Package Insert: Information for the User

NovoMix 30 FlexPen 100a 100-unit suspension for injection in a pre-filled pen

30% soluble insulin aspart and 70% crystallized insulin aspart with protamine

Read this package insert carefully before starting to use this medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

NovoMix 30 is a modern insulin (insulin analogue) with rapid and intermediate action, in a 30/70 ratio. Modern insulins are improved versions of human insulin.

NovoMix 30 is used to reduce high blood sugar levels in adults, adolescents, and children aged 10 years and older with diabetes mellitus (diabetes). Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.

NovoMix 30 will start to reduce blood sugar levels 10 – 20 minutes after injection, reaches its maximum effect between 1 and 4 hours after injection, and its effect lasts up to 24 hours.

In patients with type 2 diabetes mellitus, NovoMix 30 can be used in combination with diabetes tablets and/or injectable antidiabetic medications.

Do not use NovoMix 30

If any of this happens, do not use NovoMix 30. Consult your doctor, nurse or pharmacist.

Before using NovoMix 30

• Check the label to make sure it is the correct type of insulin.
• Always use a new needle for each injection to avoid contamination.
• Do not share needles or your NovoMix 30 FlexPen.
• NovoMix 30 FlexPen is only indicated for subcutaneous injection. Consult your doctor if you need to inject insulin by another method.

Warnings and precautions

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

• If you have kidney or liver problems, or adrenal, pituitary or thyroid gland problems. If you engage in more physical exercise than usual or if you plan to change your usual diet, as this may affect your blood sugar level.
• If you are ill, continue using your insulin and consult your doctor.
• If you are traveling abroad, traveling to different time zones may affect your insulin requirements and the timing of administration.

Changes in skin at the injection site

The injection site should be rotated to help prevent changes in the fatty tissue, such as thickening of the skin, shrinking of the skin or lumps under the skin. Insulin may not work well if injected in an area that is swollen, shrunk or thickened (see section 3, How to use NovoMix 30).

Inform your doctor if you detect any changes in the injection site. Inform your doctor if you are currently injecting in these affected areas, before starting to inject in a different area. Your doctor may advise you to check your blood sugar levels more closely, and adjust your insulin or your other diabetes medications.

Children and adolescents

•NovoMix 30 can be used in adolescents and children aged 10 years and above.

•There is limited experience with NovoMix 30 in children aged 6 to 9 years.

•No data are available for NovoMix 30 in children under 6 years.

Other medicines and NovoMix 30

Inform your doctor, nurse or pharmacist if you are using, have used recently or may need to use any other medicine. Some medicines affect your blood sugar level and this may mean that your insulin dose needs to be adjusted.

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

• Other medicines for the treatment of diabetes.
• Monamine oxidase inhibitors (MAOIs) (used to treat depression).
• Beta-blockers (used to treat high blood pressure).
• Angiotensin-converting enzyme inhibitors (ACE inhibitors) (used to treat certain heart conditions or high blood pressure).
• 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 excessive fluid retention).
• Glucocorticoids (such as "cortisone" used to treat inflammation).
• Thyroid hormones (used to treat thyroid gland disorders).
• Adrenergic agonists (such as epinephrine [adrenaline], salbutamol or terbutaline used to treat asthma).
• Growth hormone (medicine to stimulate somatic and skeletal growth that has a pronounced effect on metabolic processes).
• Danazol (medicine that acts on ovulation).

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

Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the early warning signs that may help you recognize when you have low blood sugar.

Pioglitazone (tablets used to treat type 2 diabetes)

Some patients with long-standing type 2 diabetes and pre-existing heart disease or stroke who were treated with pioglitazone and insulin developed heart failure. Inform your doctor as soon as possible if you have signs of heart failure such as unusual shortness of breath, rapid weight gain or localized inflammation (edema).

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

Alcoholic beverages and use of NovoMix 30

• If you drink alcohol, your insulin needs may change as your blood sugar level may be increased or decreased. It is recommended to monitor carefully.

Pregnancy and lactation

• If you are pregnant, think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medicine. The clinical experience with insulin aspart during pregnancy is limited. You may need to adjust your insulin dose while pregnant and after delivery. It is essential for the health of your baby to have a careful control of your diabetes, especially the prevention of hypoglycemia.
• No restrictions apply to the treatment with NovoMix 30 during lactation.

