Patient Information Leaflet: Package Insert

Tresiba 100 units/mL Penfill Injectable Solution in a Cartridge

insulin degludec

Read this entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. See section 4.

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 administered 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 be used always in combination with rapid-acting insulins administered in relation to meals.

No use Tresiba:

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use Tresiba. It is essential 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.

• Using the correct insulin – Always check the label of your insulin before each injection to avoid confusion between Tresiba and other insulins.

See section 3 if you have reduced vision.

Changes in skin at the injection site

Rotate the injection site to help prevent 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 instruct 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 aged 1 year and older. There is no experience with the use of Tresiba in children under 1 year.

Other medications and Tresiba

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

The following are the main medications that may affect your treatment with insulin:

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

• other diabetes medications (oral and injectable)
• sulfonamides, to treat infections
• anabolic steroids, such as testosterone
• beta-blockers, to treat high blood pressure. These may make it difficult 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 mild 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 growth hormone deficiency
• 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 growth hormone production. These medications may increase or decrease your blood sugar levels.

Pioglitazona: an oral antidiabetic medication used to treat type 2 diabetes mellitus. 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.

Using 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, consult your doctor or pharmacist before using this medication. You may need to adjust your insulin dose while pregnant and after delivery. During pregnancy, it is essential to carefully monitor your diabetes. Avoiding low blood sugar (hypoglycemia) is especially important for your baby's health.

Driving and operating machinery

Low or high blood sugar levels 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 impaired. 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 medication 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 insulin without help. Ask for help from a person with normal vision and trained in the use of the pen.

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 the administration schedule

• Always follow the usage recommendations of your doctor.
• 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 there are at least 8 hours between doses. There is no experience with flexibility in the administration schedule of Tresiba in children and adolescents.
• If you want to modify your usual diet, consult your doctor, pharmacist, or nurse beforehand, as a change in diet may alter your need for insulin.

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 elderly, you may need to check your blood sugar level more frequently. Talk to your doctor about the possible changes in your dose.

Patients with renal or hepatic problems

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

Medication injection

Before using Tresiba for the first time, your doctor or nurse will show you how to do it.

• Read the manual that comes with the insulin administration system.
• Check the name and concentration on the label to make sure it is Tresiba 100 units/ml.

Do not use Tresiba

• in insulin infusion pumps.
• if the cartridge or administration system you are using is damaged. Return it to your supplier. See more instructions in the administration system manual.
• if the cartridge is 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 (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 blockage, leading to inaccurate dosing. Dispose of the needle safely after each use.

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 guidelines 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, making sure there are at least 8 hours 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 cause high blood sugar levels and diabetic ketoacidosis (a condition that consists of an excessive amount of acid in the blood), see the guidelines 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 significantly, you may lose consciousness. Severe hypoglycemia can cause brain damage and be potentially fatal. If you experience symptoms of low blood sugar, take immediate action to increase your blood sugar level. See the "Low Blood Sugar" section for advice.

If you experience a severe allergic reaction (rare) to insulin or any of the components of Tresiba, stop treatment with Tresiba and consult your doctor immediately. The signs of a severe allergic reaction are:

• The local reaction spreads 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 into 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 well if injected into 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 10 people)

Local reactions: Localized reactions may occur at the injection site. Symptoms may include: pain, redness, rashes, inflammation, and itching. These reactions usually disappear within a few days. If symptoms persist for several 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 100 people)

Joint inflammation: When starting treatment, 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 1,000 people)

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 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 worry, 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 candy, 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 with 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 people you spend time with that you have diabetes. Tell them what the consequences of low blood sugar 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 and may lead to death.

Talk to your doctor if:

• You have experienced low blood sugar levels that have caused you to lose consciousness;
• You have needed glucagon;
• You have experienced several low blood sugar episodes recently.

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

• High blood sugar (hyperglycemia)

You may experience high blood sugar 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 stop 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 an accumulation 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

• Check your blood sugar level.
• Check the level of ketones in your urine or blood.
• Seek immediate medical assistance.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directlythrough thenational reporting 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 Penfill container 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 away from the freezer.

Once opened or if carrying as a spare

Do not refrigerate. You may carry your Tresiba (Penfill) cartridge with you and store it at room temperature (not above 30°C) for 8 weeks.

Always store Tresiba Penfill in the outer packaging 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 ml of solution contains 100 units of insulin degludec. Each cartridge contains 300 units of insulin degludec in 3 ml 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 packaging

Tresiba is presented as a transparent and colourless injectable solution in a cartridge (300 units per 3 ml).

Packaging sizes of 5 and 10 cartridges of 3 ml. Only some packaging sizes may be marketed.

Marketing authorization holder and manufacturer responsible

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsvaerd, Denmark

Last review 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