HUMALOG MIX50 KWIKPEN 100 U/ml INJECTABLE SUSPENSION

Introduction

Package Leaflet: Information for the User

Humalog Mix50 100 units/ml suspension for injection in cartridge

insulin lispro

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 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 or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

1. What Humalog Mix50 is and what it is used for
2. What you need to know before you use Humalog Mix50
3. How to use Humalog Mix50
4. Possible side effects
5. Storing Humalog Mix50
6. Contents of the pack and other information

1. What Humalog Mix50 is and what it is used for

Humalog Mix50 is used to treat diabetes. Humalog Mix50 is a premixed suspension. Its active substance is insulin lispro. In Humalog Mix50, 50% of insulin lispro is dissolved in water and works more quickly than normal human insulin because the insulin molecule has been changed slightly. In Humalog Mix50, 50% of insulin lispro is combined with protamine sulfate to prolong its action.

You have diabetes when your pancreas does not produce enough insulin to control the level of glucose in your blood. Humalog Mix50 is a substitute for your own insulin and is used to control glucose over a long period of time. Humalog Mix50 acts very quickly and for a longer period of time than soluble insulin. You should normally use Humalog Mix50 within 15 minutes of a meal.

Your doctor may recommend using Humalog Mix50 with a longer-acting insulin. Each of these comes with its own package leaflet that gives specific information. Do not change your insulin unless your doctor has told you to. Be very careful when changing insulin.

2. What you need to know before you use Humalog Mix50

Do not use Humalog Mix50

• If you think you are starting to have a hypoglycaemic episode(low blood sugar level). Later in this leaflet, it is explained how to deal with a mild hypoglycaemic episode (see Section 3: If you use more Humalog Mix50 than you should).
• If you are allergicto insulin lispro or any of the other ingredients of this medicine (listed in Section 6).

Warnings and precautions

• At the pharmacy, always check the name and type of insulin on the label and carton. Make sure you have been given the Humalog Mix50 that your doctor has prescribed for you.
• If your blood sugar levels are well controlled with your current insulin therapy, you may not notice the warning signs of a low blood sugar level. Later in this leaflet, these warning signs are listed. You should carefully plan when to eat, when to exercise, and how much exercise you can do. You should also closely monitor your blood sugar levels by doing regular blood glucose tests.
• Certain patients who have had hypoglycaemia after changing from animal insulin to human insulin have reported that the first warning signs were less obvious or different. If you have frequent hypoglycaemic episodes or difficulty recognising them, please tell your doctor.
• If you answer YES to any of the following questions, tell your doctor, pharmacist, or diabetes educator.

? Have you recently become ill?

? Do you have liver or kidney problems?

? Are you doing more exercise than usual?

• The amount of insulin you need may change if you drink alcohol.
• If you are planning to travel abroad, tell your doctor, pharmacist, or diabetes educator. The time difference between countries may mean you have to change your injection and meal schedule from the one you are used to.
• Some patients with type 2 diabetes mellitus of long duration and heart disease or previous stroke, who were treated with pioglitazone and insulin, developed heart failure. Tell your doctor as soon as possible if you have signs of heart failure such as difficulty breathing, rapid weight gain, or localised swelling (oedema).

Skin changes at the injection site

You should rotate the injection site to avoid changes in the skin, such as lumps under the skin. Insulin may not work well if you inject it into a lumpy area (see How to use Humalog Mix50). Contact your doctor if you are currently injecting into a lumpy area 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 anti-diabetic medicines.

Other medicines and Humalog Mix50

Your insulin needs may change if

• you are taking oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics,
• acetylsalicylic acid,
• sulfa antibiotics,
• octreotide,
• beta-2 stimulants (e.g. ritodrine, salbutamol, or terbutalina),
• beta-blockers, or
• certain antidepressants (monoamine oxidase inhibitors or selective serotonin reuptake inhibitors),
• danazol,
• certain angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril), and
• angiotensin II receptor blockers.

Tell your doctor if you are using, have recently used, or might use any other medicines, including those not prescribed.

Pregnancy and breast-feeding

Are you pregnant or breast-feeding, or thinking of becoming pregnant? The amount of insulin you need usually decreases during the first three months of pregnancy and increases during the next six months. If you are breast-feeding, you may need to adjust your insulin dose or diet. If you are pregnant, think you might be pregnant, or are planning to become pregnant, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines

Your ability to concentrate or react may be reduced if you have hypoglycaemia. Be aware of this possible problem, considering all situations that may put you or others at risk (e.g. driving a car or operating machinery). You should ask your doctor for advice on driving if you:

• have frequent episodes of hypoglycaemia
• have difficulty recognising the warning signs of a hypoglycaemic episode

Humalog Mix50 contains sodium

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

3. How to use Humalog Mix50

The 3 ml cartridges are for use in Lilly 3 ml pens only. Do not use in 1.5 ml pens.

