Novomix

Package leaflet: Information for the user

NovoMix 30 Penfill 100 units/ml suspension for injection in a cartridge

30% soluble insulin aspart and 70% protamine-crystallized insulin aspart
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse, or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

1. What NovoMix 30 is and what it is used for
2. What you need to know before using NovoMix 30
3. How to use NovoMix 30
4. Possible side effects
5. How to store NovoMix 30
6. Contents of the pack and other information

1. What NovoMix 30 is and what it is used for

NovoMix 30 is a modern insulin (an insulin analogue) with a rapid-acting and intermediate-acting component in a 30/70 ratio. Modern insulin medicines are improved versions of human insulin.
NovoMix 30 is used to lower high blood sugar levels in adults, adolescents, and children from 10 years of age onwards with diabetes mellitus (diabetes). Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.
NovoMix 30 begins to reduce blood sugar levels 10–20 minutes after administration, reaches its maximum effect between 1 and 4 hours after injection, and its action lasts up to 24 hours.
In the treatment of type 2 diabetes mellitus, NovoMix 30 may be used in combination with oral diabetes tablets and/or injectable antidiabetic medicines.

2. What you should know before using NovoMix 30

Do not use NovoMix 30
► If you are allergic to insulin aspart or to any of the other excipients of this medicine
(see section 6, Contents of the pack and other information).
► If you experience warning signs of hypoglycaemia (low blood sugar levels), see a) Summary of serious and very common adverse effects in section 4.
► In insulin infusion pumps.
► If the cartridge or the device containing the cartridge is leaking, damaged, or cracked.
► If it has not been stored correctly or has been frozen, see section 5, How to store NovoMix 30.
► If the resuspended insulin does not appear uniformly white, cloudy, and watery.
► If after resuspension, clumps or white particles are present, or if there is a frost-like appearance due to particles adhering to the bottom or walls of the cartridge.
Do not use NovoMix 30 if any of these situations occur. Speak to your doctor, nurse, or pharmacist for advice.

Before using NovoMix 30
► Check the label to make sure you are using the correct type of insulin.
► Always inspect the cartridge, including the rubber plunger at the bottom of the cartridge. Do not use if it appears damaged or if the rubber plunger has been pulled above the white band at the bottom of the cartridge, as this may indicate insulin leakage. If you suspect the cartridge has been damaged, return it to your supplier. Refer to the pen user manual for further information.
► Always use a new needle for each injection to prevent contamination.
► Needles and NovoMix 30 Penfill must not be shared with other people.
► NovoMix 30 Penfill is intended only for subcutaneous injection with a reusable pen. Speak to your doctor if you need to administer insulin by another method.

Warnings and precautions
Certain conditions and activities may affect your insulin requirements. Consult your doctor:
► If you have kidney, liver, adrenal gland, pituitary, or thyroid problems.
► If you increase your physical activity or change your usual diet, as this may affect your blood sugar levels.
► If you become ill, continue your insulin therapy and consult your doctor.
► If you plan to travel abroad, as traveling across different time zones may affect your insulin needs and dosing schedule.

Skin changes at the injection site
Rotate your injection sites to help prevent changes in the fatty tissue under the skin, such as thickening of the skin, thinning of the skin, or the development of lumps under the skin. Insulin may not work as effectively if you inject into an area with lumps, thinning, or thickening (see section 3, How to use NovoMix 30). Inform your doctor if you notice any skin changes at the injection site. If you are currently injecting into such an affected area, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Children and adolescents

• NovoMix 30 can be used in adolescents and children aged 10 years and older.
• Limited experience exists with the use of NovoMix 30 in children aged 6 to 9 years.
• No data are available for NovoMix 30 in children under 6 years of age.

Other medicines and NovoMix 30
Inform your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines affect blood sugar levels and may alter your insulin requirements. Listed below are the most important 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 hypertension
• angiotensin-converting enzyme (ACE) inhibitors used to treat certain heart conditions or hypertension
• salicylates used to relieve pain and reduce fever
• anabolic steroids such as testosterone
• sulfonamides 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 fluid retention)
• glucocorticoids (such as 'cortisone' used to treat inflammation)
• thyroid hormones (used to treat thyroid disorders)
• sympathomimetics, such as epinephrine (adrenaline), salbutamol, or terbutaline used to treat asthma
• growth hormone (a medicine used to stimulate skeletal and body growth and that significantly affects the body's metabolic processes)
• danazol (a medicine that affects ovulation).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder usually occurring in middle-aged adults, caused by excessive production of growth hormone by the pituitary gland) may either increase or decrease your blood sugar levels.

Beta-blockers (used to treat hypertension) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar levels.

Pioglitazone (tablets used to treat type 2 diabetes)
Some patients with long-standing type 2 diabetes and with heart problems or a history of stroke who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).

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

Drinking alcohol and using NovoMix 30
► If you consume alcohol, your insulin requirements may change, as your blood sugar levels may rise or fall. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. Clinical experience with insulin aspart during pregnancy is limited. Your insulin requirements may need adjustment during pregnancy and after delivery. It is important to carefully control diabetes, especially to prevent hypoglycaemic episodes, for the health of your baby.
► There are no restrictions on using NovoMix 30 during breastfeeding.
Consult your doctor, nurse, or pharmacist before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
► Consult your doctor about whether it is safe for you to drive or operate machinery:

• If you experience frequent episodes of hypoglycaemia.
• If you have difficulty recognizing the warning signs of hypoglycaemia.

If your blood glucose is high or low, your concentration and reaction ability may be impaired, and consequently your ability to drive or operate machinery may also be affected. Be aware that you could endanger yourself or others.

Important information about some ingredients of NovoMix 30
NovoMix 30 contains less than 1 mmol of sodium (23 mg) per dose, i.e., NovoMix 30 is essentially "sodium-free".

3. How to use NovoMix 30

Dose and when to take insulin
Always use insulin and adjust your dose exactly as instructed by your doctor. If you are unsure, consult your doctor, nurse, or pharmacist.
NovoMix 30 is generally taken immediately before a meal. You should eat a meal or snack within 10 minutes after the injection to avoid low blood sugar levels. When necessary, NovoMix 30 may be administered shortly after a meal. See below for information on How and where to inject.
Do not change your insulin unless your doctor tells you to do so. If your doctor has switched you from one type or brand of insulin to another, your doctor may need to adjust your dose.
When NovoMix 30 is used in combination with oral diabetes tablets and/or injectable antidiabetic medicines, your doctor may need to adjust your dose.

Use in children and adolescents
NovoMix 30 can be used in adolescents and children aged 10 years and older when a premixed insulin is preferred. Limited clinical data are available for children between 6 and 9 years of age. No data are available for NovoMix 30 in children under 6 years of age.

Use in specific patient groups
If you have kidney or liver impairment, or if you are over 65 years old, you should monitor your blood sugar regularly and discuss insulin dose adjustments with your doctor.

How and where to inject
NovoMix 30 is administered under the skin (subcutaneous use). Never inject insulin directly into a vein (intravenous use) or into muscle (intramuscular use). NovoMix 30 Penfill is intended only for subcutaneous injections using a reusable insulin pen. Talk to your doctor if you need to administer insulin by another method.
Each time you inject, always rotate the injection site within the particular area of skin you usually use. This may reduce the risk of developing lumps or skin depressions (see section 4, Possible side effects). The best sites for injection are: the abdomen (abdominal area), buttocks, front of the thigh, or upper arm. Insulin will act more quickly if injected into the abdomen. It is recommended to check your blood sugar levels regularly.
► Do not refill the cartridge.
► NovoMix 30 Penfill in cartridge is designed to be used with Novo Nordisk insulin delivery devices and NovoFine or NovoTwist needles.
► If, in addition to NovoMix 30 Penfill, you have been prescribed another insulin in Penfill cartridge, you must use two separate insulin delivery devices, one for each type of insulin.
► Always carry a spare Penfill cartridge with you in case the one in use is lost or damaged.

Resuspension of NovoMix 30
Always check that there is sufficient insulin (at least 12 units) available in the cartridge after resuspending. If there is not enough insulin remaining, use a new cartridge. See the pen user manual for further instructions.
► Each time you use a new NovoMix 30 Penfill (before inserting the cartridge into the delivery device)

• Allow the insulin to reach room temperature before use. This makes resuspension easier.
• Roll the cartridge between your palms 10 times – it is important that the cartridge is held horizontally (parallel to the ground) (see figure A).
• Move the cartridge up and down between positions a and b (see figure B) 10 times so that the glass ball can move freely between the two ends of the cartridge.
• Repeat this procedure (see figures A and B) until the liquid appears uniformly white, milky, and cloudy. Do not use the cartridge if the resuspended insulin does not appear uniformly white, milky, and cloudy.
• Proceed quickly with the next steps for injection.

