MIXTARD 30 INNOLET 100 IU/ml Injectable Suspension in Pre-filled Pen

2. What you need to know before you use 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 get hypoglycaemia (low blood sugar), see Summary of serious and frequent side effects in section 4.
• In insulin infusion pumps.
• If the InnoLet is dropped, damaged, or crushed.
• If it has not been stored correctly or has been frozen, see section 5.
• If the resuspended insulin does not look uniformly white and cloudy.

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.
• Always use a new needle for each injection to avoid contamination.
• Needles and Mixtard InnoLet must not be shared.
• Mixtard InnoLet is only intended for subcutaneous injection. Talk to your doctor if you need to inject insulin by a different method.

Warnings and precautions

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

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

• 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 should continue to use insulin and consult your doctor.
• If you are going abroad, travelling across different time zones may affect your insulin requirements and the timing of your injections.

Skin 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 you inject into a lumpy, shrunk, or thickened area (see section 3). Tell your doctor if you notice any changes in the injection site area. If you are currently injecting into these affected areas, tell your doctor before you start injecting into a different area. Your doctor may tell you to check your blood sugar levels more often and to adjust your insulin dose or other anti-diabetic medications.

Other medicines and Mixtard

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 fall (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 rise (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 hormone (used to treat thyroid disorders)
• Sympathomimetics (such as adrenaline, salbutamol, or terbutaline, used to treat asthma)
• Growth hormone (a medicine that stimulates bone and body growth and has significant effects 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 early warning symptoms that help you recognise a low blood sugar level.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with type 2 diabetes of long duration and pre-existing 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 localised swelling (oedema).

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

Using Mixtard with alcohol

? If you drink alcohol, your insulin needs may change, as your blood sugar level may rise or fall. 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. Mixtard 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 the health of your baby.

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

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

Driving and using machines

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

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

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

Mixtard contains sodium

Mixtard contains less than 1 mmol of sodium (23 mg) per dose, i.e., it 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.

Take food containing carbohydrates within 30 minutes of 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 level 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). Never inject directly into a vein (intravenous injection) or muscle (intramuscular injection). Mixtard InnoLet is only intended for subcutaneous injection. Talk to your doctor if you need to inject insulin by a different method.

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 your waist (abdomen), the buttocks, the front of your 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 handle Mixtard 30 InnoLet

Mixtard 30 InnoLet is a pre-filled pen that contains a mixture of fast-acting and long-acting human insulin in a 30/70 proportion.

Read carefully the Instructions for using Mixtard 30 InnoLet included in this leaflet. You should use the pen as described in the Instructions for using Mixtard 30 InnoLet.

Always make sure you use the correct pen before injecting.

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 frequent 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 medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Summary of serious and frequent side effects

Low blood sugar (hypoglycaemia)is a very common side effect. It may affect up to 1 in 10 people.

Your blood sugar level may fall if:

• You inject too much insulin.
• You eat less than usual or miss a meal.
• You do more physical exercise than usual.
• You drink alcohol, see Using Mixtard with alcohol in section 2.

Signs of low blood sugar: cold sweat, cool pale skin, headache, fast heartbeat, feeling sick, excessive hunger, temporary vision changes, drowsiness, unusual tiredness or weakness, nervousness or tremor, anxiety, confusion, difficulty concentrating.

A severe low blood sugar may lead to loss of consciousness. If not treated, it may cause brain damage (temporary or permanent) and even death. You may regain consciousness more quickly if someone who knows how to do so gives you an injection of glucagon. If you are given glucagon, you will also need to take glucose or a sugary snack as soon as you regain consciousness. If you do not respond to glucagon treatment, you will have to be treated in a hospital.

What to do if you get low blood sugar:

? If you get low blood sugar, eat glucose tablets or other sugary products (such as sweets, biscuits, or fruit juice). If possible, measure your blood sugar level and rest. Always carry glucose tablets or sugary products with you in case you need them.

? When the signs of low blood sugar have gone or when your blood sugar level is stabilised, continue with your normal dose of insulin.

? If your blood sugar level is so low that you pass out, if you need an injection of glucagon, or if you have had many episodes of low blood sugar, talk to your doctor. You may need to adjust your insulin dose or the frequency of injections, your diet or exercise.

