NOVORAPID PENFILL 100 U/mL INJECTABLE SOLUTION IN CARTRIDGE

2. What you need to know before you use NovoRapid

Do not use NovoRapid

? If you are allergic to insulin aspart or any of the other ingredients of this medicine (see section 6, Contents of the pack and other information).

? If you suspect you are having a hypoglycaemic attack (low blood sugar level) (see a) Summary of serious and frequent adverse reactions in section 4).

? If the cartridge or the device containing the cartridge has been dropped, damaged or crushed.

? If it has not been stored correctly or if it has been frozen (see section 5, Storing NovoRapid).

? If the insulin does not appear clear and colourless.

If any of these conditions apply to you, do not use NovoRapid. Consult your doctor, nurse or pharmacist.

Before using NovoRapid

? Check the label to ensure it is the right type of insulin.

? Always check the cartridge, including the rubber stopper, before each use. Do not use it if it is damaged or if the rubber stopper has been removed.

? Always use a new needle for each injection to prevent contamination.

? Needles and NovoRapid Penfill must not be shared.

? NovoRapid Penfill is only intended for subcutaneous injection using a Novo Nordisk insulin delivery system. Consult your doctor if you need to inject by another method.

Warnings and precautions

Certain conditions and activities may affect your insulin requirement. Consult your doctor:

? If you have kidney, liver, adrenal, pituitary or thyroid problems.

? If you are doing more physical activity than usual or if you want to change your diet, as this may affect your blood sugar level.

? If you are ill, continue your insulin treatment and consult your doctor.

? If you are going to travel across more than one time zone, the time difference between destinations may affect your insulin requirements and the timing of your injections.

Skin changes at the injection site

The injection site should be rotated to help avoid changes to the fatty tissue under the skin, such as lumps, thickening or pitting. Insulin may not work as well if you inject in a lumpy, thickened or pitted area (see section 3, How to use NovoRapid). Inform your doctor if you notice any changes at the injection site. Inform your doctor if you are currently injecting in an affected area, before you start injecting in a different area. Your doctor may tell you to check your blood sugar levels more often and to adjust your insulin dose or your other antidiabetic medications.

Children and adolescents

Do not give this medicine to children under 1 year of age, as there is no experience with the use of NovoRapid in this age group.

Other medicines and NovoRapid

Tell your doctor, nurse or pharmacist if you are using, have recently used or might use any other medicines.

Some medicines affect your blood sugar level and this may mean you need to adjust your insulin dose. The following medicines may affect your insulin requirements:

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

• other medicines for the treatment of diabetes;
• monoamine oxidase inhibitors (MAOIs) (used to treat depression);
• beta-blockers (used to treat high blood pressure);
• angiotensin-converting enzyme (ACE) inhibitors (used to treat certain heart conditions or high blood pressure);
• salicylates (used to relieve pain and lower fever);
• anabolic steroids (such as testosterone);
• sulphonamides (used to treat infections).

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

• oral contraceptives (birth control pills);
• thiazides (used to treat high blood pressure or excessive fluid retention);
• glucocorticoids (such as “cortisone” used to treat inflammation);
• thyroid hormones (used to treat thyroid problems);
• sympathomimetics (such as epinephrine [adrenaline] or salbutamol or terbutaline used to treat asthma);
• growth hormone (used to treat growth disturbances);
• danazol (a medicine used to treat menstrual disorders).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder, usually diagnosed in adults, caused by the pituitary gland producing too much growth hormone) may increase or decrease your blood sugar level.

Beta-blockers (used to treat high blood pressure) may mask the symptoms of low blood sugar and make it harder for you to recognise the warning signs.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with type 2 diabetes and long-standing heart disease or previous stroke who were treated with pioglitazone and insulin developed heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If you have taken any of the medicines mentioned above, inform your doctor, nurse or pharmacist.

Alcohol and use of NovoRapid

? If you drink alcohol, your need for insulin may be increased, as your blood sugar level may be lowered or raised. Be careful and monitor your blood sugar level.

Pregnancy and breast-feeding

? If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine. NovoRapid can be used during pregnancy. You may need to adjust your insulin dose and your blood sugar monitoring during pregnancy and after giving birth. It is very important to maintain good control of your diabetes during pregnancy, and to prevent hypoglycaemia.

• There are no restrictions on the use of NovoRapid during breast-feeding.

Ask your doctor, nurse or pharmacist for advice before using any medicine during pregnancy or breast-feeding.

Driving and using machines

? Please ask your doctor whether you can drive or operate machinery:

• If you have frequent hypoglycaemic attacks.
• If you find it hard to recognise hypoglycaemia.

