Actraphane: detailed information

Package leaflet: Information for the user

Actraphane 30 40 IU/ml (international units/ml) injectable suspension in a vial

human insulin
Read this entire leaflet carefully before using 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, pharmacist, or nurse.
This medicine has been prescribed for you only. Never give it to others. It could be harmful, even if their symptoms are the same as yours.
If you experience any side effect, talk to your doctor, pharmacist, or nurse. This includes any side effect not listed in this leaflet. See section 4.

1. What Actraphane is and what it is used for

Actraphane is a human insulin with rapid-acting and prolonged action.
Actraphane is used to reduce high blood sugar levels in patients with diabetes mellitus (diabetes).
Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.
Treatment with Actraphane helps prevent diabetes complications.
Actraphane begins to lower blood sugar levels within about 30 minutes after injection, and its effect lasts for approximately 24 hours.

2. What you need to know before using Actraphane

Do not use Actraphane
► If you are allergic to human insulin or to any of the other excipients of this medicine,
consult section 6.
► If you experience warning signs of hypoglycaemia (low blood sugar level),
consult the Summary of serious and very common adverse reactions in section 4.
► In insulin infusion pumps.
► If the protective cap is loose or missing. Each vial has a tamper-evident plastic cap. If it is not in perfect condition when you receive the vial, return it to your supplier.
► If it has not been stored correctly or has been frozen, see section 5.
► If the resuspended insulin does not appear uniformly white and cloudy.
Do not use Actraphane if any of these situations apply. Speak to your doctor, pharmacist, or nurse for advice.

Before using Actraphane
► Check the label to make sure you are using the correct type of insulin.
► Remove the protective seal.
► Always use a new needle for each injection to prevent contamination.
► Needles and syringes must not be shared.

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.
► 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, travelling across different time zones may alter 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 thickening of the skin, thinning of the skin, 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). Inform your doctor if you notice any skin changes at the injection site. If you currently inject into such an affected area, consult your doctor before switching to another 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 Actraphane
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines affect blood sugar levels, meaning your insulin dose may need adjustment. Listed below are the most common medicines that may affect 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 high blood pressure)
Angiotensin-converting enzyme (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)
Sulphonamides (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 gland disorders)
Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
Growth hormone (a medicine used to stimulate skeletal and somatic growth, significantly affecting 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 blood sugar levels.
Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar.

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

Actraphane and alcohol
► If you consume alcohol, your insulin requirement may change, as 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 to become pregnant,
ask your doctor for advice before taking this medicine. Actraphane can be used during pregnancy. Your insulin dose may need adjustment during pregnancy and after delivery. It is important to carefully manage diabetes, particularly to prevent episodes of hypoglycaemia, for the health of both mother and baby.
► There are no restrictions on the use of Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse 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.

High or low blood sugar levels may impair your concentration and reaction ability, and thus affect your ability to drive or operate machinery. Be aware that you could endanger yourself or others.

Actraphane contains sodium
Actraphane contains less than 1 mmol of sodium (23 mg) per dose, i.e., Actraphane is essentially "sodium-free".

3. How to use Actraphane

Dose and when to take insulin
Always use insulin and adjust the dose exactly as prescribed by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse.
Take a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar levels.
Do not change your insulin unless your doctor tells you to. If your doctor has changed the type or brand of insulin you are using, a dose adjustment may be necessary.

Use in children and adolescents
Actraphane can be used in children and adolescents.

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

How and where to inject
Actraphane is administered by subcutaneous injection (under the skin). Never inject insulin directly into a vein (intravenous) or into muscle (intramuscular). For each injection, rotate the injection site within the particular area of skin you usually use. This may reduce the risk of developing skin lumps or depressions, see section 4. The best areas for injection are: the abdominal area; the buttocks; the front of the thigh; or the upper arm. Your insulin will act more quickly if injected into the abdomen. Always monitor your blood glucose levels regularly.

How to inject Actraphane
Actraphane in vials is designed to be used with insulin syringes graduated in units.

Roll the vial gently between your hands until the liquid appears uniformly white and milky. Resuspension is easier when the insulin has reached room temperature.
Draw air into the syringe equal to your insulin dose. Inject this air into the vial.
Invert the vial and syringe, then draw the correct dose of insulin into the syringe. Remove the needle from the vial. Then expel air from the syringe and check that the insulin dose is correct.

How to inject Actraphane
► Inject the insulin under your skin. Use the injection technique recommended by your doctor or nurse.
► Keep the needle under the skin for at least 6 seconds to ensure the full dose has been delivered.
► Dispose of the needle and syringe after each injection.

If you take more insulin than you should
If you take too much insulin, your blood sugar level may drop too low (hypoglycaemia). See 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 (hyperglycaemia). See 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 high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects of diabetes in section 4.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Summary of serious and 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 skip meals.
You do more physical activity than usual.
You consume alcohol; see Actraphane with alcohol in section 2.

Warning symptoms of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; 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 prolonged hypoglycaemia is not treated, 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 who knows how to use it. If glucagon is administered, 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.
What to do if your blood sugar level is low:
► If your blood sugar is too low, eat sugar lumps or another snack high in sugar (sweets, biscuits, fruit juice). Measure your blood sugar if possible, then rest. Always carry sugar lumps, sweets, biscuits or fruit juice with you to use if needed.
► When symptoms of hypoglycaemia have disappeared or your blood glucose has stabilised, continue your insulin treatment.
► If you have a low blood sugar level, you may lose consciousness. If you required a glucagon injection, or if you have frequent episodes of low blood sugar, consult your doctor. A dose adjustment of insulin, changes in meal timing and physical activity may be necessary.
Inform people close to you that you are diabetic and what consequences may occur, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they must turn you onto your side and seek immediate medical help. It is important not to give you food or drink as you could choke.

Severe allergic reaction to Actraphane or one of its excipients (called systemic allergic reaction) is a rare side effect but can potentially be 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; your heartbeat is rapid; 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 thin (lipoatrophy) or thicken (lipo-hypertrophy) (may affect fewer than 1 in 100 people). Lumps under the skin may also be caused by accumulation 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. Change your injection site with each injection to prevent these skin changes.

List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (an eye disorder related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, the retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is normally a temporary phenomenon that soon disappears. If not, contact your doctor.
Painful neuropathy (nerve-related pain). If blood glucose improves very rapidly, it may cause pain originating in the nerve fibres. This is known as acute painful neuropathy and is normally transient.

Very rare side effects
May affect fewer than 1 in 10,000 people.
Visual disturbances: Visual disturbances may occur at the beginning of insulin treatment, but this reaction normally disappears.

Reporting of side effects
If you experience any of the side effects, inform your doctor, pharmacist or nurse. 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.

Effects of diabetes
High blood sugar level (hyperglycaemia)
You may have a high blood sugar level if:

You have not injected enough insulin.
You have forgotten to take insulin or stopped taking it.
You repeatedly inject less insulin than required.
You have an infection or fever.
You eat more than usual.
You do less physical activity than usual.

Warning symptoms of high blood sugar:
Symptoms develop gradually and 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 level 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 metabolising fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store Actraphane

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and on the packaging, after 'EXP'. The expiry date refers to the last day of the month.
When not in use, always keep the vial in the original packaging to protect it from light. Actraphane must be protected from excessive exposure to heat and light.
Before opening: store in a refrigerator at 2°C - 8°C. Keep away from refrigerating elements.
Do not freeze.
During use or when carried as a spare supply: do not refrigerate or freeze. It may be carried with you and stored at room temperature (below 25°C) for up to 6 weeks.
Always keep the vial in its packaging when not in use, to protect it from light.
Dispose of the needle and syringe after each injection.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Actraphane 30 contains

The active substance is human insulin. Actraphane is a mixture of 30% soluble insulin and 70% isophane human insulin. Each ml contains 40 IU of human insulin. Each vial contains 400 IU of human insulin in 10 ml of injectable suspension.
The excipients are zinc chloride, glycerol, m-cresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Description of the appearance of Actraphane and contents of the pack
Actraphane is presented as an injectable suspension. After resuspension, the liquid should appear uniformly white and milky.
Packs containing 1 or 5 vials of 10 ml or a multiple pack containing 5 packs of 1 x 10 ml vials. Not all pack sizes may be marketed.
The suspension is aqueous, white and milky.