Tell the people close to you that you have diabetes and what the risks are, such as becoming unconscious (loss of consciousness) due to a low blood sugar. Make sure they know what to do in this situation - they should turn you on your side and seek medical help right away. They should not give you anything to eat or drink, as you might choke.

A severe allergic reactionto Mixtard or any of its ingredients (called a systemic allergic reaction) is a very rare but potentially life-threatening side effect. It may affect up to 1 in 10,000 people.

See a doctor immediately:

• If the allergic reaction spreads to other parts of your body.
• If you suddenly feel unwell and have symptoms such as sweating, nausea, dizziness, fast heartbeat, or difficulty breathing.

? 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 area, the fatty tissue under the skin may shrink (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; the frequency of this side effect is not known). Insulin may not work well if you inject into a lumpy, shrunk, or thickened area (see section 3). Tell your doctor if you notice any changes in the injection site area. If you are currently injecting into these affected areas, tell your doctor before you start injecting into a different area. Your doctor may tell you to check your blood sugar levels more often and to adjust your insulin dose or other anti-diabetic medications.

List of other side effects

Uncommon side effects

May affect up to 1 in 100 people.

Allergic reactions: local allergic reactions (pain, redness, hives, inflammation, bruising, swelling, and itching) at the injection site may occur. They usually disappear within a few weeks of starting insulin treatment. If they do not disappear or spread across your body, talk to your doctor. See also the severe allergic reactions described above.

Diabetic retinopathy(eye disease related to diabetes that may cause blindness): if you have diabetic retinopathy and your blood sugar level improves very quickly, your retinopathy may get worse. In this case, talk to your doctor.

Joint inflammation: when you start using insulin, water retention may cause swelling of your ankles and other joints. This side effect usually goes away on its own. 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 get nerve-related pain. This is called acute painful neuropathy and it usually goes away on its own.

Rare side effects

May affect up to 1 in 10,000 people.

Vision problems: when you start using insulin, your vision may be affected. This is usually temporary.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

Effects of diabetes

High blood sugar (hyperglycaemia)

You may get high blood sugar if:

• You do not inject enough insulin.
• You miss an injection of 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 include:

These symptoms appear gradually and include excessive urination, thirst, loss of appetite, nausea or vomiting, drowsiness or tiredness, dry, reddened skin, dry mouth, and a fruity breath odour (acetone).

What to do if you get high blood sugar:

? If you get any of the above symptoms, check your blood sugar level and test for ketones in your urine if possible, and then talk to your doctor immediately.

? These may be signs of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood due to the body breaking down fat instead of sugar). If not treated, it could lead to a 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 expiry date which is stated on the label and carton of InnoLet after EXP. The expiry date is the last day of the month stated.

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. Can be carried and stored at room temperature (below 30°C) for up to 6 weeks.

Always keep the pen cap on your InnoLet when not in use to protect it from light.

Discard the needle after each injection.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. 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 pre-filled pen contains 300 IU of human insulin in 3 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 injections.

Appearance of the Product and Package Contents

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

Package sizes of 1, 5, and 10 pre-filled pens of 3 ml. Not all pack sizes may be marketed.

The suspension is aqueous, white, and cloudy in appearance.

Marketing Authorization Holder and Manufacturer

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

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.

Instructions for using InnoLet are included on the back.

Instructions for using Mixtard 30 injectable suspension in InnoLet

Read the instructions carefully before using your InnoLet.If you do not follow the instructions carefully, you may administer too little or too much insulin, which could lead to high or low blood sugar levels.

InnoLet is a simple and compact pre-filled pen capable of administering doses of 1 to 50 units, in increments of 1 unit. InnoLet is designed to be used with NovoFine or NovoTwist disposable needles of up to 8 mm in length. As a precautionary measure, always carry a spare insulin delivery device in case your InnoLet is lost or damaged.

First Steps

Check the name and color labelof your InnoLet to ensure it contains the correct type of insulin. This is especially important if you use more than one type of insulin. If you use the wrong type of insulin, your blood sugar level may become too high or too low. Remove the pen cap.

Resuspending the insulin will be easier when it has reached room temperature.

