Package Insert: Information for the Patient

Tresiba 200 units/mL FlexTouch pre-filled injectable solution

insulina degludec

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed to you alone, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

6. Contents of the pack and additional information

Tresiba is a long-acting basal insulin called insulin degludec. It is used in adults, adolescents, and children one year of age and older to treat diabetes mellitus. Tresiba helps the body to lower blood sugar levels. It is used once a day. When the usual administration time cannot be followed, the administration time can be varied because Tresiba has a prolonged hypoglycemic effect (see section 3, “Flexibility in administration schedule”). Tresiba can be used with rapid-acting insulins administered in relation to meals. In patients with type 2 diabetes mellitus, Tresiba may be used in combination with oral diabetes medications or with non-insulin injectable antidiabetic drugs.

In patients with type 1 diabetes mellitus, Tresiba must always be used in combination with rapid-acting insulins administered in relation to meals.

Do not use Tresiba:

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

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Tresiba. It is important that you know the following information:

• Low blood sugar (hypoglycemia) – If your blood sugar level is too low, follow the instructions in section 4.
• High blood sugar (hyperglycemia) – If your blood sugar level is too high, follow the instructions in section 4.
• Switching from other insulins – You may need to adjust your insulin dose if you switch from another type, brand or manufacturer of insulin. Talk to your doctor.
• Use of Pioglitazona with insulin – See the section “Pioglitazona” below.
• Visual disturbances – A sudden improvement in blood sugar control may cause a temporary worsening of visual disturbances due to diabetes. If you experience any vision problems, talk to your doctor.
• Use of the correct insulin – Always check the label of your insulin before each injection to avoid confusion between the different concentrations of Tresiba and other insulins.

See section 3 if you have reduced vision.

Changes in the skin at the injection site

The injection site should be rotated to help avoid changes in the fatty tissue, such as thickening of the skin, shrinking of the skin or lumps under the skin. Insulin may not work well if injected into an area that is thickened, shrunk or lumpy (see section 3 “How to use Tresiba”). Inform your doctor if you notice any changes in the injection site. Inform your doctor if you are currently injecting into these affected areas, before starting to inject into a different area. Your doctor may advise you to check your blood sugar levels more closely, and adjust your insulin or the dose of your other diabetes medications.

Children and adolescents

Tresiba can be used in adolescents and children from 1 year of age. There is no experience with the use of Tresiba in children under 1 year of age.

Other medicines and Tresiba

Inform your doctor, pharmacist or nurse if you are using, have used recently or may need to use any other medicine. Some medicines affect blood sugar levels, requiring a change in your insulin dose.

The following are the main medicines that can affect your treatment with insulin:

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

• other diabetes medicines (orals and injectables)
• sulfonamides, to treat infections
• anabolic steroids, such as testosterone
• beta-blockers, to treat high blood pressure. These may make it harder to recognize the warning signs of low blood sugar (see section 4 “Warning signs of low blood sugar”)
• acetylsalicylic acid (and other salicylates), for pain and 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 (hyperglycemia) if you take:

• danazol, to treat endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, to treat thyroid problems
• growth hormone, to treat a deficiency of this hormone
• glucocorticoids, such as cortisone, to treat inflammation
• sympathomimetics, such as epinephrine (adrenaline), 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 acromegaly, a rare disorder characterized by excessive production of growth hormone. These medicines may increase or decrease your blood sugar levels.

Pioglitazona: an oral antidiabetic used to treat type 2 diabetes. Some patients with long-standing type 2 diabetes and pre-existing heart disease or stroke who were treated with pioglitazona and insulin, developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain or localized inflammation (edema).

If you are in any of the above situations (or are unsure), consult your doctor, pharmacist or nurse.

Use of Tresiba with alcohol

If you drink alcohol, it may change your need for insulin as your blood sugar level may be increased or decreased. Therefore, you should monitor your blood sugar level more frequently than usual.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. You may need to adjust your insulin dose while pregnant and after delivery. During pregnancy, careful control of your diabetes is necessary. Avoiding low blood sugar (hypoglycemia) is especially important for the health of your baby.