Marketing Authorisation 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 updated on

Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Package leaflet: Information for the user

Actraphane 30 100 IU/ml (international units/ml) injectable suspension in vial

human insulin
Please read this leaflet carefully before using 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, pharmacist or nurse.
This medicine has been prescribed for you only. Never give it to others. It could be harmful even if their symptoms are the same as yours.
If you experience any adverse reaction, talk to your doctor, pharmacist or nurse. This includes any adverse reaction not listed in this leaflet. See section 4.

1. What Actraphane is and what it is used for

Actraphane is a human insulin with rapid-acting and prolonged action.
Actraphane is used to reduce high blood sugar levels in patients with diabetes mellitus (diabetes).
Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.
Treatment with Actraphane helps prevent complications of diabetes.
Actraphane begins to lower blood sugar levels within about 30 minutes after injection, and its effect lasts for approximately 24 hours.

2. What you need to know before using Actraphane

Do not use Actraphane
► If you are allergic to human insulin or to any of the other excipients of this medicine,
see section 6.
► If you experience warning signs of hypoglycaemia (low blood sugar levels),
see the summary of serious and very common side effects in section 4.
► In insulin infusion pumps.
► If the protective cap is loose or missing. Each vial has a tamper-proof plastic cap. If it is not in perfect condition when you receive the vial, return it to your supplier.
► If it has not been stored correctly or has been frozen, see section 5.
► If the resuspended insulin does not appear uniformly white and milky.
Do not use Actraphane if any of these situations apply. Speak with your doctor, pharmacist, or nurse for advice.

Before using Actraphane
► Check the label to make sure it is the correct type of insulin.
► Remove the protective seal.
► Always use a new needle for each injection to prevent contamination.
► Needles and syringes must not be shared.

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 these may affect 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 alter your insulin requirements and timing of doses.

Changes in the skin 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 well if you inject into an area with lumps, thinning, or thickening of the skin (see section 3). 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 medicines.

Other medicines and Actraphane
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines affect blood sugar levels, meaning your insulin dose may need to be adjusted. Listed below are the most common medicines that may affect 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 high blood pressure)
Angiotensin-converting enzyme (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 (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 gland disorders)
Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
Growth hormone (a medicine used to stimulate skeletal and somatic growth and significantly affecting the body's metabolic processes)
Danazol (a medicine that affects ovulation)

Pioglitazone (tablets used to treat type 2 diabetes mellitus)
Some patients with long-standing type 2 diabetes who have heart problems or a history of stroke and who have been 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, pharmacist, or nurse.

Actraphane and alcohol
► If you consume alcohol, your insulin requirement may change, as blood sugar levels may rise or fall. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, think you may be pregnant, or are planning a pregnancy,
ask your doctor for advice before taking this medicine. Actraphane can be used during pregnancy. Dose adjustments may be necessary during pregnancy and after delivery. It is important to carefully manage diabetes, particularly to prevent episodes of hypoglycaemia, for the health of both mother and baby.
► There are no restrictions on the use of Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse before taking any medicine during pregnancy or breastfeeding.

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

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

If your blood glucose is too high or too low, this may impair your concentration and reaction ability, and consequently your ability to drive or operate machinery. Be aware that you may put yourself and others at risk.

Actraphane contains sodium
Actraphane contains less than 1 mmol of sodium (23 mg) per dose, meaning that Actraphane is essentially “sodium-free”.

3. How to use Actraphane

Dosage and when to take insulin
Always use insulin and adjust the dose exactly as prescribed by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse.
Take a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar levels.
Do not change your insulin unless your doctor tells you to. If your doctor has changed the type or brand of insulin you are using, a dose adjustment may be necessary.

Use in children and adolescents
Actraphane can be used in children and adolescents.

How and where to inject
Actraphane is administered by subcutaneous injection (under the skin). Never inject insulin directly into a vein (intravenous route) or into muscle (intramuscular route). With each injection, rotate the injection site within the particular area of skin you usually use. This can reduce the risk of developing lumps or skin depressions; see section 4. The best areas for injection are: the abdominal area; the buttocks; the front of the thigh; or the upper arm. Insulin acts more quickly when injected into the abdomen. Always monitor your blood glucose levels regularly.

How to inject Actraphane
Actraphane in vials is designed to be used with insulin syringes calibrated in units.

Roll the vial gently between your hands until the liquid appears uniformly white and milky. Resuspension is easier when the insulin has reached room temperature.
Draw air into the syringe equal to the dose of insulin to be injected. Inject this air into the vial. Invert the vial and syringe, then withdraw the correct dose of insulin into the syringe. Remove the needle from the vial. Then expel the air from the syringe and check that the insulin dose is correct.

How to inject Actraphane
► Inject the insulin under your skin, using the injection technique recommended by your doctor or nurse.
► Keep the needle under the skin for at least 6 seconds to ensure the full dose has been delivered.
► Dispose of the needle and syringe after each injection.

If you take more insulin than you should
If you take too much insulin, your blood sugar level will drop too low (hypoglycaemia). See Summary of serious and very common adverse 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 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 what to do. Stopping treatment may lead to high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects of diabetes in section 4.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Summary of serious and very common side effects.
Low blood sugar level (hypoglycaemia) is a very common side effect. It may occur in more than 1 out of 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 Actraphane with alcohol in section 2.

Warning symptoms of low blood sugar: cold sweating; cold and pale skin; headache; rapid heartbeat; feeling unwell; hunger sensation; temporary visual 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 (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 who knows how to use 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 level 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.
► Once symptoms of hypoglycaemia have disappeared or your blood glucose has stabilized, continue your insulin treatment.
► If you have a low blood sugar level, you may lose consciousness. If you required a glucagon injection, or if you have frequent episodes of low blood sugar, consult your doctor. A dose adjustment of insulin, timing of meals, and physical activity may be necessary.
Inform people close to you that you are diabetic and explain the possible consequences, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they should turn you onto your side and immediately call for medical help. It is important that no food or drink is given to you, as you could choke.

Severe allergic reaction to Actraphane or to one of its excipients (called systemic allergic reaction) is a rare side effect but may be potentially life-threatening. It may occur in fewer than 1 out of 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; your heartbeat becomes rapid; you 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 is unknown). 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.

List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (an eye disorder related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, the retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is usually a temporary condition that resolves quickly. If not, contact your doctor.
Painful neuropathy (nerve-related pain): If your blood glucose improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy and is usually transient.

Very rare side effects
May affect fewer than 1 in 10,000 people.
Visual disturbances: Visual disturbances may occur at the beginning of insulin treatment, but this reaction usually resolves.

Reporting of side effects
If you experience any of the side effects, inform your doctor, pharmacist, or nurse. 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.

Effects of diabetes
High blood sugar level (hyperglycaemia)
You may have a high blood sugar level 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 or fever.
You eat more than usual.
You exercise less than usual.

Warning symptoms of high blood sugar:
Warning symptoms 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 level is high:
► If you experience any of these symptoms: check your blood glucose, and 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 due to the body metabolizing fat instead of sugar). If left untreated, it may lead to diabetic coma and possibly death.

