RYZODEG 100 Units/mL Injectable Solution in Pre-filled Pen

Introduction

Package Leaflet: Information for the Patient

Ryzodeg 100units/ml FlexTouch solution for injection in pre-filled pen

70% insulin degludec / 30% insulin aspart

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Ryzodeg and what is it used for
2. What you need to know before you use Ryzodeg
3. How to use Ryzodeg
4. Possible side effects
5. Storage of Ryzodeg
6. Contents of the pack and other information

1. What is Ryzodeg and what is it used for

Ryzodeg is used to treat diabetes mellitus in adults, adolescents and children from 2 years old. It helps your body to reduce the level of sugar in your blood.

This medicine contains two types of insulin:

• A basal insulin called insulin degludec, which has a long-lasting blood-sugar-lowering effect,
• A fast-acting insulin called insulin aspart, which reduces your blood sugar level shortly after injection.

2. What you need to know before you use Ryzodeg

Do not use Ryzodeg

• if you are allergic to insulin degludec, insulin aspart or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before you start using Ryzodeg. It is important that you know the following:

• Low blood sugar level (hypoglycaemia) – If your blood sugar level is too low, follow the instructions in section 4.
• High blood sugar level (hyperglycaemia) – If your blood sugar level is too high, follow the instructions in section 4.
• Change from other insulins – You may need to adjust your insulin dose if you change from another type, brand or manufacturer of insulin. Talk to your doctor.
• Use of Pioglitazone with insulin – See the section on “Pioglitazone” below.
• Vision problems – A sudden improvement in blood sugar control may cause a temporary worsening of vision problems due to diabetes. If you experience any problems with your vision, talk to your doctor.
• Make sure you use the correct type of insulin – Always check the label of your insulin before each injection to avoid mix-ups between Ryzodeg and other insulins.

In case of reduced vision, see section 3.

Changes in the skin at the injection site

You should rotate the injection site to help avoid changes in the fatty tissue, such as thickening of the skin, thinning of the skin or lumps under the skin. Insulin may not work well if you inject into a lumpy, thinned or thickened area (see section 3 “How to use Ryzodeg”). Tell your doctor if you notice any changes at the injection site. Tell your doctor if you are currently injecting into these affected areas, before starting to inject into a different area. Your doctor may tell you to check your blood sugar levels more closely and adjust your insulin dose or the dose of your other anti-diabetic medicines.

Children and adolescents

Ryzodeg can be used in adolescents and children from 2 years old with diabetes mellitus. Ryzodeg should be used with special caution in children from 2 to 5 years of age. The risk of very low blood sugar levels may be higher in this age group. There is no experience with the use of this medicine in children under 2 years old.

Other medicines and Ryzodeg

Tell your doctor, pharmacist or nurse if you are using, have recently used or might use any other medicines. Some medicines affect your blood sugar level, and your insulin dose may need to be changed.

The following are the main medicines that may affect your treatment with insulin.

Your blood sugar level may decrease (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulphonamides, to treat infections
• anabolic steroids, such as testosterone
• beta-blockers, to treat high blood pressure. These may make it harder to recognise the warning signs of a low blood sugar level (see section 4 “Warning signs of a low blood sugar level”)
• acetylsalicylic acid (and other salicylates), to relieve pain and lower fever
• monoamine oxidase inhibitors (MAOIs), to treat depression
• angiotensin-converting enzyme (ACE) inhibitors, to treat certain heart problems or high blood pressure.

Your blood sugar level may increase (hyperglycaemia) if you take:

• danazol, to treat endometriosis
• oral contraceptives (birth control pill)
• thyroid hormones, to treat thyroid problems
• growth hormone, to treat growth hormone deficiency
• glucocorticoids, such as “cortisone”, to treat inflammation
• sympathomimetics, such as adrenaline (epinephrine), salbutamol or terbutaline, to treat asthma
• thiazides, to treat high blood pressure or if your body retains too much fluid.

Octreotide and lanreotide: used to treat a rare disorder characterised by excessive production of growth hormone (acromegaly). These medicines may increase or decrease your blood sugar levels.

Pioglitazone: oral anti-diabetic used to treat type 2 diabetes mellitus. Some patients with type 2 diabetes mellitus of long standing and heart disease or previous stroke who were treated with pioglitazone and insulin developed heart failure. Tell your doctor immediately if you have signs of heart failure such as unusual shortness of breath, rapid weight gain or localised swelling (oedema).

