NOVOMIX 50 FLEXPEN 100 U/mL SUSPENSION FOR INJECTION IN A PRE-FILLED PEN

Introduction

Package Leaflet: Information for the User

NovoMix 50 FlexPen 100units/ml suspension for injection in a pre-filled pen

50% soluble insulin aspart and 50% insulin aspart crystallised with protamine

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What is NovoMix 50 and what is it used for
2. What you need to know before you start using NovoMix 50
3. How to use NovoMix 50
4. Possible side effects
5. Storing NovoMix 50
6. Contents of the pack and other information

1. What is NovoMix 50 and what is it used for

NovoMix 50 is a modern insulin (insulin analogue) with a rapid and intermediate action, in a 50/50 ratio. Modern insulins are improved versions of human insulin.

NovoMix 50 is used to reduce high blood sugar levels in patients with diabetes mellitus (diabetes). Diabetes is a disease where your body does not produce enough insulin to control your blood sugar level. NovoMix 50 can be used together with metformin.

NovoMix 50 will start to lower your blood sugar level about 10-20 minutes after injection, will have its maximum effect between 1 and 4 hours after injection and will last for 14-24 hours.

2. What you need to know before you start using NovoMix 50

Do not use NovoMix 50

• 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 starting to get hypoglycaemia (low blood sugar level), see a) Summary of serious and most frequent adverse reactions in section 4.
• In insulin infusion pumps.
• If your FlexPen is damaged or has been dropped.
• If it has not been stored correctly or has been frozen, see section 5, Storing NovoMix 50.
• If the insulin does not look like water and white suspended particles when it is resuspended.
• If after resuspending there are clumps or white solid particles stuck to the bottom or the sides of the cartridge.

If any of these apply to you, do not use NovoMix 50. Talk to your doctor, nurse or pharmacist.

Before using NovoMix 50

• Check the label to make sure it is the right type of insulin.
• Always use a new needle for each injection to avoid contamination.
• Do not share your needles or NovoMix 50 FlexPen.
• NovoMix 50 FlexPen is only intended for injection under the skin. Talk to your doctor if you need to inject by another method.

Warnings and precautions

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

• If you have kidney or liver problems, or problems with your adrenal, pituitary or thyroid glands.
• If you are doing more physical activity than usual or if you want to change your usual diet, as this may affect your blood sugar level.
• If you are ill, keep using your insulin and talk to your doctor.
• If you are going abroad, travelling over 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 to the skin at the injection site (such as lumps under the skin). The insulin may not work properly if you inject in a lumpy, indented or thickened area (see section 3, How to use NovoMix 50). Tell your doctor if you notice any changes at the injection site. If you are currently injecting in an affected area, tell your doctor before you start injecting in a different area. Your doctor may tell you to check your blood sugar levels more often, or to adjust your insulin dose or your other antidiabetic medicines.

Other medicines and NovoMix 50

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 medicines may affect your treatment with insulin:

Your blood sugar level may be lowered (hypoglycaemia) if you take:

• Other medicines for the treatment of diabetes
• MAO inhibitors (used to treat depression)
• Beta blockers (used to treat high blood pressure)
• 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 be raised (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 hormones (used to treat thyroid problems)
• Sympathomimetics (such as adrenaline [epinephrine], salbutamol or terbutaline used to treat asthma)
• Growth hormone (a medicine used to stimulate growth in children and to treat growth hormone deficiency in adults)
• Danazol (a medicine used to treat menstrual disorders)

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder) may increase or decrease your blood sugar level.

Beta blockers (used to treat high blood pressure) may mask the symptoms of low blood sugar and make it harder for you to recognise the warning signs.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with type 2 diabetes who were treated with pioglitazone and insulin developed heart failure. Tell your doctor as soon as possible if you notice any signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

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

Alcoholic drinks and use of NovoMix 50

• If you drink alcohol, your need for insulin may change, as your blood sugar level may be lowered or raised. You should be aware of this and take extra precautions to avoid hypoglycaemia.

