Insulatard FlexPen 100 IU/ml injection suspension in pre-filled pen

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Insulatard FlexPen 100UI/ml (international units/ml) injectable suspension in a pre-filled pen

Human insulin

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. Do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, talk to your doctor, pharmacist or nurse, even if they are effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Insulatard is and what it is used for

Insulatard is human insulin with a gradual onset of action and prolonged duration.

Insulatard is used to lower elevated blood glucose levels in patients with diabetes mellitus (diabetes). Diabetes is a disease in which your body does not produce enough insulin to control blood glucose levels. Treatment with Insulatard helps prevent complications of diabetes.

Insulatard begins to lower your blood glucose level approximately 1.5 hours after injection, and the effect lasts for about 24 hours. Insulatard is usually administered in combination with rapid-acting insulin preparations.

2. What you need to know before you start using Insulatard

Do not use Insulatard

• If you are allergic to human insulin or to any of the other components of this medicine, see section 6.

• If you suspect you are beginning to experience hypoglycaemia (low blood sugar levels), see Summary of serious and very common adverse effects in section 4.

• In insulin infusion pumps.

• If the FlexPen has been dropped, damaged, or broken.

• If it has not been stored correctly or if it has been frozen, see section 5.

• If the resuspended insulin does not appear uniformly white and cloudy.

If any of these circumstances apply, do not use Insulatard. Consult your doctor, pharmacist, or nurse.

Before using Insulatard

? Check the label to make sure it is the correct type of insulin.

? Always use a new needle for each injection to avoid contamination.

? Needles and Insulatard FlexPen must not be shared.

? Insulatard FlexPen is intended only for subcutaneous injection. Consult 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 problems with your kidneys, liver, adrenal glands, pituitary gland, or thyroid gland.
• If you are doing more physical exercise than usual or wish to change your usual diet, as this may affect your blood sugar levels.
• If you become ill, you must continue using insulin and consult your doctor.
• If you are travelling abroad, travelling across different time zones may affect your insulin requirements and the timing of administration.

Skin changes at the injection site

Injection sites should be rotated to help prevent changes in fatty tissue, such as thickening of the skin, skin shrinkage, or lumps under the skin. Insulin may not work as effectively if injected into an area with lumps, shrinkage, or thickening (see section 3). Inform your doctor if you notice any changes at the injection site. Inform your doctor if you are currently injecting into such affected areas before switching to a different injection site. Your doctor may advise you to monitor your blood sugar levels more closely and may adjust your insulin dose or the dose of your other antidiabetic medications.

Other medicines and Insulatard

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines.

Some medicines affect your blood sugar levels, which may require adjustment of your insulin dose. The following are common medicines that may affect your insulin treatment.

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

• Other medicines for the treatment of diabetes
• Monoamine oxidase inhibitors (MAOIs) (used to treat depression)
• Beta-blockers (used to treat high blood pressure)
• Angiotensin-converting enzyme inhibitors (ACE inhibitors) (used to treat certain heart conditions or high blood pressure)
• Salicylates (used to relieve pain and reduce fever)
• Anabolic steroids (such as testosterone)
• 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 excessive fluid retention)
• Glucocorticoids (such as cortisone, used to treat inflammation)
• Thyroid hormone (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 bone and somatic growth and with significant influence on 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 early warning symptoms that help you recognize low blood sugar levels.

Pioglitazone (tablets used for the treatment of type 2 diabetes)

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

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

Use of Insulatard with alcohol

? If you drink alcohol, your insulin requirements may change, as blood sugar levels may rise or fall. Close monitoring is recommended.

Pregnancy and breastfeeding

? If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine. Insulatard can be used during pregnancy. Your insulin dose may need to be adjusted during pregnancy and after delivery. Strict control of diabetes, especially to prevent hypoglycaemia, is important for your baby's health.

? There are no restrictions on the use of Insulatard during breastfeeding.

Consult your doctor, pharmacist, or nurse before using this medicine during pregnancy or breastfeeding.

Driving and using machines

? Ask your doctor whether you may drive or operate machinery:

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

If your blood sugar level is too high or too low, it may affect your concentration and reaction ability, and thus also your ability to drive or operate machinery. Be aware that you may endanger yourself or others.

Insulatard contains sodium

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

3. How to use Insulatard

Dosage and when to use insulin

Follow exactly the instructions for use and the dose prescribed by your doctor. If in doubt, consult your doctor, pharmacist, or nurse again.

Do not switch insulin unless instructed by your doctor. If your doctor changes your type or brand of insulin, you may need to adjust your dose.

Use in children and adolescents

Insulatard can be used in children and adolescents.

Use in special patient groups

If you have renal or hepatic impairment, or if you are over 65 years of age, you should check your blood sugar level more frequently and discuss with your doctor any possible changes to your insulin dose.

How and where to inject insulin

Insulatard is administered by injection under the skin (subcutaneous administration). It must never be injected directly into a vein (intravenous injection) or into muscle (intramuscular injection). The Insulatard FlexPen is intended only for subcutaneous injection. Consult your doctor if you need to administer insulin by another method.

