LEVEMIR FLEXPEN 100 U/mL injectable solution in a prefilled pen

Introduction

Package Leaflet: Information for the User

Levemir 100units/ml solution for injection in pre-filled pen

insulin detemir

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

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

Contents of the pack

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

1. What is Levemir and what is it used for

Levemir is a modern insulin (insulin analogue) with a long duration of action. Modern insulins are improved versions of human insulin.

Levemir is used to lower high blood sugar levels in adults, adolescents and children from 1 year of age with diabetes. Diabetes is a disease where the body does not produce enough insulin to control blood sugar levels.

Levemir can be used with fast-acting insulins administered in relation to meals.

In the treatment of type 2 diabetes mellitus, Levemir can also be used in combination with diabetes tablets and/or with non-insulin injectable antidiabetics.

Levemir has a long and steady blood sugar lowering effect for 3 to 4 hours after injection. Levemir provides basal insulin coverage for up to 24 hours.

2. What you need to know before you use Levemir

Do not use Levemir

? if you are allergic to insulin detemir or any of the other ingredients of this medicine, see section 6, Contents of the pack and other information.

? if you suspect you are going to have a hypoglycaemia (low blood sugar level), see a) Summary of serious and frequent side effects in section 4.

? in insulin infusion pumps.

• If FlexPen has been dropped, damaged or broken.
• If it has not been stored correctly or has been frozen, see section 5, Storage of Levemir.
• If the insulin does not look like water and is not clear and colourless.

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

Before using Levemir

• Check the label to ensure it is the correct type of insulin that you have been prescribed.
• Always use a new needle for each injection to prevent contamination.
• Needles and Levemir FlexPen must not be shared.
• Levemir FlexPen is only intended for subcutaneous injection. Talk to your doctor if you need to inject insulin by another method.

Warnings and precautions

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

? if you have kidney, liver, adrenal, pituitary or thyroid problems.

? if you are doing more physical exercise than usual or if you want to change your diet, as this may affect your blood sugar level.

? if you are ill, continue your insulin treatment and talk to your doctor.

? if you are going to travel abroad, the time difference between countries may affect your insulin requirement and the timing of your injections.

? if your albumin levels are very low, carefully monitor your blood sugar levels. Discuss this with your doctor.

Changes at the injection site

The injection site should be rotated to help avoid changes in the fatty tissue, such as thickening of the skin, skin shrinking or lumps under the skin. Insulin may not work well if injected into a lumpy, shrunk or thickened area (see section 3, How to use Levemir). Inform your doctor if you notice any changes at the injection site. Inform your doctor if you are currently injecting into these affected areas, before you start injecting into a different area. Your doctor may tell you to check your blood sugar levels more closely and adjust your insulin dose or the dose of your other antidiabetic medications.

Children and adolescents

Levemir can be used in adolescents and children from 1 year of age.

The safety and efficacy of Levemir in children below 1 year of age have not been established.

No data are available.

Other medicines and Levemir

Tell your doctor, nurse or pharmacist if you are using, have recently used or might use any other medicines.

Certain medicines affect your blood sugar level and this may mean you need to adjust your insulin dose. The following are the main medicines that may affect your treatment with insulin.

Your blood sugar level may be lowered (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 diseases or high blood pressure)
• salicylates (used to relieve pain and lower fever)
• anabolic steroids (such as testosterone)
• sulphonamides (used to treat infections).

Your blood sugar level may be raised (hyperglycaemia) if you take:

• oral contraceptives (birth control pills)
• thiazides (used to treat high blood pressure or excessive fluid retention)
• glucocorticoids (such as “cortisone” used to treat inflammation)
• thyroid hormones (used to treat thyroid disorders)
• sympathomimetics (such as adrenaline or salbutamol or terbutaline used to treat asthma)
• growth hormone (medicine to stimulate growth and skeletal development that has a pronounced effect on metabolic processes)
• danazol (medicine that acts on ovulation).

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

Beta-blockers (used to treat high blood pressure) may weaken or completely suppress the first warning symptoms that could help you recognise a low blood sugar level.

Pioglitazone (tablets used to treat type 2 diabetes)

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

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

Alcoholic beverages and use of Levemir

? If you drink alcohol, it may alter your insulin requirement because your blood sugar level may increase or decrease. Careful monitoring is recommended.

Pregnancy and breast-feeding

? If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine. You may need to adjust your insulin dose during pregnancy and after giving birth. It is very important for the health of your baby and for you to maintain good control of your diabetes and prevent hypoglycaemia.