► For each subsequent injection

• Move the delivery device with the cartridge inserted up and down between positions a and b (see figure B), at least 10 times, until the liquid appears uniformly white, milky, and cloudy. Do not use the cartridge if the resuspended insulin does not appear uniformly white, milky, and cloudy.
• Complete the remaining injection steps promptly.

How to inject NovoMix 30
► Inject insulin subcutaneously. Use the technique shown by your doctor or nurse and as described in the pen user manual.
► Keep the needle under the skin for at least 6 seconds. Keep the plunger fully pressed until the needle is removed from the skin. This ensures proper delivery and minimizes possible backflow of blood into the needle or insulin leakage.
► After each injection, remove and dispose of the needle, and store NovoMix 30 without the needle attached. Otherwise, liquid may leak out, leading to inaccurate dosing.

If you take more insulin than you should
If you take too much insulin, your blood sugar level will drop too low (hypoglycaemia). See a) Summary of serious and very common side effects in section 4.

If you forget to take insulin
If you forget to take your insulin, your blood sugar level will become too high (hyperglycaemia). See c) Effects of diabetes in section 4.

If you stop using insulin
Do not stop using insulin without first talking to your doctor, who will advise you on what to do. Stopping insulin treatment may 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 about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible side effects

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

a) Summary of serious and very common side effects

Low blood sugar (hypoglycaemia) is a very common side effect. It may occur in more than 1 in 10 people.

You may experience low blood sugar if:

• You inject too much insulin.
• You eat too little or skip meals.
• You exercise more than usual.
• You consume alcohol (see Drinking alcohol and using NovoMix 30 in section 2).

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; intense hunger; temporary vision disturbances; drowsiness; unusual tiredness and weakness; nervousness or trembling; anxiety; confusion; difficulty concentrating.

Severe hypoglycaemia can lead to loss of consciousness. If prolonged severe hypoglycaemia is not treated, it may cause brain damage (temporary or permanent) and may even result in death. Recovery may be faster with an injection of the hormone glucagon given 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 regain consciousness. If you do not respond to glucagon treatment, you must be taken to hospital.

What to do if your blood sugar is low:

► If your blood sugar is too low, eat sugar cubes or another sugary snack (candies, biscuits, fruit juice). Test your blood sugar if possible, then rest. Always carry sugar cubes, candies, biscuits, or fruit juice with you to use if needed.

► When symptoms of hypoglycaemia have disappeared or when blood glucose has stabilized, continue your insulin treatment.

► If you experience low blood sugar, lose consciousness, require a glucagon injection, or have frequent episodes of low blood sugar, talk to your doctor. Your insulin dose, timing of administration, food intake, and physical activity may need adjustment.

Inform people close to you that you have diabetes and what consequences may occur, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they should turn you onto your side and seek immediate medical help. It is important that food or drink is not given to you, as this could cause choking.

Severe allergic reaction to NovoMix 30 or one of its excipients (called a systemic allergic reaction) is a very rare side effect that may be potentially life-threatening. It may occur in fewer than 1 in 10,000 people.

Contact your doctor immediately:

• If signs of allergy spread to other parts of the body.
• If you suddenly feel unwell and: start sweating; feel sick (vomiting); have difficulty breathing; have a rapid heartbeat; feel dizzy.

► If you notice any of these signs, contact your doctor immediately.

Skin changes at the injection site: If you inject insulin repeatedly into the same spot, fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy) (may affect fewer than 1 in 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency not known). Insulin may not work as well as it should if injected into an area with lumps, thinning, or thickening. Change your injection site with each injection to prevent these skin changes.

b) List of other side effects

Uncommon side effects
May affect fewer than 1 in 100 people.

Signs of allergy: localized allergic reactions (pain, redness, hives, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of starting insulin treatment. If symptoms do not disappear, consult your doctor.

Vision disturbances: Vision problems may occur at the beginning of insulin treatment, but these are usually temporary.

Swollen joints: At the start of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This normally resolves quickly. If not, contact your doctor.

Diabetic retinopathy (an eye condition related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood sugar improves very rapidly, the retinopathy may worsen. Consult your doctor.

Rare side effects
May affect fewer than 1 in 1,000 people.

Painful neuropathy (pain due to nerve damage): If your blood sugar improves very rapidly, you may experience pain originating from nerve fibres. This is called acute painful neuropathy, which is usually transient.

Reporting of side effects

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

c) Effects of diabetes

High blood sugar (hyperglycaemia)

You may have high blood sugar if:

• You have not injected enough insulin.
• You have forgotten to take insulin or stopped taking it.
• You repeatedly take less insulin than required.
• You have an infection and/or fever.
• You eat more than usual.
• You exercise less than usual.

Warning signs of high blood sugar:
Symptoms develop gradually and include: increased urination; thirst; loss of appetite; feeling unwell (nausea or vomiting); drowsiness or tiredness; dry, flushed skin; dry mouth and fruity breath (acetone).

What to do if your blood sugar is high:

► If you experience any of these symptoms: check your blood glucose, test your urine for ketones if possible, and contact a doctor immediately.

► These may be symptoms of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store NovoMix 30

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label and on the
packaging after 'EXP'. The expiry date refers to the last day of the month.
When not in use, always store the cartridge in its outer packaging to protect it from
light. NovoMix 30 must be protected from excessive heat and direct sunlight.
Before opening: Unused NovoMix 30 Penfill must be stored in the refrigerator at 2°C –
8°C, away from refrigerating elements. Do not freeze.
Before using NovoMix 30 Penfill, remove it from the refrigerator. It is recommended to resuspend
the insulin according to the instructions each time a new NovoMix 30 Penfill is used. See
Resuspension of NovoMix 30 in section 3.
During use or when carried as a spare: NovoMix 30 Penfill in use or being carried
as a spare must not be stored in the refrigerator. It may be carried at room temperature
(below 30°C) for up to 4 weeks.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer in use. This will help protect the environment.

6. Package contents and other information

What NovoMix 30 contains

• The active substance is insulin aspart. NovoMix 30 is a mixture consisting of 30% soluble insulin aspart and 70% insulin aspart crystallized with protamine. 1 ml contains 100 units of insulin aspart. Each cartridge contains 300 units of insulin aspart in 3 ml of injectable suspension.
• The excipients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide and water for injections.

Description of the appearance of NovoMix 30 and package contents
NovoMix 30 is a white, opaque, aqueous suspension for injection. The cartridge contains a glass bead to facilitate resuspension. After resuspension, the liquid should appear uniformly white, cloudy and aqueous. Do not use the insulin if it does not appear uniformly white, cloudy and aqueous after resuspension.
Pack sizes of 5 or 10 cartridges of 3 ml. Not all pack sizes may be marketed.
The suspension is cloudy, white and aqueous.
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
This leaflet was last revised on
Other sources of information
More detailed information on this medicine is available on the European Medicines Agency (EMA) website: http://www.ema.europa.eu/.

Package leaflet: Information for the user

NovoMix 30 FlexPen 100 units/ml injection suspension in a pre-filled pen

30% soluble insulin aspart and 70% insulin aspart crystals with protamine
Please read this leaflet carefully before using this medicine, as it contains
important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, nurse or pharmacist. See section 4.

Contents of this leaflet:

1. What NovoMix 30 is and what it is used for
2. What you need to know before using NovoMix 30
3. How to use NovoMix 30
4. Possible side effects
5. How to store NovoMix 30
6. Contents of the pack and other information

1. What NovoMix 30 is and what it is used for

NovoMix 30 is a modern insulin (an insulin analogue) with a rapid-acting and intermediate-acting component in a 30/70 ratio. Modern insulin medicinal products are improved versions of human insulin.
NovoMix 30 is used to lower high blood sugar levels in adults, adolescents, and children from 10 years of age onwards with diabetes mellitus (diabetes). Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.
NovoMix 30 begins to lower blood sugar levels 10–20 minutes after administration, reaches its maximum effect between 1 and 4 hours after injection, and its effect lasts up to 24 hours.
In the treatment of type 2 diabetes mellitus, NovoMix 30 may be used in combination with oral antidiabetic tablets and/or injectable antidiabetic medicinal products.

2. What you need to know before using NovoMix 30

Do not use NovoMix 30
► If you are allergic to insulin aspart or to any of the other excipients of this medicine
(see section 6, Contents of the pack and other information).
► If you experience warning signs of hypoglycaemia (low blood sugar levels),
see a) Summary of serious and very common adverse effects in section 4.
► In microinfusion pumps.
► If the FlexPen is leaking, damaged or cracked.
► If it has not been stored correctly or has been frozen, see section 5, How to store NovoMix 30.
► If the resuspended insulin does not appear uniformly white, cloudy and watery.
► If after resuspension, clumps or white particles are present, or if there is a frost-like appearance due to particles adhering to the bottom or walls of the cartridge.
Do not use NovoMix 30 if any of these situations occur. Speak to your doctor, nurse or pharmacist for advice.