If you are in any of these situations (or are unsure), talk to your doctor, pharmacist or nurse.

Using Ryzodeg with alcohol

If you drink alcohol, it may alter your insulin need, as your blood sugar level may increase or decrease. Therefore, you should check your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Ryzodeg affects the unborn child or breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. You may need to adjust your insulin dose during pregnancy and after delivery. During pregnancy, it is essential to maintain good control of your diabetes to prevent complications in the mother and the unborn child.

Driving and using machines

A low or high blood sugar level may affect your ability to drive or use machines. If your blood sugar level is too low or too high, your concentration and reaction time may be impaired. This could put you or others at risk. Ask your doctor if you can drive:

• if you have frequent episodes of hypoglycaemia;
• if you find it hard to recognise the warning signs of hypoglycaemia.

Important information about some of the ingredients of Ryzodeg

This medicine contains less than 1 mmol of sodium (23 mg) per dose, which is essentially “sodium-free”.

3. How to use Ryzodeg

Follow exactly the instructions for administration of this medicine given by your doctor. If you are not sure, talk to your doctor, pharmacist or nurse.

If you are blind or have reduced vision and cannot read the dose counter on the pen, do not use this pen without help. Ask for assistance from a person with good eyesight who is trained in the use of the pre-filled FlexTouch pen.

The pre-filled pen can deliver a dose of 1-80 units in one injection, in increments of 1 unit.

Your doctor will decide with you:

• how much Ryzodeg you need each day and with which meal(s)
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in administration schedule

• Always follow your doctor’s recommendations for use.
• Ryzodeg can be used once or twice a day.
• Use with the main meal(s); you can change the time of administration each day as long as you use Ryzodeg with the main meal(s).
• If you want to change your usual diet, talk to your doctor, pharmacist or nurse first, as a change in your diet may alter your insulin need.

Depending on your blood sugar level, your doctor may change your dose.

When using other medicines, ask your doctor if you need to adjust your treatment.

Use in elderly (≥ 65 years old)

Ryzodeg can be used in elderly people, but you may need to check your blood sugar level more often. Talk to your doctor about possible changes in your dose.

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 possible changes in your dose.

Injecting the medicine

Before using Ryzodeg for the first time, your doctor or nurse will show you how to use the pre-filled pen.

• Check the name and strength on the label of the pen to ensure it is Ryzodeg 100 units/ml.

Do not use Ryzodeg

• in insulin infusion pumps.
• if the pen is damaged or has not been stored correctly (see section 5 “Storage of Ryzodeg”).
• if the insulin does not look like water and is not clear.

How to inject

• Ryzodeg is injected under the skin (subcutaneous injection). Do not inject into a vein or muscle.
• The best injection sites are the abdomen, upper arm or the front of the thigh.
• Change the injection site each day within the same area to reduce the risk of developing lumps and dips in the skin (see section 4).
• Always use a new needle for each injection. Reusing needles can increase the risk of blocked needles, leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to withdraw the solution from the pen to avoid dosing errors and possible overdose.

Detailed instructions for use are given on the other side of this leaflet.

If you use more Ryzodeg than you should

If you use too much insulin, your blood sugar level may become too low (hypoglycaemia), see the advice in section 4 “Low blood sugar level”.

If you forget to use Ryzodeg

If you miss a dose, inject the missed dose with the next main meal of the day and then continue with your regular dosing schedule. Do not inject a double dose to make up for a missed dose.

If you stop using Ryzodeg

Do not stop using your insulin without talking to your doctor first. Stopping your insulin injections could lead to a very high blood sugar level and diabetic ketoacidosis (a condition caused by too much acid in the blood), see the advice in section 4 “High blood sugar level”.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

When being treated with insulin, hypoglycemia (blood sugar level too low) may appear very frequently (it can affect more than 1 in 10 people). It can be very serious. If your blood sugar level decreases too much, you may lose consciousness. Severe hypoglycemia can cause brain damage and put your life at risk. If you have symptoms of low blood sugar, take measures to increase your blood sugar level immediately. See the tips on "Blood sugar level too low".

