NovoMix 50 FlexPen100 U/ml suspension for injection inpre-filled pen

NovoMix 50 is a modern insulin (insulin analogue) with both a rapid-acting and an intermediate-acting effect, in the ratio 50/50. Modern insulins are improved versions of human insulin.

NovoMix 50 is used to treat diabetes mellitus. Diabetes mellitus is a disease where your body does not produce enough insulin to control the level of your blood sugar.

NovoMix 50 will start to lower your blood sugar 10-20 minutes after you take it, a maximum effect occurs between 1 and 4 hours and the effect lasts for up to 14-24 hours. It may be used in combination with certain oral antidiabetic medicines.

Do not use NovoMix 50

If you are allergic hypersensitive to insulin aspart, or any of the other ingredients of NovoMix 50 see 6 Further information If you suspect hypoglycaemia low blood sugar is starting see 3 How to use NovoMix 50 In insulin infusion pumps If FlexPen is dropped, damaged or crushed If it has not been stored correctly or if it has been frozen see 5 How to store NovoMix 50 If the resuspended insulin does not appear uniformly white and cloudy If clumps of material are present or if solid white particles stick to the bottom or the wall of the cartridge giving a frosted appearance.

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 prevent contamination Needles and NovoMix 50 FlexPen must not be shared.

Take special care with NovoMix 50

If you have trouble with your kidneys or liver, or with your adrenal, pituitary or thyroid glands If you are exercising more than usual or if you want to change your usual diet, as this may affect your blood sugar level If you are ill carry on taking your insulin and consult your doctor If you are going abroad travelling over time zones may affect your insulin needs and the timing of your injections. Consult your doctor if you are planning such travelling.

Using other medicines

Some medicines affect the way glucose works in your body and this may influence your insulin dose. Listed below are the most common medicines, which may affect your insulin treatment. Tell your doctor, nurse or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. In particular, you should tell your doctor if you are using any medicine as mentioned below that affect your blood sugar level.

If you take any of the below medicines, your blood sugar level may fall (hypoglycaemia):

• Other medicines for the treatment of diabetes
• Monoamine oxidase inhibitors (MAOI) (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).

If you take any of the below medicines, your blood sugar level may rise (hyperglycaemia):

• 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 hormones (used to treat thyroid gland disorders)
• Sympathomimetics (such as epinephrine [adrenaline], or salbutamol, terbutaline used to treat asthma)
• Growth hormone (medicine for stimulation of skeletal and somatic growth and pronounced influence on the body?s metabolic processes)
• Danazol (medicine acting on ovulation).

Octreotide and lanreotide (used for treatment of acromegaly, a rare hormonal disorder that usually occurs in middle-aged adults, caused by the pituitary gland producing excess growth hormone) may both increase or decrease your sugar level.

Beta-blockers (used to treat high blood pressure) may weaken or suppress entirely the first warning symptoms which help you to recognise a hypoglycaemia.

Pioglitazone (oral antidiabetic medicine used for the treatment of type 2 diabetes mellitus) Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor as soon as possible if you experience signs of heart failure such as unusual shortness of breath or rapid increase in weight or localised swelling (oedema).

Taking NovoMix 50 with food and drink

If you are drinking alcohol your need for insulin may change as your blood sugar level may either rise or fall. Careful monitoring is recommended.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

If you are pregnant, planning a pregnancy or breast-feeding please contact your doctor for advice. There is limited clinical experience with insulin aspart in pregnancy. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes, particularly prevention of hypoglycaemia, is important, for the health of your baby.

Driving and using machines

If your blood sugar is low or high your concentration and ability to react might be affected and therefore also your ability to drive or operate a machine. Bear in mind that you could endanger yourself or others. Please ask your doctor whether you can drive a car:
- If you have frequent hypoglycaemias
- If you find it hard to recognise hypoglycaemia.

Important information about some of the ingredients of NovoMix 50

NovoMix 50 contains less than 1 mmol sodium (23 mg) pr dose, i.e. NovoMix 50 is essentially ?sodium-free?.

