glimepiride or glibenclamide), your doctor may tell you to lower your sulfonylurea dose depending on your blood sugar levels.

  Dosing time

  • Use Xultophy® once each day, preferably at the same time every day. Choose a time of the day that works best for you.

• Do not use Xultophy® if you have type 1 diabetes mellitus or if you have ‘ketoacidosis’ (a condition with a build-up of acid in the blood).

  • If it is not possible to use Xultophy® at the same time every day, it can be used at a different time of the day. Make sure to have a minimum of 8 hours between the doses.

• The use of Xultophy® is not recommended in patients with inflammatory bowel disease or delayed gastric emptying (diabetic gastroparesis).

  • You do not have to use Xultophy® with a meal.
  • Always follow your doctor’s advice for dose and dose adjustment.
  • If you want to change your usual diet, check with your doctor, pharmacist or nurse first as a change in diet may alter your need for Xultophy®.

Be especially aware of the following when using Xultophy®:

• low blood sugar (hypoglycaemia) – if your blood sugar is low, follow the advice in section 4 ‘Low blood sugar (hypoglycaemia)’.

  How to handle Xultophy®

• high blood sugar (hyperglycaemia) – if your blood sugar is high, follow the advice in section 4 ‘High blood sugar (hyperglycaemia)’.

  Xultophy® is a pre-filled dial-a-dose pen.

  • Xultophy® is administered as ‘dose steps’. The dose counter on the pen shows the number of dose steps.

• Ensuring you use the right medicine – Always check the pen label before each injection to avoid accidentally confusing Xultophy® with other products.

  • One dose step contains 1 unit of insulin degludec and 0.036 mg of liraglutide.
  • The maximum daily dose of Xultophy® is 50 dose steps (50 units of insulin degludec and 1.8 mg of liraglutide). Carefully read the ‘Instructions on how to use’ on the other side of this leaflet and use the pen as described. Always check the pen label before you inject your medicine to ensure that you use the correct pen.

Important things to know before you use this medicine:

Tell your doctor if you:

• have eye problems. Fast improvements in blood sugar control may make diabetic eye problems get worse for a short time. The long-term improvements in blood sugar control may ease the eye problems.

How to inject

• have or have had a thyroid disease.

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

Important things to know while you are using this medicine:

• Xultophy® is given as an injection under the skin (subcutaneously). Do not inject it into a vein or muscle.
• if you have a severe stomach ache which does not go away, tell your doctor – this could be a sign of inflamed pancreas (acute pancreatitis).
• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• dehydration (loss of fluids from the body) can happen if you are feeling or being sick (nausea or vomiting) or have diarrhoea – it is important to drink plenty of fluids to stop dehydration.
• Change the place within the area where you inject each day to reduce the risk of developing lumps and skin pitting (see section 4).
• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.

Children and adolescents

Do not give this medicine to children or adolescents. There is no experience with Xultophy® in children and adolescents under 18 years old.

• Do not use a syringe to remove the solution from the pen to avoid dosing errors and potential overdose. Detailed instructions for use are on the other side of this leaflet.

Other medicines and Xultophy®

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level – this may mean your Xultophy® dose has to change.

Do not use Xultophy®:

• If the pen is damaged or has not been stored correctly (see section 5).

Listed below are the most common medicines, which may affect your Xultophy® treatment.

• If the liquid you can see through the pen window does not look clear and colourless.

Your blood sugar level may fall if you take:

Use in elderly patients (65 years old or over)

• other medicines for diabetes (tablets or injections)

  Xultophy® can be used in elderly patients but if you are elderly you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

• sulfonamides – for infections
• anabolic steroids – such as testosterone

• beta-blockers – for high blood pressure. They may make it harder to recognise the warning signs of low blood sugar (see section 4 ‘Warning signs of low blood sugar – these may come on suddenly’)

  If you have kidney or liver problems

  If you have kidney or liver problems, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

• acetylsalicylic acid (and medicines called ‘salicylates’) – for pain and mild fever

  If you use more Xultophy® than you should

• monoamine oxidase (MAO) inhibitors – for depression
• angiotensin converting enzyme (ACE) inhibitors – for some heart problems or high blood pressure.

Your blood sugar level may rise if you take:

• danazol – medicine affecting ovulation

• oral contraceptives – birth control pills

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  If you forget to use Xultophy®

  If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not take a double dose.

  If you stop using Xultophy®

  Do not stop using Xultophy® without talking to your doctor. If you stop using Xultophy® this could lead to a very high blood sugar level, see the advice in section 4 ‘High blood sugar (hyperglycaemia)’.

