Label: information for the user

Humalog Mix50 100 units/mL injectable suspension in cartridge

insulin lispro

Read this 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.

Humalog Mix50 is used to treat diabetes. Humalog Mix50 is a pre-mixed suspension. Its active ingredient is insulin lispro. In Humalog Mix50, 50% 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 Mix50, a suspension of 50% 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 Mix50 is a substitute for your own insulin and is used to control glucose levels in the long term. Humalog Mix50 acts very quickly and for a longer time than soluble insulin. Normally, you should use Humalog Mix50 within 15 minutes around a meal.

Your doctor may recommend using Humalog Mix50 with 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.

Do not use Humalog Mix50

• If you think you are starting to have ahypoglycemia(low blood sugar level). Further on in this leaflet, it is indicated how to resolve a mild hypoglycemia (see Section 3: If you use more Humalog Mix50 than you should).
• If you areallergicto insulin lispro or to any of the other components of this medicine (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 cartridge in the pharmacy. Make sure you are taking the Humalog Mix50 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 leaflet, 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.
• Certain 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 doing more exercise 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-standing 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).

Changes in skin at the injection site

The injection site should be rotated to avoid changes in the skin, such as lumps under the skin. Insulin may not work well if injected into a swollen area (see How to use Humalog Mix50). Please contact your doctor if you are currently injecting into a swollen area, before starting to inject into a different area. Your doctor may instruct you to closely monitor your blood sugar levels and adjust your insulin or other antidiabetic medications.

Other medicines and Humalog Mix50

Your insulin needs may change if

• you are using contraceptives,
• steroids,
• thyroid hormone replacement therapy,
• oral hypoglycemics,
• aspirin,
• sulfonamide antibiotics,
• octreotide,
• beta2 stimulants (e.g. ritodrine, salbutamol, or terbutaline),
• beta-blockers, or
• some antidepressants (monoamine oxidase inhibitors or selective serotonin reuptake inhibitors),
• danazol,
• some angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril), and
• angiotensin II receptor blockers.

Please inform your doctor if you are using, have recently used, or may need to use any other medicine, 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 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, or think you may be pregnant, please consult your doctor or pharmacist before using this medicine.

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 a hypoglycemia or not perceiving them

Humalog Mix50 contains sodium

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

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

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 cartridge must be used only by you, even if you change the needle of the device.

Dose

• Normally, Humalog Mix50 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 use it, and how often. These instructions are specific to you. Follow them exactly and go to 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 Mix50), 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.
• Inject Humalog Mix50 under the skin. Do not use any other route of administration. Under no circumstances will Humalog Mix50 be administered intravenously.

How to prepare Humalog Mix50

• The cartridges containing Humalog Mix50 must be moved between the palms of the hands ten times and inverted 180 degrees ten times immediately before use, to resuspend the insulin, until its appearance 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 vigorously, to avoid producing foam 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 pen

• First, wash your hands. Disinfect the rubber membrane of the cartridge.
• Only use Humalog Mix50 cartridges with Lilly insulin pens. Make sure the prospect accompanying the pen refers to Humalog or Lilly cartridges. The 3 ml cartridges only fit in 3 ml pens.
• Follow the instructions that accompany the pen. Insert the cartridge into the pen.
• Adjust the dose to 1 or 2 units. Then, place the pen with the needle pointing up and give it a tap on the side to let any bubbles rise to the top. Even with the pen pointing up, press the injection mechanism. Hold it until a drop of Humalog Mix50 comes out through the needle. You may still see some small air bubbles in the pen. They 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 the 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 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, remove the needle from the pen using the external needle protector. This way, Humalog Mix50 will remain sterile and there will be no losses. It will also prevent air from entering the pen and the needle from becoming clogged. Do not share needles.Do not share your pen.Do not share your insulin.Put the cap back on the pen. Leave the cartridge inside the pen.

Subsequent injections

• Before each injection, mark 1 or 2 units and press the injection mechanism, with the pen pointing up, until a drop of Humalog Mix50 comes out through the needle. You can see how much Humalog is left by looking at the indicator on the side of the cartridge. The distance between each mark on the indicator corresponds to 20 units. If there is not enough for your dose, change the cartridge.

Do not mix any other insulin with a Humalog Mix50 cartridge. When this cartridge is empty, it cannot be used again.

If you use more Humalog Mix50 than you need

If you use more Humalog Mix50 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, 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 Mix50

If you use less Humalog Mix50 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 measures to prevent hypoglycemia or hyperglycemiaare:

• Always have spare pens and cartridges, in case you lose the pen or cartridges, or they become damaged.
• Always carry a distinctive sign indicating your diabetes condition.
• Always carry some sugar.

If you interrupt treatment with Humalog Mix50

If you use less Humalog Mix50 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

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

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

Lipodystrophy is infrequent (≥ 1/1,000 to <1amyloidosis cutis). Insulin may not work well if injected into a swollen area. Change the injection site to help prevent these skin changes.

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

Reporting of 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 thenational 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 of 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 Mix50 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:

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 hypoglycemia occurs.

1. Hyperglycemia and diabetic ketoacidosis

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

• not taking Humalog or any 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.

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

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

1. Diseases

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

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

Conserve your pen 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 your pen or the cartridges you are using in the refrigerator. The pen with the cartridge incorporated 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 stuck to the bottom or walls of the cartridge, giving it a appearance similar to frost. Check it every time you inject.

Medicines should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medications you no longer need. This way, you will help protect the environment.

Composition of Humalog Mix50 100 units/mL suspension for injection in cartridge

• The active substance 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 the rest of 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 injection. Sodium hydroxide or hydrochloric acid may have been used to adjust the pH.

Appearance of the product and contents of the pack

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

Holder of the marketing authorization and responsible manufacturer

Humalog Mix50 100 units/mL suspension for injection 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 holder of the marketing authorization is Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, Netherlands.

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

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