ACTRAPID 100 IU/mL INJECTABLE SOLUTION IN A VIAL

2. What you need to know before you start using Actrapid

Do not use Actrapid

?If you are allergic to human insulin or any of the other ingredients of this medicine, see section 6.

?If you suspect you are starting to get hypoglycaemia (low blood sugar), see Summary of serious and frequent adverse reactions in section 4.

? In insulin infusion pumps.

?If the protective cap is loose or missing. Each vial has a protective plastic cap. If the cap is not in perfect condition when you get the vial, return the vial to your supplier.

?If it has not been stored correctly or has been frozen, see section 5.

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

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

Before using Actrapid

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

? Remove the protective cap.

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

? Needles and syringes must not be shared.

Warnings and precautions

Some changes and activities can affect your insulin needs. Talk to your doctor:

?If you have problems with your kidneys, liver, adrenal, pituitary, or thyroid glands.

?If you do more physical exercise than usual or want to change your usual diet, as this may affect your blood sugar level.

?If you are ill, you must continue to use insulin and consult your doctor.

?If you are going to travel abroad, traveling across different time zones may affect your insulin requirements and the timing of your injections.

Changes at the injection site

You should rotate the injection site to help avoid changes in the fatty tissue under the skin, such as thickening of the skin, shrinking of the skin, or lumps under the skin. Insulin may not work well if injected into a lumpy, shrunk, or thickened area (see section 3). Tell your doctor if you notice any changes at the injection site. Tell your doctor if you are currently injecting in these affected areas before starting to inject in a different area. Your doctor may tell you to check your blood sugar levels more closely and adjust your insulin dose or the dose of your other anti-diabetic medications.

Other medicines and Actrapid

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take 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 most common medicines that may affect your insulin treatment.

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

• Oral contraceptives (birth control pills)
• Thiazides (used to treat high blood pressure or excessive fluid retention)
• Corticosteroids (such as cortisone, used to treat inflammation)
• Thyroid hormone (used to treat thyroid disorders)
• Sympathomimetics (such as adrenaline, salbutamol, or terbutaline, used to treat asthma)
• Growth hormone (medicine to stimulate bone and somatic growth and with significant influence on the body's 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 by excessive production of growth hormone in the pituitary gland) may increase or decrease your blood sugar level.

Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the first warning symptoms that help you recognize a low blood sugar level.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with type 2 diabetes of long duration and previous heart disease or 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 localized swelling (edema).

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

Using Actrapid with alcohol

? If you drink alcohol, your insulin needs may change, as your blood sugar level may increase or decrease. You are advised to keep a close watch on your blood sugar levels.

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. Actrapid can be used during pregnancy. You may need to adjust your insulin dose during pregnancy and after giving birth. Keeping a close watch on your diabetes, especially to prevent hypoglycaemia, is important for your baby's health.

? There are no restrictions on the use of Actrapid during breast-feeding.

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

Driving and using machines

?Ask your doctor whether you can drive a car or use machines:

• If you often get hypoglycaemia.
• If you find it hard to recognise hypoglycaemia.

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

Actrapid contains sodium

Actrapid contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

3. How to use Actrapid

Dose and when to use the insulin

Follow exactly the instructions for administration of this medicine and the dose given by your doctor. If you are not sure, talk to your doctor, pharmacist, or nurse.

Eat a meal or snack containing carbohydrates within 30 minutes of the injection to avoid a drop in blood sugar level.

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

Actrapid can be used in children and adolescents.

Use in special patient groups

If you have kidney or liver problems or if you are over 65 years old, you should check your blood sugar levels more often and talk to your doctor about possible changes in your insulin dose.

How and where to inject the insulin

Actrapid is administered by injection under the skin (subcutaneous administration). Never inject Actrapid directly into a vein (intravenous injection) or muscle (intramuscular injection). If necessary, it can be administered directly into a vein, but this should only be done by healthcare professionals.

With each injection, change the injection site within the area of skin you use. This may reduce the risk of developing lumps or hollows in the skin, see section 4. The best areas for injection are the front of the waist (abdomen), the buttocks, the front of the thighs, or the upper arm. The effect of the insulin will be faster if you inject into the abdomen. You should measure your blood sugar level regularly.

How to use Actrapid

Actrapid vials should be used with insulin syringes graduated to the insulin scale.

If you use only one type of insulin

1. Draw into the syringe the same amount of air as the dose of insulin you are going to inject. Inject the air into the vial.
2. Turn the vial and syringe upside down and draw out the correct dose of insulin into the syringe. Remove the needle from the vial. Then, draw out the 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 intermediate or long-acting insulin vial (cloudy) between your hands until the liquid has a uniformly white, cloudy appearance.
2. Draw into the syringe the same amount of air as the dose of intermediate or long-acting insulin. Inject the air into the intermediate or long-acting insulin vial and remove the needle.
3. Draw into the syringe the same amount of air as the dose of Actrapid. Inject the air into the Actrapid vial. Then, turn the vial and syringe upside down and draw out the prescribed dose of Actrapid. Draw out the air from the syringe and check that the dose is correct.
4. Insert the needle into the intermediate or long-acting insulin vial, turn the vial and syringe upside down, and draw out the prescribed dose. Draw out the air from the syringe and check that the dose is correct. Inject the mixture immediately.
5. Always mix Actrapid and intermediate or long-acting insulin in the same order.

How to inject Actrapid

?The insulin should be injected under your skin. Use the injection technique advised by your doctor or nurse.

