Label: information for the user

Humalog Mix25 KwikPen 100 units/mL injectable suspension in a pre-filled pen, insulin lispro

Each KwikPen administers 1 to 60 units in increments of 1 unit.

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

• Keep this label, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication 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 or pharmacist, even if they are not listed in this label. See section 4.

Label content

1. What Humalog Mix25 KwikPen is and for what it is used
2. What you need to know before starting to use Humalog Mix25 KwikPen
3. How to use Humalog Mix25 KwikPen
4. Possible adverse effects
5. Storage of Humalog Mix25 KwikPen
6. Contents of the package and additional information

Humalog Mix25 KwikPen is used to treat diabetes. It is a pre-mixed suspension. Its active ingredient is insulin lispro. In Humalog Mix25 KwikPen, 25% of insulin lispro has been dissolved in water and works faster than normal human insulin because the insulin molecule has been slightly changed. In Humalog Mix25 KwikPen, a suspension of 75% of insulin lispro has been incorporated along with protamine sulfate, to prolong its action.

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

Humalog Mix25 is usually used within 15 minutes of eating.

Your doctor may recommend using Humalog Mix25 KwikPen in addition to a longer-acting insulin. Each one comes with its own leaflet with specific information. Do not change your insulin unless your doctor tells 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 each time.

The number of units is shown in the dosing window, check it always 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 administer more than one injection.

Do not use Humalog Mix25 KwikPen

• If you think you are starting to havehypoglycemia(low blood sugar level). Further on in this prospectus, it is indicated how to resolve a mild hypoglycemia (see Section 3: If you use more Humalog Mix25 than you should).
• If you areallergicto insulin lispro or to any of the other components of this medication (including in Section 6).

Warnings and precautions

• Always check the name and type of insulin that appears on the packaging and the label of the pre-filled pen in the pharmacy. Make sure you are taking the Humalog Mix25 KwikPen that your doctor has prescribed.
• If your blood sugar levels are well controlled with your current insulin therapy, you may not perceive the warning symptoms that alert you that your blood sugar is dropping too low. Further on in this prospectus, these warning symptoms are specified. You must carefully organize when you should eat, when you should exercise, and to what extent you can do it. You also have to closely monitor your blood sugar levels by frequently performing blood glucose tests.
• Some patients who have experienced hypoglycemia after switching from animal insulin to human insulin have commented that the initial warning symptoms were less evident or different. If you have frequent hypoglycemias or difficulty recognizing them, please do not hesitate to inform your doctor.
• If you answer AFFIRMATIVELY to any of the following questions, please inform your doctor, pharmacist, or diabetes educator
• • Have you recently been ill?
  • Do you have liver or kidney problems?
  • Are you exercising more than usual?
• The amount of insulin you need may vary if you drink alcohol.
• If you are planning to travel abroad, please 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 following in your country.
• Some patients with long-term type 2 diabetes 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 difficulty breathing, rapid weight gain, or localized inflammation (edema).
• It is not recommended that the blind or people with visual impairments use this pen without the help of a trained person in the use of the pen.

Other medications and Humalog Mix25 KwikPen

Your insulin needs may change if

• you are using contraceptives,
• steroids,
• thyroid hormone replacement therapy,
• oral hypoglycemics,
• aspirin,
• sulfonamide antibiotics,
• octreotide,
• beta-2 stimulants (for example ritodrine, salbutamol, or terbutaline),
• beta-blockers, or
• some antidepressants (monoamine oxidase inhibitors or selective serotonin reuptake inhibitors),
• danazol,
• some angiotensin-converting enzyme inhibitors (for example captopril, enalapril), and
• angiotensin II receptor blockers.

Inform your doctor if you are using, have used recently, or may need to use any other medication, even those purchased 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 generally 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, or think you may be pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

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

• frequent episodes of hypoglycemia
• difficulty perceiving the symptoms of hypoglycemia or not perceiving them

Humalog Mix25 KwikPen contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially “sodium-free”.

