HUMALOG MIX25 KWIKPEN 100 U/ml INJECTABLE SUSPENSION

1. What Humalog Mix25 KwikPen is and what it is used for

Humalog Mix25 KwikPen is used to treat diabetes. It is a premixed suspension. The active substance is insulin lispro. In Humalog Mix25 KwikPen, 25% 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 Mix25 KwikPen, 75% of insulin lispro is suspended with protamine sulfate to prolong its action.

You have diabetes when your pancreas does not make enough insulin to control the level of glucose in your blood. Humalog Mix25 is a substitute for your own insulin and is used to control glucose over the long term. It acts very quickly and for a longer time than soluble insulin.

Normally, Humalog Mix25 is used within 15 minutes of a meal.

Your doctor may recommend using Humalog Mix25 KwikPen in addition to a longer-acting insulin. Each of these comes with its own package leaflet with specific information. Do not change your insulin unless your doctor has told you to. Be very careful when changing insulin.

The KwikPen is a disposable pre-filled pen that contains 3 ml (300 units, 100 units/ml) of insulin lispro. A KwikPen contains multiple doses of insulin. The KwikPen marks 1 unit at a time. The number of units is shown in the dose window, always check it before your injection.You can inject from 1 to 60 units in a single injection. If your dose is more than 60 units, you will need to give yourself more than one injection.

2. What you need to know before you use Humalog Mix25 KwikPen

Do not use Humalog Mix25 KwikPen

• If you think you are starting a hypoglycaemia(low blood sugar level). Later in this leaflet, it is indicated how to resolve a mild hypoglycaemia (see Section 3: If you use more Humalog Mix25 than you should).
• If you are allergicto insulin lispro or any of the other components of this medicine (listed in section 6).

Warnings and precautions

• In the pharmacy, always check the name and type of insulin that appears on the packaging and the label of the pre-filled pen. Make sure you are carrying the Humalog Mix25 KwikPen that your doctor has prescribed for you.
• If your blood sugar levels are well controlled with your current insulin therapy, you may not perceive the warning symptoms that alert you to the fact that your blood sugar is dropping too low. Later in this leaflet, these warning symptoms are specified. You must carefully plan when you should eat, exercise, and how much you can do. You also need to closely monitor your blood sugar levels by doing frequent blood glucose tests.
• Certain patients who have suffered hypoglycaemia after changing from animal insulin to human insulin have reported that the first warning symptoms were less evident or different. If you have frequent hypoglycaemias or difficulties in recognising them, please do not fail to inform your doctor.
• If you answer YES to any of the following questions, inform your doctor, pharmacist, or diabetes educator
• • Have you recently been ill?
  • Do you have liver or kidney problems?
  • Are you doing more exercise than usual?
• The amount of insulin you need may vary if you drink alcohol.
• If you are planning to travel abroad, you should inform your doctor, pharmacist, or diabetes educator. The time difference between some countries may require you to adopt a different schedule for injections and meals than the one you are taking when you are in your country.
• Some patients with type 2 diabetes mellitus of long duration and previous cardiac disease or stroke, who were treated with pioglitazone and insulin, developed cardiac insufficiency. Inform your doctor as soon as possible if you have signs of cardiac insufficiency such as difficulty breathing, rapid weight gain, or localized swelling (oedema).
• It is not recommended that blind or visually impaired persons use this pen without the help of a person trained in the use of the pen.

Other medicines and Humalog Mix25 KwikPen

Your insulin needs may change if

• you are using oral contraceptives,
• corticosteroids,
• thyroid hormone replacement therapy,
• oral hypoglycaemics,
• acetylsalicylic acid,
• sulfa antibiotics,
• octreotide,
• beta-2 stimulants (e.g. ritodrine, salbutamol, or terbutaline),
• 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.

Inform your doctor if you are using, have recently used, or might use any other medicines, including those obtained without a prescription (see section "Warnings and precautions").

Pregnancy and breastfeeding

Are you pregnant or planning to become pregnant? Are you breastfeeding? 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 breastfeeding, you may need to adjust your insulin dose or diet. If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and using machines

Your ability to concentrate or react may be reduced if you suffer from hypoglycaemia. Be aware of this possible problem, considering all situations that may be a risk for you or others (e.g. driving a vehicle or operating machinery). You should consult your doctor about the convenience of driving if you have:

• frequent episodes of hypoglycaemia
• difficulty in recognising the symptoms of a hypoglycaemia or do not recognise them

Humalog Mix25 KwikPen contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is essentially "sodium-free".

3. How to use Humalog Mix25 KwikPen

Follow the instructions for administration of this medicine exactly as indicated by your doctor. In case of doubt, consult your doctor again. To prevent the possible transmission of diseases, each pen must be used only by you, even if the needle is changed.