Resuspension of Insulin

Before each injection:

• Check that the cartridge contains at least 12 units of insulin to ensure uniform resuspension. Use a new InnoLet if there are less than 12 units.
• Move the pen up and down between positions A and B so that the glass ball in the cartridge moves from one end to the other (figure 1A) at least 20 times. Repeat this movement at least 10 times before each injection. Always repeat the movement until the liquid appears uniformly white and cloudy.
• Always make sure you have resuspended the insulin before each injection. If you do not resuspend the insulin, this could cause inaccurate dosing, which may lead to high or low blood sugar levels. After resuspension, complete the following injection steps without delay.

Attaching the Needle

• Always use a new needle for each injection. This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.
• Be careful not to bend or damage the needle before use.
• Remove the paper tab from a new disposable needle.
• Screw the needle straight and firmly onto your InnoLet (figure 1B).
• Remove the large outer needle cap and the inner needle cap. The large outer needle cap can be stored in the compartment provided.

Never attempt to put the inner needle cap back on. You may stick yourself with the needle.

Preparing to Expel Air Before Each Injection

During use, small amounts of air may remain in the needle and insulin cartridge.

To avoid injecting air and ensure accurate dosing:

• Set 2 units by turning the dose selector clockwise.
• Hold your InnoLet with the needle upwards and gently tap the cartridge with your finger several times (figure 1C) to make the air bubbles rise to the top of the cartridge.
• With the needle still upwards, press the push-button and the dose selector will return to 0.
• Always make sure a drop appears at the needle tip before injecting (figure 1C). This ensures the insulin flows. If this does not happen, change the needle and repeat the procedure a maximum of 6 times.

If a drop of insulin still does not appear, the device is defective and must not be used.

• If a drop does not appear, no insulin will be injected, even if the dose selector moves. This may indicate that the needle is blocked or damaged.

• Always check your InnoLet before injecting. If you do not check your InnoLet, you may receive too little or no insulin, which could result in high blood sugar levels.

Dose Selection

• Always check that the push-button is fully depressed and the dose selector is set to 0.
• Set the required number of units by turning the dose selector clockwise (figure 2).
• You will hear a click for each unit dialed. The dose can be corrected by turning the dose selector in both directions. Make sure you do not turn the dose selector or correct the dose once the needle is under your skin. This could result in inaccurate dosing, which may cause high or low blood sugar levels.

Before injecting the insulin, always use the dose selector and dose indicator to see how many units you have selected. Do not count the clicks of the pen. If you select a wrong dose and inject it, your blood sugar level may become too high or too low. Do not use the remaining insulin scale, as it only shows the approximate amount of insulin left in the pen.

It is not possible to select a dose greater than the number of units remaining in the cartridge.

Injecting the Insulin

• Insert the needle under the skin. Use the injection technique recommended by your doctor.
• Administer the dose by pressing the push-button fully (figure 3). You will hear clicks as the dose selector returns to 0.
• After the injection, keep the needle under the skin for at least 6 seconds to ensure that the full dose has been administered.
• Make sure you do not block the dose selector while injecting, as the dose selector must return to 0 as you press the push-button. Always make sure the dose selector returns to 0 after the injection. If the dose selector stops before reaching 0, the full dose has not been administered, which may result in high blood sugar levels.
• Discard the needle after each injection.

Removing the Needle

• Put the large outer needle cap back on and unscrew the needle (figure 4). Dispose of it carefully.
  • Put the pen cap back on your InnoLet to protect the insulin from light.

Always use a new needle for each injection. Always remove and discard the needle after each injection and keep your InnoLet without the needle attached. This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

Other Important Information

Persons caring for these patients must be careful when handling used needles to reduce the risk of accidental needlestick injuries and infections.

Dispose of your used InnoLet carefully without leaving the needle on.

Never share the pen or needles with other people. This could lead to infections.

Never share the pen with other people. Your medicine may be harmful to their health.

Always keep your InnoLet and needles out of sight and reach of other people, especially children.

Care of the Pen

InnoLet is designed to function with precision and safety. It must be handled with care. If it is dropped, damaged, or impacted, there is a risk that insulin may be expelled. This could cause inaccurate dosing, which may lead to high or low blood sugar levels.

You can clean your InnoLet with a cotton swab dampened with alcohol. Do not submerge, wash, or lubricate it. This may damage the mechanism and could cause inaccurate dosing, which may lead to high or low blood sugar levels.

Do not refill your InnoLet. Once empty, it must be discarded.