If you suffer a severe allergic reaction (rarely appears) to insulin or any of the components of Ryzodeg, stop treatment with this medicine and consult your doctor immediately. The signs of a severe allergic reaction are:

• local reactions spread to other parts of the body;
• you suddenly feel sick with sweating;
• you start to feel dizzy (vomiting);
• you experience difficulty breathing;
• you have palpitations or feel dizzy.

Other adverse effects include:

Frequent(may affect up to 1 in 10people)

Local reactions: localized reactions may appear at the injection site. Symptoms may include: pain, redness, hives, inflammation, and itching. These reactions usually disappear after a few days. If the symptoms do not disappear after a few weeks, consult your doctor. If the reactions worsen, stop treatment with Ryzodeg and consult your doctor immediately. For more information, see "severe allergic reaction" above.

Infrequent(may affect up to 1 in 100people)

Joint inflammation: when starting to use the medicine, the body may retain more fluid than it should. This causes inflammation of the ankles and other joints. This effect usually disappears quickly.

Rare(may affect up to 1 in 1,000people)

This medicine may cause allergic reactions such as hives, swelling of the tongue and lips, diarrhea, nausea, fatigue, and itching.

Frequency not known(cannot be estimated from the available data)

Changes in the skin at the injection site: If insulin is injected in the same place, the fatty tissue can shrink (lipoatrophy) or become thicker (lipohypertrophy). Lumps under the skin can also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis). Insulin may not work very well if injected into a bulging, thinned, or thickened area. Change the injection site with each injection to help avoid these skin changes.

General effects of diabetes treatment

• Blood sugar level too low (hypoglycemia)

Low blood sugar levels may appear if:

you drink alcohol, inject too much insulin, do more exercise than usual, eat very little, or skip a meal.

The warning symptoms of a blood sugar level that is too low may appear suddenly and are:

Headache, difficulty speaking, palpitations, cold sweat, cool and pale skin, dizziness, excessive hunger, tremors, nervousness or concern, fatigue, weakness, and unusual drowsiness, confusion, difficulty concentrating, temporary changes in vision.

What to do if your blood sugar level is too low

• Take glucose tablets or another sugary product, such as candies, cookies, or fruit juice (always carry glucose tablets or sugary products with you, just in case you need them).
• Measure your blood sugar level if possible and then rest. You may need to measure your blood sugar level more than once, as the recovery from the hypoglycemic period may be delayed, as with all basal insulins.
• Wait until the signs of hypoglycemia have disappeared or your blood sugar level has stabilized. Then continue with your insulin treatment as usual.

What others should do if you lose consciousness

Inform the people you spend time with that you have diabetes. Tell them what the consequences might be due to a drop in blood sugar level, including the risk of losing consciousness.

Tell them that if you become unconscious, they should do the following:

• lay you on your side
• seek immediate medical attention
• do not give you anything to eat or drink, as you may choke.

You may regain consciousness more quickly if you receive glucagon. This should only be administered by someone who knows how to do it.

• If you are given glucagon, you should take glucose or a sugary product as soon as you regain consciousness.
• If you do not respond to glucagon treatment, you should be treated in a hospital.
• If severe hypoglycemia is not treated, it can cause brain damage over time. This can be temporary or permanent. It can even lead to death.

Talk to your doctor if:

• you have had low blood sugar levels that have caused you to lose consciousness
• you have needed glucagon
• you have recently suffered several drops in blood sugar level.

You may need to adjust the amount or administration schedule of insulin, food, or exercise.

• Blood sugar level too high (hyperglycemia).

High blood sugar levels may appear if:

you eat more or do less exercise than usual, drink alcohol, have an infection or fever, do not inject enough insulin, repeatedly inject less insulin than you need, forget to inject insulin, or interrupt treatment with insulin without talking to your doctor.

The warning symptoms of a blood sugar level that is too high usually appear gradually and are:

Dry and reddened skin, drowsiness or fatigue, feeling of dryness in the mouth, fruity breath odor (acetone), increased need to urinate, thirst, loss of appetite, nausea or feeling of discomfort (vomiting).

These can be symptoms of a very serious disorder called ketoacidosis. It is an accumulation of acid in the blood because the body metabolizes fat instead of sugar. If left untreated, it can lead to diabetic coma and death.

What to do if your blood sugar level is too high

• Check your blood sugar level.
• Check the acetone level in your urine.
• Seek immediate medical attention.

Reporting adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Ryzodeg

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the label and on the box of the pen after CAD. The expiration date is the last day of the month indicated.