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

Dose

• Normally, Humalog Mix25 should be injected within 15 minutes around a meal. If necessary, it can be injected a little after a meal. However, your doctor will have indicated exactly the amount you need to use, when to apply 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 (for example, from animal or human insulin to a product with Humalog), you may need to use a greater or lesser amount than before. You may only need to do this for the first injection or may require a gradual change that lasts several weeks or months.
• Humalog Mix25 KwikPen is only indicated for injection just below the skin. Consult your doctor if you need to inject insulin by another method.

How to prepare Humalog Mix25 KwikPen

• The KwikPen must be moved between the palms of the hands ten times and turned 180 degrees ten times immediately before using it, to suspend the insulin again, until the appearance of the insulin is uniformly turbid or milky. If not, repeat the procedure indicated above until the components are mixed. The cartridges contain a small crystal bead to facilitate mixing. Do not shake it forcefully, to avoid foam formation that could interfere with the correct measurement of the dose. Check 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 frosty appearance. Check it every time you inject.

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

• Wash your hands first.
• Read the instructions on how to use your pre-filled insulin pen. Follow the instructions carefully. You will find some reminders below.
• 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 eliminated from your KwikPen. You may still see some small air bubbles in your pen, which are harmless. However, if the air bubble is too large, the dose of the injection may be less precise.

How to inject Humalog Mix25

• Before injecting, clean the skin as you have been taught. Inject just below 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 ensure you have injected the full dose. Do not rub the area where you just injected. Make sure you have injected at least 1 cm away from where you last injected and that you "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 external needle protector. This will keep the insulin sterile and prevent losses. It will also prevent air from entering the pen and clogging the needle. 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, remove all air bubbles. You can see the remaining insulin by holding the pen with the needle pointing up. The scale on the cartridge shows approximately the number of units remaining.
• Do not mix any other insulin with 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 need

If you use more Humalog Mix25 than you need or are unsure of how much you have injected, you may have low blood sugar. Check your blood sugar.

If your blood sugar is low (mild hypoglycemia), take glucose tablets, sugar, or a sweet drink. Then eat fruit, cookies, or a snack, as your doctor has instructed you, and rest afterwards. This usually helps you recover from mild hypoglycemia or a small overdose of insulin. If you get worse and your breathing is shallow and your skin is pale, call your doctor immediately. Severe hypoglycemia can be treated with a glucagon injection. 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 unsure of how much you have injected, you may have high blood sugar. Check your blood sugar.

If not treated properly, hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar) can be very serious and cause headaches, nausea, vomiting, dehydration, loss of consciousness, coma, and even death (see A and B in section 4 "Possible side effects").

Three simple measuresto avoid hypoglycemia or hyperglycemia are:

• Always have spare syringes and vials of Humalog Mix25, or extra pens and cartridges, in case you lose your KwikPen or it breaks.
• Always carry a badge that warns of your diabetes condition.
• Always carry some sugar with you.

If you interrupt treatment with Humalog Mix25

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

If you have any other questions about using this medication, ask your doctor or pharmacist.

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

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

• body rash?low blood pressure
• difficulty breathing?rapid heartbeats
• high-pitched breathing?sweating

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

Localized allergy is common (≥ 1/100 to <1

Lipodystrophy (the skin becomes thicker or forms a kind of hole) is infrequent

(≥ 1/1,000 to <1

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

Reporting side effects

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

Common problems with diabetes

1. Hypoglycemia

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

• having taken too much Humalog Mix25 or any other type of insulin;
• having missed a meal, delayed it or changed your diet;
• having worked a lot or done too much exercise immediately before or after a meal;
• having an infection or being ill (especially diarrhea or vomiting);
• having changes in your insulin needs; or
• having a worsening of a kidney or liver disease.

Alcohol and certain medications can affect your blood sugar levels.

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

• fatigue?palpitations
• nervousness and tremors?nausea
• headache?chills

Until you are sure of recognizing the alarm symptoms, avoid situations (e.g. driving a car) in which you or others may be put in danger if a hypoglycemia were to occur.

B.Hypoglycemia and diabetic ketoacidosis

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

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

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

• drowsiness?loss of appetite
• facial flushing?breath with a fruity odor
• thirst?nausea or vomiting

Severe symptoms are deep breathing and rapid pulse.Seek medical assistance immediately.