With each injection, change the injection site within the designated skin area you are using. This may reduce the risk of developing lumps or pits in the skin; see section 4. The best injection sites are: the front of the waist (abdomen), the buttocks, the front of the thigh, or the upper arm. The effect of insulin will be faster if injected into the waist (abdomen). You should measure your blood sugar level regularly.

How to handle Insulatard FlexPen

Insulatard FlexPen is a disposable pre-filled pen containing human isophane insulin (NPH).

Carefully read the Instructions for Use of Insulatard FlexPen included in this leaflet. You must use the pen exactly as described in the Instructions for Use of Insulatard FlexPen.

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

If you use more insulin than you should

If you use 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 use insulin

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

If you stop using insulin

Do not stop using insulin without first talking to your doctor, who will advise you on what to do. Stopping insulin may cause excessive increase in blood sugar levels (severe hyperglycaemia) and ketoacidosis. See Effects related to diabetes in section 4.

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

4. Possible adverse effects

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

Summary of serious and very common adverse effects

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

Your blood sugar level may drop if:

• You inject too much insulin.
• You eat very little or skip a meal.
• You do more physical exercise than usual.
• You drink alcohol – see Use of Insulatard with alcohol in section 2.

Signs of low blood sugar: cold sweat, cold and pale skin, headache, rapid heartbeat, feeling unwell, excessive hunger, temporary vision disturbances, drowsiness, unusual tiredness and weakness, nervousness or trembling, anxiety, confusion, difficulty concentrating.

A severe drop in blood sugar can lead to loss of consciousness. If untreated, it may cause brain damage (temporary or permanent) and even death. You may regain consciousness more quickly if someone who knows how to do it administers a glucagon injection. If glucagon is given, you should also take glucose or a sugary product as soon as you regain consciousness. If there is no response to glucagon treatment, you must go immediately to a hospital.

What to do if you experience low blood sugar:

? If you experience low blood sugar, take glucose tablets or another high-sugar product (for example, sweets, biscuits, fruit juice). If possible, measure your blood sugar level and rest. Always carry glucose tablets or high-sugar products with you, just in case.

? Once the symptoms of low blood sugar have disappeared or your blood sugar level has stabilized, continue your insulin treatment as usual.

? If your blood sugar level is so low that you lose consciousness, if you required a glucagon injection, or if you have had multiple episodes of low blood sugar, speak to your doctor. You may need to adjust your insulin dose or frequency, eating habits, or exercise routine.

Inform relevant people that you have diabetes and explain the possible consequences, such as the risk of fainting (loss of consciousness) due to low blood sugar. Let them know that if you faint, they should turn you onto your side and seek immediate medical help. They should not give you food or drink, as you could choke.

A severe allergic reaction to Insulatard or one of its components (called a systemic allergic reaction) is a very rare adverse effect, but it can be life-threatening. It may affect up to 1 in 10,000 people.

Contact your doctor immediately:

• If allergy symptoms spread to other parts of the body.
• If you suddenly feel unwell and have sweating, nausea, difficulty breathing, rapid heartbeat, or dizziness.

? If you notice any of these symptoms, seek medical help immediately.

Skin changes at the injection site: If you inject insulin in the same place repeatedly, fatty tissue may shrink (lipoatrophy) or become thicker (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also occur due to accumulation of a protein called amyloid (cutaneous amyloidosis; frequency unknown). Insulin may not work well if injected into a lumpy, shrunken, or thickened area. Rotate your injection sites to help prevent these skin changes.

List of other adverse effects

Uncommon adverse effects

May affect up to 1 in 100 people

Allergic symptoms: Local allergic reactions (pain, redness, rash, swelling, bruising, swelling, and itching) may occur at the injection site. These usually disappear within a few weeks of starting insulin treatment. If they do not disappear or spread to the rest of the body, contact your doctor immediately. See also the information on severe allergic reactions mentioned above.

Diabetic retinopathy (an eye disease related to diabetes that may lead to vision loss): if you have diabetic retinopathy and your blood sugar level improves rapidly, the condition may worsen. In this case, consult your doctor.

Joint swelling: When starting insulin treatment, fluid retention may cause swelling of the ankles and other joints. This effect usually disappears quickly. If it does not, speak to your doctor.

Very rare adverse effects

May affect up to 1 in 10,000 people.

Vision problems: When starting insulin treatment, your vision may be affected, but this is usually temporary.

Painful neuropathy (pain due to nerve damage): if your blood sugar level improves rapidly, you may experience nerve-related pain. This is known as acute painful neuropathy and is usually transient.

Reporting of adverse effects

If you experience any adverse effects, talk to your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

Effects related to diabetes

High blood sugar level (hyperglycaemia)

You may experience a high blood sugar level if:

• You have not injected enough insulin.
• You forget to inject insulin or stop using it.
• You repeatedly inject less insulin than you need.
• You have an infection and/or fever.
• You eat more than usual.
• You do less physical exercise than usual.