  If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following serious side effects may happen with this medicine:

• Low blood sugar (very common: may affect more than 1 in 10 people).

  If your blood sugar level gets low you may pass out (become unconscious). Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have signs of low blood sugar, take actions to increase your blood sugar level straight away. See advice in ‘Low blood sugar (hypoglycaemia)’ further down in this section.

• Serious allergic reaction (anaphylactic reaction) (not known: frequency cannot be estimated from the available data). If you have a serious allergic reaction to any of the ingredients in Xultophy®, stop using Xultophy® and see a doctor straight away. The signs of a serious allergic reaction are:

  • local reactions spread to other parts of your body
  • you suddenly feel unwell with sweating
  • you have difficulty breathing
  • you get a fast heartbeat or feel dizzy.

Other side effects include:

Common (may affect up to 1 in 10 people)

• Lower appetite, feeling or being sick (nausea or vomiting), diarrhoea, constipation, indigestion (dyspepsia), inflamed lining of the stomach (gastritis), stomach ache, heartburn or bloating – these usually go away after a few days or weeks.
• Injection site reactions. The signs may include bruising, bleeding, pain, redness, hives, swelling or itching – these usually go away after a few days. See your doctor if they do not disappear after a few weeks. Stop using Xultophy® and see a doctor straight away if they become serious.
• Increase of pancreatic enzymes, such as lipase and amylase. Uncommon (may affect up to 1 in 100 people)
• Hives (red bumps on your skin that are sometimes itchy).
• Allergic reactions (hypersensitivity) such as rash, itching and swelling of the face.
• Dehydration (loss of fluid from the body) – it is important to drink plenty of fluids to stop dehydration.
• Belching (eructation) and wind (flatulence).
• Rash.
• Itching.

• Skin changes where you give the injection (‘lipodystrophy’)

  • the fatty tissue under the skin may shrink (‘lipoatrophy’) or get thicker (‘lipohypertrophy’). Changing the place where you inject each time may reduce the risk of these skin changes. If you notice these skin changes, tell your doctor or nurse. If you keep injecting in the same place, these changes can become more severe and affect the amount of medicine your body gets from the pen.
• Increased heart rate.
• Gallstones.
• Inflamed gallbladder.

Not known (frequency cannot be estimated from the available data)

• Inflamed pancreas (pancreatitis).
• Swelling of arms or legs (peripheral oedema) – when you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

General effects from diabetes treatment

►Low blood sugar (hypoglycaemia) Low blood sugar may happen if you:

• drink alcohol
• exercise more than usual
• eat too little or miss a meal
• use too much Xultophy®.

Warning signs of low blood sugar – these may come on suddenly

Headache, slurred speech, fast heartbeat, cold sweat, cool pale skin, feeling sick (nausea), feeling very hungry, shaking, feeling nervous or worried, unusually tired, weak and sleepy or confused, difficulty concentrating, short-lasting changes in your sight.

What to do if you get low blood sugar:

• Eat glucose tablets or another high sugar snack – like sweets, biscuits or fruit juice (always carry glucose tablets or a high sugar snack, just in case).
• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once. This is because improvement in your blood sugar may not happen straight away.
• Wait until the signs of low blood sugar have gone or when your blood sugar level has settled. Then carry on with your medicine as usual.

What others need to do if you pass out:

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink – because you may choke. You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.
• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short- or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have had an injection of glucagon
• you have had low blood sugar a few times recently. This is because the dosing of your Xultophy® injections, food or exercise may need to be changed.

►High blood sugar (hyperglycaemia) High blood sugar may happen if you:

• drink alcohol

• exercise less than usual

  • eat more than usual
  • get an infection or a fever
  • have not used enough Xultophy®, keep using less Xultophy® than you need, forget to use Xultophy® or stop using Xultophy® without talking to your doctor.

Warning signs of high blood sugar – these normally appear gradually

Flushed, dry skin, feeling sleepy or tired, dry mouth, fruity (acetone) breath, urinating more often, feeling thirsty, losing your appetite, feeling or being sick (nausea or vomiting). These may be signs of a very serious condition called ‘ketoacidosis’. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get high blood sugar:

• Test your blood sugar level.
• Test your blood or urine for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via:

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Ireland

HPRA Pharmacovigilance

Website: www.hpra.ie

By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Xultophy®

Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date which is stated on the pen label and carton after ‘EXP’. The expiry date refers to the last day of that month.

Before opening

Store in a refrigerator (2°C to 8°C). Keep away from the freezing element. Do not freeze.

During use

Do not freeze. You can carry Xultophy® with you and keep it at room temperature (no more than 30°C) or in a refrigerator (2°C to 8°C) for up to 21 days. The product should be thrown away 21 days after first opening.