Before using NovoMix 30
► Check the label to make sure you have the correct type of insulin.
► Always use a new needle for each injection to prevent contamination.
► Needles and the NovoMix 30 FlexPen must not be shared with others.
► The NovoMix 30 FlexPen is intended only for subcutaneous injections. Speak to your doctor if you need to administer insulin by another method.

Warnings and precautions
Certain conditions and activities may affect your insulin requirement. Consult your doctor:
► If you have kidney, liver, adrenal gland, pituitary or thyroid disorders.
► If you have increased physical activity or changes in your usual diet, as this may alter your blood sugar levels.
► If you become ill, continue your insulin therapy and consult your doctor.
► If you plan to travel abroad; travelling across different time zones may affect your insulin requirements and timing.

Skin changes at the injection site
Rotate your injection sites to help prevent changes in the fatty tissue under the skin, such as skin thickening, skin thinning or the appearance of lumps under the skin.
Insulin may not work effectively if you inject into an area with lumps, thinning or thickening of the skin (see section 3, How to use NovoMix 30). Inform your doctor if you notice any skin changes at the injection site. If you currently inject into such affected areas, speak to your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or that of other antidiabetic medicines.

Children and adolescents

• NovoMix 30 can be used in adolescents and children aged 10 years and above.
• Limited experience exists with the use of NovoMix 30 in children aged 6–9 years.
• No data are available for NovoMix 30 in children below 6 years of age.

Other medicines and NovoMix 30
Inform your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines. Some medicines affect blood sugar levels and may alter your insulin requirements. Listed below are the most important 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 hypertension
• angiotensin-converting enzyme (ACE) inhibitors used to treat certain heart conditions or hypertension
• salicylates used to relieve pain and reduce fever
• anabolic steroids such as testosterone
• sulfonamides 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 fluid retention)
• glucocorticoids (such as 'cortisone' used to treat inflammation)
• thyroid hormones (used to treat thyroid disorders)
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline used to treat asthma
• growth hormone (a medicine used to stimulate skeletal and body growth and which significantly affects the body's metabolic processes)
• danazol (a medicine that affects ovulation)

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder usually occurring in middle-aged adults caused by excessive production of growth hormone by the pituitary gland) may either increase or decrease your blood sugar levels.
Beta-blockers (used to treat hypertension) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar levels.
Pioglitazone (tablets used to treat type 2 diabetes)
Some patients with long-standing type 2 diabetes and with heart disease or a history of stroke who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain or localized swelling (oedema).
If you are taking any of the medicines listed above, inform your doctor, nurse or pharmacist.

Drinking alcohol and using NovoMix 30
► If you drink alcohol, your insulin requirement may change, as your blood sugar level may increase or decrease. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, think you may be pregnant or are planning to become pregnant, consult your doctor before taking this medicine. Clinical experience with insulin aspart during pregnancy is limited. Your insulin requirement may need adjustment during pregnancy and after delivery. It is important to carefully control diabetes, particularly to prevent episodes of hypoglycaemia, for the health of both you and your baby.
► There are no restrictions on using NovoMix 30 during breastfeeding.
Consult your doctor, nurse or pharmacist before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
► Consult your doctor about whether it is safe for you to drive or operate machinery:

• If you have frequent episodes of hypoglycaemia.
• If you have difficulty recognizing the warning signs of hypoglycaemia.

If your blood glucose is high or low, your ability to concentrate and react may be impaired, thereby affecting your ability to drive or use machines. Be aware that you could put yourself and others at risk.

Important information about some ingredients of NovoMix 30
NovoMix 30 contains less than 1 mmol of sodium (23 mg) per dose, i.e. NovoMix 30 is essentially "sodium-free".

3. How to use NovoMix 30

Dosage and timing of insulin administration
Always use insulin and adjust the dose exactly as directed by your doctor. If you are unsure, consult your doctor, nurse, or pharmacist.
NovoMix 30 is generally taken immediately before a meal. You should eat a meal or snack within 10 minutes after injection to avoid low blood sugar levels. When necessary, NovoMix 30 may be administered right after a meal. See below for information on How and where to inject.
Do not change your insulin unless your doctor tells you to do so. If your doctor has switched you from one type or brand of insulin to another, your doctor may need to adjust your dose.
When NovoMix 30 is used in combination with oral diabetes medications and/or injectable antidiabetic medicines, your doctor may need to adjust your dose.

Use in children and adolescents
NovoMix 30 can be used in adolescents and children aged 10 years and older when a premixed insulin is preferred. Clinical data are limited for children between 6 and 9 years of age. No data are available for NovoMix 30 in children under 6 years of age.

Use in specific patient groups
If you have kidney or liver impairment, or if you are over 65 years old, you should monitor your blood sugar levels regularly and discuss insulin dose adjustments with your doctor.

How and where to inject
NovoMix 30 is administered under the skin (subcutaneous use). Never inject insulin directly into a vein (intravenous use) or into muscle (intramuscular use). The NovoMix 30 FlexPen is intended for subcutaneous injections only. Talk to your doctor if you need to administer insulin by another route.
With each injection, always rotate the injection site within the particular area of skin you usually use. This can help reduce the risk of developing lumps or skin depressions (see section 4 Possible side effects). The best sites for injection are the abdomen (abdominal area), buttocks, front of the thigh, or upper arm. Insulin will act more quickly if injected into the abdomen. Regular blood sugar monitoring is recommended.

How to use NovoMix 30 FlexPen
NovoMix 30 FlexPen is a disposable, pre-filled pen coded by color, containing a mixture of fast-acting and intermediate-acting insulin aspart in a 30/70 ratio.
Carefully read the instructions for use provided in this patient information leaflet. You must use the pen exactly as described in the Instructions for Use.
Always make sure you are using the correct pen before injecting your insulin.

If you take more insulin than you should
If you take too much insulin, your blood sugar level may drop too low (hypoglycemia). See a) Summary of serious and very common side effects in section 4.

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

If you stop insulin treatment
Do not stop insulin treatment without first talking to your doctor, who will advise you on what to do. Stopping treatment may lead to very high blood sugar levels (severe hyperglycemia) and ketoacidosis. See c) Effects of diabetes in section 4.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.

a) Summary of serious and very common side effects

Low blood sugar (hypoglycaemia) is a very common side effect. It may occur in more than 1 in 10 people.

You may experience low blood sugar if:

• You inject too much insulin.
• You eat too little or skip meals.
• You are more physically active than usual.
• You drink alcohol (see Drinking alcohol and using NovoMix 30 in section 2).

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; intense hunger; temporary visual disturbances; drowsiness; unusual tiredness and weakness; nervousness or trembling; anxiety; confusion; difficulty concentrating.

Severe hypoglycaemia can lead to loss of consciousness. If severe hypoglycaemia is left untreated, it may cause brain damage (transient or permanent) and may even result in death. You may regain consciousness more quickly with an injection of the hormone glucagon administered by someone trained in its use. If glucagon is given, you will need glucose or a sugary snack as soon as you regain consciousness. If you do not respond to glucagon treatment, you must be taken to hospital immediately.

What to do if your blood sugar is low:

► If your blood sugar is too low, eat sugar lumps or another snack high in sugar (candy, biscuits, fruit juice). Measure your blood sugar if possible, then rest. Always carry sugar lumps, candy, biscuits or fruit juice with you to use if needed.

► When hypoglycaemia symptoms have disappeared or when blood sugar has stabilized, continue your insulin treatment.

► If you experience low blood sugar, lose consciousness, require a glucagon injection, or have frequent episodes of low blood sugar, speak to your doctor. You may need adjustments to your insulin dose, timing of insulin administration, food intake, or physical activity.

Inform people close to you that you are diabetic and explain the possible consequences, including the risk of fainting due to hypoglycaemia. Make them aware that if you faint, they should turn you onto your side and seek immediate medical help. It is important not to give you food or drink, as this could cause choking.

Severe allergic reaction to NovoMix 30 or one of its excipients (called systemic allergic reaction) is a very rare side effect that may be potentially life-threatening. It may occur in fewer than 1 in 10,000 people.

Contact your doctor immediately:

• If signs of allergy spread to other parts of the body.
• If you suddenly feel unwell and: begin to sweat; feel sick (vomiting); have difficulty breathing; your heartbeat becomes rapid; or feel dizzy. ► If you notice any of these signs, contact your doctor immediately.