? If you are breast-feeding, ask your doctor for advice. You may need to adjust your insulin dose.

Ask your doctor, nurse or pharmacist for advice before taking any medicine during pregnancy or breast-feeding.

Driving and using machines

? Please ask your doctor whether you can drive or operate machinery:

• if you often have hypoglycaemias
• if you find it hard to recognise hypoglycaemia

If your blood sugar is too low or too high, it may affect your concentration and ability to react and therefore also your ability to drive a car or operate machinery. Bear in mind that you could endanger yourself or others.

Important information about some of the ingredients of Levemir

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

3. How to use Levemir

Dose and when to inject the insulin

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

Levemir can be used with fast-acting insulins administered in relation to meals.

In the treatment of type 2 diabetes mellitus, Levemir can also be used in combination with diabetes tablets and/or with non-insulin injectable antidiabetics.

Do not change your insulin unless your doctor tells you to.

Your doctor may need to adjust your dose if:

• your doctor changes you from one type or brand of insulin to another, or
• your doctor adds another medicine for the treatment of diabetes to your treatment with Levemir.

Use in children and adolescents

Levemir can be used in adolescents and children from 1 year of age.

There is no experience with the use of Levemir in children below 1 year of age.

Use in special patient groups

If you have kidney or liver problems (renal or hepatic insufficiency), or if you are over 65 years of age, you should monitor your blood sugar more frequently and consult your doctor about adjusting your insulin dose.

How often to inject

When used in combination with diabetes tablets and/or in combination with non-insulin injectable antidiabetics, Levemir should be administered once daily. When used as part of a basal-bolus regimen, Levemir should be administered once or twice daily depending on the patient’s needs. The Levemir dose should be adjusted individually. The injection can be given at any time of the day, but at the same time every day. In patients who need two daily doses to achieve optimal blood sugar control, the evening dose can be given in the evening or at bedtime.

How and where to inject

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

For each injection, change the injection site within the area of skin you usually use. This may reduce the risk of developing lumps or hollows under the skin (see section 4, Possible side effects). The best areas for injection are: the front of your thighs, the area around your waist and the upper outer part of your arm. Regularly check your blood sugar levels.

How to handle Levemir FlexPen

Levemir FlexPen is a pre-filled, disposable pen with a colour code that contains insulin detemir.

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

Always make sure you use the correct pen before injecting your insulin.

If you use more insulin than you need

If you take too much insulin, your blood sugar level may become too low (hypoglycaemia). See a) Summary of serious and frequent side effects in section 4.

If you forget to use your insulin

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

If you stop using your insulin

Do not stop using your insulin without talking to your doctor first. This could lead to very high blood sugar levels (severe hyperglycaemia) and ketoacidosis. See c) Effects of diabetes in section 4.

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

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

• Summary of serious and very frequent adverse effects

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

Low blood sugar levels may appear if:

• Too much insulin is injected.
• You eat very little or skip a meal.
• You do more exercise than usual.
• You drink alcohol (see section 2, Alcoholic beverages and use of Levemir).

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

A severe drop in blood sugar can lead to loss of consciousness. If a severe and prolonged drop in blood sugar is not treated, it can cause brain damage (transient or permanent) and even death. You can regain consciousness more quickly if someone who knows how to do it administers a glucagon injection to you. If you are given glucagon, you should take glucose or a sugary product as soon as you regain consciousness. If you do not respond to glucagon treatment, you should be treated in a hospital.

What to do if your blood sugar level is low:

? If your blood sugar level is low, take glucose tablets or a sugary product (candies, cookies, fruit juice). Measure your blood sugar level if possible and then rest. Always carry glucose tablets or sugary foods with you in case you need them.

? When the symptoms of hypoglycemia have disappeared or when blood sugar levels have stabilized, continue insulin treatment as usual.

? If you have had blood sugar levels so low that they have caused you to lose consciousness, if you have needed to be given a glucagon injection, or if you have had many drops in blood sugar levels, talk to your doctor. You may need to adjust the amount or administration schedule of insulin, food, or exercise.

Inform others that you have diabetes and what the consequences may be, including the risk of losing consciousness due to a drop in blood sugar level. Tell them that if you become unconscious, they should lay you on your side and seek immediate medical attention. They should not give you anything to eat or drink, as you could choke.

Severe allergic reactionto Levemir or any of its components (called a systemic allergic reaction) is a very rare but potentially fatal adverse effect. It can affect up to 1 in 10,000 people.