Consult your doctor, pharmacist or nurse before using any medicine while pregnant or breastfeeding.

Driving and operating machinery

• Please ask your doctor if you can drive or operate machinery:
• If you have frequent hypoglycemia.
• If you find it difficult to recognize hypoglycemia.

If your blood sugar levels are low or high, they may affect your concentration and reaction time and, therefore, also your ability to drive or operate machinery. You may put your life or the lives of others at risk.

Important information about some of the components of NovoMix 30

NovoMix 30 contains less than 1 mmol (23 mg) of sodium per dose, so NovoMix 30 is essentially "sodium-free".

Dosage and when to administer insulinand when to administer insulin

Always use the insulin and adjust the dose exactly as recommended by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

NovoMix 30 is usually administered immediately before a meal. Take some food within 10 minutes of the injection to avoid a drop in blood sugar. If necessary, NovoMix 30 can be administered shortly after a meal. For more information, see below How and where to inject.

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

When NovoMix 30 is used in combination with oral diabetes medications and/or injectable antidiabetic drugs, 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 pre-mixed insulin is preferred. For children aged 6–9 years, there are limited clinical data available. There are no available data for NovoMix 30 in children under 6 years.

Use in special patient groups

If you have kidney or liver dysfunction (renal or hepatic insufficiency), or if you are over 65 years old, you should monitor your blood sugar more frequently and consult your doctor about changes to your insulin dose.

How and where to inject

NovoMix 30 is injected under the skin (subcutaneous administration). Never inject insulin directly into a vein (intravenous administration) or muscle (intramuscular administration). NovoMix 30 FlexPen is only indicated for subcutaneous injection. Consult your doctor if you need to inject insulin by another method.

In each injection, change the injection site within the specific area of skin that you usually use. This may reduce the risk of developing lumps or depressions in the skin (see section 4, Possible side effects). The best areas for injection are: the front of the waist (abdomen), the gluteal region, the front of the thigh, or the upper arm. Insulin will act more quickly if injected in the abdominal area. You should always measure your blood sugar regularly.

How to use NovoMix 30 FlexPen

NovoMix 30 FlexPen is a disposable pre-filled pen with a color code that contains a mixture of rapid-acting and intermediate-acting insulin aspart in a ratio of 30/70.

Read the usage instructions included in this prospectus carefully. You must use the pen as described in the usage instructions.

Always make sure you are using the correct pen before injecting insulin.

If you use too much insulin

If you use too much insulin, your blood sugar level may become very low (hypoglycemia). See a) Summary of severe and very frequent adverse reactions in section 4.

If you forget to use your insulin

If you forget to use your insulin, your blood sugar level may become very high (hyperglycemia). See c) Diabetes effects in section 4.

If you interrupt your insulin treatment

Do not interrupt your insulin treatment without consulting your doctor, who will tell you what to do. This could produce very high blood sugar levels (severe hyperglycemia) and ketoacidosis. See c) Diabetes effects in section 4.

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

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

a)Summary of serious and very frequent side effects

Low blood sugar (hypoglycemia)is a very frequent side effect. It can affect more than 1 in 10 people.

Symptoms of low blood sugar may appear if::

•Too much insulin is injected.

•Not enough food is eaten or a meal is skipped.

•More exercise than usual is done.

•Alcohol is consumed (see Beverages and use of NovoMix 30 in section 2).

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

A severe hypoglycemia can cause fainting. If a severe and prolonged hypoglycemia is not treated, it can cause a transient or permanent brain injury and even death. You can regain consciousness more quickly with an injection of glucagon administered by someone who knows how to do it. If glucagon is administered to you, you should take glucose or a high-sugar food as soon as you regain consciousness. If you do not respond to glucagon treatment, you should be treated in a hospital.

What to do if your blood sugar level is low::

• Take glucose tablets or a high-sugar food (e.g. sweets, biscuits, fruit juice). If possible, measure your blood sugar level and rest. Always carry glucose tablets or high-sugar foods with you, just in case.
• When the symptoms of hypoglycemia have disappeared or when your blood sugar level has stabilized, continue your insulin treatment as usual.
• If you have fainted due to low blood sugar, if you have needed a glucagon injection, or if you have had many episodes of low blood sugar, talk to your doctor. Your doctor may need to adjust the dose or frequency of insulin administration, your diet, or your exercise routine.