Skin changes at the injection site: If you inject insulin repeatedly in the same spot, fatty tissue may thin (lipoatrophy) or thicken (lipohypertrophy) (affecting fewer than 1 in 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency not known). Insulin may not work as effectively if injected into an area with lumps, thinning, or thickening. Rotate your injection site with each injection to prevent these skin changes.

b) List of other side effects

Uncommon side effects

May affect fewer than 1 in 100 people.

Signs of allergy: localized allergic reactions (pain, redness, hives, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of starting insulin treatment. If symptoms do not resolve, consult your doctor.

Visual disturbances: visual disturbances may occur at the beginning of insulin therapy, but these are usually temporary.

Swollen joints: at the start of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This usually resolves quickly. If not, contact your doctor.

Diabetic retinopathy (an eye condition related to diabetes that may lead to vision loss): if you have diabetic retinopathy and your blood sugar improves very rapidly, the retinopathy may worsen. Speak to your doctor.

Rare side effects

May affect fewer than 1 in 1,000 people.

Painful neuropathy (pain due to nerve damage): if your blood sugar improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy, which is usually transient.

Reporting of side effects

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

c) Effects of diabetes

High blood sugar (hyperglycaemia)

You may experience high blood sugar if:

• You have not injected enough insulin.
• You have forgotten to take insulin or have stopped taking it.
• You repeatedly take less insulin than required.
• You have an infection and/or fever.
• You eat more than usual.
• You are less physically active than usual.

Warning signs of high blood sugar:

Warning signs appear gradually and include: increased urination; thirst; loss of appetite; feeling unwell (nausea or vomiting); drowsiness or tiredness; dry, flushed skin; dry mouth and fruity breath (acetone).

What to do if your blood sugar is high:

► If you experience any of these symptoms: check your blood sugar, if possible, test for the presence of ketones in your urine, and contact a doctor immediately.

► These may be symptoms of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar). If untreated, this may lead to diabetic coma and possibly death.

5. How to store NovoMix 30

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the FlexPen label and on the carton, after 'EXP'. The expiry date refers to the last day of the month.
When not in use, keep the cap on the FlexPen to protect it from light. NovoMix 30 must be protected from excessive heat and direct sunlight.
Before opening: Unused NovoMix 30 FlexPen must be stored in the refrigerator at 2°C – 8°C, away from refrigerating elements. Do not freeze.
Before using NovoMix 30 FlexPen, remove it from the refrigerator. It is recommended to resuspend the insulin according to the instructions each time you use a new pen. See Instructions for Use.
During use or when carried as a spare: NovoMix 30 FlexPen in use or being carried as a spare must not be stored in the refrigerator. It may be kept at room temperature (below 30°C) for up to 4 weeks.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What NovoMix 30 contains

• The active substance is insulin aspart. NovoMix 30 is a mixture consisting of 30% soluble insulin aspart and 70% insulin aspart crystallized 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 excipients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide and water for injections.

Description of the appearance of NovoMix 30 and contents of the pack
NovoMix 30 is a white, cloudy, aqueous injectable suspension in a pre-filled pen. The cartridge
contains a glass ball to aid resuspension. After resuspension, the liquid must appear uniformly
white, cloudy and aqueous. Do not use the insulin if it does not appear uniformly white, cloudy and
aqueous after resuspension.
Pack sizes of 1 (with or without needles), 5 (without needles) and 10 (without needles) pre-filled pens of 3 ml.
Not all pack sizes may be marketed.
The suspension is cloudy, white and aqueous.
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
For instructions on how to use your FlexPen, please turn the page.
This leaflet was last reviewed on
Further information
More detailed information on this medicine is available on the website of the European Medicines Agency (EMA): http://www.ema.europa.eu/.
Instructions for use of NovoMix 30 injectable suspension in FlexPen.
Read carefully the following instructions before using your FlexPen. If you do not follow these
instructions carefully, you may inject too much or too little insulin, which could lead to blood sugar levels that are too high or too low.
The FlexPen is a pre-filled pen for variable-dose insulin administration.
► You can select a dose between 1 and 60 units in 1-unit increments.
► The FlexPen is designed to be used with NovoFine or NovoTwist disposable needles up to 8 mm in length.
► Always carry a spare insulin delivery device in case your FlexPen is lost or damaged.

Caring for your pen
► Handle your FlexPen with care. If it leaks or has been dropped, it may be damaged and insulin may be lost. This could result in incorrect dosing, leading to blood sugar levels that are too high or too low.
► You may clean the outside of your FlexPen with a disinfectant wipe. Do not immerse, wash or lubricate the pen to avoid damaging the mechanism.
► Do not refill your FlexPen.
Resuspending the insulin
A
Check the name and the coloured label on your pen to ensure it contains the correct type of insulin. This is particularly important if you use more than one type of insulin. If you inject 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 use. This will make resuspension easier.
Remove the pen cap.

B
Before administering the first injection with a new FlexPen, you must resuspend the insulin:
Roll the pen between the palms of your hands 10 times – it is important that the pen is held horizontally (parallel to the ground).

C
Move the pen up and down 10 times between the two positions shown, so that the glass ball moves from one end of the cartridge to the other.
Repeat this procedure 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.
► Always ensure that you resuspend the insulin before each injection. This reduces the risk of blood sugar levels becoming too high or too low. After resuspending, proceed quickly through the following steps.

Always check that there are at least 12 units of insulin remaining in the cartridge to allow for proper resuspension. If there are fewer than 12 units, use a new FlexPen. 12 units are marked on the scale. See the large illustration at the beginning of these instructions.
Do not use the pen if the resuspended insulin does not appear uniformly white, cloudy and aqueous.
Attaching a needle
D
Take a new needle and remove the protective seal.
Screw the needle firmly and perpendicularly onto your FlexPen.

E
Remove the outer needle cap and keep it for later use.

F
Remove the inner needle cap and discard it.
Never try to reattach the inner needle cap to the needle. You could injure yourself with the needle.

Always use a new needle for each injection. This reduces the risk of contamination, infection, insulin leakage, needle blockage and incorrect dosing.
Be careful not to bend or damage the needle before use.
Checking insulin flow
During normal use, small amounts of air may accumulate in the cartridge. Before each injection, to avoid injecting air and to ensure the correct insulin dose is delivered:
G
Turn the dose selector to select 2 units.

H
Hold the FlexPen with the needle pointing upwards and gently tap the cartridge several times with your finger so that air bubbles collect at the top of the cartridge.

I
With the needle pointing upwards, press the injection button fully. The dose selector will return to 0.
A drop of insulin should appear at the tip of the needle. If it does not, change the needle and repeat the procedure no more than 6 times.
If a drop of insulin still does not appear, the pen is faulty and you must use a new one.

Always ensure a drop appears at the needle tip before injection. This ensures proper insulin flow. If no drop appears, you will not inject insulin, even if the dose selector moves. This may indicate a blocked or damaged needle.
Always check the flow before each injection. If you do not check the flow, you may inject too little insulin or no insulin at all, which could lead to high blood sugar levels.
Selecting the dose
Ensure the dose selector is at 0.
J
Turn the dose selector to select the number of units to be injected.
The dose can be increased or decreased by turning the selector in either direction until the indicator shows the correct dose. When turning the dose selector, take care not to press the injection button, to avoid insulin leakage.
You cannot select a dose greater than the number of units remaining in the cartridge.

Before injecting insulin, always use the dose selector and indicator to verify the number of units selected.
Do not count the clicks of the pen. If you select and inject the wrong dose, your blood sugar level may become too high or too low. Do not use the scale on the pen, which only approximately indicates how much insulin remains in the pen.
Injection
Insert the needle into the skin. Use the injection technique shown by your doctor or nurse.
K
Administer the insulin dose by fully pressing the injection button until the indicator reaches 0. Be careful to press only the injection button.
Turning the dose selector will not deliver insulin.

L
► Keep the injection button fully pressed and leave the needle under the skin for at least 6 seconds. This ensures complete delivery of the dose.
► Remove the needle from the skin only after releasing pressure on the injection button.
► Always ensure that the dose selector returns to 0 after injection. If the dose selector stops before reaching 0, the full dose has not been delivered, which may result in high blood sugar levels.

M
Place the used needle into the outer needle cap without touching it. Once the needle is covered, carefully press the outer cap fully on and then unscrew the needle.
Dispose of the needle carefully and replace the pen cap on the FlexPen.