Consult your doctor immediately:

• If the signs of allergy spread to other parts of your body.
• If you suddenly feel unwell and have sweats, vomiting, difficulty breathing, palpitations, feel dizzy.

? If you notice any of these symptoms, consult your doctor immediately.

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

• List of other adverse effects

Uncommon adverse effects

Can affect up to 1 in 100 people.

Allergic reaction signs: Local allergic reactions can occur at the injection site (pain, redness, hives, inflammation, bruising, swelling, and itching). These reactions usually disappear after a few weeks of treatment. If the symptoms do not disappear, or if they spread throughout your body, consult your doctor immediately. See also Severe allergic reaction above.

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

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

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

Rare adverse effects

Can affect up to 1 in 1,000 people.

Painful neuropathy (pain due to nerve damage): if your blood sugar level improves very quickly, you may suffer from nerve-related pain, this is what is called acute painful neuropathy and is usually transient.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

• Effects of diabetes

High blood sugar (hyperglycemia)

High blood sugar levels may appear if:

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

Warning symptoms of high blood sugar:

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

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

? If you notice any of the described symptoms: check your blood sugar level, check the ketone level in your urine if possible, and consult your doctor immediately.

? These can be symptoms of a very serious disorder called diabetic ketoacidosis (acid builds up in the blood because the body breaks down fat instead of sugar). If left untreated, it could produce a diabetic coma and death.

5. Storage of Levemir

Keep this medicine out of sight and reach of children.

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

Always keep the cap of the pen on your FlexPen when not in use to protect it from light.

Levemir must be protected from excessive heat and light.

Before opening:Unused Levemir FlexPen should be stored in the refrigerator between 2°C and 8°C, away from the cooling element. Do not freeze.

During use or when carrying as a spare:You can carry your Levemir FlexPen with you and store it at a temperature below 30°C or in the refrigerator (between 2°C and 8°C) for 6 weeks. If refrigerated, keep away from the cooling element. Do not freeze.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Levemir

• The active ingredient is insulin detemir. Each ml contains 100 units of insulin detemir. Each pre-filled pen contains 300 units of insulin detemir in 3 ml of injectable solution. 1 unit of insulin detemir corresponds to 1 international unit of human insulin.
• The other components are glycerol, phenol, metacresol, zinc acetate, disodium phosphate dihydrate, sodium chloride, hydrochloric acid, sodium hydroxide, and water for injection.

Appearance of the product and package contents

Levemir is presented as an injectable solution.

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

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

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

Manufacturer

The manufacturer can be identified by the batch number printed on the carton lid and the label:

• If the second and third characters are S6, P5, K7, R7, VG, FG, or ZF, the manufacturer is Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.

• If the second and third characters are H7 or T6, the manufacturer is Novo Nordisk Production SAS, 45 Avenue d´Orléans, F-28000 Chartres, France.

Instructions for use of FlexPen are included on the back.

Date of the last revision of this prospectus:

Other sources of information

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

Instructions for use of LEVEMIR injectable solution in FlexPen

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

FlexPen is a pre-filled insulin dosing pen. Doses of 1 to 60 units can be selected in increments of 1 unit. FlexPen is designed to be used with the NovoFine or NovoTwist disposable needles of up to 8 mm in length. As a precaution, always carry a spare insulin delivery device in case the FlexPen you are using is lost or damaged.

Pen Care

You must handle your FlexPen with care.

If it falls, is damaged, or is hit, there is a risk that insulin may leak out. This could cause inaccurate dosing, which can result in a blood sugar level that is too high or too low.

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

Do not refill your FlexPen.

Preparing Levemir FlexPen

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

A

Remove the pen cap.

B

Remove the paper tab from a new disposable needle.

Screw the needle straight and firmly onto your FlexPen.

C

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

D

Remove the inner needle cap and discard it.

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

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

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

Checking the insulin flow

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

E

Turn the dose selector until 2 units are selected.

F

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

G

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

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

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

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

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

Dose selection

Check that the dose selector is set to 0.

H

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

The dose can be corrected forward and backward by turning the dose selector in any direction until the corrected dose is aligned with the dose marker. When turning the dose selector, be careful not to press the push button, as insulin may leak out.

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

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

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

Injection

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

I

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

Turning the dose selector does not inject insulin.

J

Keep the push button fully pressed and keep the needle under the skin for at least 6 seconds. This ensures that the full dose is injected.

Remove the needle from the skin and release the push button.

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

K

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

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

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

Other important information

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

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

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

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

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