5. How to store Actraphane

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the vial label and packaging, after 'EXP'. The expiry date refers to the last day of the month.
Before opening: store in a refrigerator at 2°C - 8°C. Keep away from cooling elements.
Do not freeze.
During use or when carried as a spare: do not freeze or refrigerate. It may be carried with you and kept at room temperature (below 25°C) for up to 6 weeks.
When not in use, always keep the vial in the original packaging to protect it from light.
Dispose of the needle and syringe after each injection.
Do not dispose of medicines 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 Actraphane 30 contains

The active substance is human insulin. Actraphane is a mixture of 30% soluble insulin and 70% human isophane insulin. Each ml contains 100 IU of human insulin. Each vial contains 1000 IU of human insulin in 10 ml of injectable suspension.
The excipients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Description of the appearance of Actraphane and contents of the pack
Actraphane is presented as an injectable suspension. After resuspension, the liquid should appear uniformly white and milky.
Packs of 1 or 5 vials of 10 ml or in a multiple pack of 5 packs of 1 x 10 ml vials. Not all pack sizes may be marketed.
The suspension is aqueous, white and milky.

Marketing Authorisation 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 updated on

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Package leaflet: Information for the user

Actraphane 30 Penfill 100 UI/ml (international units/ml) injectable suspension in cartridge
human insulin
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

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

Contents of this leaflet

What Actraphane is and what it is used for
What you need to know before using Actraphane
How to use Actraphane
Possible side effects
How to store Actraphane
Contents of the pack and other information

1. What Actraphane is and what it is used for

Actraphane is a human insulin with rapid-acting and prolonged action.
Actraphane 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.
Treatment with Actraphane helps prevent complications of diabetes.
Actraphane begins to lower blood sugar levels within 30 minutes after injection, and its effect lasts for approximately 24 hours.

2. What you need to know before using Actraphane

Do not use Actraphane
► If you are allergic to human insulin or to any of the other excipients of this medicine,
see section 6.
► If you experience warning signs of hypoglycaemia (low blood sugar levels),
see the summary of serious and very common side effects in section 4.
► In insulin infusion pumps
► If the cartridge or the device containing the cartridge has been dropped, damaged, or cracked
► If it has not been stored correctly or has been frozen, see section 5
► If the resuspended insulin does not appear uniformly white and cloudy.
Do not use Actraphane if any of these situations apply. Speak to your doctor, pharmacist, or nurse
for advice.

Before using Actraphane
► Check the label to make sure you are using the correct type of insulin.
► Always inspect the cartridge, including the rubber plunger at the top of the cartridge. Do not use it if it appears damaged or if the rubber plunger has been pushed beyond the white band at the top of the cartridge. This could lead to insulin leakage.
If you suspect the cartridge is 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 Actraphane Penfill must not be shared.
► Actraphane 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 or liver problems, or disorders of the adrenal, pituitary, or thyroid glands.
► If you have increased physical activity or changes in your usual diet, as these 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
Injection sites should be rotated 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 injected into an area with lumps, thinning, or thickening (see section 3). Inform your doctor if you notice skin changes at the injection site. If you currently inject into such an affected area, consult your doctor before switching to another site. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or other antidiabetic medications.

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 high blood pressure)
Angiotensin-converting enzyme (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 (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 gland disorders)
Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
Growth hormone (a medicine used to stimulate skeletal and somatic 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 blood sugar levels.
Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar.

Pioglitazone (tablets used to treat type 2 diabetes mellitus)
Some patients with long-standing type 2 diabetes mellitus 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 (edema).
If you are taking any of the medicines listed above, inform your doctor, pharmacist, or nurse.

Actraphane with alcohol
► If you consume alcohol, your insulin requirement may change because blood sugar levels may increase or decrease. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, suspect you are pregnant, or are planning a pregnancy,
consult your doctor before using this medicine. Actraphane can be used during pregnancy.
Your insulin dose 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 mother and baby.
► There are no restrictions on using Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse 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 use machinery:

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

If your blood sugar is too high or too low, your ability to concentrate and react may be impaired, which could affect your ability to drive or operate machinery. Be aware that you may put yourself and others at risk.

Actraphane contains sodium
Actraphane contains less than 1 mmol of sodium (23 mg) per dose, meaning that Actraphane is essentially “sodium-free”.

3. How to use Actraphane

Dosage and when to take insulin
Always use insulin and adjust the dose according to your doctor's instructions. If you are unsure, consult your doctor, pharmacist, or nurse.
Take a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar levels.
Do not change your insulin unless your doctor tells you to. If your doctor has switched the type or brand of insulin you are using, a dose adjustment may be necessary.

Use in children and adolescents
Actraphane can be used in children and adolescents.

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

How and where to inject
Actraphane is administered by subcutaneous injection (under the skin). Never inject insulin directly into a vein (intravenous) or into muscle (intramuscular). Actraphane Penfill is intended only for subcutaneous injections using a reusable pen. Talk to your doctor if you need to administer insulin by another method.
With each injection, rotate the injection site within the particular area of skin you usually use. This can reduce the risk of developing lumps or skin depressions—see section 4. The best areas for injection are: the abdomen; the buttocks; the front of the thigh; or the upper arm. Insulin acts more quickly when injected into the abdomen. Always monitor your blood glucose levels regularly.
► Do not refill the cartridge. Once empty, it must be discarded.
► Actraphane Penfill cartridges are designed to be used with Novo Nordisk insulin delivery devices and NovoFine or NovoTwist needles.
► If, in addition to Actraphane Penfill, you have been prescribed another insulin in a Penfill cartridge, you must use two separate insulin delivery devices—one for each type of insulin.
► Always carry a spare cartridge with you in case the one in use is lost or damaged.

Resuspension of Actraphane
Always check that there is enough insulin remaining (at least 12 units) in the cartridge to allow for resuspension. If there is not enough insulin remaining, use a new cartridge. Refer to the pen user manual for further instructions.
► Each time you use a new Actraphane Penfill (before inserting the cartridge into the insulin device):

Allow the insulin to reach room temperature before use. This will facilitate resuspension.
Gently move the cartridge up and down between positions a and b and back again (see figure), ensuring the glass bead travels from one end of the cartridge to the other, at least 20 times.
Repeat this movement at least 10 times before each injection.
Always repeat the movement until the liquid appears uniformly white and milky.
Immediately complete the other steps illustrated below.

Linear drawing of an arm rotating between two positions indicated by a curved arrow going from position a to position b

How to inject Actraphane
► Inject the insulin under your skin. Use the injection technique recommended 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 injection button fully pressed until the needle is removed from the skin. This ensures proper delivery and minimizes the risk of blood flowing back into the needle or insulin reservoir.
► After each injection, remove and dispose of the needle. Store Actraphane without the needle attached. Otherwise, liquid may leak out, which could result in an inaccurate dose.

If you take more insulin than you should
If you take too much insulin, your blood sugar level will drop too low (hypoglycaemia). See 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 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 treatment may lead to high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects of diabetes in section 4.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Summary of serious and very common side effects.
Low blood sugar (hypoglycaemia) is a very common side effect. It may occur in more than 1 person in 10.
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 consume alcohol; see Actraphane with alcohol in section 2.

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; hunger sensation; 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 prolonged hypoglycaemia is not treated, it may cause brain damage (transient or permanent) and may even result in death. Recovery of consciousness may be faster with an injection of the hormone glucagon given by someone trained to use 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 lumps or another sugary snack (sweets, biscuits, fruit juice). Check your blood sugar if possible, then rest. Always carry sugar lumps, sweets, biscuits or fruit juice with you to use when needed.
► When symptoms of hypoglycaemia have disappeared or when your blood glucose has stabilised, continue your insulin treatment.
► If you experience low blood sugar, you may lose consciousness. If you have required a glucagon injection, or if you have frequent episodes of low blood sugar, consult your doctor. A dose adjustment of insulin, changes in meal times and physical activity may be necessary.
Inform people close to you that you are diabetic and explain the possible consequences, 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 you could choke.