Always remove the needle after each injection and store your FlexPen without a needle attached. This reduces the risk of contamination, infection, insulin leakage, needle blockage and incorrect dosing.
Other important information
Anyone caring for you should take great care when handling used needles to reduce the risk of needle-stick injuries and cross-infections.
Dispose of used FlexPens carefully, ensuring the needle has been removed.
Never share your pen or needles with other people. This could lead to cross-infections.
Never share your pen with other people. The medicine may be dangerous to their health.
Always keep the pen and needles out of sight and out of reach of others, especially children.

Package leaflet: Information for the user

NovoMix 50 Penfill 100 units/ml injection suspension in a cartridge

50% soluble insulin aspart and 50% protamine-crystallized insulin aspart
Please read this leaflet carefully before using this medicine as it contains
important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse, or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. It may be harmful to other people even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

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

NovoMix 50 is a modern insulin (insulin analogue) with a rapid-acting and intermediate-acting component in a 50/50 ratio. Modern insulin medicines are improved versions of human insulin.
NovoMix 50 is used to lower high blood sugar levels in patients with diabetes mellitus (diabetes). Diabetes is a condition in which the body does not produce enough insulin to control blood sugar levels. NovoMix 50 may be used in combination with metformin.
NovoMix 50 begins to lower blood sugar levels 10-20 minutes after administration, reaches its maximum effect between 1 and 4 hours after injection, and its effect lasts up to 14-24 hours.

2. What you need to know before using NovoMix 50

Do not use NovoMix 50
► If you are allergic to insulin aspart or to any of the other excipients of this medicine
(see section 6, Contents of the pack and other information).
► If you experience warning signs of hypoglycaemia (low blood sugar levels),
see a) Summary of serious and very common side effects in section 4.
► In insulin infusion pumps.
► If the cartridge or the device containing the cartridge is leaking, damaged, or cracked.
► If it has not been stored correctly or has been frozen, see section 5, How to store NovoMix 50.
► If the resuspended insulin does not appear uniformly white, cloudy, and watery.
► If, after resuspension, clumps or white particles are present, or if there is a frost-like appearance due to particles adhering to the bottom or walls of the cartridge.
Do not use NovoMix 50 if any of these conditions apply. Speak to your doctor, nurse, or pharmacist for advice.

Before using NovoMix 50
► Check the label to ensure that you are using the correct type of insulin.
► Always inspect the cartridge, including the rubber plunger at the bottom of the cartridge. Do not use if it appears damaged or if the rubber plunger has been pulled above the white band at the bottom of the cartridge. This could indicate insulin loss. If you suspect the cartridge has been damaged, return it to your supplier. Refer to the pen user manual for further information.
► Always use a new needle for each injection to prevent contamination.
► Needles and NovoMix 50 Penfill must not be shared with others.
► NovoMix 50 Penfill is intended only for subcutaneous injection with a reusable pen. Speak to your doctor if you need to administer insulin by another method.

Warnings and precautions
Certain conditions and activities may affect your insulin requirements. Consult your doctor:
► If you have kidney, liver, adrenal gland, pituitary, or thyroid disorders.
► If you have increased physical activity or changes in your usual diet, as this may affect your blood sugar levels.
► If you become ill, continue your insulin therapy and consult your doctor.
► If you plan to travel abroad; traveling across different time zones may alter your insulin requirements and timing.

Skin changes at the injection site
Rotate injection sites to help prevent changes in the fatty tissue under the skin, such as skin thickening, skin thinning, or the appearance of lumps under the skin.
Insulin may not work effectively if injected into an area with lumps, thinning, or thickening of the skin (see section 3, How to use NovoMix 50). Inform your doctor if you notice skin changes at the injection site. If you currently inject into such affected areas, consult your doctor before switching to another injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

Other medicines and NovoMix 50
Inform your doctor, nurse, or pharmacist if you are taking or might take any other medicines, including those obtained without a prescription. Some medicines affect blood sugar levels and may alter your insulin requirements. Listed below are the most important medicines that may affect your insulin treatment.

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

• other medicines for diabetes
• monoamine oxidase inhibitors (MAOIs) used to treat depression
• beta-blockers used to treat hypertension
• angiotensin-converting enzyme (ACE) inhibitors used to treat certain heart conditions or hypertension
• salicylates used to relieve pain and reduce fever
• anabolic steroids such as testosterone
• sulfonamides 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 fluid retention)
• glucocorticoids (such as 'cortisone' used to treat inflammation)
• thyroid hormones (used to treat thyroid disorders)
• sympathomimetics such as epinephrine (adrenaline), salbutamol, or terbutaline used to treat asthma
• growth hormone (a medicine used to stimulate skeletal and body growth and that significantly affects the body's metabolic processes)
• danazol (a medicine that affects ovulation).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder usually occurring in middle-aged adults caused by excessive production of growth hormone by the pituitary gland) may increase or decrease your blood sugar levels.
Beta-blockers (used to treat hypertension) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar levels.

Pioglitazone (tablets used to treat type 2 diabetes)
Some patients with long-standing type 2 diabetes and heart disease or a history of stroke who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (oedema).
If you are taking any of the medicines listed above, inform your doctor, nurse, or pharmacist.

Drinking alcohol and using NovoMix 50
► If you consume alcohol, your insulin requirements may change, as your blood sugar levels may increase or decrease. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before taking this medicine. Clinical experience with insulin aspart during pregnancy is limited. Your insulin requirements may need adjustment during pregnancy and after delivery. It is important to carefully control diabetes, particularly to prevent hypoglycaemic episodes, for the health of both you and your baby.
► There are no restrictions on using NovoMix 50 during breastfeeding.
Consult your doctor, nurse, or pharmacist before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
► Consult your doctor about whether it is safe for you to drive or operate machinery:

• If you experience frequent episodes of hypoglycaemia.
• If you have difficulty recognizing the warning signs of hypoglycaemia.

If your blood glucose is high or low, your ability to concentrate and react may be impaired, thereby affecting your ability to drive or operate machinery. Be aware that you may put yourself and others at risk.

Important information about some ingredients of NovoMix 50
NovoMix 50 contains less than 1 mmol of sodium (23 mg) per dose, i.e., NovoMix 50 is essentially “sodium-free”.

3. How to use NovoMix 50

Dose and when to take insulin
Always use insulin and adjust the dose exactly as instructed by your doctor. If you are unsure, consult your doctor, nurse, or pharmacist.
NovoMix 50 is generally taken immediately before a meal. You should eat a meal or snack within 10 minutes after the injection to avoid low blood sugar levels. When necessary, NovoMix 50 may be administered shortly after a meal. See below for information on How and where to inject.
When NovoMix 50 is used in combination with metformin, the dose should be adjusted according to individual needs.
Do not change your insulin unless your doctor tells you to do so. If your doctor has switched you from one type or brand of insulin to another, a dose adjustment may be required by your doctor.

Use in children and adolescents
There is no clinical experience with NovoMix 50 in children and adolescents under 18 years of age.

Use in specific patient groups
If you have kidney or liver impairment, or if you are over 65 years old, you should monitor your blood sugar levels regularly and discuss insulin dose adjustments with your doctor.

How and where to inject
NovoMix 50 is administered under the skin (subcutaneous use). Never inject insulin directly into a vein (intravenous use) or into muscle (intramuscular use). NovoMix 50 Penfill is intended only for subcutaneous injections with a reusable pen device. Talk to your doctor if you need to administer insulin by another method.
With each injection, always rotate the injection site within the particular area of skin you usually use. This may reduce the risk of developing lumps or skin depressions (see section 4, Possible side effects). The best sites for injection are: the abdomen (abdominal area); the buttocks; the front of the thigh; or the upper arm. Insulin will act more quickly if injected into the abdomen. It is recommended to check your blood sugar levels regularly.
► Do not refill the cartridge.
► The NovoMix 50 Penfill cartridge is designed to be used with Novo Nordisk insulin delivery devices and NovoFine or NovoTwist needles.
► If, in addition to NovoMix 50 Penfill, you have been prescribed another cartridge-type insulin, you must use two separate insulin delivery devices, one for each type of insulin.
► Always carry a spare Penfill cartridge with you in case the one in use is lost or damaged.

Resuspending NovoMix 50
Always check that there is sufficient insulin (at least 12 units) available in the cartridge after resuspending. If there is not enough insulin remaining, use a new cartridge. See the pen user manual for further instructions.

► Each time you use a new NovoMix 50 Penfill (before inserting the cartridge into the delivery device)

• Allow the insulin to reach room temperature before use. This makes it easier to resuspend.
• Roll the cartridge between your palms 10 times – it is important that the cartridge is held horizontally (parallel to the ground) (see figure A).
• Move the cartridge up and down between positions a and b (see figure B) 10 times so that the glass ball can move freely between the two ends of the cartridge.
• Repeat this procedure (see figures A and B) until the liquid appears uniformly white, milky, and aqueous. Do not use the cartridge if the resuspended insulin does not appear uniformly white, milky, and aqueous.
• Quickly proceed with the next steps for injection.