Follow the instructions for administration of this medicine exactly as told by your doctor. If you are not sure, ask your doctor again. To prevent possible transmission of disease, each cartridge should only be used by you, even if you change the needle.

Dose

• Normally, you should inject Humalog Mix50 within 15 minutes of a meal. If necessary, you can inject shortly after a meal. However, your doctor will tell you exactly how much to use, when to use it, and how often. These instructions are specific to you. Follow them exactly and visit your diabetes clinic regularly.
• If you change the type of insulin you use (e.g. from animal or human insulin to a product with Humalog Mix50), you may need to use a greater or lesser amount than before. This may only be for the first injection or it may require a gradual change that takes several weeks or months.
• Inject Humalog Mix50 under the skin. Do not use any other injection method. Never inject Humalog Mix50 intravenously.

How to prepare Humalog Mix50

• The cartridges containing Humalog Mix50 should be rolled between the palms of your hands ten times and inverted 180° ten times immediately before use to resuspend the insulin, until it appears uniformly cloudy or milky. If not, repeat the above procedure until the components are mixed. The cartridges contain a small glass bead to help with mixing. Do not shake vigorously to avoid creating foam, which could interfere with accurate dosing. Check the cartridges frequently and do not use them if you see clumps or white solid particles stuck to the bottom or sides of the cartridge, giving it a frosted appearance. Check this every time you inject.

How to prepare the pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• Only use Humalog Mix50 cartridges with Lilly insulin pens. Make sure the pen’s package leaflet mentions Humalog or Lilly cartridges. The 3 ml cartridges only fit in 3 ml pens.
• Follow the instructions that come with the pen. Insert the cartridge into the pen.
• Set the dose to 1 or 2 units. Then, with the pen pointing upwards, tap the side to make any air bubbles rise to the top. With the pen still pointing upwards, press the injection mechanism. Keep it like this until a drop of Humalog Mix50 appears at the needle tip. There may still be some small air bubbles left in the pen. These are harmless, but if the air bubble is too large, the dose of the injection may be less accurate.

How to inject Humalog Mix50

• Before injecting, clean your skin as you have been taught. Inject under the skin, as you have been taught. Do not inject directly into a vein. After the injection, leave the needle in the skin for 5 seconds to make sure you have injected the full dose. Do not rub the area where you have just injected. Make sure you inject at least 1 cm away from where you last injected and “rotate” the injection sites as you have been taught.

After the injection

• As soon as you have finished injecting, remove the needle from the pen using the outer needle shield. This will keep Humalog Mix50 sterile and prevent leakage. It will also prevent air from entering the pen and the needle from becoming blocked. Do not share needles.Do not share your pen. Put the pen cap back on. Leave the cartridge in the pen.

Subsequent injections

• Before each injection, dial 1 or 2 units and press the injection mechanism with the pen pointing upwards until a drop of Humalog Mix50 appears at the needle tip. You can see how much Humalog is left by looking at the gauge on the side of the cartridge. The distance between each mark on the gauge is about 20 units. If there is not enough left for a full dose, change the cartridge.

Do not mix any other insulin in a Humalog Mix50 cartridge. When the cartridge is empty, it must not be used again.

If you use more Humalog Mix50 than you should

If you use more Humalog Mix50 than you need or are unsure how much you have injected, you may have a low blood sugar level. Check your blood sugar level.

If your blood sugar level is low (mild hypoglycaemia), take glucose tablets, sugar, or a sweet drink. Then eat fruit, biscuits, or a sandwich, as your doctor has advised, and rest. This usually helps to recover from a mild hypoglycaemic episode or a small overdose of insulin. If you get worse and your breathing becomes shallow and your skin pale, call a doctor immediately. Severe hypoglycaemia can be treated with an injection of glucagon. After the glucagon injection, take glucose or sugar. If you do not respond to glucagon, you must go to hospital. Ask your doctor to tell you about glucagon.

If you forget to use Humalog Mix50

If you use less Humalog Mix50 than you need or are unsure how much you have injected, you may have a high blood sugar level. Check your blood sugar level.

If hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) are not treated properly, they can be very serious and cause headaches, nausea, vomiting, dehydration, loss of consciousness, coma, or even death (see A and B in Section 4 “Possible side effects”).