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 thin (lipoatrophy) or thicken (lipohypertrophy) (affecting fewer than 1 in 100 people). Lumps under the skin may also be caused by the accumulation 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 of the skin. Change your injection site with each injection to prevent these skin changes.

List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (an eye disorder related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, the retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is usually a temporary condition that soon resolves. If it does not, contact your doctor.
Painful neuropathy (nerve-related pain): If blood glucose improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy and is usually transient.

Other reported side effects
Very rare side effects
May affect fewer than 1 in 10,000 people.
Visual disturbances: Visual disturbances may occur at the beginning of insulin treatment, but this reaction normally resolves.

Reporting of side effects
If you experience any of the side effects, tell your doctor, pharmacist or nurse. 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.

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 stopped taking it.
You repeatedly take less insulin than required.
You have an infection or fever.
You eat more than usual.
You do less physical activity than usual.

Warning signs of high blood sugar:
Warning signs appear gradually. They 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; 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 metabolising fat instead of sugar).
If left untreated, this may lead to diabetic coma and possibly death.

5. How to store Actraphane

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 packaging, following 'EXP'. The expiry date refers to the last day of the month.
Before first use: store in a refrigerator at 2°C - 8°C. Keep away from cooling elements.
Do not freeze.
During use or when carried as a spare: do not freeze or refrigerate. It may be carried with you and kept at room temperature (below 30°C) for up to 6 weeks.
When not in use, always keep the cartridge in its original packaging to protect it from light.
Dispose of the needle after each injection.
Do not dispose of medicines 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 Actraphane 30 Contains

The active substance is human insulin. Actraphane is a mixture of 30% soluble insulin and 70% human isophane insulin. Each ml contains 100 IU of human insulin. Each cartridge contains 300 IU of human insulin in 3 ml of injectable suspension.
The excipients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Description of the Appearance of Actraphane and Contents of the Pack
Actraphane is a white, opaque injectable suspension. After resuspension, the liquid should appear uniformly white and cloudy.
Packs containing 1, 5, or 10 cartridges of 3 ml. Not all pack sizes may be marketed.
The suspension is aqueous, white, and cloudy.
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’Orleans
F-28000 Chartres,
France
This leaflet was last updated on
Other Sources of Information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Package leaflet: Information for the user

Actraphane 30 InnoLet 100 IU/ml (international units/ml) injectable suspension in pre-filled pen

human insulin
Please read all of this leaflet carefully before using 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, pharmacist, or nurse.
This medicine has been prescribed for you only. Never give it to others. This medicine may be harmful to other people even if their symptoms are the same as yours.
If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

What Actraphane is and what it is used for
What you need to know before using Actraphane
How to use Actraphane
Possible side effects
How to store Actraphane
Contents of the pack and other information

1. What Actraphane is and what it is used for

Actraphane is a human insulin with rapid-acting and prolonged action.
Actraphane 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.
Treatment with Actraphane helps prevent complications of diabetes.
Actraphane begins to lower blood sugar levels within approximately 30 minutes after injection, and its effect lasts for about 24 hours.

2. What you need to know before using Actraphane

Do not use Actraphane
► If you are allergic to human insulin or to any of the other excipients of this medicine,
consult section 6.
► If you experience warning signs of hypoglycaemia (low blood sugar),
refer to the Summary of serious and very common adverse reactions in section 4.
► In insulin pumps
► If the InnoLet has been dropped, damaged, or cracked
► If it has not been stored correctly or has been frozen; see section 5
► If the resuspended insulin does not appear uniformly white and cloudy.
Do not use Actraphane if any of these situations apply. Speak to your doctor, pharmacist, or nurse
for advice.

Before using Actraphane
► 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 Actraphane InnoLet must not be shared.
► Actraphane InnoLet is intended only for subcutaneous injection. Speak to 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 disorders, or abnormalities of the adrenal glands, pituitary gland, or thyroid
► 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; travelling 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 thickening, thinning, or the development of lumps (nodules).
Insulin may not work as effectively if injected into an area with lumps, thinning, or thickening of the skin (see section 3). Inform your doctor if you notice skin changes at the injection site. If you are currently injecting into such an affected area, consult your doctor before switching to another site. Your doctor may advise you to monitor your blood glucose more closely and possibly adjust your insulin dose or other antidiabetic medications.

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 high blood pressure)
Angiotensin-converting enzyme (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)
Sulphonamides (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 somatic growth and significantly affecting the body’s metabolic processes)
Danazol (a medicine affecting ovulation)

Pioglitazone (tablets used to treat type 2 diabetes mellitus)
Some patients with long-standing type 2 diabetes who have heart problems or a history of stroke and who are 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, pharmacist, or nurse.

Actraphane and alcohol
► If you consume alcohol, your insulin requirement may change, as blood sugar levels may rise or fall. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, think you may be pregnant, or are planning to become pregnant,
ask your doctor for advice before taking this medicine. Actraphane can be used during pregnancy.
Your insulin dose 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 mother and baby.
► There are no restrictions on using Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse before taking any medicine during pregnancy or breastfeeding.

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

If you frequently experience hypoglycaemia
If you have difficulty recognizing the warning signs of hypoglycaemia

High or low blood sugar levels can impair your concentration and reaction ability, and therefore your capacity to drive or operate machinery. Be aware that you could endanger yourself or others.

Actraphane contains sodium
Actraphane contains less than 1 mmol of sodium (23 mg) per dose, i.e. Actraphane is essentially “sodium-free”.

3. How to use Actraphane

Dose and when to take insulin
Always use insulin and adjust the dose exactly as prescribed by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse.
Take a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar (hypoglycaemia).
Do not change your insulin unless your doctor tells you to. If your doctor has changed the type or brand of insulin you use, your dose may need to be adjusted by your doctor.

Use in children and adolescents
Actraphane can be used in children and adolescents.

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
Actraphane is administered by subcutaneous injection (under the skin). Never inject insulin directly into a vein (intravenous route) or into muscle (intramuscular route). Actraphane InnoLet is intended only for subcutaneous injections. Speak with your doctor if you need to administer insulin by another method.
For each injection, rotate the injection site within the particular area of skin you usually use. This can reduce the risk of developing lumps or skin depressions—see section 4. The best areas for injection are: the abdominal area; the buttocks; the front of the thigh; or the upper arm. Your insulin will act more quickly if injected into the abdomen. Always monitor your blood glucose regularly.

How to inject Actraphane 30 InnoLet
Actraphane 30 InnoLet is a pre-filled pen containing a mixture of fast-acting insulin and long-acting human insulin in a 30/70 ratio.
Carefully read the Instructions for Use included in the package leaflet. You must use the pen exactly as described in the Instructions for Use for Actraphane 30 InnoLet.
Always make sure you are using the correct pen before administering 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 Summary of serious and very common adverse reactions 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 Effects of diabetes in section 4.

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

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

4. Possible side effects

Summary of serious and very common side effects
Low blood sugar (hypoglycaemia) is a very common side effect. It may affect 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 do more physical activity than usual.
You consume alcohol; see Actraphane with alcohol in section 2.