► For each subsequent injection

• Move the delivery device up and down between positions a and b with the cartridge inserted (see figure B), at least 10 times, until the liquid appears uniformly white, milky, and aqueous. Do not use the cartridge if the resuspended insulin does not appear uniformly white, milky, and aqueous.
• If the procedure described above is insufficient to make the liquid appear uniformly white and milky, repeat the procedure until the liquid appears uniformly white, milky, and aqueous.
• Quickly complete the other steps required for injection.

How to inject NovoMix 50
► Inject the insulin subcutaneously. Use the technique shown by your doctor or nurse and as described in the pen user manual.
► Keep the needle under the skin for at least 6 seconds. Keep the plunger fully depressed until the needle is withdrawn from the skin. This ensures proper administration and minimizes possible backflow of blood into the needle or insulin leakage.
► After each injection, make sure to remove and dispose of the needle, and store NovoMix 50 without the needle attached. Otherwise, the liquid may leak out, leading to inaccurate dosing.

If you take more insulin than you should
If you take too much insulin, your blood sugar level will drop too low (hypoglycaemia). See a) Summary of serious and very common side effects in section 4.

If you forget to take insulin
If you forget to take your insulin, your blood sugar level will become too high (hyperglycaemia). See c) Effects of diabetes in section 4.

If you stop using insulin
Do not stop treatment with insulin without first discussing it with your doctor, who will advise you on what to do. Stopping may 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 about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
a) Summary of serious and very common side effects
Low blood sugar level (hypoglycaemia) is a very common side effect. It may occur in more than 1 in 10 people.
You may experience low blood sugar if:

• You inject too much insulin.
• You eat too little or miss meals.
• You do more physical activity than usual.
• You drink alcohol (see Drinking alcohol and taking NovoMix 50 in section 2).

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; intense hunger; temporary visual disturbances; drowsiness; unusual tiredness and weakness; nervousness or trembling; anxiety; confusion; difficulty concentrating.
Severe hypoglycaemia can lead to loss of consciousness. If severe hypoglycaemia is left untreated, it may cause brain damage (transient or permanent) and even death. You may regain consciousness more quickly with an injection of the hormone glucagon given by someone trained in its use. If you are given glucagon, you will need glucose or a sweet snack as soon as you regain consciousness. If you do not respond to glucagon treatment, you must be taken to hospital immediately.
What to do if your blood sugar is low:
► If your blood sugar is too low, eat sugar cubes or another sugary snack (candy, biscuits, fruit juice). Check your blood sugar if possible, then rest. Always carry sugar cubes, candy, biscuits or fruit juice with you to use if needed.
► When symptoms of hypoglycaemia have disappeared or when blood glucose has stabilized, continue your insulin treatment.
► If you have low blood sugar, lose consciousness, require a glucagon injection, or experience frequent episodes of low blood sugar, speak with your doctor. You may need adjustments to your insulin dose, timing, food intake, or physical activity.
Inform people close to you that you have diabetes and what the consequences may be, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they should turn you onto your side and seek immediate medical help. It is important not to give you food or drink, as this could cause choking.
Severe allergic reaction to NovoMix 50 or one of its excipients (called systemic allergic reaction) is a very rare side effect that may be potentially life-threatening. It may occur in fewer than 1 in 10,000 people.
Contact your doctor immediately:

• if signs of allergy spread to other parts of the body
• if you suddenly feel unwell and: start sweating; feel sick (vomiting); have difficulty breathing; have a rapid heartbeat; feel dizzy. ► If you notice any of these signs, contact your doctor immediately.

Skin changes at the injection site: If you inject insulin in the same spot repeatedly, fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy) (may affect fewer than 1 in 100 people). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency not known). Insulin may not work as effectively if injected into an area with lumps, thinning, or thickening of the skin. Change your injection site with each injection to prevent these skin changes.
b) List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: localized allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of starting insulin treatment. If symptoms do not disappear, consult your doctor.
Visual disturbances: visual disturbances may occur at the beginning of insulin treatment, but these are usually temporary.
Swollen joints: at the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This usually resolves quickly. If not, contact your doctor.
Diabetic retinopathy (an eye condition related to diabetes that may lead to vision loss): if you have diabetic retinopathy and your blood sugar improves very rapidly, diabetic retinopathy may worsen. Consult your doctor.
Rare side effects
May affect fewer than 1 in 1,000 people.
Painful neuropathy (pain due to nerve damage): if your blood sugar improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy, which is usually transient.
Reporting of side effects
If you experience any of the side effects, tell your doctor, nurse, or pharmacist. This includes any side effect not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.
c) Effects of diabetes
High blood sugar level (hyperglycaemia)
You may have high blood sugar if:

• You have not injected enough insulin.
• You forgot to take insulin or stopped taking it.
• You repeatedly take less insulin than needed.
• You have an infection and/or fever.
• You eat more than usual.
• You do less physical activity than usual.

Warning signs of high blood sugar:
Symptoms develop gradually. They include: passing more urine than normal; thirst; loss of appetite; feeling unwell (nausea or vomiting); drowsiness or tiredness; dry, flushed skin; dry mouth and fruity breath (acetone).
What to do if your blood sugar is high:
► If you experience any of these symptoms: check your blood glucose, and if possible, check for ketones in your urine, and contact a doctor immediately.
► These may be symptoms of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store NovoMix 50

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 cartridge label and on the
packaging, after 'EXP'. The expiry date refers to the last day of the month.
When not in use, always store the cartridge in its outer packaging to protect it from light. NovoMix 50 must be protected from excessive heat and direct sunlight.
Before opening: Unused NovoMix 50 Penfill must be stored in the refrigerator at 2°C - 8°C, away from refrigerating elements. Do not freeze.
Before using NovoMix 50 Penfill, remove it from the refrigerator. It is recommended to resuspend the insulin according to the instructions each time you use a new NovoMix 50 Penfill. See Resuspension of NovoMix 50 in section 3.
During use or when carried as a spare: NovoMix 50 Penfill in use or carried as a spare must not be stored in the refrigerator. It may be carried at room temperature (below 30°C) for up to 4 weeks.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

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 crystallized with protamine. 1 ml contains 100 units of insulin aspart. Each cartridge contains 300 units of insulin aspart in 3 ml of injectable suspension.
• The excipients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide and water for injections.

Description of the appearance of NovoMix 50 and package contents
NovoMix 50 is a white, opaque, aqueous injectable suspension. The cartridge contains a glass bead to facilitate resuspension. After resuspension, the liquid should appear uniformly white, milky and aqueous. Do not use the insulin if it does not appear uniformly white, milky and aqueous after resuspension.
Pack sizes of 1, 5 or 10 cartridges of 3 ml. Not all pack sizes may be marketed.
The suspension is white, milky and aqueous.
Marketing Authorization Holder and Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark
This leaflet was last reviewed on
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA): http://www.ema.europa.eu/.

Package leaflet: Information for the user

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

50% soluble insulin aspart and 50% crystallized insulin aspart with protamine
Please read this leaflet carefully before using this medicine as it contains
important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, nurse, or pharmacist.
• This medicine has been prescribed for you only. Never give it to others. It may be harmful to other people even if their symptoms are the same as yours.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, nurse, or pharmacist. See section 4.

In this leaflet:

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

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

NovoMix 50 is a modern insulin (insulin analogue) with a rapid-acting and intermediate-acting component in a 50/50 ratio. Modern insulin medicines 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 condition in which the body does not produce enough insulin to control blood sugar levels. NovoMix 50 may be used in combination with metformin.
NovoMix 50 begins to lower blood sugar levels within 10–20 minutes after administration, reaches its maximum effect between 1 and 4 hours after injection, and its effect lasts up to 14–24 hours.

2. What you should know before using NovoMix 50

Do not use NovoMix 50
► If you are allergic (hypersensitive) to insulin aspart or to any of the other excipients of this
medicinal product (see section 6, Contents of the pack and other information).
► If you experience warning signs of hypoglycemia (low blood sugar), see a) Summary of serious and very common adverse effects in section 4.
► In insulin infusion pumps (microinfusers).
► If the FlexPen is leaking, damaged, or cracked.
► If it has not been stored correctly or has been frozen; see section 5, How to store NovoMix 50.
► If, after resuspension, the insulin does not appear uniformly white, cloudy, and watery.
► If, after resuspension, clumps or white particles are present, or if the cartridge has a frost-like appearance due to particles adhering to the bottom or walls of the cartridge.
Do not use NovoMix 50 if any of these situations occur. Speak with your doctor, nurse, or pharmacist for advice.