C.Illnesses

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

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

Store your Humalog Mix25 KwikPen in use at room temperature (below 30°C) and discard after 28 days. Do not leave it near any heat source or in direct sunlight. Do not store the KwikPen in use in the refrigerator. The KwikPen should not be stored with the needle attached.

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

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

Do not use this medication if you observe lumps or white solid particles adhered to the bottom or walls of the cartridge, giving it an appearance similar to frost. Check it each time you inject.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

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 DNA recombinant technology process. It is a modified form of human insulin and, therefore, differs from other human insulins and animal 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 contents of the package

Humalog Mix25 KwikPen 100 units/mL injectable suspension is a sterile, white suspension containing 100 units of insulin lispro in each milliliter of injectable suspension (100 units/mL). A 25% of insulin lispro in Humalog Mix25 is dissolved in water. In Humalog Mix25, a suspension of 75% of 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 formed by 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 Humalog Mix25 cartridges. The KwikPen simply has a cartridge incorporated. When the KwikPen is empty, it cannot be reused.

Holder of the marketing authorization and responsible 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 holder of the marketing authorization is Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.

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

Belgium/België/Belgien

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

Tel: + 32-(0)2 548 84 84

Lithuania

Eli Lilly Lietuva

Tel: +370 (5) 2649600

...

...

Luxembourg/Luxemburg

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

Tel: + 32-(0)2 548 84 84

Czech Republic

ELI LILLY CR, s.r.o.

Tel: + 420 234 664 111

Hungary

Lilly Hungária Kft.

Tel: + 36 1 3 28 5100

Denmark

Eli Lilly Danmark A/S

Tlf: +45 45 26 6000

Malta

Charles de Giorgio Ltd.

Tel: + 356 25600 500

Germany

Lilly Deutschland GmbH

Tel: + 49-(0) 6172 273 2222

Eli Lilly Nederland B.V.

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

Estonia

Eli Lilly Nederland B.V.

Tel: +372 6817 280

Norway

Eli Lilly Norge A.S.

Tlf: + 47 22 88 18 00

Greece

ΦΑΡΜΑΣΕΡΒ-ΛΙΛΛΥ Α.Ε.Β.Ε.

Tel: +30 210 629 4600

Austria

Eli Lilly Ges. m.b.H.

Tel: + 43-(0) 1 711 780

Spain

Lilly S.A.

Tel: + 34-91 663 50 00

Poland

Eli Lilly Polska Sp. z o.o.

Tel: +48 22 440 33 00

France

Lilly France S.A.S.

Tel: +33-(0) 1 55 49 34 34

Portugal

Lilly Portugal - Produtos Farmacêuticos, Lda

Tel: + 351-21-4126600

Croatia

Eli Lilly Hrvatska d.o.o.

Tel: +385 1 2350 999

Romania

Eli Lilly România S.R.L.

Tel: + 40 21 4023000

Ireland

Eli Lilly and Company (Ireland) Limited

Tel: + 353-(0) 1 661 4377

Slovenia

Eli Lilly farmacevtska družba, d.o.o.

Tel: +386 (0) 1 580 00 10

Iceland

Icepharma hf.

Tel: + 354 540 8000

Slovakia

Eli Lilly Slovakia s.r.o.

Tel: + 421 220 663 111

Italy

Eli Lilly Italia S.p.A.

Tel: + 39- 055 42571

Finland

Oy Eli Lilly Finland Ab

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

Cyprus

Phadisco Ltd

Tel: +357 22 715000

Sweden

Eli Lilly Sweden AB

Tel: + 46-(0) 8 7378800

Lithuania

Eli Lilly (Suisse) S.A Parstavnieciba Latvija

Tel: +371 67364000

United Kingdom

Eli Lilly and Company Limited

Tel: + 44-(0) 1256 315000

Last review date of this leaflet:

USER MANUAL

The user manual text is included at the end.

More detailed information about this medication is available on the European Medicines Agency website:http://www.ema.europa.eu.