Label: information for the user

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

Human insulin

Read this label carefully before starting to use this medicine, as it contains important information for you.

–Keep this label, as you may need to read it again.

–If you have any questions, consult your doctor, pharmacist, or nurse.

–This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.

–If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label.See section 4.

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

Insulatard is used to reduce elevated 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. Insulatard treatment helps to prevent diabetes complications.

Insulatard begins to reduce blood sugar levels approximately 1and a half hours after injection and the effect lasts approximately 24hours. Insulatard is usually administered in combination with rapid-acting insulin preparations.

No 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 that you are starting to experience hypoglycemia (low blood sugar level), see the Summary of serious and very frequent adverse reactions in section 4.
• In insulin infusion pumps.
• If the FlexPen has fallen, been 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 have a uniformly white and turbid appearance.

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

Before using Insulatard

?Check the label to ensure that 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 only indicated for subcutaneous injection. Consult your doctor if you need to inject insulin by another method.

Warnings and precautions

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

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

Changes in the skin at the injection site

The injection site should be rotated to help prevent changes in the fatty tissue, such as thickening of the skin, shrinking of the skin or lumps under the skin. Insulin may not work well if injected in an area that is thickened, shrunk or lumpy (see section 3). Inform your doctor if you notice any changes in the injection site. Inform your doctor if you are currently injecting in these affected areas, before starting to inject in a different area. Your doctor may instruct you to check your blood sugar levels more closely, and adjust your insulin or your other diabetes medications.

Other medicines and Insulatard

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

Some medicines affect your blood sugar level, and this may mean that your insulin dose needs to be adjusted. The following medicines are the most common ones that may affect your insulin treatment:

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

•Other diabetes medications

•Monamine oxidase inhibitors (MAOIs) (used to treat depression)

•Beta-blockers (used to treat high blood pressure)

•Angiotensin-converting enzyme inhibitors (ACE inhibitors) (used to treat certain heart conditions or high blood pressure)

•Salicylates (used to relieve pain and reduce fever)

•Anabolic steroids (such as testosterone)

•Sulfonamides (used to treat infections)

Your blood sugar level may increase (hyperglycemia) if you take:

•Oral contraceptives (birth control pills)

•Thiazides (used to treat high blood pressure or excessive fluid retention)

•Glucocorticoids (such as cortisone, used to treat inflammation)

•Thyroid hormone (used to treat thyroid gland disorders)

•Adrenergic agonists (such as epinephrine [adrenaline], salbutamol or terbutaline, used to treat asthma)

•Growth hormone (medicine to stimulate bone and somatic growth and with significant influence on the body's metabolic processes)

•Danazol (medicine that acts on ovulation)

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

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

Pioglitazone (tablets used to treat type 2 diabetes)

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

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

Use of Insulatard with alcohol

?If you drink alcohol, your insulin needs may change, as your blood sugar level may increase or decrease. It is recommended to follow a strict control.

Pregnancy and breastfeeding

?If you are pregnant, think you may be pregnant or intend to become pregnant, consult your doctor before using this medicine. Insulatard can be used during pregnancy. You may need to adjust your insulin dose during pregnancy and after delivery. Strictly controlling your diabetes, especially to prevent hypoglycemia, is important for your baby's health.

?There are no restrictions on the treatment with Insulatard during breastfeeding.

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

Driving and operating machinery

?Ask your doctor if you can drive vehicles or operate machinery:

•If you experience frequent episodes of hypoglycemia.

•If you find it difficult to recognize the symptoms of hypoglycemia.

If your blood sugar level is high or low, it may affect your concentration and reaction time, and therefore also your ability to drive or operate machinery. Be aware that you may put yourself or others at risk.

Insulatard contains sodium

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

Dosage and when to use insulin

Follow exactly the administration instructions for this medication and the dose indicated by your doctor. In case of doubt, consult your doctor, pharmacist, or nurse again.