Before using NovoMix 50
► Check the label to make sure you are using the correct type of insulin.
► Always use a new needle for each injection to prevent contamination.
► Needles and NovoMix 50 FlexPen must not be shared with others.
► NovoMix 50 FlexPen is intended only for subcutaneous injection. Speak with your doctor if you need to administer insulin by another route.

Warnings and precautions
Certain conditions and activities may affect your insulin requirements. Consult your doctor:
► If you have kidney or liver problems, or disorders of the adrenal glands, pituitary gland, or thyroid gland.
► If you have increased physical activity or changes in your usual diet, as this may alter your blood sugar levels.
► If you become ill, continue your insulin therapy and consult your doctor.
► If you plan to travel abroad, traveling across different time zones may affect your insulin requirements and timing of doses.

Skin changes at the injection site
Rotate your injection sites to help prevent changes in the fatty tissue under the skin, such as skin thickening, skin thinning, or the appearance of lumps under the skin.
Insulin may not work as effectively if you inject into an area with lumps, thinning, or thickening of the skin (see section 3, How to use NovoMix 50). Inform your doctor if you notice skin changes at the injection site. If you currently inject into one of these affected areas, consult your doctor before switching to a new injection site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or that of other antidiabetic medications.

Other medicines and NovoMix 50
Inform your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines. Some medicines affect blood sugar levels and may alter your insulin requirements. Listed below are the most important 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 hypertension
• angiotensin-converting enzyme (ACE) inhibitors used to treat certain heart conditions or hypertension
• salicylates used to relieve pain and reduce 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 fluid retention)
• glucocorticoids (such as 'cortisone' used to treat inflammation)
• thyroid hormones (used to treat thyroid disorders)
• sympathomimetics such as epinephrine (adrenaline), salbutamol, or terbutaline used to treat asthma
• growth hormone (a medicine used to stimulate skeletal and body growth and that significantly affects the body's metabolic processes)
• danazol (a medicine that affects ovulation).

Octreotide and lanreotide (used to treat acromegaly, a rare hormonal disorder usually occurring in middle-aged adults, caused by excessive production of growth hormone by the pituitary gland) may either increase or decrease your blood sugar levels.
Beta-blockers (used to treat hypertension) may weaken or completely suppress the warning symptoms that help you recognize hypoglycemia.

Pioglitazone (tablets used to treat type 2 diabetes)
Some patients with long-standing type 2 diabetes and heart problems or a history of stroke who were treated with pioglitazone and insulin have developed heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid weight gain, or localized swelling (edema).

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

Drinking alcohol and using NovoMix 50
► If you consume alcohol, your insulin requirements may change, as your blood sugar levels may increase or decrease. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor before using this medicine. Clinical experience with insulin aspart during pregnancy is limited. Your insulin requirements may need adjustment during pregnancy and after delivery. It is important to carefully control diabetes, particularly to prevent episodes of hypoglycemia, for the health of your baby.
► There are no restrictions on the use of NovoMix 50 during breastfeeding.
Consult your doctor, nurse, or pharmacist before taking any medicine during pregnancy or breastfeeding.

Driving and using machines
► Consult your doctor about whether it is safe for you to drive or operate machinery:

• if you experience frequent episodes of hypoglycemia.
• if you have difficulty recognizing the warning signs of hypoglycemia.

If your blood glucose is high or low, your ability to concentrate and react may be impaired, thereby affecting your ability to drive or operate machinery. Be aware that you may be putting yourself or others at risk.

Important information about some ingredients of NovoMix 50
NovoMix 50 contains less than 1 mmol of sodium (23 mg) per dose, meaning that NovoMix 50 is essentially “sodium-free”.

3. How to use NovoMix 50

Dose and when to take insulin
Always use insulin and adjust the dose as directed by your doctor. If you are unsure, consult your doctor, nurse, or pharmacist.
NovoMix 50 is generally taken immediately before a meal. You must eat a meal or snack within 10 minutes after the injection to avoid low blood sugar levels. When necessary, NovoMix 50 may be administered shortly after a meal. See below for information on How and where to inject.
When NovoMix 50 is used in combination with metformin, the dose should be adjusted according to individual needs.
Do not change your insulin unless your doctor tells you to do so. If your doctor has switched you from one type or brand of insulin to another, your doctor may need to adjust your dose.

Use in children and adolescents
There is no clinical experience with NovoMix 50 in children and adolescents under 18 years of age.

Use in specific patient groups
If you have renal or hepatic impairment, or if you are over 65 years old, you should monitor your blood sugar regularly and discuss insulin dose adjustments with your doctor.

How and where to inject
NovoMix 50 is administered subcutaneously (under the skin). Never inject insulin directly into a vein (intravenous use) or into muscle (intramuscular use). The NovoMix 50 FlexPen is intended for subcutaneous injections only. Speak with your doctor if you need to administer insulin by another method.
With each injection, always rotate the injection site within the particular area of skin you usually use. This may reduce the risk of developing lumps or skin depressions (see section 4 Possible side effects). The best sites for injection are: the abdomen (abdominal area), buttocks, front of the thigh, or upper arm. Insulin will act more quickly if injected into the abdomen. Regular blood sugar monitoring is recommended.

How to use NovoMix 50 FlexPen
NovoMix 50 FlexPen is a pre-filled, disposable pen coded with a colour, containing a 50/50 mixture of fast-acting and intermediate-acting insulin aspart.
Read carefully the instructions for use provided in this leaflet. You must use the pen exactly as described in the Instructions for Use.
Always make sure you are using the correct pen before injecting your insulin.

If you take more insulin than you should
If you take too much insulin, your blood sugar level will drop too low (hypoglycaemia). See a) Summary of serious and very common side effects in section 4.

If you forget to take insulin
If you forget to take your insulin, your blood sugar level will become too high (hyperglycaemia). See c) Effects of diabetes in section 4.

If you stop treatment with insulin
Do not stop treatment with insulin without first talking to your doctor, who will advise you on what to do. Stopping treatment may 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 about the use of this medicine, ask your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
a) Summary of serious and very common side effects
Low blood sugar level (hypoglycaemia) is a very common side effect. It may occur in more than 1 person out of 10.
You may experience low blood sugar if:

• You inject too much insulin.
• You eat too little or skip meals.
• You do more physical activity than usual.
• You consume alcohol (see Drinking alcohol and using NovoMix 50 in section 2).

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; intense hunger; temporary visual disturbances; drowsiness; unusual tiredness or weakness; nervousness or trembling; anxiety; confusion; difficulty concentrating.
Severe hypoglycaemia can lead to loss of consciousness. If severe prolonged hypoglycaemia is not treated, it may cause brain damage (transient or permanent) and may even result in death. You may regain consciousness more quickly with an injection of the hormone glucagon given by someone who knows how to administer it. If you are given glucagon, you will need glucose or a sweet snack as soon as you regain consciousness. If you do not respond to glucagon treatment, you must be taken to hospital immediately.
What to do if your blood sugar is low:
► If your blood sugar is too low, eat sugar cubes or another snack high in sugar (candy, biscuits, fruit juice). Check your blood sugar if possible, then rest. Always carry sugar cubes, candy, biscuits or fruit juice with you to use if needed.
► When symptoms of hypoglycaemia have disappeared or when blood glucose has stabilized, continue your insulin treatment.
► If you have low blood sugar, lose consciousness, have required a glucagon injection, or have frequent episodes of low blood sugar, speak with your doctor. Your doctor may need to adjust your insulin dose, timing of administration, food intake, or physical activity.
Inform people close to you that you have diabetes and what consequences may occur, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they should turn you onto your side and seek immediate medical help. It is important that food or drink not be given, as this could cause choking.
Severe allergic reaction to NovoMix 50 or one of its excipients (called systemic allergic reaction) is a very rare side effect that may be potentially life-threatening. It may occur in fewer than 1 person out of 10,000.
Contact your doctor immediately:

• if signs of allergy spread to other parts of the body
• if you suddenly feel unwell and: begin to sweat; feel sick (vomiting); have difficulty breathing; have a rapid heartbeat; feel dizzy. ► If you notice any of these signs, contact your doctor immediately.