Pregnancy and breast-feeding

• If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. There is limited clinical experience with insulin aspart during pregnancy. You may need to adjust your insulin dose and your diet during pregnancy and after giving birth. It is very important to maintain good control of your diabetes during pregnancy, especially avoiding hypoglycaemia.
• There are no restrictions on the use of NovoMix 50 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 or use a machine:
• If you often have hypoglycaemia.
• If you find it hard to recognise hypoglycaemia.

If your blood sugar is too low or too high, it may affect your concentration and ability to react, and therefore also your ability to drive or operate machinery. You may put yourself and others at risk.

Important information about some of the ingredients of NovoMix 50

NovoMix 50 contains less than 1 mmol (23 mg) of sodium per dose, which means it is essentially “sodium-free”.

3. How to use NovoMix 50

Dose and when to inject NovoMix 50

Always use your insulin and adjust your dose exactly as your doctor has told you. If you are not sure, talk to your doctor, pharmacist or nurse.

NovoMix 50 is usually injected immediately before a meal. You should eat a meal within 10 minutes of injecting to avoid hypoglycaemia. If necessary, NovoMix 50 can be injected shortly after a meal. For more information, see below “How and where to inject”.

When NovoMix 50 is used together with metformin, the dose of metformin should be adjusted.

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

Use in children and adolescents

No clinical studies have been conducted with NovoMix 50 in children and adolescents under the age of 18.

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 adjusting your insulin dose.

How and where to inject

NovoMix 50 is injected under the skin (subcutaneously). Never inject NovoMix 50 directly into a vein (intravenously) or muscle (intramuscularly). NovoMix 50 FlexPen is only intended for injection under the skin. Talk to your doctor if you need to inject by another method.

Each time you inject, change the injection site within the area of skin you use. This may reduce the risk of developing lumps or hollows under the skin (see section 4, Possible side effects). The best places to inject are: the front of your waist (abdomen), the buttocks, the front of your thighs or the upper arm. The insulin will work more quickly if you inject into the waist area. Always check your blood sugar levels regularly.

How to use NovoMix 50 FlexPen

NovoMix 50 FlexPen is a pre-filled pen that contains a mixture of rapid-acting and intermediate-acting insulin aspart in a 50/50 ratio.

Read the instructions carefully before you start using your pen. You must use the pen as described in the instructions.

Always check that you have the correct pen before injecting.

If you use more NovoMix 50 than you should

If you inject too much insulin, your blood sugar level may become too low (hypoglycaemia). See a) Summary of serious and most 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 NovoMix 50

Do not stop using NovoMix 50 without talking to your doctor first. 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 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 frequent adverse effects

Low blood sugar (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 too little or skip a meal.
• You do more exercise than usual.
• You drink alcohol (see Alcohol and use of NovoMix 50 in section 2).

Symptoms of low blood sugar: Cold sweat, cold and pale skin, headache, palpitations, nausea, excessive hunger, temporary changes in vision, drowsiness, fatigue and unusual weakness, nervousness or tremors, feeling of anxiety, feeling of confusion, difficulty concentrating.

A severe hypoglycemic episode can cause you to faint. If a severe and prolonged hypoglycemic episode is not treated, it can cause brain injury (transient or permanent) and even death. You can recover consciousness more quickly with an injection of the hormone glucagon administered by someone who knows how to do it. If you are given glucagon, you should take glucose or a sugary food as soon as you regain consciousness. If you do not respond to glucagon treatment, you should be taken to 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 food (e.g., sweets, cookies, fruit juice). Measure your blood sugar if possible and rest. Always carry glucose tablets or sugary foods with you, just in case.
• When the symptoms of hypoglycemia have disappeared or when your blood sugar level has stabilized, continue your insulin treatment as usual.
• If you have had a blood sugar level so low that you have fainted, if you have needed a glucagon injection, or if you have had many episodes of low blood sugar, talk to your doctor. It may be necessary to adjust the dose or frequency of insulin administration, your diet, or the exercise you do.

Inform others that you are diabetic and what the consequences may be, including the risk of fainting (losing consciousness) due to a drop in your blood sugar level. Let them know that if you faint, they should lay you on your side and seek immediate medical attention. They should not give you any food or drink, as you may choke.

