NOVORAPID 100 U/ML INJECTABLE SOLUTION IN VIAL

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 going to have a hypoglycaemia (low blood sugar level) (see a) Summary of serious and frequent adverse reactions in section 4).

? If the vial does not have a security seal or if it is loose. Each vial has a plastic security seal. If it is not in perfect condition, return the vial to your supplier.

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

? If the insulin does not look like water or is not clear.

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

Before using NovoRapid

? Check the label to make sure it is the type of insulin that you have been prescribed.

? Remove the security seal.

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

? Needles and syringes must not be shared.

Warnings and precautions

Some 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 exercise than usual or if you want to change your diet, as this may affect your blood sugar level.

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

? If you plan to travel abroad, time differences between countries may affect your insulin requirement and administration schedule.

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 as well if it is injected into a thickened, shrunk or lumpy 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 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 dose or the dose of your other anti-diabetic medications.

Children and adolescents

Do not give this medicine to children under 1 year of age, as clinical trials have not been conducted in children under 1 year of age.

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

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 diseases 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 disorders);
• sympathomimetics (such as adrenaline or salbutamol or terbutaline used to treat asthma);
• growth hormone (medicine to stimulate growth and skeletal development that has a pronounced effect on metabolic processes);
• danazol (medicine that acts on ovulation).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults, caused when the pituitary gland produces too much growth hormone) may increase or decrease your blood sugar levels.

Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the first warning symptoms that could help you recognise when you have low blood sugar levels.

Pioglitazone (tablets used to treat type 2 diabetes)

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

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

Alcoholic beverages and use of NovoRapid

? If you drink alcohol, your need for insulin may change as your blood sugar level may be increased or decreased. Careful monitoring is recommended.

Pregnancy and breast-feeding

? If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking 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 for your baby’s health that your diabetes is well controlled, especially avoiding hypoglycaemia.

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

Ask your doctor, nurse or pharmacist for advice before taking this medicine if you are pregnant or breast-feeding.

Driving and using machines

? Please ask your doctor whether you can drive or use machines:

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

If your blood sugar is too low or too high, your concentration and ability to react may be impaired, which can affect your ability to drive or use machines. Bear in mind that you could endanger yourself or others.

A consequence of the rapid onset of action of NovoRapid is that if hypoglycaemia occurs, it may occur sooner after injection than with human soluble insulin.

Important information about some of the ingredients of NovoRapid

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

3. How to use NovoRapid

Dosage and when to administer the insulin

Follow exactly the instructions for administration and dose adjustment given by your doctor. If in doubt, 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 immediately after a meal. For further information, see below “How and where to inject”.

Do not change your insulin unless your doctor tells you to. If your doctor switches you from one type or brand of insulin to another, 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 administer in relation to meals.

Use in special patient groups

If you have kidney or liver problems, or if you are over 65 years of age, you should check your blood sugar more frequently and consult your doctor for advice on adjusting your insulin dose.

How and where to inject

NovoRapid should be injected under the skin (subcutaneously) or by continuous subcutaneous infusion in an insulin pump. Your healthcare professional should teach you how to administer insulin with an insulin pump. Never inject yourself directly into a vein (intravenously) or into a muscle (intramuscularly). If necessary, NovoRapid can also be administered directly into a vein, but only by a doctor or other healthcare professional.

For each injection, change the injection site within the area of skin that you usually use. This may reduce the risk of developing lumps or hollows under the skin (see section 4, Possible side effects). The best areas for injection are the front of your waist (abdomen), the upper arm or the front of your thighs. Insulin will work more quickly if injected into the front of your waist. Always check your blood sugar levels regularly.

NPH insulin is the only type of insulin that can be mixed with NovoRapid and the mixture should be injected immediately under the skin (subcutaneously). NovoRapid should be drawn into the syringe first.

How to use NovoRapid

If you use only one type of insulin

1. Draw an amount of air into the syringe that is equal to the dose of insulin you are going to inject. Inject the air into the vial.
2. Invert the vial and syringe, and draw the correct dose of insulin into the syringe. Remove the needle from the vial. Remove any air from the syringe and check that the dose is correct.

If you need to mix two types of insulin

1. Just before use, roll the NPH insulin between your hands until the liquid is uniformly cloudy.
2. Draw an amount of air into the syringe that is equal to the dose of NPH insulin. Inject the air into the vial containing the NPH insulin and remove the needle.
3. Draw an amount of air into the syringe that is equal to the dose of NovoRapid. Inject the air into the vial containing NovoRapid. Invert the vial and syringe, and draw the prescribed dose of NovoRapid into the syringe. Remove any air from the syringe and check that the dose is correct.
4. Insert the needle into the vial of NPH insulin, invert the vial and syringe, and draw the prescribed dose of NPH insulin into the syringe. Remove any air from the syringe and check the dose. Inject the mixture immediately.
5. Always mix NovoRapid and NPH insulin in the same order.

How to inject NovoRapid

? Inject the insulin under the skin. Use the injection technique advised by your doctor or nurse.

? Keep the needle under the skin for at least 6 seconds, to make sure that the entire dose is injected.

? Dispose of the needle after each injection.

Use in an insulin infusion pump

NovoRapid must not be mixed with other insulins when used in a pump.

Follow your doctor’s instructions and recommendations for the use of NovoRapid in a pump. Before using NovoRapid in an insulin pump, you must have been instructed on how to use the pump, and how to take action if you become unwell, if your blood sugar level becomes too low or too high, or if the pump fails.

• Before inserting the needle, wash your hands and the skin where you are going to insert the needle with soap and water to avoid any infection at the infusion site.
• When filling a new reservoir, make sure that there are no air bubbles in the syringe or the infusion set.
• The infusion set (needle and cannula) should be changed in accordance with the instructions provided with the infusion set.

To get the most out of insulin infusion and to detect any possible pump failure, it is recommended that you regularly check your blood sugar level.

What to do in case of pump failure

You should always have an alternative insulin delivery system available in case the pump fails.

If you use more insulin than you need

If you use 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, he will tell you what to do. This could lead to very high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See c) Effects of diabetes in section 4.

If you have any other questions about 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 level (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 (temporary or permanent) and even death. You can recover 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 (caramels, 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 your blood sugar levels have stabilized, continue your 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 your insulin, diet, 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 level. 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 to 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 unwell 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 can occur 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 (an eye disease related to diabetes that can lead to vision loss): if you have diabetic retinopathy and your blood sugar level improves very quickly, the retinopathy can 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 nerve-related pain. This is called acute painful neuropathy and is usually temporary.

Reporting of 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 leaflet. You can also report them directly through the Spanish Medicines Monitoring System for Human Use: 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 level (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 dizzy (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 can 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 can lead to 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 expiry date that appears on the label of the vial and on the carton, after EXP. The expiry date is the last day of the month indicated.

Keep the vial in the outer carton to protect it from light.

Before opening:store in a refrigerator at 2°C to 8°C, away from the walls or the cooling element of the refrigerator. Do not freeze.

During use or when carried as a spare: the product can be stored for a maximum of 4 weeks. Store below 30°C. Do not refrigerate or freeze.

Discard the needle after each injection.

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 NovoRapid

• The active substance is insulin aspart. Each ml contains 100 units of insulin aspart. Each vial contains 1,000 units of insulin aspart in 10 ml of injectable solution.
• The other components 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.

Packages containing 1 or 5 vials of 10 ml or in a multipack of 5 packs of 1 vial x 10 ml. Not all pack sizes may be marketed.

The solution is clear and colorless.

Marketing Authorization Holder and Manufacturer

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

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.