Skin changes at the injection site: If you inject insulin in the same spot repeatedly, fatty tissue may become thinner (lipoatrophy) or thicker (lipohypertrophy) (may affect fewer than 1 person in 100). Lumps under the skin may also be caused by the buildup of a protein called amyloid (cutaneous amyloidosis; frequency is unknown). Insulin may not work as effectively if you inject into an area with lumps, thinning, or thickening. Change your injection site with each injection to prevent these skin changes.
b) List of other side effects
Uncommon side effects
May affect fewer than 1 person in 100.
Signs of allergy: localized allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of starting insulin treatment. If symptoms do not resolve, consult your doctor.
Vision disturbances: vision problems may occur at the beginning of insulin treatment, but these are usually temporary.
Swollen joints: at the start of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This usually resolves quickly. If not, contact your doctor.
Diabetic retinopathy (an eye condition related to diabetes that may lead to vision loss): if your blood sugar level improves very rapidly, diabetic retinopathy may worsen. Consult your doctor.
Rare side effects
May affect fewer than 1 person in 1,000.
Painful neuropathy (pain due to nerve damage): if your blood sugar level improves very rapidly, you may experience pain originating from nerve fibres, known as acute painful neuropathy, which is usually transient.
Reporting of side effects
If you experience any of the side effects, inform your doctor, nurse, or pharmacist. This includes any side effect not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.
c) Effects of diabetes
High blood sugar level (hyperglycaemia)
You may have a high blood sugar level:

• If you have not injected enough insulin.
• If you have forgotten to take insulin or have stopped taking it.
• If you repeatedly take less insulin than required.
• If you have an infection and/or fever.
• If you eat more than usual.
• If you do less physical activity than usual.

Warning signs of high blood sugar:
Warning signs appear gradually. They include: passing more urine than normal; thirst; loss of appetite; feeling unwell (nausea or vomiting); drowsiness or tiredness; dry, flushed skin; dry mouth and fruity breath (acetone).
What to do if your blood sugar is high:
► If you experience any of these symptoms: check your blood glucose, if possible check for the presence of ketones in your urine, and contact a doctor immediately.
► These may be symptoms of a very serious condition called diabetic ketoacidosis (build-up of acid in the blood because the body is metabolizing fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store 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 FlexPen label and on the
packaging, after 'EXP'. The expiry date refers to the last day of the month.
When not in use, keep the cap on the FlexPen to protect it from light. NovoMix 50
must be protected from excessive heat and direct sunlight.
Before opening: Unused NovoMix 50 FlexPen must be stored in a refrigerator at 2°C –
8°C, away from cooling elements. Do not freeze.
Before using NovoMix 50 FlexPen, remove it from the refrigerator. It is recommended to resuspend
the insulin according to the instructions each time you use a new pen. See Instructions for Use.
During use or when carried as a spare: NovoMix 50 FlexPen in use or being
carried as a spare must not be stored in the refrigerator. It may be kept at room temperature (below 30°C) for up to 4 weeks.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

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 crystallized 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 excipients are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide, and water for injections.

Description of the Appearance of NovoMix 50 and Contents of the Package
NovoMix 50 is an injectable suspension contained in a pre-filled pen. The cartridge
contains a glass ball to aid resuspension. After resuspension, the liquid should appear uniformly white, milky, and watery. Do not use the insulin if it does not appear uniformly white, milky, and watery after resuspension.
Packages containing 1, 5, or 10 pre-filled pens of 3 ml. Not all pack sizes may be marketed.
The suspension is milky, white, and watery.
Marketing Authorization Holder and Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark
For instructions on how to use your FlexPen, please turn the page.
This leaflet was last reviewed on
Additional Sources of Information
More detailed information on this medicinal product is available on the website of the European Medicines Agency (EMA): http://www.ema.europa.eu/.
Instructions for using NovoMix 50 injectable suspension in FlexPen.
Read the following instructions carefully before using your FlexPen. If you do not follow these instructions carefully, you may inject too much or too little insulin, which could lead to blood sugar levels that are too high or too low.
FlexPen is a pre-filled pen for variable-dose insulin administration.
► You can select a dose between 1 and 60 units in increments of 1 unit.
► FlexPen is designed to be used with NovoFine or NovoTwist disposable needles up to 8 mm in length.
► Always carry a spare insulin delivery device in case your FlexPen is lost or damaged.

Caring for the Pen
► Handle your FlexPen with care. If it leaks or has been subjected to impact, it may be damaged and insulin may be lost. This could result in incorrect dosing, leading to blood sugar levels that are too high or too low.
► You may clean the exterior of your FlexPen with a disinfectant wipe. Do not immerse, wash, or lubricate the pen to avoid damaging its mechanism.
► Do not refill your FlexPen.
Resuspending the Insulin
A
Check the name and colored label on your pen to ensure it contains the correct type of insulin. This is especially important if you use more than one type of insulin. Administering the wrong type of insulin may cause your blood sugar level to become too high or too low.
Each time you use a new pen
Allow the insulin to reach room temperature before use. This will make resuspension easier.
Remove the pen cap.

B
Before administering the first injection with a new FlexPen, you must resuspend the insulin:
Roll the pen between your palms 10 times—ensure the pen is held horizontally (parallel to the ground).

C
Move the pen up and down 10 times between the two positions shown, so that the glass ball moves from one end of the cartridge to the other.
Repeat this procedure until the liquid appears uniformly white, milky, and watery.
For each subsequent injection
Move the pen up and down at least 10 times between the two positions until the liquid appears uniformly white, milky, and watery. If the procedure described above is insufficient to achieve a uniformly white, milky, and watery appearance, repeat the procedure (see B and C) until the liquid appears uniformly white, milky, and watery.
► Always ensure the insulin is properly resuspended before each injection. This reduces the risk of high or low blood sugar. After resuspending, proceed quickly with the following steps.

Always check that at least 12 units of insulin remain in the cartridge to allow proper resuspension. If less than 12 units remain, use a new FlexPen. 12 units are indicated on the graduated scale. See the large illustration at the beginning of these instructions.
Do not use the pen if the resuspended insulin does not appear uniformly white, milky, and watery.
Attaching a Needle
D
Take a new needle and remove the protective seal.
Screw the needle perpendicularly and securely onto your FlexPen.

E
Remove the outer needle cap and keep it for later use.

F
Remove the inner needle cap and discard it.
Never attempt to reinsert the inner needle cap onto the needle. You may injure yourself.

Always use a new needle for each injection. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and incorrect dosing.
Be careful not to bend or damage the needle before use.
Checking Insulin Flow
During normal use, small amounts of air may accumulate in the cartridge. Before each injection, to avoid injecting air and to ensure the correct insulin dose is delivered:
G
Turn the dose selector to select 2 units.

H
Hold the FlexPen with the needle pointing upwards and gently tap the cartridge several times with your finger so that air bubbles collect at the top of the cartridge.

I
With the needle pointing upwards, press the injection button fully. The dose selector will return to zero.
A drop of insulin should appear at the tip of the needle. If not, change the needle and repeat the procedure no more than 6 times.
If no drop appears after 6 attempts, the pen is defective and you must use a new one.

Always ensure a drop appears at the needle tip before injection. This confirms insulin flow. If no drop appears, no insulin will be injected, even if the dose selector moves. This may indicate a blocked or damaged needle.
Always check the flow before each injection. Failure to do so may result in injecting too little insulin or no insulin at all, which could lead to high blood sugar levels.
Selecting the Dose
Ensure the dose selector is at zero.
J
Turn the dose selector to set the number of units to be injected.
The dose can be increased or decreased by turning the selector in either direction until the indicator shows the correct dose. While turning the dose selector, take care not to press the injection button, as this may cause insulin to leak out.
You cannot select a dose greater than the number of units remaining in the cartridge.

Before injecting insulin, always use the dose selector and indicator to verify the number of units selected.
Do not count the clicks of the pen. If you select or inject the wrong dose, your blood sugar level may become too high or too low. Do not use the graduated scale, which only approximately indicates how much insulin remains in the pen.
Injection
Insert the needle into the skin. Use the injection technique shown by your doctor or nurse.
K
Administer the insulin dose by pressing the injection button fully until the indicator reaches zero. Be careful to press only the injection button.
Turning the dose selector will not deliver insulin.

L
► Keep the injection button fully pressed and leave the needle under the skin for at least 6 seconds. This ensures complete dose delivery.
► Remove the needle from the skin after releasing pressure on the injection button.
► Always ensure the dose selector returns to zero after injection. If the dose selector stops before reaching zero, the full dose has not been delivered, which may result in high blood sugar levels.

M
Place the needle into the outer cap without touching it. Once the needle is covered, press the outer cap firmly and then unscrew the needle.
Dispose of the needle carefully and replace the cap on the FlexPen.

Always remove the needle after each injection and store your FlexPen without a needle attached. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and incorrect dosing.
Other Important Information
Anyone handling the needles must take great care to reduce the risk of needle-stick injuries and cross-infections.
Dispose of used FlexPens carefully, ensuring the needle has been removed.
Never share your pen or needles with other people. This could lead to cross-infections.
Never share your pen with other people. The medicine may be harmful to their health.
Always keep the pen and needles out of sight and reach of others, especially children.