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

Severe allergic reactionsto NovoMix 30 or any of its components (systemic allergic reaction) is a very rare but potentially life-threatening side effect. It can affect up to 1 in 10,000 people.

Consult your doctor immediately:

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

Changes in skin at the injection site: If insulin is injected in the same place, the fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (it can affect up to 1 in 100 people). Bumps under the skin can also occur due to the accumulation of a protein called amyloid (cutaneous amyloidosis; it is not known how often this occurs). Insulin may not work well if injected in a thickened, shrunk, or swollen area. Change the injection site to help prevent these skin changes.

b)Other side effects list

Frequent side effects

They can affect up to 1 in 100 people.

Allergic symptoms:: Local allergic reactions (pain, redness, urticaria, inflammation, hematomas, swelling, and itching) may occur at the injection site. These usually disappear after a few weeks of treatment. If symptoms do not disappear, consult your doctor.

Visual problems:: You may experience visual problems when starting insulin treatment, but this alteration is usually temporary.

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

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

Rare side effects

They can affect up to 1 in 1,000 people.

Painful neuropathy:(pain due to nerve damage):If your blood sugar level improves rapidly, you may experience nerve pain. This is called acute painful neuropathy and is usually temporary.

Reporting side effects

Inform your doctor, pharmacist, or nurse if you experience any type of side effect, even if it is not listed in this leaflet. You can also report side effects directly to the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

c)Diabetes effects

High blood sugar (hyperglycemia)

Symptoms of high blood sugar may appear if:

•Not enough insulin is injected.

•Insulin is forgotten or treatment is interrupted.

•Repeatedly less insulin than needed is injected.

•An infection and/or fever is present.

•More food is eaten than usual.

•Less physical exercise than usual is done.

Symptoms of high blood sugar warning:

The warning symptoms appear gradually. These include: increased need to urinate, thirst, loss of appetite, feeling dizzy (nausea or vomiting), drowsiness or fatigue, dry and red skin, feeling of dryness in the mouth, and breath with a fruity odor (acetone).

What to do if your blood sugar level is high::

• Check your blood sugar level, check your urine ketone level if possible, and consult your doctor immediately if you notice any of the symptoms described.
• These may be symptoms of a severe condition called diabetic ketoacidosis (acid accumulates in the blood due to the body breaking down fat instead of sugar). If not treated, it can cause diabetic coma and death.

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

Do not use this medication after the expiration date that appears on the packaging and on the FlexPen label, after CAD. The expiration date is the last day of the month indicated.

Always keep the cap on FlexPen when not in use, to protect it from light. NovoMix 30 must be protected from excessive heat and light.

Before opening: NovoMix 30 FlexPen not in usemust be stored in the refrigerator between 2°C and 8°C, away from the refrigeration element. Do not freeze.

Before using NovoMix 30 FlexPen, take it out of the refrigerator. It is recommended to resuspend the insulin as instructed each time you use a new pen. See usage instructions.

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

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of packaging and unused medications. This will help protect the environment.

Composition of NovoMix 30

• The active principle is insulin aspart. NovoMix 30 is a mixture composed of 30% soluble insulin aspart and 70% insulin aspart crystallized with protamine. 1ml contains 100units of insulin aspart. Each pre-filled pen contains 300units of insulin aspart in 3ml of injectable suspension.
• The other components are glycerol, phenol, metacresol, zinc chloride, disodium phosphate dihydrate, sodium chloride, protamine sulfate, hydrochloric acid, sodium hydroxide, and water for injectable preparations.

Appearance of NovoMix 30 and contents of the package

NovoMix 30 is presented as an injectable suspension in a pre-filled pen. The cartridge contains a glass bead to facilitate resuspension. After resuspension, the liquid should have a uniformly white, turbid, and aqueous appearance. Do not use the pen if the resuspended insulin does not appear uniformly white, turbid, and aqueous.

Package sizes of 1(with or without needles), 5(without needles), and 10(without needles) pre-filled pens of 3ml. Not all presentations may be marketed.

The suspension is turbid, white, and aqueous.

Marketing Authorization Holder

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark

Responsible for Manufacturing

Novo Nordisk A/S

Novo Allé

DK-2880 Bagsværd, Denmark.