Severe allergic reactionsto NovoMix 50 or to any 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 the symptoms of allergy spread to other parts of your body.
• If you suddenly feel unwell: you sweat, start to feel nauseous (vomit), have difficulty breathing, palpitations, or feel dizzy.
• If you notice any of these symptoms, consult your doctor immediately.

Changes in the skin at the injection site: If insulin is injected 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 not known). 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. These usually disappear after a few weeks of treatment. If the symptoms do not disappear, you should consult your doctor.

Visual problems: When starting insulin treatment, you may have problems with your vision, but this alteration is usually temporary.

Joint inflammation: When starting insulin treatment, fluid retention can cause inflammation of the ankles and other joints. This effect usually disappears quickly. If it does not, consult your doctor.

Diabetic retinopathy (a disease of the eyes related to diabetes that can lead to loss of vision): If you have diabetic retinopathy and your blood sugar level improves very quickly, the retinopathy may worsen. Consult your doctor.

Rare Adverse Effects

May 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 suffer from nerve-related pain. This is called acute painful neuropathy and is usually transient.

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 Spanish Pharmacovigilance System for Human Use Medicines: 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 (hyperglycemia)

High blood sugar levels may appear if:

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

Warning symptoms of high blood sugar:

The warning symptoms appear gradually. These include: increased need to urinate, thirst, loss of appetite, feeling of dizziness (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 may 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 could lead to a diabetic coma and death.

5. Storage of NovoMix 50

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

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

Always keep the cap on the FlexPen when not in use, to protect it from light. NovoMix 50 should be protected from heat and excessive light.

Before opening: NovoMix 50 FlexPen that is not in use should be stored in a refrigerator at 2°C to 8°C, away from the cooling element. Do not freeze.

Before using NovoMix 50 FlexPen, take it out of the refrigerator. It is recommended to resuspend the insulin as instructed each time you use a new pen. See instructions for use.

During use or when carried as a spare: NovoMix 50 FlexPen that is in use or carried as a spare should not be stored in the refrigerator. It can be carried and stored at room temperature (below 30°C) for 4 weeks.

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. Container Contents and Additional Information

Composition of NovoMix 50

• The active substance is insulin aspart. NovoMix 50 is a mixture composed of 50% soluble insulin aspart and 50% crystallized insulin aspart with protamine. 1 ml contains 100 units of insulin aspart. Each pre-filled pen contains 300 units of insulin aspart in 3 ml of injectable suspension.
• The other components are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide, and water for injectable preparations.

Appearance of NovoMix 50 and Container Contents

NovoMix 50 is presented as an injection suspension in a pre-filled pen. The cartridge contains a glass ball to facilitate resuspension. After resuspension, the liquid must have a uniformly white, cloudy, and aqueous appearance. Do not use the pen if the resuspended insulin does not appear uniformly white, cloudy, and aqueous.

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

The suspension is cloudy, white, and aqueous.

Marketing Authorization Holder and Manufacturer

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

On the back, you will find detailed instructions on how to use your FlexPen.

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu.

Instructions for Use of NovoMix 50 Injectable Suspension in FlexPen.

Read the Following Instructions Carefully Before Using Your FlexPen.If you do not follow the instructions carefully, you may administer too little or too much insulin, which could result in a blood sugar level that is too high or too low.

FlexPen is a pre-filled insulin dosing pen.

• Doses of 1 to 60 units can be selected, in increments of 1 unit.
• FlexPen is designed to be used with NovoFine or NovoTwist disposable needles of up to 8 mm in length.
• Always carry a spare insulin delivery device in case your FlexPen is lost or damaged.

Pen Care

• You must handle your FlexPen with care. If it is dropped, damaged, or impacted, there is a risk of insulin loss. This could cause inaccurate dosing, resulting in a blood sugar level that is too high or too low.

• You can clean the outside of your FlexPen with a cotton swab dipped in alcohol. Do not submerge, wash, or lubricate it, as the pen may be damaged.

• Do not refillyour FlexPen.

Resuspension of Insulin

A

Check the Name and Color of the Labelon your pen 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.