Driving and operating machinery

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

• you experience frequent episodes of hypoglycemia;
• you find it difficult to recognize the warning signs of hypoglycemia.

Important information about some of the components of Tresiba

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

Follow exactly the administration instructions of this medication as indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

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 help from a person with no vision problems and trained in the use of the FlexTouch pre-filled pen.

Tresiba in pre-filled pen is available in two doses. “Tresiba 100 units/mL” or “Tresiba 200 units/mL” is clearly indicated on the pen label and carton. Additionally, the carton and label of Tresiba 100 units/mL are light green and the carton and label of Tresiba 200 units/mL are dark green with stripes and a red box highlighting the dose.

For both doses, the required dose is selected in units. However, the dose units vary between the two Tresiba doses.

The 200 units/mL pre-filled pen can provide a dose of 2–160 units in an injection, in increments of 2 units. The dose counter on the pre-filled pen shows the number of units of insulin to be injected. Do not make any dose calculations.

Your doctor will decide with you:

• what amount of Tresiba you will need each day
• 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 usage recommendations.
• Use Tresiba once a day, preferably at the same time every day.
• In some cases, when it is not possible to use Tresiba at the same time of day, you can use it at a different time of day. Make sure that at least 8 hours pass between doses. There is no experience with flexibility in administration schedule in children and adolescents.
• If you want to modify your usual diet, consult your doctor, pharmacist, or nurse first, as a change in diet may alter your insulin needs.

Your doctor may change your dose based on your blood sugar level.

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

Use in elderly patients (≥65 years)

Tresiba can be used in elderly patients, but if you are an elderly patient, you may need to check your blood sugar level more frequently.

Use in patients with renal or hepatic impairment

If you have renal or hepatic impairment, you may need to monitor your blood sugar level more frequently. Talk to your doctor about possible changes in your dose.

Medication injection

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

• Check the name and concentration on the pen label to ensure that it is Tresiba 200 units/mL.
• The dose counter on your pen shows the exact number of units of insulin. Do not recalculate the dose.

Do not use Tresiba

• in insulin infusion pumps.
• if the pen has been damaged or not stored properly (see section 5 “Storage of Tresiba”).
• if the insulin does not have a transparent and colorless appearance.

How to inject

• Tresiba is injected under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best areas for injection are the front of the thigh, the upper arm, and the front of the abdomen.
• Change the injection site every day to reduce the risk of developing lumps and depressions in the skin (see section 4).
• Always use a new needle for each injection. Reusing needles may increase the risk of needle blockage, leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to extract the solution from the pen to avoid dosing errors and possible overdoses.

Instructions for use are provided on the other side of this leaflet.

If you use more Tresiba than you should

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

If you forget to use Tresiba

If you forget to administer a dose, inject the missed dose as soon as you remember, ensuring at least 8 hours pass between doses. If you discover that you have forgotten the previous dose at the time of injecting the next dose, do not inject a double dose, inject your usual daily dose.

If you interrupt treatment with Tresiba

Do not stop treatment with your insulin without consulting your doctor. Stopping insulin administration could produce high blood sugar levels and diabetic ketoacidosis (a condition that consists of an excessive amount of acid in the blood), see the advice in section 4 “Blood sugar level too high”.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

When you are being treated with insulin, you may experience hypoglycemia (low blood sugar) very frequently (it may affect more than 1 in 10 people). It can be very serious. If your blood sugar level drops too low, you may lose consciousness. Severe hypoglycemia can cause brain damage and be potentially fatal. If you experience symptoms of low blood sugar, take measures to increase your blood sugar level immediately. See the "Low Blood Sugar" guidelines.

If you experience a severe allergic reaction (rarely) to insulin or any of the components of Tresiba, 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 feel suddenly unwell with sweating
• you start to feel dizzy (vomiting)
• you experience difficulty breathing
• you have palpitations or feel dizzy.

Changes in skin at the injection site:

If you inject insulin in the same place, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (it may affect up to 1 in 100 people). Bumps under the skin may also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; it is not known how often this occurs). Insulin may not work very well if injected in a thickened, shrunk, or swollen area. Change the injection site to help prevent these skin changes.