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; 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 prolonged severe hypoglycaemia is not treated, it may cause brain damage (transient or permanent) and may even result in death. Recovery may be faster with an injection of the hormone glucagon given by someone trained to administer 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 immediately.
What to do if your blood sugar is low:
► If your blood sugar is too low, eat sugar lumps or another sugary snack (candies, biscuits, fruit juice). Test your blood sugar if possible, then rest. Always carry sugar lumps, candies, biscuits or fruit juice with you to use if needed.
► Once symptoms of hypoglycaemia have subsided or your blood glucose has stabilised, continue your insulin treatment.
► If you experience low blood sugar, lose consciousness, require a glucagon injection, or have frequent episodes of low blood sugar, consult 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 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 you could choke.

Severe allergic reaction to Actraphane or one of its excipients (called systemic allergic reaction) is a rare side effect but may be potentially life-threatening. It may affect 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; your heartbeat becomes rapid; you 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 thin (lipoatrophy) or thicken (lipohypertrophy) (may affect fewer than 1 in 100 people). Lumps under the skin may also be caused by the accumulation 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.

List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (a diabetes-related eye disorder that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, your retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is usually a temporary condition that soon resolves. If not, contact your doctor.
Painful neuropathy (nerve-related pain). If your blood glucose improves very rapidly, it may cause pain originating in the nerve fibres. This is known as acute painful neuropathy and is usually temporary.

Very rare side effects
May affect fewer than 1 in 10,000 people
Visual disturbances. Visual disturbances may occur at the beginning of insulin treatment, but this reaction normally resolves spontaneously.

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 stopped taking it.
You repeatedly take less insulin than required.
You have an infection or fever.
You eat more than usual.
You do less physical activity 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, 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 due to the body metabolising fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store Actraphane

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the InnoLet label and on the packaging after 'EXP'. The expiry date refers to the last day of the month.
Before opening: store in a refrigerator at 2°C - 8°C. Keep away from refrigerating elements.
Do not freeze.
During use or when carried as a spare: do not refrigerate or freeze. It may be carried with you and kept at room temperature (below 30°C) for up to 6 weeks.
When not in use, always keep the pen cap on the InnoLet to protect it from light.
Dispose of the needle after each injection.
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. Package Contents and Other Information

What Actraphane 30 Contains

The active substance is human insulin. Actraphane is a mixture of 30% soluble human insulin and 70% isophane human insulin. Each ml contains 100 IU of human insulin. Each pre-filled pen contains 300 IU of human insulin in 3 ml of injectable suspension.
The excipients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Description of the Appearance of Actraphane and Contents of the Package
Actraphane is a white, opaque injectable suspension. After resuspension, the liquid should appear uniformly white and cloudy.
Pack sizes: 1, 5, and 10 pre-filled pens of 3 ml. Not all pack sizes may be marketed.
The suspension is aqueous, white, and cloudy.
Marketing Authorization Holder and Manufacturer
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark
This leaflet was last updated on
Other Sources of Information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.
For instructions on how to use your InnoLet, please turn the page
Instructions for using Actraphane 30 injectable suspension in InnoLet.
Read these instructions carefully before using your InnoLet. If you do not follow these instructions exactly, you may inject too much or too little insulin, which could lead to blood sugar levels that are too high or too low.
The InnoLet is a simple, compact pre-filled pen capable of delivering 1 to 50 units of insulin in 1-unit increments. The InnoLet is designed to be used with NovoFine or NovoTwist disposable needles up to 8 mm in length. As a precaution, always carry a spare insulin delivery device in case your InnoLet is lost or damaged.

Blue technical diagrams of a medical device InnoLet with graduated dial, millimetric scale, separated components, and assembly instructions

Getting Started
Check the name and the colored label of your InnoLet to ensure it contains the correct type of insulin. This is especially important if you use more than one type of insulin. Using the wrong type of insulin may cause your blood sugar level to become too high or too low.
Remove the pen cap. It is easier to resuspend the insulin if it has reached room temperature.

Resuspending the Insulin
Before each injection:

To ensure uniform mixing, verify that at least 12 units of insulin remain in the cartridge. If less than 12 units remain, use a new InnoLet.
Gently move the pen between positions A and B back and forth so that the glass ball moves from one end of the insulin cartridge to the other at least 20 times (Figure 1A). Repeat this movement 10 times before each subsequent use. Always continue this motion until the liquid appears uniformly white and cloudy.
Always resuspend the insulin before each injection. Failure to resuspend the insulin may result in inaccurate dosing, which could cause your blood sugar level to become too high or too low. After resuspending, proceed immediately with the steps illustrated below.

Medical illustration showing a hand rotating a medical device from

Attaching the Needle

Always use a new needle for each injection. This reduces the risk of infection, insulin contamination, insulin leakage, needle blockage, and incorrect dosing.
Be careful not to bend or damage the needle before use.
Remove the protective seal from a new disposable needle.
Screw the needle firmly and perpendicularly onto the InnoLet (Figure 1B).
Remove the outer large needle cap and the inner needle cap. You may find it helpful to store the large outer needle cap in its designated compartment.
Never attempt to re-screw the inner needle cap back onto the needle. You may injure yourself with the needle.

Technical illustration of a medical device with a blue curved arrow indicating counterclockwise rotation of the upper cap

Preparing to Remove Air Before Each Injection
Small amounts of air may accumulate in the needle and insulin cartridge during normal use.
To avoid injecting air and to ensure the correct dose of insulin is delivered:

Select 2 units by turning the dose selector clockwise.
Hold the InnoLet with the needle pointing upward and gently tap the insulin cartridge several times with your fingers (Figure 1C), so that air bubbles collect at the top of the cartridge.
While keeping the needle pointing upward, press the injection button fully. The dose selector will return to 0.
Always ensure a drop of insulin appears at the tip of the needle (Figure 1C) before injection. This confirms insulin flow. If no drop appears, change the needle and repeat the procedure no more than 6 times.

If no drop of insulin appears after repeated attempts, the device may be defective and must not be used.

If no drop appears, insulin will not be injected, even if the dose selector moves. This may indicate a blocked or damaged needle.
Always check your InnoLet before injection. If you do not check it, you may inject too little insulin or none at all, which could lead to high blood sugar levels.

A hand holds a graduated syringe containing liquid

Selecting the Dose

Always ensure the injection button is fully pressed and the dose selector is set to 0.
Select the number of units to be injected by rotating the dose selector clockwise (Figure 2).
You will hear a click for each single unit selected. The dose can be adjusted by rotating the selector in either direction. Do not rotate the dose selector or adjust the dose while the needle is inserted into the skin, as this may result in inaccurate dosing, leading to blood sugar levels that are too high or too low.

Always use the dose scale and dose selector to verify how many units you have selected before injecting insulin. 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 remaining scale—it only approximately indicates how much insulin is left in the pen.
You cannot select a dose greater than the number of units remaining in the cartridge.

Diagram of a timer with numbers from 0 to 50 and two blue curved arrows indicating clockwise rotation between numbers 0 and 30

Injecting the Insulin

Insert the needle into the skin. Use the injection technique recommended by your doctor.
Administer the insulin dose by fully pressing the injection button (Figure 3). You will hear clicks as the dose selector returns to 0.
After injection, wait at least 6 seconds before removing the needle to ensure complete delivery of the dose.
Ensure the dose selector is not blocked during injection, as it must be free to return to 0 when the injection button is pressed. Always confirm 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.
Remove the needle after each injection.

Two hands hold a circular medical device with a numbered dial from 0 to 50 and a blue arrow pointing downward

Removing the Needle

Place the large outer protective cap on the needle and unscrew it (Figure 4). Dispose of the needle carefully.
Replace the pen cap on your InnoLet to protect the insulin from light.