Before first use

Store in the refrigerator (between 2 °C and 8 °C). Do not freeze. Do not store near the refrigeration element. Keep the pen with the cap on to protect it from light.

Once opened or if carried as a spare

You can carry your preloaded Ryzodeg (FlexTouch) pen with you and store it at room temperature (not above 30 °C) or in the refrigerator (between 2 °C and 8 °C) for 4 weeks.

Always keep the pen with the cap on when not in use to protect it from light.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Container Content and Additional Information

Composition of Ryzodeg

• The active substances are insulin degludec and insulin aspart. Each ml of solution contains 100 units of insulin degludec/insulin aspart in a 70/30 ratio (equivalent to 2.56 mg of insulin degludec and 1.05 mg of insulin aspart). Each pre-filled pen contains 300 units of insulin degludec/insulin aspart in 3 ml of solution.
• The other components are glycerol, metacresol, phenol, sodium chloride, zinc acetate, hydrochloric acid, and sodium hydroxide (for pH adjustment) and water for injectable preparations (see section 2).

Appearance of the Product and Container Content

Ryzodeg is presented as a clear and colorless injectable solution in a pre-filled pen (300 units per 3 ml).

Container sizes of 1 (with or without needles), 5 (without needles), and a multiple container of 10 (2 x 5) (without needles) pre-filled 3 ml pens.

Only some container sizes may be marketed.

Marketing Authorization Holder

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

Manufacturer

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd

Denmark

Novo Nordisk Production SAS

45, Avenue d’Orléans

28000 Chartres

France

Date of Last Revision of this Leaflet:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

Instructions for Use of Ryzodeg 100 units/ml FlexTouch Solution for Injection in Pre-filled Pen

Read these instructions carefully before using your pre-filled pen.

If you do not follow the instructions carefully, you may administer too little or too much insulin, which could lead to high or low blood sugar levels.

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

Start by checking the pen to make sure it contains Ryzodeg 100 units/mland then look at the illustrations to familiarize yourself with the different parts of the pen and needle.

If you are blind or have reduced vision and cannot read the dose counter on the pen, do not use this pen without help.Seek help from a person who can see well and is trained in the use of the pre-filled FlexTouch pen.

Your pen is a pre-filled insulin doser that contains 300 units of insulin. You can select a maximum of 80 unitsper administration, in increments of 1 unit. The pen is designed to be used with disposable NovoTwist or NovoFine needles up to 8 mm in length for single use.

• Important Information

Pay special attention to these notes because they are important for the correct use of the pen.

1 Preparation of the Pen

• Check the name and concentration on the label of your pen to ensure it contains Ryzodeg 100 units/ml. This is especially important if you use more than one type of insulin. If you use the wrong type of insulin, your blood sugar level may become too high or too low.

• Remove the pen cap.

• Check that the insulin in the pen has a clear and colorless appearance.

Look through the insulin window. If the insulin appears cloudy, do not use the pen.

• Take a new needle and remove the paper tab.

• Place the needle straight onto the pen. Screw it on until it is secure.

• Remove the outer needle cap and set it aside for later. You will need it after the injection to properly remove the needle from the pen.

• Remove the inner needle cap and discard it. If you try to put it back on, you may accidentally prick yourself with the needle.

A drop of insulin may appear at the tip of the needle. This is normal, but you must still check the insulin flow.

Always use a new needle for each injection.

This reduces the risk of contamination, infection, loss of insulin, needle blockage, and inaccurate dosing.

Never use bent or damaged needles.

2 Checking the Insulin Flow

• Always check the insulin flow before starting. This will help ensure you receive the full insulin dose.
• Turn the dose selector until 2 units are selected. Make sure 2 appears in the dose counter.

• Hold the pen with the needle pointing upwards.

Gently tap the top of the pena few times to make any air bubbles rise.

• Press and hold the dose button until the dose counter returns to 0.

The 0 should line up with the dose marker.

A drop of insulin should appear at the tip of the needle.

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

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

If, despite this, no insulin drop appears,discard the pen and use a new one.

Always make sure a drop appearsat the tip of the needle before injecting. This ensures the insulin is flowing.

If no drop appears, do notinject, even if the dose counter moves. This may indicate the needle is blocked or damaged.