Dose

Talk about your insulin dose with your doctor and nurse. Make sure you get the colour-coded NovoMix 50 FlexPen that your doctor and nurse have told you to use and follow their advice carefully.
When NovoMix 50 is used in combination with metformin the dose should be adjusted. If your doctor has switched youfrom one type or brand of insulin to another, your dose may have to be adjusted by your doctor. Do not change your insulin unless your doctor tells you to. Eat a meal or snack containing carbohydrates within 10 minutes of the injection to avoid hypoglycaemia. NovoMix 50 is generally given immediately before the meal. When necessary, NovoMix 50 can be given soon after the meal.

Use in children

No clinical studies with NovoMix 50 have been carried out in children and adolescents under the age of 18 years. Therefore only use NovoMix 50 in children and adolescents below this age, if your doctor has specifically told you to.

Use in special populations

As with all insulin medicines, in elderly patients and patients with renal or hepatic impairment, glucose monitoring should be intensified and insulin aspart dose adjusted on an individual basis.

Method of administration

NovoMix 50 is for injection under the skin (subcutaneously). Never inject your insulin directly into a vein (intravenously) or muscle (intramuscularly).
Always vary the sites you inject within the same region, to avoid lumps (see 4 Possible side effects). The best places to give yourself an injection are: the front of your waist (abdomen); your buttocks; the front of your thighs or upper arms. The insulin will work more quickly if you inject around the waist. You should always measure your blood glucose regularly.

If you take more NovoMix 50 than you should

If you take too much insulin your blood sugar gets too low (this is called hypoglycaemia or hypo). This may also happen:

• If you eat too little or miss a meal
• If you exercise more than usual.

The warning signs of a hypo may come on suddenly and can include: cold sweat; cool pale skin; headache; rapid heart beat; feeling sick; feeling very hungry; temporary changes in vision; drowsiness; unusual tiredness and weakness; nervousness or tremor; feeling anxious; feeling confused; difficulty in concentrating.

If you feel a hypo coming on: take a high sugar snack and then measure your blood sugar. If your blood sugar is too low: eat glucose tablets or another high sugar snack (sweets, biscuits, fruit juice), then rest.
Always carry glucose tablets, sweets, biscuits or fruit juice with you, just in case.

When symptoms of hypoglycaemia have disappeared or when blood glucose level is stabilised continue insulin treatment.
Tell relevant people you have diabetes and what may be the consequences, including the risk of passing out due to a hypo.
Tell relevant people that if you pass out (become unconscious), they must turn you on your side and get medical help straight away. They must not give you any food or drink. It could choke you.

You may recover more quickly from unconsciousness with an injection of the hormone glucagon by someone who knows how to use it. If you are given glucagon you will need glucose or a sugary snack as soon as you are conscious. If you do not respond to glucagon treatment, you will have to be treated in a hospital. Contact your doctor or an emergency ward after an injection of glucagon: you need to find the reason for your hypo to avoid getting more.
- If prolonged severe hypoglycaemia is not treated, it can cause brain damage (temporary or permanent) and even death
- If you have a hypo that makes you pass out, or a lot of hypos, talk to your doctor. The amount or timing of insulin, food or exercise may need to be adjusted.

If you forget to take NovoMix 50

If you forget to take your insulin your blood sugar may get too high (this is called hyperglycaemia). This may also happen:

• If you repeatedly take less insulin than you need
• If you get an infection or a fever
• If you eat more than usual
• If you exercise less than usual.

The warning signs appear gradually. They include: increased urination; feeling thirsty; losing your appetite; feeling sick (nausea or vomiting); feeling drowsy or tired; flushed, dry skin; dry mouth and a fruity (acetone) smell of the breath.
If you get any of these signs: test your blood sugar level, test your urine for ketones if you can, then seek medical advice immediately.
These may be signs of a very serious condition called diabetic ketoacidosis. If you do not treat it, this could lead to diabetic coma and eventually death.

If you stop taking NovoMix 50

This could lead to severe hyperglycaemia (very high blood sugar) and ketoacidosis (build-up of acid in the blood because the body is breaking down fat instead of sugar). Do not stop taking your insulin without speaking to a doctor, who will tell you what needs to be done.