Always use a new needle for each injection.
Always remove and dispose of the needle after each injection, and store the InnoLet without a needle attached. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and inaccurate dosing.
Additional Important Information
Anyone handling used needles must take great care to reduce the risk of needle-stick injuries and cross-infections.
Dispose of used InnoLet pens carefully, ensuring the needle has been removed.
Never share the pen or needles with other people. This may lead to cross-infection.
Never share the pen with other people. The medicine may be dangerous to their health.
Always keep the InnoLet and needles out of sight and reach of others, especially children.
Pen Maintenance
Your InnoLet is designed to function accurately and safely. Handle it with care. If it has been dropped, damaged, or compromised, insulin leakage may occur. This could lead to incorrect dosing, resulting in blood sugar levels that are too high or too low.
You may clean the exterior of the InnoLet by wiping it with a disinfectant swab. Do not immerse, wash, or lubricate it, as this may damage the mechanism and cause incorrect dosing, leading to high or low blood sugar levels.
Do not refill the InnoLet. Once empty, it must be discarded.

Package leaflet: Information for the user

Actraphane 30 FlexPen 100 IU/ml (international units/ml) injectable suspension in a pre-filled pen

Human insulin
Please read this leaflet carefully before you start 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, pharmacist, or nurse.
This medicine has been prescribed for you only. Never give it to others. It may be harmful even if their symptoms are the same as yours.
If you experience any side effect, talk to your doctor, pharmacist, or nurse. This includes any side effect not listed in this leaflet. See section 4.

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

1. What Actraphane is and what it is used for

Actraphane is human insulin with rapid-acting and prolonged action.
Actraphane 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.
Treatment with Actraphane helps prevent complications of diabetes.
Actraphane begins to lower blood sugar levels within 30 minutes after injection, and its effect lasts for approximately 24 hours.

2. What you should know before using Actraphane

Do not use Actraphane
► If you are allergic to human insulin or to any of the other excipients of this medicine,
see section 6.
► If you are experiencing warning signs of hypoglycaemia (low blood sugar level),
see the Summary of serious and very common side effects in section 4.
► In insulin pumps.
► If the FlexPen has been dropped, damaged, or cracked.
► If it has not been stored correctly or has been frozen, see section 5.
► If the resuspended insulin does not appear uniformly white and cloudy.
Do not use Actraphane if any of these situations apply. Speak to your doctor, pharmacist, or nurse
for advice.

Before using Actraphane
► 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 Actraphane FlexPen must not be shared.
► Actraphane FlexPen is intended only for subcutaneous injection. Speak to 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 disorders, or abnormalities affecting the adrenal gland, pituitary gland, or thyroid gland.
► 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.

Changes in the skin at the injection site
Injection sites should be rotated 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 injected into an area with lumps, thinning, or thickening of the skin (see section 3). Inform your doctor if you notice skin changes at the injection site. If you are currently injecting 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 adjust your insulin dose or other antidiabetic medications.

Other medicines and Actraphane
Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines affect blood sugar levels, meaning your insulin dose may need to be adjusted. Listed below are the most common medicines that may affect 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 high blood pressure)
Angiotensin-converting enzyme (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)
Sulphonamides (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 gland disorders)
Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
Growth hormone (a medicine used to stimulate skeletal and somatic growth and significantly affecting 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 blood sugar levels.
► Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the warning symptoms that help you recognize low blood sugar levels.

Pioglitazone (an oral antidiabetic tablet used to treat type 2 diabetes mellitus)
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, pharmacist, or nurse.

Actraphane and alcohol
► If you consume alcohol, your insulin requirement may change because blood sugar levels may rise or fall. Careful monitoring is recommended.

Pregnancy and breastfeeding
► If you are pregnant, think you may be pregnant, or are planning to become pregnant,
ask your doctor for advice before taking this medicine. Actraphane can be used during pregnancy.
Your insulin dose may need to be adjusted during pregnancy and after delivery. It is important to carefully manage your diabetes, particularly to prevent episodes of hypoglycaemia, for the health of both you and your baby.
► There are no restrictions on the use of Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse 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 too high or too low, your ability to concentrate and react may be impaired, thereby affecting your ability to drive or operate machinery. Be aware that this could put yourself and others at risk.

Actraphane contains sodium
Actraphane contains less than 1 mmol of sodium (23 mg) per dose, i.e., Actraphane is essentially “sodium-free”.

3. How to use Actraphane

Dose and when to take insulin
Always use insulin and adjust the dose exactly as prescribed by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse.
Eat a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar (hypoglycaemia).
Do not change your insulin unless your doctor tells you to. If your doctor has switched the type or brand of insulin you are using to another, your dose may need to be adjusted by your doctor.

Use in children and adolescents
Actraphane can be used in children and adolescents.

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

How and where to inject
Actraphane is administered by subcutaneous injection (injected under the skin). Do not inject insulin directly into a vein (intravenous route) or into a muscle (intramuscular route). The Actraphane FlexPen is intended only for subcutaneous injections. Talk to your doctor if you need to administer insulin by another method.
With each injection, rotate your 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. The best areas for injection are: the abdominal area; the buttocks; the front of the thigh; or the upper arm. Insulin will act more quickly if injected into the abdomen. Always monitor your blood glucose levels regularly.

How to inject Actraphane 30 FlexPen
Actraphane 30 FlexPen is a pre-filled pen containing a mixture of fast-acting insulin and long-acting human insulin in a 30/70 ratio.
Read carefully the Instructions for Use included in the package leaflet.
You must use the pen exactly as described in the Instructions for Use for Actraphane 30 FlexPen.
Always make sure you are using the correct pen before administration.

If you take more insulin than you should
If you take too much insulin, your blood sugar level may drop too low (hypoglycaemia). See 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 (hyperglycaemia). See Effects of diabetes in section 4.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Summary of serious and 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 Actraphane with alcohol in section 2.

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; hunger sensation; temporary visual 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 can 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 trained in its use. If glucagon is administered, 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 level is low:
► If your blood sugar is too low, eat sugar cubes or another sugary snack (candies, biscuits, fruit juice). Check your blood sugar if possible, then rest. Always carry sugar cubes, candies, biscuits or fruit juice with you to use if needed.
► Once symptoms of hypoglycaemia have disappeared or 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, consult your doctor. A dose adjustment of insulin, as well as changes in meal timing and physical activity, may be necessary.
Inform people close to you that you are diabetic and explain the possible consequences, including the risk of fainting due to hypoglycaemia. Explain that if you faint, they should turn you on your side and seek immediate medical help. It is important not to give you food or drink as you could choke.

Severe allergic reaction to Actraphane or to any of its excipients (called systemic allergic reaction) is a rare side effect but 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: start sweating; feel sick (nausea or vomiting); have difficulty breathing; your heartbeat becomes rapid; you 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 not known). Insulin may not work as effectively if injected into areas with lumps, thinning, or thickening. Rotate your injection site with each injection to prevent these skin changes.

List of other side effects
Uncommon side effects
May affect fewer than 1 person in 100
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (an eye disorder related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, the retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is usually a temporary condition that resolves quickly. If not, contact your doctor.
Painful neuropathy (nerve-related pain): If blood glucose improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy and is usually transient.

Very rare side effects
May affect fewer than 1 person in 10,000
Visual disturbances: Visual disturbances may occur at the beginning of insulin treatment, but this reaction normally resolves spontaneously.

Reporting of side effects
If you experience any of the side effects, tell your doctor, pharmacist, or nurse. 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.

Effects of diabetes
High blood sugar level (hyperglycaemia)
You may experience 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 or fever.
You eat more than usual.
You do less physical activity 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 level 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 due to the body metabolizing fat instead of sugar).
If left untreated, it may lead to diabetic coma and possibly death.

