INSULATARD 100 IU/ml INJECTABLE SUSPENSION IN VIAL

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

Do not use Insulatard

• 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 suffer from hypoglycemia (low blood sugar level), see Summary of serious and very common side effects in section 4.
• In insulin infusion pumps.
• If the protective cap is missing or is loose. All vials have a plastic safety cap. If this is not in perfect condition when you acquire the vial, return it to the supplier.
• If it has not been stored correctly or if it has been frozen, see section 5.
• If the resuspended insulin does not have a uniformly white and cloudy appearance.

If any of these circumstances apply, do not use Insulatard. Consult your doctor, pharmacist, or nurse.

Before using Insulatard

?Check the label to ensure it is the correct 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. Consult your doctor:

• If you have kidney, liver, adrenal, pituitary, or thyroid problems.
• If you do more physical exercise than usual or if you want to change your usual diet, as this may affect your blood sugar level.
• If you are ill, you should continue using insulin and consult your doctor.
• If you are going to travel abroad, traveling to different time zones may affect your insulin requirement and the time of administration.

Skin changes 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 very well if injected into a thickened, shrunk, or lumpy area (see section 3). 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 advise you to check your blood sugar levels more closely and adjust your insulin or the dose of your other antidiabetic medications.

Other medicines and Insulatard

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 that your insulin dose needs to be adjusted. The following are the most common medicines that may affect your insulin treatment.

Your blood sugar level may decrease (hypoglycemia) 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 inhibitors (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)
• Sulfonamides (used to treat infections).

Your blood sugar level may increase (hyperglycemia) 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 hormone (used to treat thyroid disorders)
• Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
• Growth hormone (medication to stimulate bone and somatic growth and with significant influence on the body's metabolic processes)
• Danazol (medication that acts on ovulation).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults, caused by excess 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 early warning symptoms that help recognize low blood sugar levels.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with long-standing type 2 diabetes and previous heart disease or stroke who were treated with pioglitazone and insulin developed heart failure. Inform 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, inform your doctor, pharmacist, or nurse.

Using Insulatard with alcohol

? If you drink alcohol, your insulin needs may change, as your blood sugar level may increase or decrease. Strict monitoring is recommended.

Pregnancy and breastfeeding

? If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Insulatard can be used during pregnancy. It may be necessary to adjust the insulin dose during pregnancy and after delivery. Keeping a strict control of diabetes, especially to prevent hypoglycemia, is important for the health of your baby.

? There are no restrictions on the use of Insulatard during breastfeeding.

Consult your doctor, pharmacist, or nurse before using this medicine during pregnancy or breastfeeding.

Driving and using machines

? Ask your doctor if you can drive vehicles or operate machinery:

• If you have frequent episodes of hypoglycemia.
• If you have difficulty recognizing the symptoms of hypoglycemia.

If your blood sugar level is high or low, it may affect your concentration and reaction ability and, therefore, your ability to drive or operate machinery. Be aware that you may put yourself or others at risk.

Insulatard contains sodium

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

3. How to use Insulatard

Dose and when to use the insulin

Follow the instructions for administration of this medicine and the dose indicated by your doctor exactly. If you are in doubt, consult your doctor, pharmacist, or nurse again.

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

Use in children and adolescents

Insulatard can be used in children and adolescents.

Use in special patient groups

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

How and where to inject the insulin

Insulatard is administered by injection under the skin (subcutaneous administration). It should never be injected directly into a vein (intravenous injection) or muscle (intramuscular injection).

With each injection, change the injection site within the area of skin you use. This can reduce the risk of developing lumps and depressions in the skin, see section 4. The best areas for injection are: the front of the waist (abdomen), the gluteal region, the front of the thigh, or the upper arm. The effect of the insulin will be faster if the injection is made in the waist (abdomen). You should measure your blood sugar level regularly.

How to use Insulatard

Insulatard vials must be used with insulin syringes graduated in the corresponding unit scale.

If you only use one type of insulin

1. Turn the vial between your hands until the liquid has a uniformly white and cloudy appearance. Resuspension is easier when the insulin has reached room temperature. 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, expel 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, turn the Insulatard vial between your hands until the liquid has a uniformly white and cloudy appearance. Resuspension is easier when the insulin has reached room temperature.
2. Draw into the syringe the same amount of air as the dose of Insulatard. Inject the air into the vial containing Insulatard and remove the needle.
3. Draw into the syringe the same amount of air as the dose of fast-acting insulin. Inject the air into the vial containing the fast-acting insulin. Then, turn the vial and syringe upside down and draw out the prescribed dose of fast-acting insulin. Expel the air from the syringe and check that the dose is correct.
4. Insert the needle into the Insulatard vial, turn the vial and syringe upside down, and draw out the prescribed dose. Expel the air from the syringe and check that the dose is correct. Inject the mixture immediately.
5. Always mix Insulatard and fast-acting insulin in the same order.

How to inject Insulatard

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

?Keep the needle under the skin for at least 6 seconds to ensure that all the insulin is injected.

? Discard the needle and syringe after each injection.

If you use more insulin than you should

If you use too much insulin, your blood sugar level will drop too low (hypoglycemia). See Summary of serious and very common side effects in section 4.

If you forget to use the insulin

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

If you stop using the insulin

Do not stop using the insulin without talking to your doctor first, who will explain what you should do. Stopping the insulin may cause a high increase in your blood sugar level (severe hyperglycemia) and ketoacidosis. See Effects of diabetes in section 4.

If you have any other questions about 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

Decrease in 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 Insulatard 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, difficulty concentrating.

A severe drop in blood sugar level can lead to loss of consciousness. If left untreated, 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). If possible, measure your blood sugar level and rest. Always carry glucose tablets or sugary products 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 usual insulin treatment.

? 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.

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

A Severe Allergic Reactionto Insulatard 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 your body.
• If you suddenly do not feel well and have sweats, feeling of discomfort (nausea), difficulty breathing, rapid heartbeat, or dizziness.

? 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 (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

May 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 a few weeks after starting insulin use. If they do not disappear or spread throughout the body, you should consult your doctor immediately. Also, see the severe allergic reactions mentioned above.

Diabetic Retinopathy(eye disease related to diabetes that can cause vision loss): if you have diabetic retinopathy and your blood sugar level improves very quickly, retinopathy can worsen. In this case, you should consult your doctor.

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.

Very Rare Adverse Effects

May affect up to 1 in 10,000 people.

Vision Problems:when starting insulin treatment, your vision may be affected, but it is usually temporary.

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 transitory.

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 high blood sugar levels 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 high blood sugar levels:

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

What to do in case of high blood sugar levels:

? If you experience any of the above symptoms: check your blood sugar level and the presence of ketones in your urine if possible, and then consult your doctor immediately.

? 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 could lead to a diabetic coma and even death.

5. Storage of Insulatard

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 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 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 packaging 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 medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Insulatard

• The active ingredient is human insulin. Insulatard is an isophane human insulin (NPH) suspension. Each ml contains 100 IU of human insulin. Each vial contains 1,000 IU of human insulin in 10 ml of injectable suspension.

• The other ingredients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injectable preparations.

Appearance of the Product and Package Contents

Insulatard is presented as an injectable suspension. After resuspension, the liquid should have a uniformly white and cloudy appearance.

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 suspension is aqueous, white, and cloudy in appearance.

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 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 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.