Other side effects include:

Frequent(may affect up to 1 in 10people)

Local reactions: local reactions may occur at the injection site. Symptoms may include: pain, redness, rashes, inflammation, and itching. These reactions usually disappear after a few days. If symptoms do not disappear after a few weeks, consult your doctor. If reactions worsen, stop treatment with Tresiba 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 rashes, swelling of the tongue and lips, diarrhea, nausea, fatigue, and pruritus.

General effects of diabetes treatment

• Low blood sugar (hypoglycemia)

You may experience low blood sugar levels if:

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

Warning signs of low blood sugar, which may appear suddenly:

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

What to do if your blood sugar level is too low

• Take glucose tablets or a sweet product, such as candies, cookies, or fruit juice (always carry glucose tablets or sweet 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, like all basal insulins, recovery may be delayed.
• Wait until the hypoglycemia symptoms 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 of low blood sugar levels may be, including the risk of losing consciousness.

Inform them that, if you become unconscious, they should:

• turn you onto your side
• seek immediate medical assistance
• do notgive you anything to eat or drink, as you may choke.

You may recover 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 sweet 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 may cause brain damage over time. This may be temporary or permanent. It may even cause death.

Consult your doctor if:

• you have experienced blood sugar levels that are too low and you have lost consciousness
• you have needed glucagon
• you have recently experienced several low blood sugar episodes.

You may need to adjust the dose or frequency of your insulin injections, diet, or exercise.

• High blood sugar (hyperglycemia)

You may experience high blood sugar levels if:

you eat more or exercise less 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 insulin treatment without consulting your doctor.

Warning signs of high blood sugar, which usually appear gradually:

dry and red skin, drowsiness or fatigue, dry mouth, fruity-smelling breath (acetone), increased need to urinate, thirst, loss of appetite, nausea, or vomiting.

These may be symptoms of a serious condition called ketoacidosis. This is a buildup of acid in the blood due to the body metabolizing fat instead of sugar. If not treated, it may cause diabetic coma and death.

What to do if your blood sugar level is too high

• Monitor your blood sugar level.
• Monitor ketone levels in urine or blood.
• Seek immediate medical assistance.

Reporting side effects

If you experienceany type ofside effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

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

Before first use

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

Once opened or as a spare

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

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

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medicines that you no longer need. This will help protect the environment.

Composition of Tresiba

• The active ingredient is insulin degludec. Each milliliter of solution contains 200 units of insulin degludec. Each pre-filled pen contains 600 units of insulin degludec in 3 milliliters of solution.

• The other components are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid, and sodium hydroxide (for pH adjustment) and water for injection (see section 2).

Appearance of the product and contents of the package

Tresiba is presented as a transparent and colorless injectable solution in a pre-filled pen (600 units per 3 milliliters).

Package sizes of 1 (with or without needles), 2 (without needles), 3 (without needles), 5 (without needles) and a multiple pack of 6 (2 x 3) (without needles) pre-filled pens of 3 milliliters. Only some package sizes may be commercially available.

Marketing authorization holder and manufacturer responsible

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsvaerd, Denmark

Last revision date of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Instructions for use of Tresiba 200 units/mL FlexTouch injectable solution in a pre-filled pen

Read these instructions carefully before using your FlexTouch pen. If you do not follow the instructions carefully, you may administer too little or too much insulin, which could result in a level of blood sugar that is too high or too low.

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

Start by checking the pen to ensure it contains Tresiba 200 units/mL, and then observe the illustrations to familiarize yourself with the different parts of the pen and the needle.

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

Your pen is a pre-filled insulin dosing pen that contains 600 units of insulin. You can select a maximum of 160 units per administration, in increments of 2 units.

Do not recalculate the dose. The dose counter on the pen shows the exact number of units of insulin.

Important information

1. Preparation of the pen

• Check the name and concentration on the label of your pen to ensure it contains Tresiba 200 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 cap from the pen.