?Keep the needle under your skin for at least 6 seconds to make sure you have injected all the insulin.

? Throw away the needle and syringe after each injection.

If you use more Actrapid than you should

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

If you forget to use Actrapid

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

If you stop using Actrapid

Do not stop using your insulin without talking to your doctor first. If you stop using your insulin, your blood sugar level may become too high (severe hyperglycaemia) and you may develop ketoacidosis. See Effects of diabetes in section 4.

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

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 Common Adverse Effects

Low Blood Sugar Level (Hypoglycemia)is a very common adverse effect. It can affect more than 1 in 10 people.

Blood sugar levels can drop if:

• Too much insulin is injected.
• You eat very little or skip a meal.
• You do more physical exercise than usual.
• You drink alcohol, see Use of Actrapid with alcohol in section 2.

Signs of a drop in blood sugar level: cold sweat, cold and pale skin, headache, rapid heartbeat, feeling of discomfort, excessive appetite, temporary visual disturbances, drowsiness, unusual fatigue and weakness, nervousness or tremors, anxiety, confusion, and difficulty concentrating.

A severe drop in blood sugar level can lead to loss of consciousness. If the low blood sugar level is prolonged and not treated, it can cause brain damage (temporary 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 also take glucose or a sugary product as soon as you regain consciousness. If you do not respond to glucagon treatment, you should go to the hospital immediately.

What to do if you suffer from a drop in blood sugar level:

? If you suffer from a drop in blood sugar level, take glucose tablets or another product with a high sugar content (e.g., candies, cookies, fruit juice). Measure your blood sugar level, if possible, and rest. Always carry glucose tablets or products with a high sugar content with you, just in case.

? When the symptoms of low blood sugar have disappeared or when your blood sugar level has stabilized, continue with your insulin treatment as usual.

? If your blood sugar level is so low that you faint, if you have needed a glucagon injection, or if you have had many episodes of low blood sugar, talk to your doctor. You may need to adjust the dose or frequency of insulin administration, your eating habits, or exercise.

Tell the relevant people that you have diabetes and what the consequences may be, such as the risk of fainting (losing consciousness) due to low blood sugar. Let them know that if you faint, they should turn you onto your side and seek immediate medical help. They should not give you food or drinks, as you may choke.

Severe Allergic Reactionto Actrapid or one of its components (called a systemic allergic reaction) is a very rare but potentially life-threatening adverse effect. It can affect up to 1 in 10,000 people.

Consult your doctor immediately:

• If allergy symptoms spread to other parts of the body.
• If you suddenly feel unwell and have sweats, feeling of discomfort (nausea and vomiting), difficulty breathing, rapid heartbeat, and a feeling of losing consciousness.

? If you notice any of these symptoms, seek medical help 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 (lipohipertrophy) (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.

Allergy Symptoms:local allergic reactions (pain, redness, hives, inflammation, bruising, swelling, and itching) can occur at the injection site. They usually disappear within a few weeks of starting insulin use. If they do not disappear or spread throughout the body, talk to your doctor immediately. Also, see the severe allergic reactions mentioned earlier.

Vision Problems:when starting insulin treatment, it can affect your vision, but usually only temporarily.

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

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

Very Rare Adverse Effects

Can affect up to 1 in 10,000 people.

Diabetic Retinopathy(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. In this case, you should consult your doctor.

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 not listed in this leaflet. You can also report them directly through the Spanish Medicines Agency's website: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

Effects Derived from Diabetes

High Blood Sugar Level (Hyperglycemia)

You may experience a high blood sugar level if:

• Not enough insulin is injected.
• You forget to inject insulin or stop using it.
• You repeatedly inject less insulin than you need.
• You have an infection and/or fever.
• You eat more than usual.
• You do less physical exercise than usual.

Warning signs of a high blood sugar level:

The warning signs appear gradually and include frequent urination, thirst, loss of appetite, feeling of discomfort (nausea and vomiting), drowsiness or fatigue, dry and reddened skin, dry mouth, and fruity breath odor (acetone).

What to do if you suffer from a high blood sugar level:

? If you experience any of the above symptoms: check your blood sugar level and ketone level in your urine, if possible, and then seek immediate medical help.

? They can be symptoms of a very serious condition called diabetic ketoacidosis (acid buildup in the blood due to the body breaking down fat instead of sugar). If left untreated, it can lead to a diabetic coma and even death.

5. Storage of Actrapid

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

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

Before Opening:store in a refrigerator (between 2°C and 8°C). Keep away from the cooling element. Do not freeze.

During Use or if Carried as a Spare:do not refrigerate or freeze. It can be carried and stored at room temperature (below 25°C) for up to 6 weeks.

Always keep the vial in the outer carton when not in use to protect it from light.

Discard the needle and syringe 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 medicines. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Actrapid

• The active substance is human insulin. Each ml contains 100 IU of human insulin. Each vial contains 1,000 IU of human insulin in 10 ml of injectable solution.
• The other ingredients are zinc chloride, glycerol, metacresol, sodium hydroxide, hydrochloric acid, and water for injectable preparations.

Appearance of the Product and Package Contents

Actrapid is presented as an injectable solution.

Package sizes of 1 or 5 vials of 10 ml or a multipack of 5 packs of 1 vial of 10 ml. Not all pack sizes may be marketed.

The solution is clear and colorless.

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 and the label:

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

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

Date of the Last Revision of this Leaflet:

Other Sources of Information

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