If your blood sugar is too low or too high, your ability to concentrate and react may be impaired, which could affect your ability to drive or operate machinery. You might put yourself and others at risk.

A consequence of the rapid onset of action of NovoRapid is that hypoglycaemia may occur more quickly after injection, compared to human soluble insulin.

Important information about some of the ingredients of NovoRapid

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

3. How to use NovoRapid

Dose and when to inject the insulin

Follow exactly the instructions for injecting insulin and adjusting the dose, as instructed by your doctor. If you are not sure, consult your doctor, nurse or pharmacist.

NovoRapid should normally be administered immediately before a meal. Take some food within 10 minutes after the injection to avoid hypoglycaemia. When necessary, NovoRapid can be administered soon after a meal. For more information, see below “How and where to inject”.

Do not change your insulin unless your doctor tells you to. If your doctor switches you to another type or brand of insulin, you may need to adjust your dose.

Use in children and adolescents

NovoRapid can be used in adolescents and children from 1 year of age in place of human soluble insulin, when a fast-acting insulin is preferred. For example, when it is difficult to inject in relation to meals.

Use in special patient groups

If you have kidney or liver problems, or if you are over 65 years old, you should monitor your blood sugar level more often and consult your doctor for advice on dose adjustment.

How and where to inject

NovoRapid should be injected under the skin (subcutaneously). Never inject yourself directly into a vein (intravenously) or into a muscle (intramuscularly). NovoRapid Penfill is only intended for subcutaneous injection using a Novo Nordisk insulin delivery system. Consult your doctor if you need to inject by another method.

For each injection, change the injection site within the same region to reduce the risk of developing lumps, thickening or pitting under the skin (see section 4, Possible side effects). The best areas for injection are the front of your waist (abdomen), the top of your leg (thigh) or the upper arm. The insulin will work more quickly if injected into the front of your waist. Always check your blood sugar levels regularly.

? Do not refill the cartridge. Once empty, it must be discarded.

? NovoRapid Penfill cartridges are designed to be used with Novo Nordisk insulin delivery systems and NovoFine or NovoTwist needles.

? If you are using NovoRapid Penfill and another insulin Penfill cartridge, you should use two different delivery systems, one for each type of insulin.

? Always keep a spare cartridge in case one is lost or damaged.

How to inject NovoRapid

? The insulin should be injected under the skin. Use the injection technique advised by your doctor or nurse and described in the user manual that comes with your delivery system.

? Keep the needle under the skin for at least 6 seconds. Keep the injection button fully pressed until the needle is removed from the skin. This will ensure correct dosing and will help to prevent blood entering the cartridge or the needle.

? After each injection, remove and discard the needle and store NovoRapid without the needle attached. Otherwise, the liquid may leak out which can cause inaccurate dosing.

If you use more insulin than you need

If you take too much insulin, your blood sugar level may become too low (hypoglycaemia). See a) Summary of serious and frequent adverse reactions in section 4.

If you forget to use your insulin

If you forget to inject your insulin, your blood sugar level may become too high (hyperglycaemia). See c) Effects of diabetes in section 4.

If you stop using your insulin

Do not stop using your insulin without consulting your doctor, as this may lead to very high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See c) Effects of diabetes in section 4.

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

4. Possible Adverse Effects

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

• Summary of serious and very frequent adverse effects

Low blood sugar (hypoglycemia)is a very frequent adverse effect. It can affect more than 1 in 10 people.

Low blood sugar levels may appear if:

• too much insulin is injected;
• you eat very little or skip a meal;
• you do more exercise than usual;
• you drink alcohol (see Alcohol and use of NovoRapid in section 2).

Warning signs of low blood sugar: cold sweat, cold and pale skin, headache, palpitations, nausea, excessive hunger, temporary changes in vision, drowsiness, unusual fatigue and weakness, nervousness or tremors, anxiety, confusion, and difficulty concentrating.

A severe drop in blood sugar can lead to loss of consciousness. If a severe and prolonged drop in blood sugar is not treated, it can cause brain damage (transient or permanent) and even death. You can regain consciousness more quickly if someone who knows how to do it administers a glucagon injection to you. 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.

What to do if your blood sugar level is low:

? If your blood sugar level is low, take glucose tablets or a sugary product (candies, cookies, fruit juice). Measure your blood sugar level if possible and then rest. Always carry glucose tablets or sugary foods with you in case you need them.

? When the symptoms of hypoglycemia have disappeared or when blood sugar levels have stabilized, continue insulin treatment as usual.

? If you have had blood sugar levels so low that they have caused you to lose consciousness, if you have needed to be given a glucagon injection, or if you have had many drops in blood sugar levels, talk to your doctor. You may need to adjust the amount or administration schedule of insulin, food, or exercise.