Novo Nordisk Production SAS

45, Avenue d’Orléans

F-28000 Chartres

France

The back of the package contains detailed instructions on how to use your FlexPen.

Last revision date of this leaflet:

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.

Instructions for use of NovoMix 30 injectable suspension in FlexPen.

Read these instructions carefully before using your FlexPen.If you do not follow the instructions carefully, you may administer too little or too much insulin, which could result in a level of blood sugar that is too high or too low.

FlexPen is a pre-filled pen insulin dosing device.

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

Care of the pen

• You must handle your FlexPen with care. If it falls, is damaged, or is hit, there is a risk of insulin loss. This could result in an inaccurate dose, which may cause a level of blood sugar that is too high or too low.

• You can clean the outer part of your FlexPen with an alcohol-impregnated cotton swab. Do not submerge it, wash it, or lubricate it, as the pen may be damaged.

• Do not refill your FlexPen.

Resuspension of insulin

A

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

Each time you use a new pen

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

Remove the pen cap.

B

Before administering the first injection with a new FlexPen, you must resuspend the insulin:

Turn the pen between your palms 10times, making sure the pen remains in a horizontal position(parallel to the floor).

C

Moving the pen from top to bottom 10times between the two positions, so that theglass beadmovesfrom one end to the other of the cartridge.

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

For each subsequent injection

Moving the pen from top to bottom between the two positions at least 10times until the liquid appears uniformly white, turbid, and aqueous.

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

Always check that there are at least12units of insulinremaining in the cartridge to allow for resuspension. If there are fewer than 12units, use a new FlexPen. On the insulin scale remaining, you can see if there are 12units. See the large drawing at the beginning of these instructions.

Do not use the pen if the resuspended insulin does not appear uniformly white, turbid, and aqueous.

Insertion of the needle

D

Take a new needle and remove the paper clip.

Insert the straight needle firmly into your FlexPen.

E

Remove the large outer needle cap and store it for later use.

F

Remove the small inner needle cap and discard it.

Do not attempt to reattach the small inner needle cap. You may prick yourself with the needle.

Always use a new needle for each injection.This reduces the risk of contamination, infection, insulin loss, needle blockage, and inaccurate dosing.

Be careful not to bend or damage the needle before use.

Check the insulin flow

Before each injection, small amounts of air may be present in the cartridge during normal use. To avoid injecting air and ensure proper dosing:

G

Turn the dose selector until 2units are selected.

H

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

I

Keeping the needle pointing upwards, press the plunger all the way down. The dose selector returns to 0.

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

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

Always ensure that a drop appears at the needle tip before injecting. This ensures that the insulin flows. If no drop appears, no insulin will be injected, although the dose selector may move. This may indicate that the needle is blocked or damaged.

Always check the flow before injecting.If you do not check the flow,you may receive an insufficient or non-existent dose of insulin, which could result in a level of blood sugar that is too high.

Selecting the dose

Check that the dose selector marks 0.

J

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

Thedose can beadjustedforward and backward by turning the dose selector in either direction until the correct dose is aligned with the dose marker. When turning the dose selector, be careful not to press the plunger, as insulin may 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 dose marker to see how many units you have selected.

Do not count the clicks of the pen. If you select an incorrect dose and inject it, your level of blood sugar may become too high or too low. Do not use the remaining insulin scale, as it only shows the approximate amount of insulin remaining in the pen.

Injection

Insert the needle under the skin. Use the injection technique recommended by your doctor or nurse.

K

Inject the dose by pressing the plunger all the way down so that 0 is aligned with the dose marker. Be careful only to press the plunger when injecting.

Turning the dose selector will not inject insulin.

L

• Keepthe plungercompletely pressedand keep the needle under the skin forat least 6seconds. This ensures that the full dose is administered.

• Remove the needle from the skin and once you have done so, stop pressing the plunger.

• Always ensure that the dose selector returns to 0 after the injection. If the dose selector stops before reaching 0, the full dose has not been administered, which may result in a level of blood sugar that is too high.

M

Secure the needle with the large outer needle cap without touching it. When the needle is covered, press the large outer needle cap firmly and then unscrew the needle.

Dispose of it carefully and replace the pen cap on your FlexPen.

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

Other important information

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

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

Never share the pen or needles with others. This may cause infections.

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

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