MIXTARD 30 100 IU/ml INJECTABLE SUSPENSION IN VIAL

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

Do not use Mixtard

• 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 hypoglycaemia (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 buy the vial, return it to your supplier.
• If it has not been stored correctly or has been frozen, see section 5.
• If the resuspended insulin does not have a uniformly white and cloudy appearance.

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

Before using Mixtard

• 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

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

• If you have problems with your kidneys, liver, adrenal glands, pituitary or thyroid gland.
• 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 to use your 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 in the skin 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 you inject into a lumpy, shrunk or thickened area (see section 3). 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 you start injecting into a different area. Your doctor may tell you to check your blood sugar levels more closely and to adjust your insulin dose or other antidiabetic medications.

Other medicines and Mixtard

Tell your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.

Certain 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 (a medicine used to stimulate bone and somatic growth and has significant influence on the body's metabolic processes)
• Danazol (a medicine that affects ovulation)

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

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with long-standing type 2 diabetes and a history of 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 (oedema).

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

Using Mixtard 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 check on this.

Pregnancy and breastfeeding

? 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. Mixtard can be used during pregnancy. You may need to adjust your insulin dose during pregnancy and after delivery. Keeping a close check on your diabetes, especially to prevent hypoglycaemia, is important for the health of your baby.

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

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

Driving and using machines

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

• If you often have episodes of hypoglycaemia.
• If you find it hard to recognize the warning signs of hypoglycaemia.

If your blood sugar is too high or too low, it may affect your concentration and ability to react, which could put you or others in danger.

Mixtard contains sodium

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

3. How to use Mixtard

Dose and when to use the insulin

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

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

Mixtard 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

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

For 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 Mixtard

Mixtard vials are to be used with insulin syringes graduated to match the dose of insulin to be injected.

1. Turn the vial between your hands until the liquid has a uniformly white and cloudy appearance. Resuspension will be easier when the insulin has reached room temperature.
2. Put the same amount of air into the syringe as the dose of insulin you are going to inject. Inject the air into the vial.
3. 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.

How to inject Mixtard

• Inject the insulin 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.
• 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 may become too low (hypoglycaemia). See Summary of serious and very common side effects in section 4.

If you forget to use your insulin

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 your insulin

Do not stop using your insulin without talking to your doctor first. Stopping your insulin may lead to very high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects of diabetes in section 4.

If you have any further questions on the use of this product, 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 Frequent Adverse Effects

Low Blood Sugar Level (Hypoglycemia)is a very frequent 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 Mixtard 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 will need to receive hospital treatment.

What to do if you suffer from low blood sugar:

? If you suffer from low blood sugar, 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 immediate medical attention. They should not give you food or drinks, as you may choke.

Severe Allergic Reactionto Mixtard 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 feel unwell 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

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 a few weeks after starting insulin therapy. If they do not disappear or spread throughout the body, you should consult your doctor immediately. See also 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, the retinopathy can worsen. In this case, you should consult your doctor.

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

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

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects 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.

Effects Derived from Diabetes

High Blood Sugar Level (Hyperglycemia)

You may experience high blood sugar 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:

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 (acetone).

What to do in case of high blood sugar:

? 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 can lead to diabetic coma and even death.

5. Storage of Mixtard

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 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

Mixtard 30 Composition

• The active substance is human insulin. Mixtard is a mixture consisting of 30% soluble human insulin and 70% isophane human insulin. 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.

Product Appearance and Package Contents

Mixtard 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

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

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 website: http://www.ema.europa.eu.