Dose

• Normally, you should inject Humalog Mix25 within 15 minutes of a meal. If necessary, you can inject shortly after a meal. However, your doctor will have indicated exactly how much you should use, when to use it, and how often. These instructions are specific to you. Follow them exactly and go to your diabetes clinic frequently.
• If you change the type of insulin you use (e.g. from animal or human insulin to a product with Humalog), you may need to use a greater or lesser amount than before. This may only be the case for the first injection or may require a gradual change that lasts several weeks or months.
• Humalog Mix25 KwikPen is only intended for injection under the skin. Consult your doctor if you need to inject the insulin by another method.

How to prepare Humalog Mix25 KwikPen

• The KwikPen must be moved between the palms of the hands ten times and inverted 180° ten times immediately before use, to resuspend the insulin, until the appearance of the insulin is uniformly cloudy or milky. Otherwise, repeat the procedure indicated above until the components are mixed. The cartridges contain a small glass pearl to facilitate mixing. Do not shake vigorously to avoid producing foam that could interfere with the correct measurement of the dose. Examine the cartridges frequently and do not use them if you see lumps or white solid particles stuck to the bottom or walls of the cartridge, giving it a appearance similar to frost. Check it every time you inject.

How to prepare the KwikPen (please read the user manual)

• First, wash your hands.
• Read the instructions on how to use your pre-filled insulin pen. Follow the instructions carefully. Below are some reminders.
• Use a new needle. (Needles are not included).
• Purge your KwikPen before each use. This verifies that the insulin comes out and that air bubbles are removed from your KwikPen. There may still be some small air bubbles in your pen; these are harmless. But if the air bubble is too large, the injection dose could be less accurate.

How to inject Humalog Mix25

• 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 five seconds to make sure you have injected the full dose. Do not rub the area where you have just injected. Make sure you have injected at least 1 cm away from where you last injected and "rotate" the injection sites, as you have been explained.

After the injection

• As soon as you finish injecting, unscrew the needle from the KwikPen using the outer needle protector. This keeps the insulin sterile and prevents leakage. It also prevents air from entering the pen and the needle from becoming clogged. Do not share needles.Do not share your pen. Put the cap back on the pen.

Subsequent injections

• Each time you use a KwikPen, you must use a new needle. Before each injection, eliminate all air bubbles. You can see the remaining insulin by holding the KwikPen with the needle pointing upwards. The scale on the cartridge shows approximately the number of units remaining.
• Do not mix any other insulin in the disposable pen. When the KwikPen is empty, it cannot be used again. Dispose of the pen responsibly - your pharmacist or diabetes educator will tell you how to do it.

If you use more Humalog Mix25 than you should

If you use more Humalog Mix25 than you need or are not sure how much you have injected, you may have low blood sugar. Check your blood sugar.

If your blood sugar is low (mild hypoglycaemia), take glucose tablets, sugar, or a sweet drink. Then eat fruit, biscuits, or a snack, as your doctor has indicated, and rest afterwards. This usually allows you to overcome a mild hypoglycaemia or a small overdose of insulin. If you get worse and your breathing becomes shallow and your skin turns pale, call your doctor immediately. Severe hypoglycaemias can be treated with an injection of glucagon. After the glucagon injection, take glucose or sugar. If you do not respond to glucagon, you should go to the hospital. Ask your doctor to inform you about glucagon.

If you forget to use Humalog Mix25

If you use less Humalog Mix25 than you need or are not sure how much you have injected, you may have high blood sugar. Check your blood sugar.

If left untreated, hypoglycaemia (low blood sugar) or hyperglycaemia (high blood sugar) can be very serious and cause headache, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see A and B in section 4 "Possible side effects").

Three simple measuresto avoid hypoglycaemia or hyperglycaemia are:

• Always have extra Humalog Mix25 syringes and vials, or extra pens and cartridges, in case you lose your KwikPen or it breaks.
• Always carry a badge that indicates you are diabetic.
• Always carry something sweet with you.

If you stop using Humalog Mix25

If you use less Humalog Mix25 than you need, you may have high blood sugar. Do not change your insulin unless your doctor has told you to.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

• body rash ? low blood pressure
• difficulty breathing ? rapid heartbeat
• wheezing ? sweating

If you think you are suffering from this type of allergy with Humalog Mix25, speak to your doctor immediately.

Localised allergy is common (≥ 1/100 to <1>

Lipodystrophy (the skin becomes thicker or a pit forms) is uncommon (≥ 1/1,000 to <1>

If you notice that the skin where you inject becomes thicker or a pit forms, inform your doctor.

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

Common problems of diabetes

1. Hypoglycaemia

Hypoglycaemia (low blood sugar) means that you do not have enough sugar in your blood. It can be caused because:

• you have injected too much Humalog Mix25 or any other type of insulin;
• you have missed a meal, delayed it, or changed your diet;
• you have worked too much or done too much exercise immediately before or after a meal;
• you have an infection or are ill (especially diarrhoea or vomiting);
• there have been changes in your insulin needs; or
• you have a worsening of a kidney or liver condition.

Alcohol and certain medicines can affect your blood sugar levels.

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

• fatigue ? palpitations
• nervousness and tremors ? nausea
• headache ? cold sweats

Until you are sure you can recognise the warning symptoms, avoid situations (e.g. driving a car) where you or others could be at risk if you have a hypoglycaemia.