Always keep the cap on the pre-filled pen when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Xultophy® contains

• The active substances are insulin degludec and liraglutide. Each mL of solution contains 100 units of insulin degludec and 3.6 mg liraglutide. Each unused pre-filled pen (3 mL) contains 300 units of insulin degludec and 10.8 mg liraglutide.
• The other ingredients are glycerol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment), and water for injections. See also section 2 `Important information about some of the ingredients of Xultophy®’ for information on sodium.

What Xultophy® looks like and contents of the pack

Xultophy® is a clear and colourless solution.

Pack sizes of 1, 3, 5 and a multipack containing 10 (2 packs of 5) pens of 3 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

Now turn over for information on how to use your pre-filled pen.

This leaflet was last revised in 05/2020

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.

Xultophy®, NovoTwist® and NovoFine® are trademarks owned by Novo Nordisk A/S,

Denmark.

© 2020

Novo Nordisk A/S

8-9553-01-002-8

Length: Max. 20 mm (100%) Code: 100% Direction

Code centered

1 mm Xultophy®

100 units/mL + 3.6 mg/mL solution for injection insulin degludec + liraglutide

One dose step contains 1 unit of insulin degludec and 0.036 mg of liraglutide

8 mm

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Instructions on how to use Xultophy® 100 units/mL + 3.6 mg/mL solution for injection

1 Prepare your pen with a new needle

2 Check the flow

3 Select your dose

This may prevent blocked needles, contamination, infection, leakage of solution and inaccurate dosing. 4 Inject your dose

5 After your injection

Turn the dose selector to

Check the name and

Turn the dose selector to select the dose you need.

Insert the needle into

Lead the needle tip into the outer needle

A

A

A

A

A

coloured label of your

your skin as your doctor

select 2 dose steps.

pen, to make sure that it

Make sure the dose

or nurse has shown you.

cap on a flat surface

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

contains Xultophy®.

counter shows 2.

The dose counter shows

without touching the

Make sure you can see

This is especially

the dose in dose steps.

needle or the outer cap.

Do not use the pen without proper training from your doctor or nurse.

The dose counter and

the dose counter. Do

important if you take

If you select a wrong

the dose pointer show

not cover it with your

more than one type of

dose, you can turn the

Start by checking your pen to make sure that it contains Xultophy® 100 units/mL + 3.6 mg/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

how many dose steps of

fingers. This could

injectable medicine.

dose selector forward or

Xultophy® you select.

interrupt the injection.

Taking the wrong

backward to the correct

medicine could be

dose.

steps selected Examples

Once the needle is

B

harmful to your health.

The pen can dial up to

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the Xultophy® pre-filled pen. Xultophy® is a medicine that contains insulin degludec and liraglutide. Xultophy® is administered as ‘dose steps’. One dose step contains 1 unit insulin degludec + 0.036 mg liraglutide.

covered, carefully push

a maximum of

Press and hold down the dose button until the dose counter

B

2 dose steps

Pull off the pen cap.

the outer needle cap completely on.

50 dose steps.

selected 5 dose

B Check that the solution

shows 0.

Unscrew the needle

in your pen is clear and

The 0 must line up with

and dispose of it carefully

colourless. Look through

the dose pointer. You

as instructed by your

Hold the pen with the

B

the pen window. If the

may then hear or feel

doctor or nurse.

needle pointing up.

left 24 dose steps selected

solution looks cloudy, do

a click.

Tap the top of the pen

not use the pen.

Your pen is a pre-filled dial-a-dose pen. It contains 3 mL of Xultophy® solution. It delivers doses from:

Put the pen cap on

C

gently a few times to let

your pen after each use

any air bubbles rise to

• 1 dose step

  to protect the solution

  the top.

  Keep the needle in

• to a maximum of 50 dose steps (50 units insulin degludec + 1.8 mg liraglutide)

  C

  Count slowly:

  from light.

  The dose selector changes the number of dose steps. Only the dose counter and dose pointer will show how many dose steps you select per dose.

  your skin after the dose

  Caregivers must be very careful when handling used needles – to prevent needle injury and cross-infection. Take a new needle, and

  Do not try to repair your pen or pull it apart. C

  counter has returned to 0

Your pen delivers doses in increments of 1 dose step. Do not do any conversion of your dose. The dose steps dialled equal the number shown in the dose counter. Your pen is designed to be used with NovoTwist® or NovoFine® disposable needles up to a length of 8 mm and as thin as 32G. Needles are not included in the pack.

1-2-3-4-5-6

tear off the paper tab.

and count slowly to 6.

