TRESIBA 100 units/mL Penfill Injectable Solution in Cartridge

2. What you need to know before you use Tresiba

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

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

• Low blood sugar level (hypoglycemia) – If your blood sugar level is too low, follow the instructions in section 4.
• High blood sugar level (hyperglycemia) – 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.
• Visual disturbances – A sudden improvement in blood sugar control may cause a temporary worsening of visual disturbances due to diabetes. If you experience any problems with your vision, talk to your doctor.

• Using the correct insulin – Always check the label of your insulin before each injection to avoid mix-ups between Tresiba 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, shrinking of the skin, or lumps under the skin. Insulin may not work well if injected into a thickened, shrunk, or lumped area (see section 3, “How to use Tresiba”). Inform your doctor if you notice any changes at 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 antidiabetic 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

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 (hypoglycemia) if you take:

• other diabetes medicines (oral and injectable)
• 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 a low blood sugar level (see section 4, “Warning signs of a low blood sugar level”)
• 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 production of growth hormone. These medicines may increase or decrease your blood sugar levels.

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

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

Using Tresiba with alcohol

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, 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. Avoiding low blood sugar levels (hypoglycemia) is especially important for your baby’s health.

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 your life or the lives of others at risk. Ask your doctor if you can drive if:

• you have frequent episodes of hypoglycemia
• you find it hard to recognize the warning signs of hypoglycemia.

Important information about some of the ingredients of Tresiba

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

3. How to use Tresiba

Follow the instructions for administration of this medicine exactly as told 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 insulin without help. Ask for help from a person with no visual problems and who is trained in the use of the pen.

Your doctor will decide with you:

• how much Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in dosing schedule

• Always follow your doctor’s recommendations.
• Use Tresiba once a day, preferably at the same time every day.
• On occasions when it is not possible to use Tresiba at the same time of the day, you can use it at a different time of the day. Make sure that at least 8 hours pass between doses. There is no experience with flexibility in dosing schedule of Tresiba in children and adolescents.
• If you want to change your usual diet, talk to your doctor, pharmacist, or nurse first, as a change in 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 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 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 Tresiba for the first time, your doctor or nurse will show you how to do it.

• Read the manual that comes with the insulin delivery system.
• Check the name and strength on the label to ensure it is Tresiba 100 units/ml.

Do not use Tresiba

• in insulin infusion pumps.
• if the cartridge or the delivery system you are using is damaged. Return them to your supplier. See more instructions in the delivery system manual.
• if the cartridge is damaged or has not been stored correctly (see section 5, “Storing Tresiba”).
• if the insulin does not look like water and is not colorless.

How to inject

• Tresiba is injected under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best injection sites are the front of the thigh, the upper arm, and the front of the waist (abdomen).
• Change the injection site each day within the same area to reduce the risk of developing lumps or hollows under the skin (see section 4).
• Always use a new needle for each injection. Reusing needles can increase the risk of needle 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 become too low (hypoglycemia), see the advice in section 4, “Low blood sugar level”.

If you forget to use Tresiba

If you miss a dose, inject the missed dose when you discover the mistake, making sure that at least 8 hours pass between doses. If you discover that you missed the previous dose at the time of the next dose, do not inject a double dose, inject your usual daily dose.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor first. Stopping your insulin may cause high blood sugar levels and diabetic ketoacidosis (a condition with 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 you are 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 drops too low, you may lose consciousness. Severe hypoglycemia can cause brain damage and be potentially fatal. If you have symptoms of low blood sugar, take measures to increase your blood sugar level immediately. See the advice on "Blood sugar level too low".

If you suffer a severe allergic reaction (rarely appears) to insulin or any of the components of Tresiba, discontinue treatment with Tresiba 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 nauseous (vomiting)
• you experience difficulty breathing
• you have palpitations or feel dizzy.

Changes in the skin at the injection site:

If you inject insulin in the same place, the fatty tissue can shrink (lipoatrophy) or become thicker (lipohipertrophy) (it can affect up to 1 in 100people). Lumps under the skin can 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 it is injected into a lumpy, shrunken, or thickened area. Change the injection site to help avoid these skin changes.

Other adverse effects include:

Frequent(can affect up to 1 in 10people)

Local reactions: localized reactions may appear at the injection site. Symptoms can include: pain, redness, hives, swelling, 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, discontinue treatment with Tresiba and consult your doctor immediately. For more information, see "severe allergic reaction" above.

Uncommon(can 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(can affect up to 1 in 1,000people)

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

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.

Warning symptoms of a blood sugar level too low, which can appear suddenly:

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

What to do if your blood sugar level is too low

• Take glucose tablets or a 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 recovery 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 of low blood sugar might be, 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 notgive 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 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 had several episodes of low blood sugar recently.

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

Warning symptoms of a blood sugar level too high, which usually appear gradually:

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

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects that are not listed in this leaflet. You can also report them directly through the national reporting system included in Annex V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Tresiba

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

Do not use this medicine after the expiry date stated on the label and on the carton of Penfill after "EXP". The expiry date is the last day of the month indicated.

Before the first use

Store in a refrigerator (between 2°C and 8°C). Do not freeze. Keep away from the freezer.

Once opened or if carried as a spare

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

Always keep Tresiba Penfill in the outer packaging when not in use to protect it from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Tresiba

• The active substance 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 ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid, and sodium hydroxide (for pH adjustment) and water for injections (see section 2).

Appearance and Package Contents

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

Package sizes of 5 and 10 cartridges of 3 ml. Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Novo Nordisk A/S

Novo Alle 1

DK-2880 Bagsvaerd, Denmark

Date of Last Revision of this Leaflet:

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