Do not change insulin unless your doctor tells you to. If your doctor changes you from one type or brand of insulin to another, 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 kidney or liver failure or if you are over 65 years old, you must check your blood sugar level more frequently and talk to your doctor about possible changes in your insulin dose.

How and where to inject insulin

Insulatard is administered by subcutaneous injection under the skin. Never inject it directly into a vein (intravenous injection) or muscle (intramuscular injection).Insulatard FlexPenis only indicated for injection under the skin.Consult your doctor if you need to inject insulin by another method.

With each injection, change the injection site within the designated area of the skin you use. This may reduce the risk of developing lumps and skin depressions, see section 4.The best areas for injection are the following: the front of the waist (abdomen), the gluteal region, the front of the thigh, or the upper arm. The effect of insulin will be faster if the injection is made in the waist (abdomen). You must measure your blood sugar level regularly.

How to handle InsulatardFlexPen

InsulatardFlexPenis a disposable pre-filled pen containing human insulin isophane (NPH).

Read the Instructions for using Insulatard FlexPen included in this leaflet carefully. You must use the pen as described in the Instructions for using Insulatard FlexPen.

Always make sure to use 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 (hypoglycemia). See Severe and very common adverse reactions in section 4.

If you forget to use insulin

If you forget to use insulin, your blood sugar level may rise too high (hyperglycemia). See Diabetes-related effects in section 4.

If you interrupt insulin treatment

Do not stop using insulin without first talking to your doctor, who will explain what you should do. Stopping insulin may cause a severe increase in blood sugar level (severe hyperglycemia) and ketoacidosis. See Diabetes-related effects in section 4.

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

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

Summary of serious and very common side effects

Hypoglycemia (low blood sugar)is a very common side effect. It can affect more than 1 in 10people.

The blood sugar level can drop if:

•Too much insulin is injected.

•Very little food is eaten or a meal is skipped.

•More physical exercise than usual is done.

•Alcohol is consumed, see Insulatard with alcohol use in section 2.

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

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

What to do if you experience low blood sugar:

?Take glucose tablets or another sugary product (such as candy, cookies, or fruit juice). If possible, measure your blood sugar level and rest. Always carry glucose tablets or sugary products with you, just in case.

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

?If your blood sugar level is so low that you faint, if you have needed a glucagon injection, or if you have had many episodes of low blood sugar, talk to your doctor. You may need to adjust the dose or frequency of insulin, your eating habits, or exercise.

Inform relevant people that you have diabetes and what the consequences may be, 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 on your side and seek medical help immediately. Do not give you food or drinks, as you may choke.

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

Consult your doctor immediately:

• If allergy symptoms spread to other partsof the body.
• If you suddenly feel unwell and have sweating, feeling unwell (vomiting), difficulty breathing, rapid heartbeat, or dizziness.

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

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

List of other side effects

Infrequent side effects

They can affect up to 1 in 100people

Allergic symptoms:local allergic reactions (pain, redness, rashes, inflammation, bruises, swelling, and itching) can occur at the injection site. They usually disappear a few weeks after starting insulin use. If they do not disappear or spread to the entire body, you should consult your doctor immediately. Also see the severe allergic reactions mentioned earlier.

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

Joint inflammation:when starting insulin treatment, fluid accumulation can cause joint inflammation. This effect usually disappears quickly. If it does not, talk to your doctor.

Rare side effects

They can affect up to 1 in 10,000people.

Visual problems:starting insulin treatment can affect your vision, but it is usually temporary.

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

Reporting side effects

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

Effects related to diabetes

High blood sugar (hyperglycemia)

You may experience high blood sugar if:

• Not enough insulin is injected.
• You forget to inject insulin or stop using it.
• You inject less insulin than you need repeatedly.
• 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 signs appear gradually and include abundant urine, thirst, loss of appetite, feeling unwell (nausea or vomiting), drowsiness or fatigue, dry and red skin, dry mouth, and breath with a fruity odor (acetone).

What to do in case of high blood sugar:

?If you experience any of the symptoms described above: check your blood sugar level and the presence of ketones in your urine if possible, and then consult your doctor immediately.