You can select up to 50 dose steps per dose. When your pen contains less than 50 dose steps, the dose counter stops at the number of dose steps left.

Press and hold in the

C

If the needle is removed

dose button until the

earlier, you may see

dose counter returns

a stream of solution

Always dispose of the needle after each injection

The dose selector clicks differently when turned forward, backward or past the number of dose steps left. Do not count the pen clicks.

to 0.

coming from the needle

to ensure the use of a sharp needle and prevent blocked needles. If the needle is blocked, you will not inject any medicine.

The 0 must line up with

tip. If so, the full dose

the dose pointer.

will not be delivered, and

A drop of solution should

you should increase the

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

Important information

Push the needle straight onto the pen.

appear at the needle tip.

How much solution is left? D

frequency of checking

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

your blood sugar level.

Always use the dose counter and the dose pointer to see how many dose steps you have selected before injecting the medicine.

Turn until it is on tight.

Remove the needle from your skin.

D

If blood appears at the

Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get high or low.

Xultophy® pre-filled pen and needle (example)

injection site, press

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

lightly. Do not rub the

area.

Do not use the pen scale, it only shows approximately how much solution is left in your pen.

A small drop may remain at the needle tip, but it will not be injected.

Always remove the needle from your pen after each injection.

pen.

Pull off the outer needle cap and keep it

E

Pen cap Outer

If no drop appears, repeat steps 2A to 2C up to 6 times. If there is still no drop, change the needle and repeat steps 2A to 2C once more.

needle cap

for later. You will need it

after the injection, to

If a drop of solution still does not appear, dispose of the pen and use a new one.

safely remove the needle

You may see a drop of solution at the needle tip after injecting. This is normal and does not affect your dose. A

from the pen.

The pen scale shows you

Inner needle cap

approximately how

much solution is left in

Always watch the dose counter to know how many dose steps you inject. Hold the dose button down until the dose counter shows 0. If the dose counter does not return to 0, the full dose has not been delivered, which may lead to high blood sugar level.

your pen.

Pull off the inner needle cap and throw

F

Approx. how much solution is

Always make sure that a drop appears at the needle tip before you inject. This makes sure that the solution flows.

it away. If you try to put

Needle

it back on, you may

If no drop appears, you will not inject any medicine, even though the dose counter may move. This may indicate a blocked or damaged needle.

accidentally stick yourself

with the needle.

How to identify a blocked or damaged needle?

A drop of solution may

To see precisely how much solution is left,

Dose counter stopped: 42 dose steps left B

Paper tab

• If 0 does not appear in the dose counter after continuously pressing the dose button, you may have used a blocked or damaged needle.

appear at the needle tip.

It is important always to check the flow before you inject. If you do not check the flow, you may get too little medicine, or no medicine at all. This may lead to high blood sugar level.

This is normal, but you

use the dose counter:

must still check the flow.

Turn the dose selector

• In this case - you have not received any medicine - even though the dose counter has moved from the original dose that you have set.

Do not attach a new needle to your pen until you are ready to take your injection.

until the dose counter

stops.

If it shows 50, at least

Pen scale

50 dose steps are left in

Example

How to handle a blocked needle?

your pen. If it shows less

Change the needle as described in section 5 and repeat all steps starting with section 1: Prepare your pen with a new needle. Make sure you select the full dose you need.

than 50, the number

Pen window

shown is the number of

dose steps left in your

Always use a new needle for each injection.

Never touch the dose counter when you inject.

This may prevent blocked needles, contamination, infection and inaccurate dosing.

This can interrupt the injection.

Pen label

Never use a bent or damaged needle.

If you need more medicine than what is left in your pen, you can split your dose between two pens.

Dose counter

Be very careful to calculate correctly if splitting your dose.

Dose pointer

If in doubt, take the full dose with a new pen. If you split the dose wrongly, you will inject too little or too much medicine. This may make your blood sugar level high or low.

Dose button with

Dose selector

smooth surface

Dose button

Caring for your pen

Further important information Always keep an extra pen and new needles, in case of loss or damage.

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

Do not drop your pen or knock it against hard surfaces.

Never share your pen with other people. Your medicine might be harmful to their health.

If you drop it or suspect a problem, attach a new needle and check the flow before you inject.

Do not store your pen at temperatures above 30°C.

Always keep your pen and needles out of sight and reach of others, especially children.

Never share your needles with other people. It might lead to cross-infection.

Do not expose your pen to dust, dirt or liquid.

Do not try to refill your pen. Once empty, it must be disposed of.

Do not wash, soak or lubricate your pen. If necessary, clean it with mild detergent on a moistened cloth.