B.

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

• you have not injected Humalog or other insulin;
• you have injected less insulin than your doctor has prescribed;
• you have eaten much more than your diet allows; or
• you have a fever, infection, or emotional stress.

Hyperglycaemia can end in diabetic ketoacidosis. The first symptoms occur slowly, over many hours or days. These symptoms include:

• drowsiness ? lack of appetite
• flushing ? fruity breath odour
• thirst ? nausea or vomiting

Severe symptoms are heavy breathing and rapid pulse. Get medical help immediately.

C.

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

5. Storing Humalog Mix25 KwikPen

Before the first use, store Humalog Mix25 KwikPen in the refrigerator (between 2°C and 8°C). Do not freeze.

Keep your Humalog Mix25 KwikPen 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 the KwikPen pen you are using in the refrigerator. The KwikPen pen should not be stored with the needle attached.

Keep this medicine out of 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 notice 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 thrown down the drain or into the trash. 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 Mix25 KwikPen 100 units/ml injectable suspension

• 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, disodium 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 Mix25 KwikPen 100 units/ml injectable suspension is a sterile, white suspension that contains 100 units of insulin lispro in each milliliter of injectable suspension (100 units/ml). 25% of insulin lispro in Humalog Mix25 is dissolved in water. In Humalog Mix25, a suspension of 75% insulin lispro has been incorporated along with protamine sulfate. Each Humalog Mix25 KwikPen contains 300 units (3 milliliters). Humalog Mix25 KwikPen is presented in a package of 5 pre-filled pens or in a multiple package consisting of 2 packages of 5 pre-filled pens. Not all presentations may be marketed. The Humalog Mix25 contained in your KwikPen is the same as that presented in loose Humalog Mix25 cartridges. The KwikPen simply has a built-in cartridge. When the KwikPen is empty, it cannot be reused.

Marketing authorization holder and manufacturer

Humalog Mix25 KwikPen 100 units/ml injectable suspension 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:

Belgique/België/Belgien

Eli Lilly Benelux S.A./N.V.

Tél/Tel: + 32-(0)2 548 84 84

Lietuva

Eli Lilly Lietuva

Tel. +370 (5) 2649600

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?? "??? ???? ?????????" ?.?. - ????????

???. + 359 2 491 41 40

Luxembourg/Luxemburg

Eli Lilly Benelux S.A./N.V.

Tél/Tel: + 32-(0)2 548 84 84

Ceskárepublika

ELI LILLY CR, s.r.o.

Tel: + 420 234 664 111

Magyarország

Lilly Hungária Kft.

Tel: + 36 1 328 5100

Danmark

Eli Lilly Danmark A/S

Tlf: +45 45 26 6000

Malta

Charles de Giorgio Ltd.

Tel: + 356 25600 500

Deutschland Nederland

170

Lilly Deutschland GmbH

Tel. + 49-(0) 6172 273 2222

Eli Lilly Nederland B.V.

Tel: + 31-(0) 30 60 25 800

Eesti

Eli Lilly Nederland B.V.

Tel: +372 6817 280

Norge

Eli Lilly Norge A.S.

Tlf: + 47 22 88 18 00

Ελλ?δα

ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.

Τηλ: +30 210 629 4600

Österreich

Eli Lilly Ges. m.b.H.

Tel: + 43-(0) 1 711 780

España

Lilly S.A.

Tel: + 34-91 663 50 00

Polska

Eli Lilly Polska Sp. z o.o.

Tel: +48 22 440 33 00

France

Lilly France S.A.S.

Tél: +33-(0) 1 55 49 34 34

Portugal

Lilly Portugal - Produtos Farmacêuticos, Lda

Tel: + 351-21-4126600

Hrvatska

Eli Lilly Hrvatska d.o.o.

Tel: +385 1 2350 999

România

Eli Lilly România S.R.L.

Tel: + 40 21 4023000

Ireland

Eli Lilly and Company (Ireland) Limited

Tel: + 353-(0) 1 661 4377

Slovenija

Eli Lilly farmacevtska družba, d.o.o.

Tel: +386 (0) 1 580 00 10

Ísland

Icepharma hf.

Sími + 354 540 8000

Slovenská republika

Eli Lilly Slovakia s.r.o.

Tel: + 421 220 663 111

Italia

Eli Lilly Italia S.p.A.

Tel: + 39- 055 42571

Suomi/Finland

Oy Eli Lilly Finland Ab

Puh/Tel: + 358-(0) 9 85 45 250

Κ?προς

Phadisco Ltd

Τηλ: +357 22 715000

Sverige

Eli Lilly Sweden AB

Tel: + 46-(0) 8 7378800

Latvija

Eli Lilly (Suisse) S.A Parstavnieciba Latvija

Tel: +371 67364000

United Kingdom

Eli Lilly and Company Limited

Tel: + 44-(0) 1256 315000

Date of last revision of this prospectus:

USER MANUAL

The text of the user manual is included at the end.

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