Always check the flow before injecting.If you do not check the flow, you may receive too little or no insulin, which could lead to high blood sugar levels.

3 Selecting the Dose

• Check that the dose counter shows 0 before starting.

The 0 should line up with the dose marker.

• Turn the dose selector to select the dose you need, following the instructions of your doctor or nurse.

If you have selected a wrong dose, you can turn the dose selector forward or backward until you select the correct dose.

The pen can select up to a maximum of 80 units.

The dose selector changes the number of units. Only the dose counter and dose marker show how many units you have selected for each administration.

You can select up to 80 units for each administration. When the pen contains less than 80 units, the dose counter stops when it reaches the number of units left.

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

Before injecting the insulin, always use the dose counter and dose marker to see how many units you have selected.

Do not count the pen clicks. If you select a wrong dose and inject it, your blood sugar level may become too high or too low. Do not use the insulin scale, as it only shows the approximate amount of insulin left in the pen.

4 Injecting the Dose

• Insert the needle under the skin as your doctor or nurse has taught you.

• Check that you can see the dose counter.

Do not touch the dose counter with your fingers. This could interrupt the injection.

• Press and hold the dose button until the dose counter returns to 0.

The 0 should line up with the dose marker.

You may hear or feel a click.

• Keep the needle under the skin for at least 6 seconds to ensure the full dose is administered.

• Keep the needle and pen straight, then pull them out of the skin.

If blood appears at the injection site, press lightly with a cotton swab. Do not rub the area.

A drop of insulin may appear at the tip of the needle after the injection. This is normal and does not affect the dose.

Always check the dose counter to see how many units you inject.

The dose counter shows the exact number of units. Do not count the pen clicks.

Keep the dose button pressed until the dose counter returns to 0 after the injection. If the dose counter stops before reaching 0, the full dose has not been administered, which could result in high blood sugar levels.

5 After the Injection

• Put the needle tip into its outer cap, placed on a flat surface, without touching the needle or the outer cap.

• When the needle is covered, carefully press the outer cap fully on.

• Unscrew the needle and dispose of it carefully.

• Put the pen cap back on the pen after each use to protect the insulin from light.

Always discard the needle after each injectionin an appropriate sharps container. This reduces the risk of contamination, infection, loss of insulin, needle blockage, and inaccurate dosing. If the needle is blocked, do notinject insulin.

When the pen is empty, discard it withoutthe needle attached, following the instructions of your doctor, nurse, pharmacist, or local authorities. Do not throw away the used needle in household waste.

Never try to put the inner needle cap back on.You could prick yourself with it.

Always remove the needle after each injectionand store your pen without the needle attached.

This reduces the risk of contamination, infection, loss of insulin, needle blockage, and inaccurate dosing.

6 How Much Insulin is Left?

• The insulin scale shows the approximate amount of insulin left in the pen.

• To find out exactly how much insulin is left, use the dose counter:

Turn the dose selector until the dose counterstops.

If it shows 80, it means there are at least 80units left in the pen.

If it shows less than 80, the number indicates the amount of units left in the pen.

• Turn the dose selector backward until the dose counter shows 0.

• If you need more insulin than the units left in the pen, you can split the dose between two pens.

• Be very careful when doing the calculation if you split your dose.

In case of doubt, inject the full dose with a new pen. If you incorrectly split the dose, you may inject too little or too much insulin, which could lead to high or low blood sugar levels.

More Important Information

• Always carry the pen with you.

• Always carry a spare pen and new needles with you, in case of loss or breakage.

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

• Never share the pen or needles with others. This could lead to infections.

• Never share the pen with others. Your medication could be harmful to their health.

• People caring for patients should be careful when handling used needles to reduce the risk of needlestick injuries and infections.

Care of the Pen

Treat your pen with care. Rough handling or misuse can cause inaccurate dosing, which could lead to high or low blood sugar levels.

• Do not leave the pen in a car or other location where it could become too hot or too cold.

• Do not expose the pen to dust, dirt, or liquids.

• Do not wash, soak, or lubricate the pen. If necessary, clean it with a damp cloth and a mild detergent.

• Make sure the pen does not fall or hit hard surfaces.

If you drop the pen or suspect it may have a problem, put a new needle on and check the insulin flow before injecting.

• Do not attempt to refill the pen. Once empty, it must be discarded.

• Do not attempt to repair the pen or disassemble it.