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

How to handle NovoMix 50 FlexPen

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

Read carefully the NovoMix 50 FlexPen instructions for use included in this package leaflet. You must use the pen as described in the Instructions for Use.

Like all medicines, NovoMix 50 can cause side effects, although not everybody gets them.

Side effects may occur with certain frequencies, which are defined as follows:

• Very common: affects more than 1 user in 10
• Common: affects 1 to 10 users in 100
• Uncommon: affects 1 to 10 users in 1,000
• Rare: affects 1 to 10 users in 10,000
• Very rare: affects less than 1 user in 10,000
• Not known: frequency cannot be estimated from the available data.

Very common side effects

Low blood sugar (hypoglycaemia).

Uncommon side effects

Signs of allergy. Reactions (pain, redness, hives, inflammation, swelling and itching) at the injection site may occur (local allergic reactions). These usually disappear after a few weeks of taking your insulin. If they do not disappear, see your doctor.
Seek medical advice immediately:
- If signs of allergy spread to other parts of your body, or
- If you suddenly feel unwell, and you: start sweating; start being sick (vomiting); have difficulty in breathing; have a rapid heart beat; feel dizzy.

Vision problems. When you first start your insulin treatment, it may disturb your vision, but the disturbance is usually temporary.

Changes at the injection site (lipodystrophy). If you inject yourself too often at the same site, fatty tissue under the skin at this site may shrink (lipoatrophy) or thicken (lipohypertrophy). Changing the site with each injection may help to prevent such skin changes. If you notice your skin pitting or thickening at the injection site, tell your doctor or nurse because these reactions can become more severe, or they may change the absorption of your insulin if you inject in such a site.

Swollen joints. When you start taking insulin, water retention may cause swelling around your ankles and other joints. Normally, this soon disappears.

Diabetic retinopathy (an eye disease related to diabetes which can lead to loss of vision). If you have diabetic retinopathy and your blood glucose level improve very fast, the retinopathy may get worse. Ask your doctor about this.

Rare side effects

Painful neuropathy (pain due to nerve damage). If your blood glucose level improve very fast, you may get nerve related pain, this is called acute painful neuropathy and is usually transient.

Very rare side effects

Serious allergic reaction to NovoMix 50 or one of its ingredients (called a systemic allergic reaction). See also the warning in 2 Before you use NovoMix 50.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor, nurse or pharmacist.

Keep out of the reach and sight of children.
Do not use NovoMix 50 after the expiry date which is stated on the FlexPen label and carton, after ?EXP?. The expiry date refers to the last day of that month.
NovoMix 50 FlexPen that is not being used is to be stored in the refrigerator at 2°C ? 8°C, away from the cooling element. Do not freeze.
NovoMix 50 FlexPen that is being used or carried as a spare is not to be kept in the refrigerator. After removing NovoMix 50 FlexPen from the refrigerator it is recommended to mix the insulin as instructed for the first time use, See Instructions for use. You can carry it with you and keep it at room temperature (below 30°C) for up to 4 weeks.
Always keep the cap on your FlexPen when you are not using it in order to protect it from light. NovoMix 50 must be protected from excessive heat and light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What NovoMix 50 contains

The active substance is insulin aspart. NovoMix 50 is a mixture consisting of 50 soluble insulin aspart and 50 insulin aspart crystallised with protamine. 1 ml contains 100 U of insulin aspart. Each pre-filled pen contains 300 U of insulin aspart in 3 ml suspension for injection The other ingredients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulphate, hydrochloric acid, sodium hydroxide and water for injections.

What NovoMix 50 looks like and contents of the pack

NovoMix 50 comes as a white suspension in a pre-filled pen. The cartridge contains a glass ball to facilitate resuspension. After resuspension the liquid shall appear uniformly white and cloudy.

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

Marketing Authorisation Holder and Manufacturer

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

Now turn over for information on how to use your FlexPen.

This leaflet was last approved in

NOVOMIX 50 suspension for injection in a pre-filled pen. FlexPen. INSTRUCTIONS FOR USE

Please read the following instructions carefully before using your NovoMix 50 FlexPen.