?They may be symptoms of a very serious condition called diabetic ketoacidosis (formation of acid in the blood due to the body breaking down fat instead of sugar). If not treated, it can cause diabetic coma and even death.

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

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

Before opening:store in refrigerator (between2°Cand8°C). Keep away from the refrigerator element.Do not freeze.

During use or when carrying a spare:do not refrigerate or freeze. It canbe carried on the person andstoredat room temperature (below 30ºC)for up to 6weeks.

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

Dispose of the needle after each injection.

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

Composition of Insulatard

–The active principle is human insulin.Insulatard is a suspension of human insulin isophane (NPH). Each ml contains 100UI of human insulin. Each pre-filled pen contains 300UI of human insulin in 3ml of injectable suspension.

–The other components are zinc chloride, glycerol, metacresol, phenol,phosphatedihydrate, sodium hydroxide, hydrochloric acid, protamine sulfate, and water for injectable preparations.

Appearance of the product and contents of the pack

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

Pen sizes of 1, 5, and 10pre-filled pens of 3ml. Only some pen sizes may be commercially available.

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

Holder of the marketing authorization and manufacturer responsible

Holder of the marketing authorization

Novo Nordisk A/S,

Novo Allé, DK-2880 Bagsværd, Denmark

Manufacturer responsible

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

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

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

Date of the last review of this leaflet:

Other sources of information

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

Instructions for use are included on the back of the leaflet.

Instructions for use of Insulatard suspension for injection in FlexPen.

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

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

Care of the pen

You must handle your FlexPen with care.

If it falls, is damaged, or is knocked, there is a risk that the insulin will leak out.This could result in an inaccurate dose, which may cause a level of blood sugar that is too high or too low.

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

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

Preparation of Insulatard FlexPen

A

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

Whenever you use a new pen

Allow the insulin to reach room temperature before using it.

This makes it easier to resuspend.

Remove the pen cap (seeA).

B

Before administering the first injection with a new FlexPen, you must resuspend the insulin:Move the pen up and down twenty times between the two positions as indicated, so that the glass ball moves from one end of the cartridge to the other. Repeat the procedure until the liquid appears uniformly white and turbid.

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

Always ensure that you have resuspended the insulin before each injection. This reduces the risk of achieving blood sugar levels that are too high or too low.After resuspending the insulin, complete the following injection steps without delay.

Always check that there are at least 12units of insulin left in the cartridge to allow for resuspension. If there are fewer than 12units, use a new FlexPen. The 12units are marked on the residual scale. See the large image at the top of this instruction.

Do not use the pen if the resuspended insulin does not have a uniformly white and turbid appearance.

Assembly of the needle

C

Remove the paper tab from a new disposable needle.

Twist the straight needle firmly onto your FlexPen.

D

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

E

Remove the small inner needle cap and discard it.

Do not attempt to put the small inner needle cap back on. You may prick yourself with the needle.

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

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

Check the insulin flow

F

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

Turn the dose selector to 2units.

G

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

H

Keeping the needle pointing upwards, press the plunger all the way down. 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 6times.

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

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

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

Select the dose

I

Check that 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 corrected forward and backward by turning the dose selector in either direction until the correct dose is aligned with the dose marker. When turning the dose selector, be careful not to press the plunger, as insulin may leak out.

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

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

Do not count the clicks of the pen. If you select an incorrect dose and inject it, your level of blood sugar may become too high or too low. Do not use the 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 all the way down so that the 0aligns with the dose marker. Be careful only to press the plunger when injecting.

Turning the dose selector will not inject insulin.

K

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

Remove the needle from the skin and once you have done so, release the plunger.

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

L

Put the needle cap back on without touching it. When the needle is covered, press the cap firmly and then twist the needle off.

Dispose of the needle carefully and put the pen cap back on.

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 must be extremely careful when handling used needles to reduce the risk of accidental puncture and infection.

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

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

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

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