5. How to store Actraphane

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.
Before opening: store in a refrigerator at 2°C - 8°C. Keep away from cooling elements.
Do not freeze.
During use or when carried as a spare: do not refrigerate or freeze. It may be carried with you
and kept at room temperature (below 30°C) for up to 6 weeks.
When not in use, always keep the pen cap on the FlexPen to protect it from light.
Dispose of the needle after each injection.
Do not dispose of medicines 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 Actraphane 30 Contains

The active substance is human insulin. Actraphane is a mixture of 30% soluble insulin and 70% isophane insulin. Each ml contains 100 IU of human insulin. Each pre-filled pen contains 300 IU of human insulin in 3 ml of injectable suspension.
The excipients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

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’Orleans
F-28000 Chartres,
France

This leaflet was last updated on
Other Sources of Information
More detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.
For instructions on how to use your FlexPen, please turn the page.
Instructions for using Actraphane 30 injectable suspension in FlexPen.
Read these instructions carefully before using the FlexPen. If you do not follow these instructions exactly, 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 single-use, pre-filled pen for variable-dose insulin administration. You can select a dose between 1 and 60 units in 1-unit increments. The FlexPen has been designed and tested for use with NovoFine or NovoTwist disposable needles up to 8 mm in length. As a precaution, always carry a spare insulin delivery device in case your FlexPen is lost or damaged.

Exploded diagram of a blue injector pen with separated components including cap, graduated body, orange cap, caps, and needle

Pen Maintenance
Handle your FlexPen with care.
If it leaks or has been dropped, it may be damaged and insulin may be lost. This could lead to incorrect dosing, resulting in 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, as this may damage its mechanism.
Do not refill your FlexPen. Once empty, it must be discarded.

Preparing Actraphane 30 FlexPen
A
Check the name and the colored label on your pen to ensure it contains the correct type of insulin. This is very 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 makes resuspension easier. Remove the pen cap (see A).

A hand holds a blue and white cylindrical medical device while an arrow indicates a sliding movement to the right

B
Before each injection with a new FlexPen, you must resuspend the insulin:
Turn the pen upside down and back up 20 times as shown, ensuring the glass ball moves from one end of the cartridge to the other. Repeat this procedure until the liquid appears uniformly white and milky.
For each subsequent injection, turn the pen upside down and back up at least 10 times until the liquid appears uniformly white and milky.
Always resuspend the insulin before each injection. This reduces the risk of high or low blood sugar levels. After resuspending, proceed quickly to the next steps.

Medical illustration showing a hand rotating a syringe from a vertical to a horizontal position via a blue curved arrow

Always ensure there are at least 12 units of insulin remaining in the cartridge to allow proper resuspension. If less than 12 units remain, use a new FlexPen. 12 units are marked on the scale. Refer to the large illustration at the top of the instructions.
Do not use the pen if the resuspended insulin does not appear uniformly white and milky.

Attaching the Needle
C
Remove the protective seal from a new disposable needle.
Screw the needle firmly and perpendicularly onto your FlexPen.

A hand holds an injection pen with a blue arrow indicating removal of the protective cap upward

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

A hand holds a medical device and inserts it with a movement indicated by a blue arrow into another cylindrical component

E
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 to prevent contamination. 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
F
During normal use, small amounts of air may accumulate in the cartridge before each injection. To avoid injecting air and to ensure you deliver the correct dose of insulin:
Rotate the dose selector to select 2 units.

Illustration of a hand rotating the upper part of a blue injection pen with a curved arrow and a dosage detail on a numerical scale

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

Illustration of a hand next to a medical vial with a needle inserted into the stopper for drug preparation

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

Medical illustration showing a hand lifting a blue injection device with an upward-pointing arrow

Always ensure a drop appears at the needle tip before injecting. This confirms insulin is flowing. 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. 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
I
Ensure the dose selector is at 0.
Rotate the dose selector to set the number of units to be injected.
You can increase or decrease the dose by rotating the selector in either direction until the indicator shows the correct dose. While rotating the dose selector, be careful not to press the injection button, as this may cause insulin to leak.
You cannot select a dose greater than the number of units remaining in the cartridge.

Illustration of an injection pen with an arrow indicating rotation of the dial to adjust dosage between 4-6 and 24-26 units

Before injecting insulin, always use the dose selector and indicator to confirm the selected dose.
Do not count the clicks of the pen. Selecting or injecting the wrong dose may cause your blood sugar level to become too high or too low. Do not rely on the scale on the pen body, which only roughly indicates how much insulin remains in the pen.

Injection
J
Insert the needle into the skin. Use the injection technique shown by your doctor or nurse.
Administer the insulin dose by pressing the injection button fully until the indicator reaches 0. Be sure to press only the injection button.
Rotating the dose selector will not deliver insulin.

A hand presses a finger on the cap of a blue vial while a

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

Medical illustration of a syringe-shaped medical device positioned vertically above a flat, clear surface

L
Place the needle tip into the outer needle cap without touching it. Once covered, carefully press the outer cap fully onto the needle and then unscrew the needle.
Dispose of the needle carefully and replace the pen cap.

Two diagrams show how to separate and then rejoin components of a medical device using blue directional arrows on a white background

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 must 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 others. The medicine may be harmful to their health.
Always keep the pen and needles out of sight and reach of others, especially children.

Package leaflet: Information for the user

Actraphane 50 Penfill 100 IU/ml (international units/ml) injectable suspension in cartridge
human insulin
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. It may be harmful to others, even if their symptoms are the same as yours.
If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet

What Actraphane is and what it is used for
What you need to know before using Actraphane
How to use Actraphane
Possible side effects
How to store Actraphane
Contents of the pack and other information

1. What Actraphane is and what it is used for

Actraphane is a human insulin with rapid and prolonged action.
Actraphane is used to reduce high blood sugar levels in patients with diabetes mellitus (diabetes).
Diabetes is a disease in which the body does not produce enough insulin to control blood sugar levels.
Treatment with Actraphane helps prevent complications of diabetes.
Actraphane begins to reduce blood sugar levels approximately 30 minutes after injection, and its effect lasts for about 24 hours.

What you need to know before using Actraphane

Do not use Actraphane

► If you are allergic to human insulin or to any of the other excipients of this medicine, see section 6.
► If you experience warning signs of hypoglycaemia (low blood sugar), see the Summary of serious and very common adverse reactions in section 4.
► In insulin infusion pumps.
► If the cartridge or the device containing the cartridge has been dropped, damaged, or cracked.
► If it has not been stored correctly or has been frozen; see section 5.
► If the resuspended insulin does not appear uniformly white and cloudy.

Do not use Actraphane if any of these situations apply. Speak to your doctor, pharmacist, or nurse for advice.

Before using Actraphane

► Check the label to ensure you are using the correct type of insulin.
► Always inspect the cartridge, including the rubber plunger at the top of the cartridge. Do not use if it appears damaged or if the rubber plunger has been pushed beyond the white band at the top of the cartridge, as this may result in insulin loss.
If you suspect the cartridge is 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 Actraphane Penfill must not be shared.
► Actraphane Penfill is intended only for subcutaneous injection using 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 or liver disorders, or abnormalities affecting the adrenal gland, pituitary gland, or thyroid gland.
► If you consume alcohol: be cautious of symptoms indicating hypoglycaemia, and never drink alcohol on an empty stomach.
► 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 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 formation of lumps under the skin.
Insulin may not work as effectively if injected into an area with lumps, thinning, or thickening of the skin (see section 3). Inform your doctor if you notice skin changes at the injection site. If you currently inject into such an affected area, consult your doctor before switching to a different site. Your doctor may advise you to monitor your blood glucose more closely and adjust your insulin dose or that of other antidiabetic medicines.