Inform others that you have diabetes and what the consequences may be, including the risk of losing consciousness due to a drop in blood sugar levels. Tell them that if you become unconscious, they should lay you on your side and seek immediate medical attention. They should not give you anything to eat or drink as you may choke.

Severe allergic reactionsto NovoRapid or any of its components (called a systemic allergic reaction) is a very rare but potentially fatal adverse effect. It can affect up to 1 in 10,000 people.

Consult your doctor immediately:

• if the signs of allergy spread to other parts of your body.
• if you suddenly feel sick and have sweats, vomiting, difficulty breathing, palpitations, feel dizzy.

? If you notice any of these symptoms, consult your doctor immediately.

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 (lipohypertrophy) (can affect up to 1 in 100 people). Lumps under the skin can also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; the frequency of this is unknown). Insulin may not work very well if injected into a lumpy, shrunken, or thickened area. Change the injection site to help avoid these skin changes.

• List of other adverse effects

Uncommon adverse effects

Can affect up to 1 in 100 people.

Allergic reactions: local allergic reactions may appear at the injection site (pain, redness, hives, inflammation, bruising, swelling, and itching). These reactions usually disappear after a few weeks of treatment. If the symptoms do not disappear or if they spread throughout your body, consult your doctor immediately. See also Severe allergic reactions above.

Visual problems: when starting insulin treatment, you may have problems with your vision, but this alteration is usually temporary.

Joint swelling: when starting insulin treatment, fluid accumulation can cause inflammation of the ankles and other joints. This effect usually disappears quickly. If it does not, consult your doctor.

Diabetic retinopathy (a diabetes-related eye disease that can lead to vision loss): if you have diabetic retinopathy and your blood sugar level improves very quickly, the retinopathy may worsen. Consult your doctor.

Rare adverse effects

Can affect up to 1 in 1,000 people.

Painful neuropathy (pain due to nerve damage): if your blood sugar level improves very quickly, you may experience pain related to the nerve. This is called acute painful neuropathy and is usually temporary.

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 does not appear in this leaflet. You can also report them directly through the Spanish Medicines Monitoring System: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

• Effects of diabetes

High blood sugar (hyperglycemia)

High blood sugar levels may appear if:

• you have not injected enough insulin;
• you forget to inject insulin or interrupt insulin treatment;
• you repeatedly inject less insulin than you need;
• you have an infection or fever;
• you eat more than usual;
• you do less physical exercise than usual;

Warning signs of high blood sugar:

the warning signs appear gradually. These include: increased need to urinate, thirst, loss of appetite, feeling of dizziness (nausea or vomiting), drowsiness or fatigue, dry and reddened skin, feeling of dryness in the mouth, and fruity breath odor (acetone).

What to do if your blood sugar level is high:

? If you notice any of the symptoms described: check your blood sugar level, check the ketone level in your urine if possible, and consult your doctor immediately.

? These may be symptoms of a very serious disorder called diabetic ketoacidosis (acid builds up in the blood because the body breaks down fat instead of sugar). If left untreated, it could produce a diabetic coma and death.

5. Storage of NovoRapid

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

Do not use this medicine after the expiration date that appears on the cartridge label and on the packaging, after EXP. The expiration date is the last day of the month indicated.

Always keep the cartridge in the outer packaging when not in use to protect it from light. NovoRapid must be protected from excessive heat and light.

Before opening:the unused NovoRapid Penfill must be stored in a refrigerator between 2°C and 8°C, away from the walls or the cooling component of the refrigerator. Do not freeze.

During use or when carrying as a spare: the NovoRapid Penfill in use or carried as a spare must not be stored in a refrigerator. It can be carried and stored at room temperature (below 30°C) for 4 weeks.

Medicines should not be disposed of via 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. Package Contents and Additional Information

Composition of NovoRapid

• The active ingredient is insulin aspart. Each ml contains 100 units of insulin aspart. Each cartridge contains 300 units of insulin aspart in 3 ml of injectable solution.
• The other ingredients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide, and water for injectable preparations.

Appearance of the Product and Package Contents

NovoRapid is presented as a solution for injection.

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

The solution is transparent and colorless.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark

Manufacturer

The manufacturer can be identified by the batch number printed on the carton lid and on the label:

• If the second and third characters are S6, P5, K7, R7, VG, FG, or ZF, the manufacturer is Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.

• If the second and third characters are H7 or T6, the manufacturer is Novo Nordisk Production SAS, 45 Avenue d’Orléans, F-28000 Chartres, France.

Date of the Last Revision of this Leaflet:03/2023

Other Sources of Information

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