Three simple measuresto avoid hypoglycaemia or hyperglycaemia are:

• Always carry spare pens and cartridges with you, in case you lose or damage them.
• Always carry something to show you are diabetic.
• Always carry some sugar with you.

If you stop using Humalog Mix50

If you use less Humalog Mix50 than you need, you may have a high blood sugar level. Do not change your insulin unless your doctor has told you to.

If you have any other questions about using 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.

Systemic allergy is rare (≥1/10,000 to <1>

If you think you are suffering from this type of allergy with Humalog Mix50, speak to your doctor immediately.

Localized allergy is frequent (≥1/100 to <1>

Lipodystrophy is infrequent (≥1/1,000 to <1>

There have been cases of edema (e.g., swelling in the arms, ankles; fluid retention), especially at the beginning of insulin treatment or during a change in treatment to improve blood sugar control.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

Common Diabetes Problems

1. Hypoglycemia

Hypoglycemia (low blood sugar level) means that you do not have enough sugar in your blood.

It can be caused by:

• taking too much Humalog Mix50 or any other type of insulin;
• skipping a meal, delaying it, or changing your diet;
• working too hard or exercising too much immediately before or after a meal;
• having an infection or being sick (especially diarrhea or vomiting);
• having changes in your insulin needs; or
• having a worsening kidney or liver condition.

Alcohol and certain medications can affect your blood sugar levels.

The first symptoms of low blood sugar usually appear suddenly and are accompanied by:

Until you are sure you can recognize the warning symptoms, avoid situations (e.g., driving a car) where you or others could be in danger if hypoglycemia occurs.

1. Hyperglycemia and Diabetic Ketoacidosis

Hyperglycemia (too much sugar in the blood) means that the body does not have enough insulin. Hyperglycemia can be caused by:

• not taking Humalog or other insulin;
• taking less insulin than prescribed by the doctor;
• eating much more than your diet allows; or
• having a fever, infection, or emotional stress.

Hyperglycemia can lead to diabetic ketoacidosis. The first symptoms appear slowly, over many hours or several days. Among these symptoms are:

Severe symptoms are heavy breathing and rapid pulse. Seek medical attention immediately.

1. Illnesses

If you are sick, especially if you have nausea or vomiting, the amount of insulin you need may vary. Even if you are not eating as usual, you still need to receive insulin.Have your urine or blood tested, follow the instructions you have been given for when you are sick, and call your doctor.

5. Storage of Humalog Mix50

Before the first use, store Humalog Mix50 in the refrigerator (between 2°C and 8°C). Do not freeze.

Keep your cartridge in use at room temperature (below 30°C) and discard it after 28 days. Do not leave it near any heat source or in the sun. Do not store your pen or the cartridges you are using in the refrigerator. The pen with the incorporated cartridge should not be stored with the needle attached.

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

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

Do not use this medicine if you observe lumps or white solid particles stuck to the bottom or walls of the cartridge, giving it a frosty appearance. Check it every time you inject.

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 Humalog Mix50 100 units/ml injectable suspension in cartridge

• The active ingredient is insulin lispro. Insulin lispro is manufactured in the laboratory by a process of "recombinant DNA technology". It is a modified form of human insulin and, therefore, differs from other human insulins and animal-derived insulins. Insulin lispro is closely related to human insulin, which is a natural hormone produced by the pancreas.
• The other components are protamine sulfate, m-cresol, phenol, glycerol, dibasic sodium phosphate.7H2O, zinc oxide, and water for injectable preparations. Sodium hydroxide or hydrochloric acid may have been used to adjust the acidity.

Appearance of the Product and Package Contents

Humalog Mix50 100 units/ml injectable suspension is a white, sterile suspension that contains 100 units of insulin lispro in each milliliter of injectable suspension (100 units/ml). In Humalog Mix50, 50% of insulin lispro is dissolved in water. A 50% suspension of insulin lispro with protamine sulfate has been incorporated. Each cartridge contains 300 units (3 milliliters). The packages contain 5 or 10 cartridges. Not all presentations may be marketed.

Marketing Authorization Holder and Manufacturer

Humalog Mix50 100 units/ml injectable suspension in cartridge is manufactured by:

• Lilly France, S.A.S., Rue du Colonel Lilly, 67640 Fegersheim, France,
• Eli Lilly Italia S.p.A., Via Gramsci 731-733, 50019 Sesto Fiorentino, (FI) Italy.

The marketing authorization holder is Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Prospectus:

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