• Check that the insulin in the pen has a transparent and colorless appearance. Look through the insulin window. If the insulin appears cloudy, do not use the pen.

Check the pen for any visible signs of damage or leakage.

• Take a new needle and remove the paper tab.

• Insert the needle straight into the pen. Twist it until it is securely attached.

• Remove the outer cap from the needle and set it aside. You will need it later to remove the needle from the pen correctly.

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

You may see a small drop of insulin at the tip of the needle. This is normal, but you should still check the flow of insulin.

Always use a new needle for each injection.

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

Never use bent or damaged needles.

2 Checking the flow of insulin

• Always check the flow of insulin before starting.

This will help ensure that you receive the full dose of insulin.

• Turn the dose selector until it shows 2 units. Make sure the 2 appears on the dose counter.

• Hold the pen with the needle pointing upwards.

Gently tap the top of the pen a few times to allow any air bubbles to rise.

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

The 0 should be aligned with the dose marker.

You should see a small drop of insulin at the tip of the needle.

You may see a small air bubble 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 no drop still appears, change the needle and repeat steps 2A to 2C once more.

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

Always make sure a drop appears at the tip of the needle before injecting insulin.

If no drop appears, no insulin will be injected, although the dose counter may move. This may indicate that the needle is blocked or damaged.

Always check the flow before injecting insulin. If you do not check the flow, you may receive an insufficient or non-existent dose of insulin, which could result in a level of blood sugar that is too high.

3 Selecting the dose

• Make sure the dose counter shows 0 before starting.

The 0 should be aligned with the dose marker.

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

• The dose counter shows the selected dose in units. Do not recalculate the dose.

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

The pen can select up to a maximum of 160 units.

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

You can select 160 units for each administration as a maximum. When the pen contains less than 160 doses, the dose counter stops when it reaches the number of units remaining.

The dose selector makes a different clicking sound when turned forward, backward, or when passing the remaining number of units. Do not count the clicks of the pen.

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

Do not count the clicks of the pen. If you select the 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 remaining in the pen.

4 Injecting the dose

• Insert the needle under the skin as instructed by your doctor or nurse.

• Make sure you can see the dose counter.

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

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

The 0 should be aligned with the dose marker.

You may hear or feel a click at this point.

• Hold the needle and pen straight and remove them from the skin.

If blood appears at the injection site, press gently with an alcohol swab. Do not rub the area.

You may see a small drop of insulin at the tip of the needle after the injection. This is normal and does not affect the dose.

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

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

Press and hold the dose button until the dose counter returns to 0 after the injection. If the dose counter stops before reaching 0, the dose has not been fully administered, which may result in a level of blood sugar that is too high.

5 After the injection

• Insert the tip of the needle into the outer cap, which should be placed on a flat surface, without touching the needle or the outer cap of the needle.

• Press the outer cap firmly and carefully until it is fully seated.

• Twist the needle off and discard it carefully.

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

Always discard the needle after each injection in an appropriate sharps container. This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

When the pen is empty, discard it without the needle attached, following the instructions of your doctor, nurse, pharmacist, or local authorities. Do not throw the used needle in household trash.

Never attempt to reattach the inner cap of the needle. You may prick yourself with it.

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

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

6 How much insulin is left?

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

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

Turn the dose selector until the dose counter stops.

If it shows 160, it means there are at least 160 units remaining in the pen.

If it shows less than 160, the number indicates the amount of units remaining in the pen.

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

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

Be very careful to calculate correctly if you divide your dose.

If you divide incorrectly, you may inject too little or too much insulin, which may result in a level of blood sugar that is too high or too low.

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 other people, especially children.

• Never share the pen or needles with others. This may cause infections.

• Never share the pen with others. Your medicine may be harmful to their health.

• People who care for patients must be very careful when handling used needles to reduce the risk of accidental needlesticks and infections.

Care of the pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which may result in a level of blood sugar that is too high or too low.

• Do not leave the pen in the car or in any other place where it may become overheated or overcooled.

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

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

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

If the pen falls or you suspect a problem, attach a new needle and check the flow of insulin 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.