Warning signs of high blood sugar:

Warning symptoms appear gradually and include frequent urination, thirst, loss of appetite, feeling unwell (nausea or vomiting), drowsiness or tiredness, dry and flushed skin, dry mouth, and fruity-smelling breath (acetone).

What to do if blood sugar rises:

? If you experience any of the symptoms described above: check your blood sugar level and test for ketones in your urine if possible, then contact your 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 breaking down fat instead of sugar). If untreated, this could lead to diabetic coma and even death.

5. Storage of Insulatard

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 packaging after EXP. The expiry date refers to the last day of the month indicated.

Before first use: store in a refrigerator (between 2°C and 8°C). Keep away from the cooling element. Do not freeze.

During use or when carried as a spare: do not refrigerate or freeze. May be carried with you and stored at room temperature (below 30°C) for up to 6 weeks.

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

Dispose of the needle after each injection.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Insulatard

• The active substance is human insulin. Insulatard is an isophane (NPH) suspension of 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 other components are zinc chloride, glycerol, metacresol, phenol, disodium phosphate dihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injections.

Appearance of the product and contents of the pack

Insulatard is presented as an injectable suspension. After resuspension, the liquid should have a uniformly white and cloudy appearance.

Pack sizes of 1, 5, and 10 pre-filled pens of 3 ml. Only certain pack sizes may be commercially available.

The suspension is aqueous, white, and cloudy in appearance.

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 box lid and on 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.

Date of the most recent revision of this leaflet:

Other sources of information

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

Instructions for using FlexPen are included on the reverse.

Instructions for using Insulatard injectable suspension 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 blood sugar levels that are too high or too low.

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

Care of the pen

Handle your FlexPen with care.

If it is dropped, damaged, or subjected to impact, insulin may leak out. This could lead to inaccurate dosing, which may result in blood sugar levels that are too high or too low.

You may clean the outside of your FlexPen with an alcohol-soaked cotton pad. Do not immerse, wash, or lubricate it, as this may damage the pen.

Do not refill your FlexPen. Once empty, it must be discarded.

Preparing Insulatard FlexPen

A

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.

Whenever using a new pen

Allow the insulin to reach room temperature before use.

This makes resuspension easier.

Remove the pen cap (see A).

B

Before administering the first injection with a new FlexPen, the insulin must be resuspended: Move the pen up and down 20 times between the two positions shown in the illustration, so that the glass bead moves from one end of the cartridge to the other. Repeat the procedure until the liquid appears uniformly white and cloudy.

For each subsequent injection, move the pen up and down at least 10 times between the two positions until the liquid appears uniformly white and cloudy.

Always ensure that the insulin has been resuspended before each injection. This reduces the risk of excessively high or low blood sugar levels. After resuspending the insulin, complete the following injection steps without delay.

Always ensure that at least 12 units of insulin remain in the cartridge to allow proper resuspension. If less than 12 units remain, use a new FlexPen. The 12 units are marked on the residual scale. See the large image at the top of these instructions.

Do not use the pen if the resuspended insulin does not appear uniformly white and cloudy.

Attaching the needle

C

Remove the paper tab from a new disposable needle.

Screw the needle straight and firmly onto your FlexPen.

D

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

E

Remove the inner needle cap and discard it.

Never attempt to reinsert the inner needle cap, as you may prick yourself with the needle.

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

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

Checking insulin flow

F

Small amounts of air may accumulate in the cartridge during normal use before each injection. To avoid injecting air and ensure accurate dosing:

Turn the dose selector to select 2 units.

G

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

H

With the needle still pointing upward, press the plunger fully. The dose selector returns to 0.

A drop of insulin should appear at the tip of the needle. 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 must use a new one.

Always ensure a drop appears at the needle tip before injecting. This ensures insulin is flowing. 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 the flow before injecting. If you do not check the flow, you may receive an insufficient or no insulin dose, which could lead to high blood sugar levels.

Selecting the dose

I

Ensure the dose selector is set to 0.

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

The dose can be adjusted forward or backward by turning the dose selector in either direction until the correct dose aligns with the dose marker. When turning the dose selector, be careful not to press the plunger, as insulin may be released.

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

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

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

Injection

J

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

Inject the dose by pressing the plunger fully, so that 0 aligns with the dose marker. Be careful to press the plunger only when injecting.

Turning the dose selector will not inject insulin.

K

Keep the plunger fully pressed and keep the needle under the skin for at least 6 seconds. This ensures the full dose is delivered.

Remove the needle from the skin, and once removed, release the plunger.

Always ensure 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 high blood sugar levels.

L

Cover the needle with the large outer cap without touching it. Once covered, carefully press the large outer cap fully onto the needle, then unscrew the needle.

Dispose of it safely and replace the pen cap.

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

Other important information

People caring for these patients must take great care 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 cause infections.

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

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