Your FlexPen is a unique dial-a-dose insulin pen. You can select doses from 1 to 60 units in increments of 1 unit. FlexPen is designed to be used with NovoFine or NovoTwist disposable needles up to a length of 8 mm. Be sure you are not using any counterfeit needles. Ask your pharmacist. As a precautionary measure, always carry a spare insulin delivery device in case your FlexPen is lost or damaged.

The colour of the pen in the illustrations differs from your FlexPen.

NovoMix 50 FlexPen Pen cap Cartridge Residual scale Doseselector 12 units PointerPush- button Glass ball Needle example Big outer needle cap NeedleInner needle cap Protective ta

Maintenance

Your FlexPen is designed to work accurately and safely. It must be handled with care. If it is dropped or crushed, there is a risk of damage and leakage of insulin.

You can clean the exterior of your FlexPen by wiping it with a medicinal swab. Do not soak it, wash or lubricate it as it may damage the pen.

Do not refill your FlexPen.

Preparing your NovoMix 50 FlexPen

Check the label to make sure that your FlexPen contains the correct type of insulin. Before your first injection with a new FlexPen you must resuspend the insulin:

A

Let the insulin reach room temperature before you use it.
This makes it easier to resuspend.

Pull off the pen cap.

A

B

Roll the pen between your palms ten times ? it is important that the pen is kept horizontal.

B

C

Then move the pen up and down ten times between the two positions as shown, so the glass ball moves from one end of the cartridge to the other.

Repeat rolling and moving the pen until the liquid appears uniformly white and cloudy.

For every following injection move the pen up and down between the two positions at least ten times until the liquid appears uniformly white and cloudy. If the moving procedure alone is not enough to give a uniformly white and cloudy liquid, repeat the rolling and moving procedures (see B and C) until the liquid does appear uniformly white and cloudy.

After you have resuspended the insulin, complete all the following steps of injection without delay.

C

• Always check there are at least 12 units of insulin left in the cartridge to allow resuspension. If there are less than 12 units left, use a new FlexPen.

Attaching a needle

D

Remove the protective tab from a new disposable needle.

Screw the needle straight and tightly onto your FlexPen.

D

E

Pull off the big outer needle cap and keep it for later.

E

F

Pull off the inner needle cap and dispose of it.

F

• Always use a new needle for each injection to prevent contamination.
• Be careful not to bend or damage the needle before use.
• To reduce the risk of unexpected needle sticks, never put the inner needle cap back on when you have removed it from the needle.

Checking the insulin flow

Prior to each injection small amounts of air may collect in the cartridge during normal use. To avoid injection of air and ensure proper dosing:

G

Turn the dose selector to select 2 units.

G

2 units-
selected

H

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

H

I

Keeping the needle 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 no more than six times.

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

I

Selecting your dose

Check that the dose selector is set at 0.

J

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

The dose can be corrected either up or down by turning the dose selector in either direction until the correct dose lines up with the pointer. When turning the dose selector be careful not to push the push-button as insulin will come out.

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

J

5 units
selected

24 units
selected

• Do not use the residual scale to measure your dose of insulin.

Making the injection

Insert the needle into your skin. Use the injection technique shown by your doctor or nurse.

K

Inject the dose by pressing the push-button all the way in until 0 lines up with the pointer. Be careful only to push the push-button when injecting.

Turning the dose selector will not inject insulin.

K

L

Keep the push-button fully depressed after the injection until the needle has been withdrawn from the skin.
The needle must remain under the skin for at least six seconds. This will ensure that the full dose has been injected.

L

M

Lead the needle into the big outer needle cap without touching the big outer needle cap. When the needle is covered, carefully push the big outer needle cap completely on and then unscrew the needle.

Dispose of it carefully and put the cap back on.

M

• Always remove the needle after each injection and store your FlexPen without the needle attached. Otherwise, the liquid may leak out which can cause inaccurate dosing.
• Caregivers should be most careful when handling used needles to avoid needle sticks.
• Dispose of the used FlexPen carefully without the needle attached.
• Needles and NovoMix 50 FlexPen must not be shared.