Other medicines and Actraphane

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might take any other medicines.
Some medicines affect blood sugar levels, meaning your insulin dose may need to be adjusted. Listed below are the most common medicines that may affect insulin treatment.

Blood sugar levels 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 high blood pressure)
Angiotensin-converting enzyme (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)
Sulphonamides (used to treat infections)

Blood sugar levels 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 gland disorders)
Sympathomimetics (such as epinephrine [adrenaline], salbutamol, or terbutaline, used to treat asthma)
Growth hormone (a medicine used to stimulate skeletal and somatic growth and that significantly affects the body's metabolic processes)
Danazol (a medicine that affects ovulation)

Pioglitazone (tablets used to treat type 2 diabetes mellitus)
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 (oedema).
If you are taking any of the medicines listed above, inform your doctor, pharmacist, or nurse.

Actraphane and alcohol

► If you consume alcohol, your insulin requirements may change, as blood sugar levels may rise or fall. 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 using this medicine. Actraphane may be used during pregnancy. Dose adjustments may be necessary during pregnancy and after delivery. It is important to carefully manage diabetes, particularly to prevent episodes of hypoglycaemia, for the health of both mother and child.
► There are no restrictions on using Actraphane during breastfeeding.
Consult your doctor, pharmacist, or nurse 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 sugar is too high or too low, your ability to concentrate and react may be impaired, thereby affecting your ability to drive or operate machinery. Be aware that this could endanger yourself or others.

Actraphane contains sodium

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

3. How to use Actraphane

Dosage and when to take insulin
Always use insulin and adjust the dose exactly as prescribed by your doctor. If you are unsure, consult your doctor, pharmacist, or nurse.
Have a meal or a snack containing carbohydrates within 30 minutes after the injection to avoid low blood sugar levels.
Do not change the insulin unless your doctor tells you to. If your doctor has changed the type or brand of insulin you are using, your dose may need to be adjusted by your doctor.

Use in children and adolescents
Actraphane can be used in children and adolescents.

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
Actraphane is intended for subcutaneous injection (under the skin). Never inject insulin directly into a vein (intravenous route) or into muscle (intramuscular route). Actraphane Penfill is suitable only for subcutaneous injections with a reusable pen. Talk to your doctor if you need to administer insulin by another method.
With each injection, rotate the injection site within the particular area of skin you usually use. This can reduce the risk of developing lumps or skin depressions—see section 4. The best areas for injection are: the abdominal area; the buttocks; the front of the thigh; or the upper arm. Your insulin will act more quickly if injected into the abdomen. Always monitor your blood glucose levels regularly.

► Do not refill the cartridge. Once empty, it must be discarded.
► Actraphane Penfill cartridges are designed to be used with Novo Nordisk insulin delivery devices and NovoFine or NovoTwist needles.
► If, in addition to Actraphane Penfill, another type of insulin in Penfill cartridge has been prescribed for you, 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 Actraphane
Always check that there is enough insulin remaining (at least 12 units) in the cartridge to allow resuspension. If there is not enough insulin remaining, use a new cartridge. Refer to the pen user manual for further instructions.

► Each time you use a new Actraphane Penfill (before inserting the cartridge into the insulin delivery device):

Allow the insulin to reach room temperature before use. This will facilitate resuspension.
Move the cartridge up and down between positions a and b and vice versa (see figure) so that the glass ball moves from one end of the cartridge to the other at least 20 times.
Repeat this movement at least 10 times before each injection.
Always repeat the movement until the liquid appears uniformly white and milky.
Immediately complete the other steps described below.

Linear drawing of an arm rotating from a vertical position with hand raised to a horizontal position with hand lowered via a curved arrow

How to inject Actraphane
► Inject the insulin under your skin. Use the injection technique recommended 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 injection button fully pressed until the needle is removed from the skin. This ensures proper administration and minimizes the possibility of blood flowing into the needle or insulin reservoir.
► After each injection, remove and dispose of the needle, and store Actraphane without the needle attached. Otherwise, liquid may leak out, which could result in an inaccurate dose.

If you take more insulin than you should
If you take too much insulin, your blood sugar level may drop too low (hypoglycaemia). See 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 (hyperglycaemia). See Effects of diabetes in section 4.

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Summary of serious and 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 are more physically active than usual.
You consume alcohol – see Actraphane with alcohol in section 2.

Warning signs of low blood sugar: cold sweating; cold, pale skin; headache; rapid heartbeat; feeling unwell; hunger sensation; 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 prolonged hypoglycaemia is not treated, it may cause brain damage (transient or permanent) and may even result in death. Recovery of consciousness may be faster with an injection of the hormone glucagon administered by someone who knows how to use 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 level is low:
► If your blood sugar is too low, eat sugar cubes or another snack high in sugar (candies, biscuits, fruit juice). Measure 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 your blood glucose has stabilized, continue your insulin treatment.
► If you have a low blood sugar level, lose consciousness, require a glucagon injection, or experience frequent episodes of low blood sugar, contact your doctor. You may need adjustments to your insulin dose, timing of meals, 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. Explain that if you faint, they should turn you onto your side and immediately call for medical help. It is important not to give you food or drink, as you could choke.
Severe allergic reaction to Actraphane or one of its excipients (called a systemic allergic reaction) is a rare side effect but 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: 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 thin (lipoatrophy) or thicken (lipohypertrophy) (may affect fewer than 1 in 100 people). Lumps under the skin may also be caused by the accumulation of a protein called amyloid (cutaneous amyloidosis; frequency unknown). Insulin may not work as effectively if you inject into an area with lumps, thinning, or thickening of the skin. Rotate your injection site with each injection to prevent these skin changes.

List of other side effects
Uncommon side effects
May affect fewer than 1 in 100 people.
Signs of allergy: Local allergic reactions (pain, redness, urticaria, inflammation, bruising, swelling, and itching) at the injection site. These symptoms usually disappear within a few weeks of treatment. If symptoms do not disappear or spread to other parts of the body, contact your doctor immediately. See also Severe allergic reaction.
Diabetic retinopathy (an eye disorder related to diabetes that may lead to vision loss): If you have diabetic retinopathy and your blood glucose improves very rapidly, the retinopathy may worsen. Consult your doctor for further information.
Swollen joints: At the beginning of insulin treatment, fluid retention may cause swelling around the ankles and other joints. This is normally a temporary condition that soon resolves. If it does not, contact your doctor.
Painful neuropathy (nerve-related pain). If your blood glucose improves very rapidly, you may experience pain originating from nerve fibres. This is known as acute painful neuropathy, which is usually transient.

Effects of diabetes
High blood sugar level (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 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 level 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 Actraphane

Keep out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cartridge label and packaging.
The expiry date refers to the last day of the month.
Before opening: store in a refrigerator at 2°C - 8°C. Keep away from cooling elements.
Do not freeze.
During use or when carried as a spare: do not refrigerate or freeze. It may be carried with you
and kept at room temperature (below 30°C) for up to 6 weeks.
When not in use, always store the cartridge in its original packaging to protect it from light.
Dispose of the needle and syringe after each injection.
Do not dispose of medicines 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 Actraphane 50 contains

The active substance is human insulin. Actraphane is a mixture of 50% soluble insulin and 50% isophane insulin. Each ml contains 100 IU of human insulin. Each cartridge contains 300 IU of human insulin in 3 ml of injectable suspension.
The excipients are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Description of the appearance of Actraphane and contents of the pack
Actraphane is a white, opaque injectable suspension. After resuspension, the liquid should appear uniformly white and cloudy. Packs of 1, 5 and 10 cartridges of 3 ml. Not all pack sizes may be marketed.
The suspension is aqueous, white and cloudy.
Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark
This leaflet was last updated on
Other sources of information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu/.