Each Time You Use a New Pen

Allow the insulin to reach room temperature before using it. This makes it easier to resuspend.

Remove the pen cap.

B

Before Putting on the First Injection with a New FlexPen, You Must Resuspend the Insulin:

Rotate the pen between your palms 10 times, making sure the pen is kept in a horizontalposition (parallel to the ground).

C

Move the pen up and down 10 times between the two positions, as shown, so that the glass ballmoves from one end of the cartridge to the other.

Repeat both movements until the liquid appears uniformly white, cloudy, and aqueous.

For Each Subsequent Injection

Move the pen up and down between the two positions at least 10 times until the liquid appears uniformly white, cloudy, and aqueous. If this movement alone is not enough to make the liquid uniformly white, cloudy, and aqueous, repeat the procedure described above (see Figures B and C) until the liquid appears with this appearance.

• Always make sure you have resuspended the insulin before each injection. This reduces the risk of having a blood sugar level that is too high or too low. After you have resuspended the insulin, complete the following injection steps without delay.

Always check that there are at least 12unitsof insulin left in the cartridge to perform the resuspension. If there are less than 12 units left, use a new FlexPen. The remaining insulin scale shows if there are 12 units left. See the large diagram at the beginning of these instructions.

Do not use the pen if the resuspendedinsulin does not appear uniformly white, cloudy, and aqueous.

Needle Attachment

D

Take a new needle and pull off the paper tab.

Screw the needle straight and firmly onto your FlexPen.

E

Remove the large outer needle cap and set it aside for later.

F

Remove the inner needle cap and discard it.

Never try to put the inner needle cap back on. You could stick yourself with 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.

Insulin Flow Check

Before Each Injection, Small Amounts of Air May Form in the Cartridge During Normal Use. To Avoid Injecting Air and Ensure Accurate Dosing:

G

Turn the dose selector until 2 units are selected.

H

Hold your FlexPen with the needle pointing upwards and gently tap the cartridge with your finger a few times to make any air bubbles rise to the top of the cartridge.

I

With the needle still pointing upwards, press the push button all the way in. The dose selector returns to 0.

A drop of insulin should appear at the needle tip. If not, change the needle and repeat the procedure up to a maximum of 6 times.

If a drop of insulin still does not appear, the pen is defective and you must use a new one.

Always make sure a drop appears at the needle tip before injecting. This ensures that the insulin flows. If a drop does not appear, you will not inject insulin, even if the dose selector moves. This may indicate that the needle is blocked or damaged.

Always check the flow before injecting. If you do not check the flow, you may receive too little or no insulin. This could result in a blood sugar level that is too high.

Dose Selection

Check that the Dose Selector is Set to 0.

J

Turn the dose selector to select the number of units you need to inject.

The dose can becorrectedforwards and backwards by turning the dose selector in either direction until the correct dose is aligned with the dose marker. When turning the dose selector, be careful not to press the push button, as insulin may be released.

You cannot select a dose greater than the number of units left in the cartridge.

Before injecting the insulin, always use the dose selector and the dose marker to see how many units you have selected.

Do not count the pen clicks. If you select an incorrect 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.

Injection

Insert the Needle Under the Skin. Use the Injection Technique Indicated by Your Doctor or Nurse.

K

Inject the dose by pressing the push button all the way in, so that the 0 is aligned with the dose marker. Be careful to press the push button only when injecting.

Turning the dose selector will not inject insulin.

L

• Keep the Push Button Fully Pressedand keep the needle under the skin for at least 6seconds. This ensures that the full dose is injected.

• Remove the needle from the skin and, once you have done so, stop pressing 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 a blood sugar level that is too high.

M

Cover the needle with the large outer cap without touching it. When the needle is covered, carefully press the large outer cap all the way on and then unscrew the needle.

Dispose of it carefully and put the pen cap back on the FlexPen.

Always remove the needle after each injection and store your FlexPen without the needle attached. This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

Other Important Information

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

Dispose of your used FlexPen carefully without leaving the needle attached.

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

Never share the pen with other people. Your medication could be harmful to their health.

Always keep the pen and needles out of sight and reach of other people, especially children.